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Qu Y, Shourabizadeh H, Subramanian A, Aleman DM, Rousseau LM, Law AD, Viswabandya A, Michelis FV. Differential impact of CD34+ cell dose for different age groups in allogeneic hematopoietic cell transplantation for acute leukemia: a machine learning-based discovery. Exp Hematol 2025; 141:104684. [PMID: 39581301 DOI: 10.1016/j.exphem.2024.104684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 11/04/2024] [Accepted: 11/13/2024] [Indexed: 11/26/2024]
Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) presents a potentially curative treatment for hematologic malignancies yet carries associated risks and complications. Continuous research focuses on predicting outcomes and identifying risk factors. Notably, the influence of CD34+ cell dose on overall survival (OS) has been the subject of numerous studies yielding contradictory results. We developed machine learning (ML) models to predict allo-HCT outcomes and, through the application of SHapley Additive exPlanations (SHAP), an explainable artificial intelligence (XAI) technique enabled the identification of new and clinically relevant feature-outcome relationships. In particular, we identified a clear interaction between CD34+ cell dose of peripheral blood stem cell (PBSC) grafts and patient age at allo-HCT for patients with acute leukemia. Results of multivariable analysis validated the interaction effect: in young patients with acute leukemia (aged ≤45 years), low dose of CD34+ cells (<4.3 × 106 CD34+/kg) was associated with better OS against high dose (≥7 ×106 CD34+/kg) (hazard ratio [HR], 0.38; p = 0.019), while for older patients with acute leukemia (>45 years), low CD34+ cell dose (<3.8 ×106 CD34+/kg) was associated with worse OS against high dose (≥6.1 ×106 CD34+/kg) (HR, 1.58; p = 0.033). In conclusion, our findings suggest that tailoring CD34+ cell dose by patient age may benefit patients with acute leukemia undergoing allo-HCT, while XAI showcases excellent proficiency in revealing such interactions.
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Affiliation(s)
- Yiyang Qu
- Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada
| | - Hamed Shourabizadeh
- Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada
| | - Aravind Subramanian
- Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada
| | - Dionne M Aleman
- Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada
| | - Louis-Martin Rousseau
- Department of Mathematical and Industrial Engineering, Polytechnique Montreal, Montreal, Quebec, Canada
| | - Arjun D Law
- Hans Messner Allogeneic Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Auro Viswabandya
- Hans Messner Allogeneic Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Fotios V Michelis
- Hans Messner Allogeneic Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
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2
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Huang L, Lin B, Mu Y, Li Y, Chen M, Zhou Y, Zhu G, Jiang E, Xia Y. Sysmex XN-HPC: study of reference intervals and clinical decision limits in healthy allogeneic donors mobilised with G-CSF. Clin Exp Med 2024; 24:197. [PMID: 39180670 PMCID: PMC11344708 DOI: 10.1007/s10238-024-01467-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 08/18/2024] [Indexed: 08/26/2024]
Abstract
The Sysmex XN series haematopoietic progenitor cell (XN-HPC) is a novel tool for assessing stem cell yield before allogeneic haematopoietic stem cell transplantation. This study aimed to establish a reference interval (RI) for XN-HPC in peripheral blood allogeneic transplant donors following granulocyte colony-stimulating factor (G-CSF) stimulation and determine its clinical significance. All specimens were analysed using Sysmex XN-20. Samples were collected and analysed using non-parametric percentile methods to define the RIs. Quantile regression was used to explore the dependency of the RIs on sex and age. Samples were included in clinical decision limits for apheresis based on receiver operating characteristic curve analysis. The non-parametrically estimated RI for XN-HPC was 623.50 (90% confidence interval [CI90%] 510.00-657.00) to 4,144.28 (CI90% 3,761.00-4,547.00). The RIs for the XN-HPC were not age-dependent but were sex-dependent. The RI for males was 648.40 (CI90% 582.00-709.00)-4,502.60 (CI90% 4,046.00-5,219.00) and for females was 490.90 (CI90% 311.00-652.00)-3,096.90 (CI90% 2,749.00-3,782.00). Comparisons based on XN-HPC values between the poor and less-than-optimal groups, good and less-than-optimal groups, and good and non-good groups had areas under the curve of 0.794 (P < 0.001), 0.768 (P < 0.001), and 0.806 (P < 0.001), respectively, indicating a good predictive value for mobilisation effectiveness. XN-HPC data exceeding 3974 × 106/L suggested that a sufficient number of stem cells could be collected clinically. Values > 5318 < 106/L indicated 100% mobilisation effectiveness. We established an RI for XN-HPC in peripheral blood allogeneic transplant donors following G-CSF stimulation and determined clinical decision thresholds for mobilisation efficiency.
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Affiliation(s)
- Lunhui Huang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- Tianjin Institutes of Health Science, Tianjin, China
| | - Binbin Lin
- Department of Epidemiology and Statistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking, Union Medical College, Beijing, China
| | - Yueyi Mu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- Tianjin Institutes of Health Science, Tianjin, China
| | - Yong Li
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- Tianjin Institutes of Health Science, Tianjin, China
| | - Miao Chen
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- Tianjin Institutes of Health Science, Tianjin, China
| | - Yunxia Zhou
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- Tianjin Institutes of Health Science, Tianjin, China
| | - Guoqing Zhu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
- Tianjin Institutes of Health Science, Tianjin, China.
| | - Erlie Jiang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
- Tianjin Institutes of Health Science, Tianjin, China.
| | - Yonghui Xia
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
- Tianjin Institutes of Health Science, Tianjin, China.
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3
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Oyama T, Fujiwara SI, Tominaga R, Yokoyama D, Noguchi A, Furuki S, Koyama S, Murahashi R, Nakashima H, Hyodo K, Ikeda T, Kawaguchi SI, Toda Y, Nagayama T, Umino K, Minakata D, Morita K, Ashizawa M, Yamamoto C, Hatano K, Sato K, Otsuki I, Ohmine K, Kanda Y. Effects of CD34 + cell dose on engraftment and long-term outcomes after allogeneic bone marrow transplantation. Clin Transplant 2024; 38:e15313. [PMID: 38581299 DOI: 10.1111/ctr.15313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 03/21/2024] [Accepted: 03/24/2024] [Indexed: 04/08/2024]
Abstract
BACKGROUND The number of CD34+ cells in the graft is generally associated with time to engraftment and survival in transplantation using cord blood or allogeneic peripheral blood stem cells. However, the significance of abundant CD34+ in bone marrow transplantation (BMT) remained unclear. METHODS We retrospectively reviewed 207 consecutive adult patients who underwent their first BMT at Jichi Medical University between January 2009 and June 2021. RESULTS The median nucleated cell count (NCC) and CD34+ cell dose were 2.17 × 108/kg (range .56-8.52) and 1.75 × 106/kg (.21-5.84), respectively. Compared with 104 patients in the low CD34+ group (below the median), 103 patients in the high CD34+ group (above the median) showed faster engraftment at day +28 in terms of neutrophil (84.6% vs. 94.2%; p = .001), reticulocyte (51.5% vs. 79.6%; p < .001), and platelet (39.4% vs. 72.8%; p < .001). There were no significant differences in overall survival, relapse, nonrelapse mortality, acute or chronic graft-versus-host disease, or infectious complications between the two groups in univariate and multivariate analyses. Low or high NCC had no significant effect on overall survival, nonrelapse mortality, cumulative incidence of relapse and graft-versus-host disease, either. While a positive correlation was observed between NCC and the CD34+ cell dose, a high CD34+ cell dose was associated with rapid hematopoietic recovery, even in patients with NCC below the median. CONCLUSION Measurement of CD34+ cell dose in addition to NCC was useful for predicting hematopoietic recovery, but seemed to have little influence on the long-term outcome in BMT.
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Affiliation(s)
- Takashi Oyama
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Shin-Ichiro Fujiwara
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
- Division of Cell Transplantation and Transfusion, Jichi Medical University, Tochigi, Japan
| | - Ryutaro Tominaga
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Daizo Yokoyama
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Atsuto Noguchi
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Shuka Furuki
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Shunsuke Koyama
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Rui Murahashi
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Hirotomo Nakashima
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Kazuki Hyodo
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Takashi Ikeda
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Shin-Ichiro Kawaguchi
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Yumiko Toda
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Takashi Nagayama
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
- Division of Cell Transplantation and Transfusion, Jichi Medical University, Tochigi, Japan
| | - Kento Umino
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Daisuke Minakata
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Kaoru Morita
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Masahiro Ashizawa
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Chihiro Yamamoto
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Kaoru Hatano
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Kazuya Sato
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Ikuko Otsuki
- Division of Cell Transplantation and Transfusion, Jichi Medical University, Tochigi, Japan
| | - Ken Ohmine
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Yoshinobu Kanda
- Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
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Maruyama Y, Nishikii H, Kurita N, Sakamoto T, Hattori K, Suehara Y, Yokoyama Y, Kato T, Obara N, Sakata-Yanagimoto M, Chiba S. Impact of CD34 positive cell dose in donor graft on the outcomes after haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide - A retrospective single-center study with a Japanese cohort. Blood Cells Mol Dis 2024; 105:102820. [PMID: 38199143 DOI: 10.1016/j.bcmd.2023.102820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 12/17/2023] [Accepted: 12/18/2023] [Indexed: 01/12/2024]
Abstract
BACKGROUND Haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with post-transplant cyclophosphamide (PTCy) is an important therapeutic option for patients lacking an HLA-matched donor. However, the significance of CD34+ cell dose in grafts has not been fully elucidated. OBJECTIVE We aimed to explore the impact of CD34+ cell dose on outcomes after haplo-PBSCT with PTCy. STUDY DESIGN We retrospectively investigated 111 consecutive patients who underwent haplo-PBSCT with PTCy or HLA-matched PBSCT from related donors. RESULTS There were no statistically significant differences in 3-year overall survival (p = 0.559) or progression-free survival (p = 0.974) between haplo-PBSCT and matched PBSCT. Delayed neutrophil engraftment and a lower incidence of graft-versus-host disease were observed in haplo-PBSCT. The median dose of CD34+ cells was 4.9 × 106 /kg in 57 haplo-PBSCT and 4.5 × 106 /kg in 54 matched PBSCTs. Importantly, patients who underwent haplo-PBSCT with the administration of CD34+ cell at a dose of ≥4.0 × 106 /kg significantly had improved OS (p = 0.015) and decreased incidence of disease relapse (p = 0.001) without increasing incidence of GVHD. CONCLUSION Our data suggest that a higher dose of CD34+ cells in haplo-PBSCT with PTCy positively impacts the outcomes without an increase of GVHD.
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Affiliation(s)
- Yumiko Maruyama
- Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan
| | - Hidekazu Nishikii
- Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan; Department of Hematology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Naoki Kurita
- Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan; Department of Hematology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Tatsuhiro Sakamoto
- Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan; Department of Hematology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Keiichiro Hattori
- Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan; Department of Hematology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Yasuhito Suehara
- Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan
| | - Yasuhisa Yokoyama
- Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan; Department of Hematology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Takayasu Kato
- Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan; Department of Hematology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Naoshi Obara
- Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan; Department of Hematology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Mamiko Sakata-Yanagimoto
- Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan; Department of Hematology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan; Division of Advanced Hemato-Oncology, Transborder Medical Research Center, University of Tsukuba, Tsukuba, Japan
| | - Shigeru Chiba
- Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan; Department of Hematology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
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5
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Salhotra A, Yuan S, Ali H. Fifty years of BMT: risk stratification, donor matching, and stem cell collection for transplantation. Front Oncol 2023; 13:1196564. [PMID: 37700828 PMCID: PMC10493308 DOI: 10.3389/fonc.2023.1196564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 07/07/2023] [Indexed: 09/14/2023] Open
Abstract
In this review, we discuss recipient risk assessment for allo-HCT regarding comorbidities present at baseline to predict non relapse mortality. We further reviewed the incorporation of remission status and cytogenetic risk prior to allograft transplantation to predict relapse rates for hematologic malignancies. HCT-CI and DRI are tools available to physicians to assess the risk-benefit of allo-HCT in patients referred for transplantation. Next, we discuss our algorithm for donor selection and criteria for donor selection in case matched donors are not available. Finally, we discuss our approach for stem cell mobilization, especially in donors failing G-CSF, and our approach for the use of plerixafor and data supporting its use.
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Affiliation(s)
- Amandeep Salhotra
- Department of Hematology and Hematopoietic Cell Transplantation (HCT), City of Hope National Medical Center, Duarte, CA, United States
| | - Shan Yuan
- Division of Transfusion Medicine, Department of Pathology and Laboratory Medicine, City of Hope National Medical Center, Duarte, CA, United States
| | - Haris Ali
- Department of Hematology and Hematopoietic Cell Transplantation (HCT), City of Hope National Medical Center, Duarte, CA, United States
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6
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Parmar G, Allan DS, Morris G, Dibdin N, Ganz K, Mostert K, Paulson K, Petraszko T, Stevens N, Seftel MD. The Effect of the COVID-19 Pandemic on Unrelated Allogeneic Hematopoietic Donor Collections and Safety. Curr Oncol 2023; 30:3549-3556. [PMID: 36975483 PMCID: PMC10047865 DOI: 10.3390/curroncol30030270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/19/2023] [Accepted: 03/20/2023] [Indexed: 03/29/2023] Open
Abstract
BACKGROUND AND OBJECTIVES The COVID-19 pandemic profoundly influenced unrelated donor (UD) allogeneic peripheral blood stem cell (PBSC) collections. Changes included efforts to minimize COVID-19 exposure to donors and cryopreservation of products. The extent to which the efficacy and safety of PBSC donations were affected by the pandemic is unknown. METHODS Prospective cohort analysis of PBSC collections comparing pre-pandemic (01 April 2019-14 March 2020) and pandemic (15 March 2020-31 March 2022) eras. RESULTS Of a total of 291 PBSC collections, cryopreservation was undertaken in 71.4% of pandemic donations compared to 1.1% pre-pandemic. The mean requested CD34+ cell dose/kg increased from 4.9 ± 0.2 × 106 pre-pandemic to 5.4 ± 0.1 × 106 during the pandemic. Despite this increased demand, the proportion of collections that met or exceeded the requested cell dose did not change, and the mean CD34+ cell doses collected (8.9 ± 0.5 × 106 pre-pandemic vs. 9.7 ± 0.4 × 106 during the pandemic) remained above requested targets. Central-line placements were more frequent, and severe adverse events in donors increased during the pandemic. CONCLUSION Cryopreservation of UD PBSC products increased during the pandemic. In association with this, requested cell doses for PBSC collections increased. Collection targets were met or exceeded at the same frequency, signaling high donor and collection center commitment. This was at the expense of increased donor or product-related severe adverse events. We highlight the need for heightened vigilance about donor safety as demands on donors have increased since the pandemic.
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Affiliation(s)
- Gaganvir Parmar
- Stem Cells, Canadian Blood Services, Ottawa, ON K2E 8A6, Canada
- Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
| | - David S Allan
- Stem Cells, Canadian Blood Services, Ottawa, ON K2E 8A6, Canada
- Department of Medicine and Biochemistry, Microbiology & Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Gail Morris
- Stem Cells, Canadian Blood Services, Ottawa, ON K2E 8A6, Canada
| | - Nicholas Dibdin
- Stem Cells, Canadian Blood Services, Ottawa, ON K2E 8A6, Canada
| | - Kathy Ganz
- Stem Cells, Canadian Blood Services, Ottawa, ON K2E 8A6, Canada
| | - Karen Mostert
- Stem Cells, Canadian Blood Services, Ottawa, ON K2E 8A6, Canada
| | - Kristjan Paulson
- Cell Therapy and Transplant Canada, Winnipeg, MB R3P 2R8, Canada
- Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0V9, Canada
| | - Tanya Petraszko
- Stem Cells, Canadian Blood Services, Ottawa, ON K2E 8A6, Canada
- Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC V1Y 1T3, Canada
| | - Nora Stevens
- Stem Cells, Canadian Blood Services, Ottawa, ON K2E 8A6, Canada
| | - Matthew D Seftel
- Stem Cells, Canadian Blood Services, Ottawa, ON K2E 8A6, Canada
- Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC V1Y 1T3, Canada
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7
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Pedraza A, Salas MQ, Rodríguez-Lobato LG, Charry P, Suárez-Lledo M, Martínez-Cibrian N, Doménech A, Solano MT, Arcarons J, de Llobet N, Rosiñol L, Gutiérrez-García G, Avilés FF, Urbano-Ispízua Á, Rovira M, Martínez C. Effect of CD34 + Cell Dose on the Outcomes of Allogeneic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide. Transplant Cell Ther 2023; 29:181.e1-181.e10. [PMID: 36526259 DOI: 10.1016/j.jtct.2022.12.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/28/2022] [Accepted: 12/05/2022] [Indexed: 12/23/2022]
Abstract
The impact of infused CD34+ cell dose on outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) using standard graft-versus-host disease (GVHD) prophylaxis remains controversial. Information on this subject is scarce for alloHSCT using high-dose post-transplantation cyclophosphamide (PTCy). We aimed to assess the effect of CD34+ cell dose in peripheral blood stem cell (PBSC) grafts on the outcome of alloHSCT using PTCy-based GVHD prophylaxis. To do so, we conducted a single-center retrospective analysis of 221 consecutive adult patients who underwent PTCy alloHSCT from HLA-matched sibling donors (MSDs; n = 22), HLA-matched unrelated donors (MUDs; n = 83), mismatched unrelated donors (MMUDs; n = 73), and haploidentical donors (n = 43). Based on the binary partitioning method, 5 × 106/kg was used as the optimal cutoff for CD34+ cell dose. According to our institutional protocol, the maximum CD34+ cell dose was capped at 8 × 106/kg. The study cohort was divided into 2 groups based on CD34+ cell dose: high dose (>5 to 8 × 106/kg) and low dose (≤5 × 106/kg). Patients receiving high-dose CD34+-containing grafts had significantly shorter median times to neutrophil engraftment and platelet engraftment compared to those who received low-dose CD34+ (19 days versus 21 days [P = .002] and 16 days versus 22 days [P = .04], respectively). There were no differences between the high-dose and low-dose groups in the cumulative incidence of day +100 acute GVHD (grade II-IV: 25% versus 23% [P = .7]; grade III-IV: 5% versus 4% [P = .4], respectively) or 2-year chronic GVHD (moderate/severe GVHD: 9% versus 6%; P = .5). There was no impact of CD34+ cell dose on survival outcomes with the use of MSDs, MUDs, or MMUDs. Recipients of haploidentical alloHSCT using low-dose CD34+ cells had significantly worse overall survival (hazard ratio [HR], 6.01; P = .004) and relapse-free survival (HR, 4.57; P = .004). In recipients of PBSC PTCy alloHSCT, infused CD34+ cell doses >5 to 8 × 106/kg were associated with faster neutrophil and platelet engraftment, independent of donor type. Our study suggests an impact of CD34+ cell dose on survival outcomes only with haploidentical donors, for whom the administration of a CD34+ cell dose ≤5 × 106/kg significantly decreased survival outcomes.
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Affiliation(s)
- Alexandra Pedraza
- Blood Bank Department, Hematopoietic Transplantation Unit, Banc de Sang i Teixits, Hospital Clínic, Barcelona, Spain.
| | - María Queralt Salas
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain
| | - Luis Gerardo Rodríguez-Lobato
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain
| | - Paola Charry
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain
| | - María Suárez-Lledo
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain
| | - Nuria Martínez-Cibrian
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain
| | - Ariadna Doménech
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain
| | - Maria Teresa Solano
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain
| | - Jordi Arcarons
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain
| | - Noemí de Llobet
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain
| | - Laura Rosiñol
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain
| | - Gonzalo Gutiérrez-García
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain
| | - Francesc Fernández Avilés
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain; Institute Josep Carreras, Hospital Clínic, Barcelona, Spain
| | - Álvaro Urbano-Ispízua
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain; Institute Josep Carreras, Hospital Clínic, Barcelona, Spain
| | - Montserrat Rovira
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain; Institute Josep Carreras, Hospital Clínic, Barcelona, Spain
| | - Carmen Martínez
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain; Institute Josep Carreras, Hospital Clínic, Barcelona, Spain
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8
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Yegin ZA, Bostankolu Değirmenci B, Yazıcı Şener G, Savaş EM, Özkurt ZN, Koç HN, İlhan Ç. Variable impact of graft CD3 + cell content on graft versus host disease in hematopoietic stem cell transplant recipients: Is the role of donor CD3 + cells overestimated? Transfus Apher Sci 2021; 61:103349. [PMID: 34974969 DOI: 10.1016/j.transci.2021.103349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 12/23/2021] [Accepted: 12/28/2021] [Indexed: 10/19/2022]
Abstract
Graft cellular composition is considered as a significant determinant of transplant outcome. Donor CD3+ cells were shown to have a significant association with the development of graft vs host disease (GvHD). The aim of this study was to investigate the impact of graft CD3+ cell content on transplant outcome, particularly in terms of GvHD and relapse. We retrospectively analysed the records of 515 allo-HCT recipients [median age: 37(15-71) years; male/female: 323/192]. The optimal threshold of infused CD3+ cell count for acute GvHD development was estimated to be 197.5 × 106/kg (AUC: 0.572; 95 % CI: 0.513-0.631; p = 0.018) and 198.5 × 106/kg (AUC: 0.6; 95 % CI: 0.520-0.679; p = 0.019) for the general population and reduced-intensity conditioning (RIC) subgroup, respectively. Acute GvHD was more frequent in low-CD3+ group in the whole study population, particularly in RIC transplants. The incidence of cytomegalovirus reactivation was higher in low-CD3+ group and neutrophil engraftment occured earlier in the same group of patients. Overall survival and non-relapse mortality were comparable between high and low-CD3+ groups. Age, ECOG performance status, hypogammaglobulinemia, chronic GvHD and post-transplant relapse were found to predict prognosis in multivariate analysis. By focusing mainly on donor T cells, the potential role of host immune cells in the early post-transplant milieu may have been underestimated. Drawing a more detailed profile of graft and host immune cells in the joint microenvironment may elucidate our way to a better understanding of GvHD pathogenesis. By this way a comprehensive pre-transplant risk assessment could be improved to generate more personalized approaches.
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Affiliation(s)
- Zeynep Arzu Yegin
- Gazi University Faculty of Medicine, Department of Hematology, Ankara, Turkey.
| | | | - Görkem Yazıcı Şener
- Gazi University Faculty of Medicine, Department of Internal Medicine, Ankara, Turkey
| | - Emine Merve Savaş
- Gazi University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Zübeyde Nur Özkurt
- Gazi University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Hande Nur Koç
- Gazi University Faculty of Medicine, Department of Internal Medicine, Ankara, Turkey
| | - Çiğdem İlhan
- Gazi University Faculty of Medicine, Department of Hematology, Ankara, Turkey
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9
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Gauntner TD, Brunstein CG, Cao Q, Weisdorf D, Warlick ED, Jurdi NE, Maakaron JE, Arora M, Betts BC, Bachanova V, Holtan SG, He FC. Association of CD34 Cell Dose with 5-Year Overall Survival after Peripheral Blood Allogeneic Hematopoietic Cell Transplantation in Adults with Hematologic Malignancies. Transplant Cell Ther 2021; 28:88-95. [PMID: 34774817 DOI: 10.1016/j.jtct.2021.11.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 10/14/2021] [Accepted: 11/07/2021] [Indexed: 11/18/2022]
Abstract
Higher CD34 cell dose is associated with improved engraftment after peripheral blood allogeneic hematopoietic stem cell transplantation (alloHCT) but also may increase the risk of long-term complications, such as graft-versus-host disease (GVHD). Prior studies examining the relationship between CD34 cell dose and long-term survival outcomes have yielded conflicting results. In this study, we sought to clarify the prognostic impact of CD34 cell dose by examining a large contemporary cohort of patients undergoing alloHCT with a matched sibling peripheral blood stem cell (PBSC) donor. We retrospectively examined the impact of CD34 cell dose on overall survival (OS), neutrophil engraftment, platelet engraftment, treatment-related mortality, relapse, acute GVHD grade II-IV and III-IV, and chronic GVHD in 377 consecutive patients undergoing alloHCT with a PBSC graft source from a matched sibling donor at the University of Minnesota between 2002 and 2015. The patients were classified into 3 groups based on the tertile (T) of CD34 cell dose received: T1, <5 × 106 cells/kg; T2, 5 to 7.5 × 106 cells/kg; and T3, ≥7.5 × 106 cells/kg. Multivariable analysis demonstrated that high CD34 cell dose was associated with superior 5-year OS (hazard ratio [HR], 0.57; P = .01) and more rapid platelet engraftment (HR, 1.70; P < .01). Higher CD34 cell dose also was associated with improved absolute neutrophil count engraftment (T2: HR, 1.54; T3: HR, 1.52; P < .01). There was no association between CD34 cell dose and TRM or relapse at 5 years. Although higher CD34 cell dose was not associated with acute GVHD grade II-IV, it was associated with chronic GVHD (T2: HR, 1.68; T3: HR, 1.50; P = .04). Our data indicate that higher CD34 cell dose (>7.5 × 106/kg) is associated with superior OS at 5 years and improved engraftment but carries an increased risk of chronic GVHD. These data support a target CD34 cell dose goal of 7.5 × 106/kg for sibling PBSC graft donors.
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Affiliation(s)
| | - Claudio G Brunstein
- Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota
| | - Qing Cao
- Department of Medicine and Biostatistics and Informatics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
| | - Daniel Weisdorf
- Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota
| | - Erica D Warlick
- Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota
| | - Najla El Jurdi
- Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota
| | - Joseph E Maakaron
- Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota
| | - Mukta Arora
- Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota
| | - Brian C Betts
- Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota
| | - Veronika Bachanova
- Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota
| | - Shernan G Holtan
- Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota
| | - Fiona C He
- Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota.
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10
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Romon I, Castillo C, Cid J, Lozano M. Use of plerixafor to mobilize haematopoietic progenitor cells in healthy donors. Vox Sang 2021; 117:6-16. [PMID: 34159611 DOI: 10.1111/vox.13175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 04/09/2021] [Accepted: 04/29/2021] [Indexed: 11/29/2022]
Abstract
Increased transplant activity calls for improved stem cell collection, especially when peripheral blood is the preferred source of haematopoietic progenitor cells (HPCs). Plerixafor is a bicyclam molecule that mobilizes CD34+ cells by reversibly disrupting CXCR4-CXCL12-supported HPC retention. Plerixafor is given with granulocyte colony-stimulating factor (G-CSF) to help harvest autologous CD34+ cells for transplantation when mobilization with G-CSF fails. Mobilization protocols with the same doses of plerixafor and G-CSF have been used off-label in healthy allogeneic donors, with equal success and scarce side effects, both in adult and paediatric patients. Plerixafor has also been used as a sole mobilization agent. Plerixafor alone or coupled with G-CSF might lead to harvesting distinct cellular populations conferring improved engraftment properties and increased survival. Those characteristics might make plerixafor an especially attractive mobilization agent, particularly for non-related donations. However, available data are limited, and long-term follow-up is needed to clarify the best scenario for using plerixafor with or without G-CSF in healthy donors. In this review, we will summarize the evidence supporting this practice, highlighting the practical aspects and providing clues for an expanded use of plerixafor.
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Affiliation(s)
- Iñigo Romon
- Transfusion Service, Hematology and Hemotherapy Service, University Hospital Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - Carlos Castillo
- Apheresis & Cellular Therapy Unit, Department of Hemotherapy and Hemostasis, ICMHO, Hospital Clínic, IDIBAPS, UB, Barcelona, Spain
| | - Joan Cid
- Apheresis & Cellular Therapy Unit, Department of Hemotherapy and Hemostasis, ICMHO, Hospital Clínic, IDIBAPS, UB, Barcelona, Spain
| | - Miquel Lozano
- Apheresis & Cellular Therapy Unit, Department of Hemotherapy and Hemostasis, ICMHO, Hospital Clínic, IDIBAPS, UB, Barcelona, Spain
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11
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Reshef R. Peripheral blood stem cell grafts in allogeneic hematopoietic cell transplantation: It is not all about the CD34+ cell dose. Transfus Apher Sci 2021; 60:103081. [PMID: 33593707 DOI: 10.1016/j.transci.2021.103081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Allogeneic Hematopoietic Cell Transplantation is a curative approach in various malignant and non-malignant disorders. The majority of adult transplants in the current era are performed using mobilized stem cells, harvested from the peripheral blood by leukapheresis. Peripheral blood stem cell (PBSC) collections are designed to target a dose of stem cells that will result in safe engraftment and hematopoietic recovery; however, 99 % of the cells contained in a PBSC graft are not stem cells and a growing number of studies attempt to characterize the associations between graft composition and transplant outcomes. A better understanding of the impact of the quantity and quality of various cell types in PBSC grafts may lead to development of novel collection strategies or improved donor selection algorithms. Here we review relevant findings from recent studies in this area.
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Affiliation(s)
- Ran Reshef
- Blood and Marrow Transplantation and Cell Therapy Program, Columbia University Irving Medical Center, New York, NY, 630 W. 168th St. Mailbox 127, New York, NY, United States.
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12
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Li J, Wang S, Zhang Y, Lou S, Liu Y, Kong P, Zhang C, Gao L, Peng X, Wang P, Deng X, Gao L, Zhang X. Is It Better to Mobilize Hematopoietic Stem Cells With Pegfilgrastim in Healthy Donors During Allogeneic Hematopoietic Stem Cell Transplantation? Front Oncol 2020; 10:1598. [PMID: 33014813 PMCID: PMC7494731 DOI: 10.3389/fonc.2020.01598] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 07/23/2020] [Indexed: 11/13/2022] Open
Abstract
The mobilization of hematopoietic stem cells (HSCs) using granulocyte colony-stimulating factor is a classic method. Recently, a single injection of pegfilgrastim was used to mobilize CD34+ cells in some small-sample studies. To confirm the efficacy and safety of pegfilgrastim in the mobilization of CD34+ cells from healthy donors, we conducted a retrospective multicenter study. A total of 146 healthy donors who all received subcutaneous pegfilgrastim (12 mg) on day 1 were enrolled in our study. Donor HSC apheresis was conducted on day 5. The primary endpoint was the percentage of donors from whom ≥4 × 106 CD34+ cells/kg were collected in a single apheresis session. The median number of CD34+ cells in donors was significantly higher on day 5 than that on day 4 (82.26 μL vs. 51.65 μL, P ¡ 0.001). In 111 of the 146 donors, an optimal number of CD34+ cells (≥4 × 106 kg) were collected in a single apheresis procedure. Bone pain and headache were the main adverse events, but the side effects did not require treatment. The number of white blood cells in most donors dropped to normal levels within 1 week after apheresis. Nearly 97% of patients achieved neutrophil and platelet engraftment. Pegfilgrastim for mobilization could be used to obtain an optimal number of CD34+ cells in a single session. Pegfilgrastim-induced mobilization not only was effective and safe but also avoided the pain of multiple injections and apheresis procedures in donors. However, prospective randomized controlled trials should be conducted in the future.
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Affiliation(s)
- Jiali Li
- Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, China.,State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China
| | - Sanbin Wang
- Department of Hematology, 920th Hospital of Joint Logistics Support Force, Yunnan, China
| | - Yicheng Zhang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shifeng Lou
- Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yao Liu
- Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, China.,State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China
| | - Peiyan Kong
- Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, China.,State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China
| | - Cheng Zhang
- Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, China.,State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China
| | - Lei Gao
- Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, China.,State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China
| | - Xiangui Peng
- Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, China.,State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China
| | - Ping Wang
- Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, China.,State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China
| | - Xiaojuan Deng
- Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, China.,State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China
| | - Li Gao
- Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, China.,State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China
| | - Xi Zhang
- Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, China.,State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China
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13
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Maffini E, Labopin M, Blaise D, Ciceri F, Gülbas Z, Deconinck E, Leblond V, Chevallier P, Sociè G, Araujo MC, Koc Y, Savani BN, Gorin NC, Lanza F, Nagler A, Mohty M. CD34+ cell dose effects on clinical outcomes after T-cell replete haploidentical allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia using peripheral blood stem cells. A study from the acute leukemia working Party of the European Society for blood and marrow transplantation (EBMT). Am J Hematol 2020; 95:892-899. [PMID: 32303111 DOI: 10.1002/ajh.25826] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 03/23/2020] [Accepted: 04/08/2020] [Indexed: 12/15/2022]
Abstract
Previous observations have reported controversial conclusions regarding cell dose and survival endpoints after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a retrospective analysis on 414 adult patients (median age 54 years, range, 18-74 years) with acute myeloid leukemia (AML) in first and second complete remission. They received a T-cell replete allogeneic HSCT from haploidentical donors, using peripheral blood stem cells, between 2006-2018. Median number of infused CD34+ was 6.58 × 106 /kg (range, 2.2-31.2 × 106 /kg). Graft-vs-host disease (GVHD) prophylaxis was post-transplant cyclophosphamide in 293 patients and anti-lymphocyte serum in 121 patients. Conditioning was myeloablative in 179 patients and reduced-intensity in 235 patients. After a median follow-up of 23.3 months (range, 12.1-41.8 months), 2-year overall survival (OS) was 64.5% (95% CI 59.3%-69.7%) with leukemia-free survival (LFS) of 57.3% (95% CI 51.8%-62.7%) and non-relapse mortality (NRM) of 23.3% (95% CI 19%-27.7%). Grades III-IV acute GVHD day+100 incidence was 14.6% while extensive chronic GVHD was 14.4% at 2-years. Thirteen (3.2%) patients experienced graft failure. We found the optimal CD34+/kg threshold defining high (n = 334) vs low cell dose (n = 80) at 4.96 × 106 . Recipients of >4.96 × 106 /kg CD34+ cells experienced less NRM (Hazard ratio [HR] 0.48; 95% CI 0.30-0.76) and prolonged LFS (HR 0.63; 95% CI 0.43-0.91) and OS (HR 0.60; 95% CI 0.40-0.88) compared to those in the lower cell dose cohort. Larger cohort studies are needed to confirm these findings.
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Affiliation(s)
| | - Myriam Labopin
- Acute Leukemia Working Party OfficeHospital Saint Antoine Paris France
- Assistance Publique‐Hopitaux de ParisHospital Saint Antoine Paris France
- University Pierre et Marie Curie Paris France
- Institut National de la Santè et de la Recherche Médicale Unitè Mixte de Recherche en Santè Paris France
| | - Didier Blaise
- Programme de Transplantation & Therapie CellulaireCentre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes Marseille France
| | - Fabio Ciceri
- Ospedale San RaffaeleHaematology and BMT Milan Italy
| | - Zafer Gülbas
- Anadolu Medical Center HospitalBone Marrow Transplantation Department Kocaeli Turkey
| | - Eric Deconinck
- Hopital Jean MinjozService d'Hématologie Besancon France
| | - Veronique Leblond
- Universite Paris IVHopital la Pitié‐Salpêtrière, Hematologie Clinique Paris France
| | - Patrick Chevallier
- Centre Hospitalier Universitaire NantesDept. D'Hematologie Nantes France
| | - Gerard Sociè
- Hopital Saint‐LouisService d'Hematologie – BMT Paris France
| | - Mercedes C. Araujo
- Hospital U. Marqués de ValdecillaServicio de Hematología‐Hemoterapia Santander Spain
| | - Yener Koc
- Medical Park HospitalsStem Cell Transplant Unit Antalya Turkey
| | - Bipin N. Savani
- Division of Hematology and Medical OncologyVanderbilt University Medical Center Nashville Tennessee USA
| | | | | | - Arnon Nagler
- Hematology and Bone Marrow Transplantation DivisionChaim Sheba Medical Center Tel‐Hashomer Israel
- Sackler School of MedicineTel Aviv University Tel Aviv Israel
| | - Mohamad Mohty
- Saint‐Antoine Hospital Paris France
- Sorbonne University Paris France
- INSERM UMRs 938 Paris France
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14
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Philip J, Bajaj AK, Sharma S, Kushwaha N, Kumar S, Kumar Biswas A. Allogeneic Peripheral Blood Stem Cell Transplant: Correlation of Donor Factors with Yield, Engraftment, Chimerism, and Outcome: Retrospective Review of a Single Institute During a 3-Year Period. Lab Med 2020; 51:362-369. [PMID: 31758694 DOI: 10.1093/labmed/lmz069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Donor factors have a variable correlation with cluster of differentiation (CD)34+ cell dose in allogeneic peripheral blood stem cell (PBSC) harvests. CD34+ cell dose affects the speed of hematopoietic recovery and percentage of donor chimerism in the recipient. METHODS A total of 25 allogeneic PBSC transplants performed during a 3-year period were included. All donors underwent mobilization with filgrastim. Leukapheresis, flowcytometric CD34+ cell enumeration, and chimerism analysis were performed and correlated with recipient outcome. RESULTS Besides age, all other donor parameters had a positive correlation with CD34+ cell count. Engraftment kinetics and chimerism had a positive correlation with the CD34+ yield of the PBSC product. Acute graft-vs-host disease (GVHD) was observed in patients with complete chimerism at day 30 after transplantation. CONCLUSION Adequate CD34+ cell yield happens in healthy donors, independent of donor demographic patterns with G-CSF only. A diverse population of donors can thus be approached for Matched Unrelated Donor (MUD) transplants. An accurate quantitative analysis of early donor chimerism in the recipient (at day 30) is an excellent tool for post-transplant monitoring for acute GvHD.
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Affiliation(s)
- Joseph Philip
- Department of Immunohematology & Blood Transfusion (IH & BT), Armed Forces Medical College (AFMC), Pune, India
| | - Anantpreet Kaur Bajaj
- Department of Immunohematology & Blood Transfusion (IH & BT), Armed Forces Medical College (AFMC), Pune, India
| | | | - Neerja Kushwaha
- Department of Immunohematology & Blood Transfusion (IH & BT), Armed Forces Medical College (AFMC), Pune, India
| | - Sudeep Kumar
- Department of Immunohematology & Blood Transfusion (IH & BT), Armed Forces Medical College (AFMC), Pune, India
| | - Amit Kumar Biswas
- Department of Immunohematology & Blood Transfusion (IH & BT), Armed Forces Medical College (AFMC), Pune, India
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15
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Garnier A, Guillaume T, Peterlin P, Le Bourgeois A, Mahé B, Dubruille V, Blin N, Touzeau C, Gastinne T, Lok A, Tessoulin B, Duquesne A, Eveillard M, Le Gouill S, Moreau P, Béné MC, Chevallier P. Absence of influence of peripheral blood CD34+ and CD3+ graft cell counts on outcomes after reduced-intensity conditioning transplantation using post-transplant cyclophosphamide. Ann Hematol 2020; 99:1341-1350. [DOI: 10.1007/s00277-020-04031-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Accepted: 04/10/2020] [Indexed: 12/14/2022]
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16
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Remberger M, Grønvold B, Ali M, Mattsson J, Egeland T, Lundin KU, Myhre A, Abrahamsen I, Heldal D, Dybedal I, Tjønnfjord GE, Gedde-Dahl T, Fløisand Y. The CD34 + Cell Dose Matters in Hematopoietic Stem Cell Transplantation with Peripheral Blood Stem Cells from Sibling Donors. Clin Hematol Int 2020; 2:74-81. [PMID: 34595446 PMCID: PMC8432346 DOI: 10.2991/chi.d.200221.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 02/08/2020] [Indexed: 11/16/2022] Open
Abstract
The effect of CD34+ cell dose in allogeneic hematopoietic stem cell transplantation (HSCT) on overall survival (OS) and incidence of acute and chronic graft-versus-host disease (GvHD) has not been established and few studies have been performed. Our single center analysis included 189 patients with hematological malignancies who received peripheral blood stem cell (PBSC) grafts from sibling donors. Myeloablative conditioning was used in 88 cases and 101 received reduced intensity conditioning. The median CD34+ cell dose was 5.6 × 106/kg (0.6–17.0). In the multivariate analysis, a CD34 cell dose of 6–7 × 106/kg was associated with better OS and lower transplant-related mortality (TRM), while a dose of <5 × 106/kg led to increased relapse and reduced chronic GVHD (cGVHD). A high CD34 cell-dose (>6.5 × 106/kg) correlated with less acute GVHD (aGVHD) II–IV. We conclude that the CD34 cell dose has an impact on the outcome of HSCT from sibling donor PBSCs.
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Affiliation(s)
- M Remberger
- Department of Hematology, Oslo University Hospital, Oslo, Norway.,Department of Medical Sciences, Uppsala University and KFUE, Uppsala University Hospital, Uppsala, Sweden
| | - B Grønvold
- Department of Hematology, Oslo University Hospital, Oslo, Norway
| | - M Ali
- Department of Hematology, Oslo University Hospital, Oslo, Norway
| | - J Mattsson
- Hans Messner Allogeneic Transplant Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada
| | - T Egeland
- Department of Immunology, Oslo University Hospital, Oslo, Norway
| | - K U Lundin
- Department of Immunology, Oslo University Hospital, Oslo, Norway
| | - A Myhre
- Department of Hematology, Oslo University Hospital, Oslo, Norway
| | - I Abrahamsen
- Department of Hematology, Oslo University Hospital, Oslo, Norway
| | - D Heldal
- Department of Hematology, Oslo University Hospital, Oslo, Norway
| | - I Dybedal
- Department of Hematology, Oslo University Hospital, Oslo, Norway
| | - G E Tjønnfjord
- Department of Hematology, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - T Gedde-Dahl
- Department of Hematology, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Y Fløisand
- Department of Hematology, Oslo University Hospital, Oslo, Norway.,Centre for Cancer Cell Reprogramming, Department of Molecular Cell Biology, Oslo University Hospital, Montebello, N-0379 Oslo, Norway
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17
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Yokoyama Y, Maie K, Fukuda T, Uchida N, Mukae J, Sawa M, Kubo K, Kurokawa M, Nakamae H, Ichinohe T, Atsuta Y, Chiba S. A high CD34 + cell dose is associated with better disease-free survival in patients with low-risk diseases undergoing peripheral blood stem cell transplantation from HLA-matched related donors. Bone Marrow Transplant 2020; 55:1726-1735. [PMID: 32042104 DOI: 10.1038/s41409-020-0817-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Revised: 01/14/2020] [Accepted: 01/27/2020] [Indexed: 11/09/2022]
Abstract
To elucidate the impact of infused CD34+ cell doses on transplant outcome, we retrospectively analyzed 851 adult patients who received peripheral blood stem cell transplantation (PBSCT) from human leukocyte antigen (HLA)-matched related donors. The patients were divided into high- and low-CD34 groups at the cutoff value of 4.5 × 106/kg. Overall, the high CD34 group showed early neutrophil and platelet recovery. Stratification of disease risks demonstrated that among the patients with low-risk diseases, the high-CD34 group showed better disease-free survival (DFS) (64.9% vs. 55.5%, P = 0.0415) than did the low-CD34 group, without any increase in graft-versus-host disease (GVHD). Meanwhile, a higher CD34+ cell dose had no impacts on the outcomes of patients with high-risk diseases. Multivariate analyses for the patients with low-risk diseases revealed that a high CD34+ cell dose (hazard ratio [HR] 0.72, P = 0.048) and development of grade III-to-IV acute GVHD (HR 1.64, P = 0.018) were significantly associated with DFS. An excessive dose of CD34+ cells (>8.0 × 106/kg) led to an increase in acute GVHD. By stratification of disease risk, a CD34+ cell dose between 4.5 and 8.0 × 106/kg can be suggested for patients with low-risk diseases who undergo PBSCT from HLA-matched related donors.
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Affiliation(s)
- Yasuhisa Yokoyama
- Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Koichiro Maie
- Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Takahiro Fukuda
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | - Naoyuki Uchida
- Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital, Tokyo, Japan
| | - Junichi Mukae
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Masashi Sawa
- Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan
| | - Kohmei Kubo
- Department of Hematology, Aomori Prefectural Central Hospital, Aomori, Japan
| | - Mineo Kurokawa
- Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital, Tokyo, Japan
| | - Hirohisa Nakamae
- Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Tatsuo Ichinohe
- Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Yoshiko Atsuta
- Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan.,Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shigeru Chiba
- Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
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Salas MQ, Atenafu EG, Bautista MR, Prem S, Lam W, Datt Law A, Shaibani ZA, Kim DDH, Michelis FV, Lipton JH, Viswabandya A, Mattsson J, Kumar R. Impact of CD34+ cell dose on reduced intensity conditioning regimen haploidentical hematopoietic stem cell transplantation. Eur J Haematol 2019; 104:36-45. [PMID: 31549435 DOI: 10.1111/ejh.13332] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Revised: 09/19/2019] [Accepted: 09/20/2019] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Haploidentical hematopoietic stem cell transplant (haplo-SCT) has been associated with higher rates of graft rejection, and a higher dose of CD34+ cell dose is frequently requested. We aim to explore the impact of CD34+ cell dose in peripheral blood stem cell (PBSC) grafts using reduced intensity conditioning (RIC) in haplo-SCT. METHODS Sixty-eight consecutive haplo-SCT in adult patients were included. Graft-vs-host disease (GVHD) prophylaxis consisted on ATG, PTCy, and CsA. The cohort was divided in two groups using CD34+ dose of ≥ 9 × 106 CD34+/Kg as cutoff point. Median follow-up was 8.9 months. RESULTS Median cell dose infused was 9.32 × 106 CD34+/Kg. Forty (58.8%) recipients received grafts with CD34+ cells ≥9 × 106 /kg. The infusion ≥ 9 × 106 CD34+/Kg cell dose had a negative impact in overall survival (P = .03) after adjusting for age at transplant. The cumulative incidence of acute GVHD and graft failure were not significantly influenced per CD34+ cell dose. Only four recipients had grade III aGVHD, and all of them received grafts with a CD34+ cell dose ≥ 9 × 106 . CONCLUSION In RIC haplo-SCT, recipients may not benefit from PBSC grafts with a CD34+/kg cell dose higher than 9 × 106 cells/kg, as it can have an adverse impact in post-transplant outcome.
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Affiliation(s)
- Maria Queralt Salas
- Section of Medical Oncology and Hematology, Department of Internal Medicine, University of Toronto, ON, Canada.,Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Eshetu G Atenafu
- Department of Biostatistics, Princes Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Maria Rhida Bautista
- Section of Medical Oncology and Hematology, Department of Internal Medicine, University of Toronto, ON, Canada.,Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Shruti Prem
- Section of Medical Oncology and Hematology, Department of Internal Medicine, University of Toronto, ON, Canada.,Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Wilson Lam
- Section of Medical Oncology and Hematology, Department of Internal Medicine, University of Toronto, ON, Canada.,Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Arjun Datt Law
- Section of Medical Oncology and Hematology, Department of Internal Medicine, University of Toronto, ON, Canada.,Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Zeyad-Al Shaibani
- Section of Medical Oncology and Hematology, Department of Internal Medicine, University of Toronto, ON, Canada.,Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Dennis Dong Hwan Kim
- Section of Medical Oncology and Hematology, Department of Internal Medicine, University of Toronto, ON, Canada.,Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Fotios V Michelis
- Section of Medical Oncology and Hematology, Department of Internal Medicine, University of Toronto, ON, Canada.,Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Jeffrey Howard Lipton
- Section of Medical Oncology and Hematology, Department of Internal Medicine, University of Toronto, ON, Canada.,Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Auro Viswabandya
- Section of Medical Oncology and Hematology, Department of Internal Medicine, University of Toronto, ON, Canada.,Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Jonas Mattsson
- Section of Medical Oncology and Hematology, Department of Internal Medicine, University of Toronto, ON, Canada.,Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Rajat Kumar
- Section of Medical Oncology and Hematology, Department of Internal Medicine, University of Toronto, ON, Canada.,Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
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19
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Saad A, Lamb L, Wang T, Hemmer MT, Spellman S, Couriel D, Alousi A, Pidala J, Abdel-Azim H, Agrawal V, Aljurf M, Beitinjaneh AM, Bhatt VR, Buchbinder D, Byrne M, Cahn JY, Cairo M, Castillo P, Chhabra S, Diaz MA, Farhan S, Floisand Y, Frangoul HA, Gadalla SM, Gajewski J, Gale RP, Gandhi M, Gergis U, Hamilton BK, Hematti P, Hildebrandt GC, Kamble RT, Kanate AS, Khandelwal P, Lazaryan A, MacMillan M, Marks DI, Martino R, Mehta PA, Nishihori T, Olsson RF, Patel SS, Qayed M, Rangarajan HG, Reshef R, Ringden O, Savani BN, Schouten HC, Schultz KR, Seo S, Shaffer BC, Solh M, Teshima T, Urbano-Ispizua A, Verdonck LF, Vij R, Waller EK, William B, Wirk B, Yared JA, Yu LC, Arora M, Hashmi S. Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation. Biol Blood Marrow Transplant 2019; 25:1875-1883. [PMID: 31085303 PMCID: PMC7071947 DOI: 10.1016/j.bbmt.2019.05.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 05/02/2019] [Accepted: 05/03/2019] [Indexed: 01/24/2023]
Abstract
Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3+ T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3+ T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3+ T cell dose cutoff of 14 × 107 cells/kg identified MSD/low CD3+ (n = 223) and MSD/high CD3+ (n = 1214), and a dose of 15 × 107 cells/kg identified MUD/low CD3+ (n = 197) and MUD/high CD3+ (n = 1102). On univariate analysis, the MSD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3+ group (33% versus 25%; P = .009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3+ group (49% versus 41%; P = .04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3+ T cell dose and the risk of either aGVHD grade II-IV (P = .10 and .07, respectively) or cGVHD (P = .80 and .30, respectively). Subanalysis of CD4+ T cells, CD8+ T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3+ T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4+ and CD8+ T cell doses were not possible given our small sample size.
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Affiliation(s)
- Ayman Saad
- Division of Hematology, The Ohio State University, Columbus, Ohio
| | - Lawrence Lamb
- University of Alabama at Birmingham, Birmingham, Alabama
| | - Tao Wang
- Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wisconsin; Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Michael T Hemmer
- Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Stephen Spellman
- Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be the Match, Minneapolis, Minnesota
| | - Daniel Couriel
- Utah Blood and Marrow Transplant Program, Salt Lake City, Utah
| | - Amin Alousi
- Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas
| | - Joseph Pidala
- Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, Florida
| | - Hisham Abdel-Azim
- Division of Hematology, Oncology and Blood and Marrow Transplantation, Children's Hospital of Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California
| | - Vaibhav Agrawal
- Division of Hematology-Oncology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Mahmoud Aljurf
- Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | | | - Vijaya Raj Bhatt
- The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska
| | - David Buchbinder
- Division of Pediatric Hematology, Children's Hospital of Orange County, Orange, California
| | - Michael Byrne
- Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jean-Yves Cahn
- Department of Hematology, CHU Grenoble Alpes, Grenoble, France
| | - Mitchell Cairo
- Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, New York, New York
| | - Paul Castillo
- UF Health Shands Children's Hospital, Gainesville, Florida
| | - Saurabh Chhabra
- Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Miguel Angel Diaz
- Department of Hematology/Oncology, Hospital Infantil Universitario Nino Jesus, Madrid, Spain
| | - Shatha Farhan
- Henry Ford Hospital Bone Marrow Transplant Program, Detroit, Michigan
| | | | - Hadar A Frangoul
- Children's Hospital at TriStar Centennial and Sarah Cannon Research Institute, Nashville, Tennessee
| | - Shahinaz M Gadalla
- Division of Cancer Epidemiology & Genetics, Clinical Genetics Branch, National Cancer Institute, Rockville, Maryland
| | | | - Robert Peter Gale
- Hematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom
| | - Manish Gandhi
- Division of Transfusion Medicine, Mayo Clinic, Rochester, Minnesota
| | - Usama Gergis
- Hematologic Malignancies & Bone Marrow Transplant, Department of Medical Oncology, New York Presbyterian Hospital/Weill Cornell Medical Center, New York, New York
| | - Betty Ky Hamilton
- Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio
| | - Peiman Hematti
- Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, Wisconsin
| | | | - Rammurti T Kamble
- Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas
| | - Abraham S Kanate
- Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, Morgantown, West Virginia
| | - Pooja Khandelwal
- Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Aleksandr Lazaryan
- Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, Florida
| | - Margaret MacMillan
- University of Minnesota Blood and Marrow Transplant Program, Pediatrics, Minneapolis, Minnesota
| | - David I Marks
- Adult Bone Marrow Transplant, University Hospitals Bristol NHS Trust, Bristol, United Kingdom
| | - Rodrigo Martino
- Division of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Parinda A Mehta
- Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Taiga Nishihori
- Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, Florida
| | - Richard F Olsson
- Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden; Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden
| | - Sagar S Patel
- Blood and Marrow Transplant Program, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Muna Qayed
- Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
| | - Hemalatha G Rangarajan
- Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Nationwide Children's Hospital, Columbus, Ohio
| | - Ran Reshef
- Blood and Marrow Transplantation Program and Columbia Center for Translational Immunobiology, Columbia University Medical Center, New York, New York
| | - Olle Ringden
- Translational Cell Therapy Research, Karolinska Institute, Stockholm, Sweden
| | - Bipin N Savani
- Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Harry C Schouten
- Department of Hematology, Academische Ziekenhuis, Maastricht, Netherlands
| | - Kirk R Schultz
- Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, British Columbia's Children's Hospital, The University of British Columbia, Vancouver, Britich Columbia, Canada
| | - Sachiko Seo
- Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan
| | | | - Melhem Solh
- The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, Georgia
| | | | - Alvaro Urbano-Ispizua
- Department of Hematology, Hospital Clinic, University of Barcelona, IDIBAPS, and Josep Carreras Institute of Research, Barcelona, Spain
| | - Leo F Verdonck
- Department of Hematology/Oncology, Isala Clinic, Zwolle, The Netherlands
| | - Ravi Vij
- Division of Hematology and Oncology, Washington University School of Medicine, St Louis, Missouri
| | - Edmund K Waller
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Basem William
- Division of Hematology, The Ohio State University, Columbus, Ohio
| | - Baldeep Wirk
- Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, Washington
| | - Jean A Yared
- Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Maryland
| | - Lolie C Yu
- Division of Hematology/Oncology and HSCT, Center for Cancer and Blood Disorders, Children's Hospital/Louisiana State University Medical Center, New Orleans, Louisiana
| | - Mukta Arora
- Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, Minnesota.
| | - Shahrukh Hashmi
- Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
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20
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Kim H, Lee KH, Sohn SK, Kim I, Kim SH, Park Y, Choi JH, Kwak JY, Kim MK, Bae SH, Shin HJ, Won JH, Lee WS, Choi Y. Effect of Stem Cell Source and Dose on Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Idiopathic Aplastic Anemia: Data from the Korean Aplastic Anemia Trials. Acta Haematol 2019; 143:232-243. [PMID: 31390612 DOI: 10.1159/000501496] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 06/08/2019] [Indexed: 11/19/2022]
Abstract
OBJECTIVE We aimed to evaluate the effect of stem cell source and dose on the survival of various donor subgroups, such as matched sibling donor (MSDs) and alternative donors (ADs), upon bone marrow (BM) or peripheral blood stem cell (PBSC) infusion in aplastic anemia (AA). METHODS We retrospectively investigated the effects of stem cell source and dose on allogeneic hematopoietic stem cell transplantation (alloHSCT) in AA. RESULTS A total of 267 patients were included in this analysis. The BM-treated group showed an association with low incidence of any-grade acute graft versus host disease (GvHD) (p < 0.001). A higher stem cell dose was related with a low incidence of extensive chronic GvHD in MSDs (p = 0.025). Multivariate analysis for overall survival (OS) revealed that only age at alloHSCT <31 years (p = 0.010) and prior platelet transfusion <86 U (p = 0.046) in MSDs and higher stem cell dose (hazard ratio = 2.596, p = 0.045) in ADs were favorable prognostic factors. CONCLUSION PBSCs could be preferred in AD because high stem cell dose may be easily achieved to improve the OS at the expense of acute GvHD. However, BM stem cells are preferred in MSDs.
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Affiliation(s)
- Hawk Kim
- Division of Hematology, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea,
| | - Kyoo-Hyung Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang Kyun Sohn
- Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Inho Kim
- Seoul National University Hospital, Seoul, Republic of Korea
| | - Sung-Hyun Kim
- Dong-A University Medical Center, Busan, Republic of Korea
| | - Yong Park
- Korea University Anam Hospital, Seoul, Republic of Korea
| | - Jung Hye Choi
- Hanyang University Hospital, Guri, Republic of Korea
| | - Jae-Yong Kwak
- Chonbuk National University Hospital, Jeonju, Republic of Korea
| | - Min Kyoung Kim
- Yeungnam University Medical Center, Gyeongsan, Republic of Korea
| | - Sung Hwa Bae
- Daegu Catholic University Hospital, Daegu, Republic of Korea
| | - Ho-Jin Shin
- Pusan National University Hospital, Busan, Republic of Korea
| | - Jong Ho Won
- Soonchunhyang University Hospital Seoul, Seoul, Republic of Korea
| | - Won Sik Lee
- Inje University Busan Paik Hospital, Busan, Republic of Korea
| | - Yunsuk Choi
- Division of Hematology and Cellular Therapy, Ulsan University Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea
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21
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Zaucha-Prażmo A, Sadurska E, Pieczonka A, Goździk J, Dębski R, Drabko K, Zawitkowska J, Lejman M, Wachowiak J, Styczyński J, Kowalczyk JR. Risk Factors for Transplant Outcomes in Children and Adolescents with Non-Malignant Diseases Following Allogeneic Hematopoietic Stem Cell Transplantation. Ann Transplant 2019; 24:374-382. [PMID: 31235684 PMCID: PMC6611216 DOI: 10.12659/aot.915330] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND The objective of this study was the analysis of transplant outcomes and survival in children treated with allogeneic hematopoietic cell transplantation (alloHCT) for non-malignant disorders, with a focus on risk factor analysis of transplant-related mortality (TRM). MATERIAL AND METHODS The treatment outcome was analyzed retrospectively in 10 consecutive years in 4 pediatric transplant centers in Poland. To compare the outcomes, patient data were analyzed according to the diagnosis, age at transplant, donor type, stem cell source, conditioning regimens, transplanted CD34+ cells dose, and pediatric TRM score. RESULTS From 183 analyzed patients, 27 (14.8%) died, all of them due to transplant-related complications. TRM occurred more frequently in matched unrelated donor (MUD) transplant recipients vs. matched sibling donor (MSD) transplant recipients (p=0.02); in peripheral blood (PB) recipients vs. bone marrow (BM) recipients (p=0.004); and in patients receiving >5×10⁶/kg CD34+ cells (p<0.0001). OS differed significantly according to underlying disease comparing to other diagnoses. Lower survival was found in patients transplanted from MUD (p=0.02). OS was higher in patients receiving BM (p=0.001) and in those receiving ≤5×10⁶/kg CD34+ cells (p<0.001). Multivariate analysis showed lower probability of TRM in BM recipients (p=0.04). The probability of TRM was higher in SCID patients (p=0.02) and in patients receiving >5×10⁶/kg CD34+ cells (p=0.0001). CONCLUSIONS Underlying disease, stem cell source, and CD34+ dose higher than 5×10⁶/kg were the most important risk factors for TRM, and they all affected OS.
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Affiliation(s)
- Agnieszka Zaucha-Prażmo
- Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, University Children's Hospital, Lublin, Poland
| | - Elżbieta Sadurska
- Department of Pediatric Cardiology, Medical University of Lublin, University Children's Hospital, Lublin, Poland
| | - Anna Pieczonka
- Department of Pediatric Oncology, Hematology, and Transplantology, University of Medical Sciences, Poznań, Poland
| | - Jolanta Goździk
- Department of Transplantation, Clinical Immunology and Transplantation Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Children's University Hospital, Cracow, Poland
| | - Robert Dębski
- Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Katarzyna Drabko
- Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, University Children's Hospital, Lublin, Poland
| | - Joanna Zawitkowska
- Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, University Children's Hospital, Lublin, Poland
| | - Monika Lejman
- Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, University Children's Hospital, Lublin, Poland
| | - Jacek Wachowiak
- Department of Pediatric Oncology, Hematology, and Transplantology, University of Medical Sciences, Poznań, Poland
| | - Jan Styczyński
- Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Jerzy R Kowalczyk
- Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, University Children's Hospital, Lublin, Poland
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22
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Peripheral blood stem cell for haploidentical transplantation with post-transplant high dose cyclophosphamide: detailed analysis of 181 consecutive patients. Bone Marrow Transplant 2019; 54:1730-1737. [DOI: 10.1038/s41409-019-0500-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 02/08/2019] [Accepted: 02/15/2019] [Indexed: 01/08/2023]
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23
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Svenberg P, Wang T, Uhlin M, Watz E, Remberger M, Ringden O, Mattsson J, Uzunel M. The importance of graft cell composition in outcome after allogeneic stem cell transplantation in patients with malignant disease. Clin Transplant 2019; 33:e13537. [PMID: 30873642 DOI: 10.1111/ctr.13537] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2018] [Revised: 03/08/2019] [Accepted: 03/09/2019] [Indexed: 11/29/2022]
Abstract
BACKGROUND Graft-versus-host disease (GVHD) and relapse remain majobstacles ftreatment success in allogeneic hematopoietic stem cell transplantation (HSCT). In the present study, we evaluated the immune cell profile of the graft to outcome after HSCT. STUDY DESIGN AND METHOD Flow cytometry data of graft cell subsets [CD34+ , CD3+ , CD19+ , CD4+ , CD8+ , CD3-CD56+ CD16+ , CD4+ CD127low CD25high ] from G-CSF primed peripheral blood stem cell (PBSC) donors was collected retrospectively from 299 patients with hematological malignancies undergoing HSCT between 2006 and 2013. The association to overall survival, transplant-related mortality (TRM), GVHD and probability of relapse was analyzed. Patients outcome from HLA-identical sibling (Sib) (n = 97) and unrelated donors (URD) (n = 202) were analyzed separately as all URD patients received anti-thymocyte globulin (ATG). RESULTS Five-year overall survival was similar in the two cohorts (68% (Sib) vs 65% (URD)). The relapse incidence was significantly lower in the Sib cohort (24% vs 35%, P = 0.04). Multivariate analysis in the URD group revealed an association between a higher CD8+ dose and less relapse (HR, 0.94; 95%CI, 0.90-0.98; P = 0.006) as well as an association between higher CD34+ dose and both higher TRM (HR, 1.09; 95%CI, 1.02-1.20; P = 0.02) and relapse (HR, 1.09; 95%CI, 1.01-1.17; P = 0.025). The Sib analysis showed an association between a higher graft CD19+ dose and more severe acute GVHD (HR, 1,09; 95%CI, 1.03-1.15; P = 0.003) and TRM (HR, 1.09; 95%CI, 1.01-1.17; P = 0.036). In addition, a higher CD4+ graft content was associated to an increased risk for chronic GVHD (HR, 1.02; 95%CI 1.00-1.04; P = 0.06). CONCLUSION These data indicate an importance of PBSC dongraft composition in patients with a hematological malignancy.
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Affiliation(s)
- Petter Svenberg
- Pediatric Oncology/Coagulation Section, Karolinska University Hospital, Solna, Sweden.,Department of Clinical Research Center, Karolinska Institute, Stockholm, Sweden
| | - Tengyu Wang
- Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden.,Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Michael Uhlin
- Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
| | - Emma Watz
- Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Mats Remberger
- Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.,Department of Medical Sciences, Uppsala University Hospital, Uppsala University and KFUE, Uppsala, Sweden
| | - Olle Ringden
- Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
| | - Jonas Mattsson
- Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.,Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
| | - Mehmet Uzunel
- Department of Clinical Research Center, Karolinska Institute, Stockholm, Sweden
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24
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Amouzegar A, Dey BR, Spitzer TR. Peripheral Blood or Bone Marrow Stem Cells? Practical Considerations in Hematopoietic Stem Cell Transplantation. Transfus Med Rev 2018; 33:43-50. [PMID: 30528986 DOI: 10.1016/j.tmrv.2018.11.003] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Revised: 11/02/2018] [Accepted: 11/06/2018] [Indexed: 01/10/2023]
Abstract
Although peripheral blood stem cells (PBSC) have worldwide become the predominant source of progenitor cells for hematopoietic stem cell transplantation (HSCT), debate about their role compared with bone marrow (BM) has recently intensified, in large part based on the results of a multicenter Clinical Trials Network study which showed lower incidence of chronic graft-versus-host disease (cGVHD) and improved quality of life in recipients of myeloablative HLA-matched unrelated BM compared with PBSC transplants. However, in certain patient populations, PBSC may lead to improved clinical outcomes due to faster hematologic recovery, a lower risk of graft failure, and possibly a lower probability of relapse. This review will provide a comprehensive summary of studies comparing PBSC with BM as the graft source in terms of acute and chronic GVHD incidence, time to engraftment, and disease-free and overall survival probabilities after HLA-matched related and unrelated donor transplantation and haploidentical donor transplantation. Recommendations based on these studies regarding the use of PBSC versus BM for HSCT are offered.
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Affiliation(s)
- Afsaneh Amouzegar
- Department of Medicine, Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, MA
| | - Bimalangshu R Dey
- Department of Medicine, Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, MA
| | - Thomas R Spitzer
- Department of Medicine, Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, MA.
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25
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Abstract
Transplants using peripheral blood hemopoietic stem/progenitor (PBHS) cells are widely performed for the treatment of patients with hematologic disorders in routine practice and clinical trials. Although the process from mobilization to infusion of PBHS cells has been mostly established, optimal conditions for each process remain undetermined. Adverse reactions caused by PBHS cell infusions have not been systematically recorded. In transplants using PBHS cells, a number of problems still exist. In this section, the current status of and future perspectives regarding PBHS cells are described.
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Affiliation(s)
- Kazuo Muroi
- Division of Cell Transplantation and Transfusion, Jichi Medical University Hospital, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
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26
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Czerw T, Labopin M, Schmid C, Cornelissen JJ, Chevallier P, Blaise D, Kuball J, Vigouroux S, Garban F, Lioure B, Fegueux N, Clement L, Sandstedt A, Maertens J, Guillerm G, Bordessoule D, Mohty M, Nagler A. High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia - an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Oncotarget 2017; 7:27255-66. [PMID: 27036034 PMCID: PMC5053647 DOI: 10.18632/oncotarget.8463] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Accepted: 03/23/2016] [Indexed: 12/18/2022] Open
Abstract
Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 x 10^6/kg and >8.25 x 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes.
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Affiliation(s)
- Tomasz Czerw
- Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Gliwice, Poland
| | - Myriam Labopin
- Clinical Hematology and Cellular Therapy Department, The Acute Leukemia Working Party of the EBMT Office, Hopital Saint-Antoine APHP Paris, France.,INSERM UMRs 938, Paris, France.,Université Pierre et Marie Curie (UPMC, Paris VI), Paris, France
| | | | - Jan J Cornelissen
- Department of Hematology, Erasmus University medical center Cancer Institute, Rotterdam, The Netherlands
| | | | - Didier Blaise
- Unité de Transplantation et de Thérapie Cellulaire, Institut Paoli Calmettes, Marseille, France
| | - Jürgen Kuball
- University Medical Centre, Department of Haematology, Utrecht, The Netherlands
| | | | - Frédéric Garban
- Hopital A. Michallon, Hématologie Clinique, Pole Cancérologie, Grenoble, France
| | | | - Nathalie Fegueux
- CHU Lapeyronie, Département d`Hématologie Clinique, Montpellier, France
| | - Laurence Clement
- Hôpital de Brabois, Centre Hospitalier Universitaire (CHU) de Nancy, Vandoeuvres les Nancy, France
| | - Anna Sandstedt
- University Hospital, Department of Hematology, Linköping, Sweden
| | - Johan Maertens
- University Hospital Gasthuisberg, Department of Hematology, Leuven, Belgium
| | | | | | - Mohamad Mohty
- Clinical Hematology and Cellular Therapy Department, The Acute Leukemia Working Party of the EBMT Office, Hopital Saint-Antoine APHP Paris, France.,INSERM UMRs 938, Paris, France.,Université Pierre et Marie Curie (UPMC, Paris VI), Paris, France
| | - Arnon Nagler
- Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel.,Clinical Hematology and Cellular Therapy Department, The Acute Leukemia Working Party of the EBMT Office, Hopital Saint-Antoine APHP Paris, France
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27
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Yamamoto C, Ogawa H, Fukuda T, Igarashi A, Okumura H, Uchida N, Hidaka M, Nakamae H, Matsuoka KI, Eto T, Ichinohe T, Atsuta Y, Kanda Y. Impact of a Low CD34 + Cell Dose on Allogeneic Peripheral Blood Stem Cell Transplantation. Biol Blood Marrow Transplant 2017; 24:708-716. [PMID: 29196077 DOI: 10.1016/j.bbmt.2017.10.043] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Accepted: 10/14/2017] [Indexed: 11/29/2022]
Abstract
Although the CD34+ cell dose in allogeneic peripheral blood stem cell transplantation (PBSCT) is considered to be associated with transplantation outcomes, a lower acceptable threshold has not been defined. We retrospectively analyzed 2919 adult patients with hematologic malignancies who underwent related PBSCT in Japan between 2001 and 2014. According to the number of CD34+ cells in the graft, we categorized 2494 patients in the standard group (2 to 5 × 106 cells/kg), 377 patient in the low group (1 to 2 × 106 cells/kg), and 48 patients in the very low group (<1 × 106 cells/kg). Compared with the standard group, the low and very low groups showed delayed neutrophil recovery (93.8%, 89.5%, and 78.3%, respectively at day +28; P < .001) and platelet recovery (69.3%, 53.0%, and 45.5%, respectively at day +28; P < .001). The 2-year overall survival (OS) in the 3 groups was 45.5%, 45.3%, and 29.8%, respectively, with inferior survival in the very low group. However, a higher percentage of high-risk patients may account for the inferior survival in the very low group, and no significant difference in OS was found in a multivariate analysis. There were no differences in relapse, nonrelapse mortality, or the development of graft-versus-host disease among the 3 groups. In conclusion, allogeneic PBSCT with low CD34+ cell doses of 1 to 2 × 106 cells/kg gives acceptable results, whereas further investigations are needed to evaluate the effects of lower doses of <1 × 106 cells/kg owing to the smaller number and the higher percentage of patients with adverse prognostic factors in this cohort.
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Affiliation(s)
- Chihiro Yamamoto
- Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan
| | - Hiroyasu Ogawa
- Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Takahiro Fukuda
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | - Aiko Igarashi
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Hirokazu Okumura
- Department of Internal Medicine (Hematology), Toyama Prefectural Central Hospital, Toyama, Japan
| | - Naoyuki Uchida
- Department of Hematology, Toranomon Hospital, Tokyo, Japan
| | - Michihiro Hidaka
- Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan
| | - Hirohisa Nakamae
- Department of Hematology, Osaka City University Hospital, Osaka, Japan
| | - Ken-Ichi Matsuoka
- Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan
| | - Tetsuya Eto
- Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
| | - Tatsuo Ichinohe
- Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Yoshiko Atsuta
- Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan; Nagoya University Graduate School of Medicine, Department of Healthcare Administration, Nagoya, Japan
| | - Yoshinobu Kanda
- Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan.
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28
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De Vos J, de Berranger E, Jubert C, Pochon C, Letellier C, Mialou V, Sirvent A, Yakoub-Agha I, Dalle JH. [Preservation/congelation of hematopoietic stem cell grafts in a pediatric context: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. Bull Cancer 2017; 104:S136-S141. [PMID: 29169651 DOI: 10.1016/j.bulcan.2017.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Accepted: 04/30/2017] [Indexed: 11/25/2022]
Abstract
The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th allogeneic hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2016 in Lille, France. The objective of our workshop is to provide a discussion on the conservation and congelation of hematopoietic stem cells in a pediatric setting as well as our recommendations for this technique.
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Affiliation(s)
- John De Vos
- CHU de Montpellier, unité de thérapie cellulaire, 80, avenue Fliche, 34295 Montpellier cedex 5, France
| | - Eva de Berranger
- CHRU de Lille, hôpital Jean-de-Flandre, service pédiatrie et hématologie, rue Eugène-Avinée, 59037 Lille cedex, France
| | - Charlotte Jubert
- CHU Bordeaux, hôpital des enfants, unité d'hématologie oncologie pédiatrique, place Amélie-Raba-Léon, 33000 Bordeaux, France
| | - Cécile Pochon
- CHU de Nancy, service d'hématologie, unité de transplantation médullaire allogénique, 54500 Vandœuvre-lès-Nancy, France
| | | | - Valérie Mialou
- Centre hospitalier Lyon Sud, établissement français du sang (EFS) Rhône Alpes, cell therapy laboratory, 69310 Pierre-Bénite, France
| | - Anne Sirvent
- CHRU de Montpellier, département d'onco-hématologie pédiatrique, 34295 Montpellier, France
| | | | - Jean-Hugues Dalle
- Université Paris 7, hôpital Robert-Debré, service d'hémato-immunologie, 75019 Paris, France.
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29
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Abstract
In contemporary clinical practice, almost all allogeneic transplantations and autologous transplantations now capitalize on peripheral blood stem cells (PBSCs) as opposed to bone marrow (BM) for the source of stem cells. In this context, granulocyte colony-stimulating factor (G-CSF) plays a pivotal role as the most frequently applied frontline agent for stem cell mobilization. For patients classified as high-risk, chemotherapy based mobilization regimens can be preferred as a first choice and it is notable that this also used for remobilization. Mobilization failure occurs at a rate of 10%-40% with traditional strategies and it typically leads to low-efficiency practices, resource wastage, and delayed in treatment intervention. Notably, however, several factors can impact the effectiveness of CD34+ progenitor cell mobilization, including patient age and medical history (prior chemotherapy or radiotherapy, disease and marrow infiltration at the time of mobilization). In recent years, main (yet largely ineffective) approach was to increase G-CSF dose and add SCF, but novel and promising pathways have been opened up by the synergistic impact of a reversible inhibitor of CXCR4, plerixafor, with G-CSF. The literature shows to its favorable results in upfront and failed mobilizers, and it is necessary to use plerixafor (or equivalent agents) to optimize HSC harvest in poor mobilizers. Different CXCR4 inhibitors, growth hormone, VLA4 inhibitors, and parathormone, have been cited as new agents for mobilization failure in recent years. In view of the above considerations, the purpose of this paper is to examine the mobilization of PBSC while focusing specifically on poor mobilizers.
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Affiliation(s)
- Sinem Namdaroglu
- Izmir Bozyaka Training and Research Hospital, Department of Hematology, Izmir, Turkey.
| | - Serdal Korkmaz
- University of Health Sciences, Ankara Oncology Training and Research Hospital, Department of Hematology, BMT Unit, Ankara, Turkey
| | - Fevzi Altuntas
- University of Health Sciences, Ankara Oncology Training and Research Hospital, Department of Hematology, BMT Unit, Ankara, Turkey; Yıldırım Beyazıt University, Medical Faculty, Department of Hematology, Ankara, Turkey
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30
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The Role of Low-dose Anti-thymocyte Globulin as Standard Prophylaxis in Mismatched and Matched Unrelated Hematopoietic Peripheral Stem Cell Transplantation for Hematologic Malignancies. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2017; 17:658-666. [DOI: 10.1016/j.clml.2017.06.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 06/04/2017] [Accepted: 06/08/2017] [Indexed: 01/22/2023]
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31
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Kariminia A, Ivison S, Ng B, Rozmus J, Sung S, Varshney A, Aljurf M, Lachance S, Walker I, Toze C, Lipton J, Lee SJ, Szer J, Doocey R, Lewis I, Smith C, Chaudhri N, Levings MK, Broady R, Devins G, Szwajcer D, Foley R, Mostafavi S, Pavletic S, Wall DA, Couban S, Panzarella T, Schultz KR. CD56 bright natural killer regulatory cells in filgrastim primed donor blood or marrow products regulate chronic graft- versus-host disease: the Canadian Blood and Marrow Transplant Group randomized 0601 study results. Haematologica 2017; 102:1936-1946. [PMID: 28935847 PMCID: PMC5664398 DOI: 10.3324/haematol.2017.170928] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2017] [Accepted: 09/15/2017] [Indexed: 11/29/2022] Open
Abstract
Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease. One hundred and twenty-one evaluable filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow patient donor products were immunologically characterized by flow cytometry and tested for their association with acute and chronic graft-versus-host disease within 2 years of transplantation. The immune populations evaluated included, regulatory T cells, central memory and effector T cells, interferon γ positive producing T cells, invariate natural killer T cells, regulatory natural killer cells, dendritic cell populations, macrophages, and activated B cells and memory B cells. When both filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow were grouped together, a higher chronic graft-versus-host disease frequency was associated with lower proportions of CD56bright natural killer regulatory cells and interferon γ-producing T helper cells in the donor product. Lower CD56bright natural killer regulatory cells displayed differential impacts on the development of extensive chronic graft-versus-host disease between filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow. In summary, while controlling for the potential impact of filgrastim on marrow, our studies demonstrated that CD56bright natural killer regulatory cells had a much stronger impact on filgrastim-stimulated apheresis peripheral blood than on filgrastim-stimulated bone marrow. This supports the conclusion that a lower proportion of CD56bright natural killer regulatory cells results in the high rate of chronic graft-versus-host disease seen in filgrastim-stimulated apheresis peripheral blood. clinicaltrials.gov Identifier: 00438958.
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Affiliation(s)
- Amina Kariminia
- Michael Cuccione Childhood Cancer research Program, BC Children's Hospital, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Sabine Ivison
- Michael Cuccione Childhood Cancer research Program, BC Children's Hospital, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Bernard Ng
- Department of Statistics, University of British Columbia, Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada
| | - Jacob Rozmus
- Michael Cuccione Childhood Cancer research Program, BC Children's Hospital, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Susanna Sung
- Michael Cuccione Childhood Cancer research Program, BC Children's Hospital, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Avani Varshney
- Michael Cuccione Childhood Cancer research Program, BC Children's Hospital, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Mahmoud Aljurf
- King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
| | - Sylvie Lachance
- Hôpital Maisonneuve-Rosemont, Université de Montréal, QC, Canada
| | - Irwin Walker
- Hamilton Health Sciences Centre and McMaster University, Hamilton, ON, Canada
| | - Cindy Toze
- Leukemia/Bone Marrow Transplant Program of BC, Vancouver General Hospital, British Columbia Cancer Agency and the University of British Columbia, Vancouver, BC, Canada
| | - Jeff Lipton
- Princess Margaret Cancer Centre University of Toronto, ON, Canada
| | | | - Jeff Szer
- Royal Melbourne Hospital and University of Melbourne, Australia
| | - Richard Doocey
- Auckland City and Starship Children's Hospital, Auckland, New Zealand
| | - Ian Lewis
- Institute of Medical and Veterinary Sciences, Adelaide, Australia
| | - Clayton Smith
- General Hematology, Blood Cancers and Bone Marrow Transplant Program, University of Colorado Hospital, Aurora, CO, USA
| | - Naeem Chaudhri
- King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
| | - Megan K Levings
- BC Children's Hospital Research Institute and Department of Surgery, University of British Columbia, Vancouver, BC, Canada
| | - Raewyn Broady
- Leukemia/Bone Marrow Transplant Program of BC, Vancouver General Hospital, British Columbia Cancer Agency and the University of British Columbia, Vancouver, BC, Canada
| | - Gerald Devins
- Princess Margaret Cancer Centre University of Toronto, ON, Canada
| | | | - Ronan Foley
- Hamilton Health Sciences Centre and McMaster University, Hamilton, ON, Canada
| | - Sara Mostafavi
- Department of Statistics, University of British Columbia, Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada
| | - Steven Pavletic
- Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Donna A Wall
- The Hospital for Sick Children and University of Toronto, ON, Canada
| | - Stephan Couban
- Nova Scotia Health Authority and Dalhousie University, Halifax, NS, Canada
| | - Tony Panzarella
- Princess Margaret Cancer Centre University of Toronto, ON, Canada
| | - Kirk R Schultz
- Michael Cuccione Childhood Cancer research Program, BC Children's Hospital, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
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32
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Damlaj M, Ghazi S, Mashaqbeh W, Gmati G, Salama H, Abuelgasim KA, Rather M, Hajeer A, Al-Zahrani M, Jazieh AR, Hejazi A, Al Askar A. Lymphocyte recovery is an independent predictor of relapse in allogeneic hematopoietic cell transplantation recipients for acute leukemia. World J Transplant 2017; 7:235-242. [PMID: 28900606 PMCID: PMC5573899 DOI: 10.5500/wjt.v7.i4.235] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2017] [Revised: 07/06/2017] [Accepted: 07/24/2017] [Indexed: 02/05/2023] Open
Abstract
AIM To examine the optimal absolute lymphocyte count (ALC) cut-off utilizing receiver operator characteristics (ROC) in addition to graft characteristics associated with early ALC recovery.
METHODS Patients who received T-cell replete peripheral hematopoietic cell transplantation (HCT) for acute leukemia were identified. ALC cut-off was established using ROC analysis and subsequently the cohort was stratified. Time to endpoint analysis and cox regression modelling was computed to analyze outcomes.
RESULTS A total of 72 patients met the inclusion criteria and were analyzed. Optimal ALC cut-off was established to be on day 14 (D14) with ALC > 0.3 × 109/L. At 2 years, cumulative incidence of relapse was 16.9% vs 46.9% (P = 0.025) for early and delayed lymphocyte recovery cohorts, respectively. Chronic graft vs host disease was more prevalent in the early lymphocyte recovery (ELR) group at 70% vs 27%, respectively (P = 0.0006). On multivariable analysis for relapse, ELR retained its prognostic significance with HR = 0.27 (0.05-0.94, P = 0.038).
CONCLUSION ELR is an independent predictor for relapse in patients receiving allogeneic HCT for acute leukemia. ELR was influenced by graft characteristics particularly CD34 count.
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Affiliation(s)
- Moussab Damlaj
- Division of Hematology and HSCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
| | - Samer Ghazi
- Division of Hematology and HSCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
| | - Walid Mashaqbeh
- Division of Hematology and HSCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
| | - Gamal Gmati
- Division of Hematology and HSCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
| | - Hend Salama
- Division of Hematology and HSCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
| | - Khadega A Abuelgasim
- Division of Hematology and HSCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
| | - Mushtaq Rather
- Division of Hematology and HSCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
| | - Ali Hajeer
- King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia
| | - Mohsen Al-Zahrani
- Division of Hematology and HSCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
| | - Abdul-Rahman Jazieh
- Division of Hematology and HSCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
| | - Ayman Hejazi
- Division of Hematology and HSCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
| | - Ahmad Al Askar
- Division of Hematology and HSCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
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33
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Konuma T, Kato S, Oiwa-Monna M, Tanoue S, Ogawa M, Isobe M, Tojo A, Takahashi S. Cryopreserved CD34 + Cell Dose, but Not Total Nucleated Cell Dose, Influences Hematopoietic Recovery and Extensive Chronic Graft-versus-Host Disease after Single-Unit Cord Blood Transplantation in Adult Patients. Biol Blood Marrow Transplant 2017; 23:1142-1150. [DOI: 10.1016/j.bbmt.2017.03.036] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Accepted: 03/23/2017] [Indexed: 01/08/2023]
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34
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Akahoshi Y, Kimura SI, Gomyo A, Hayakawa J, Tamaki M, Harada N, Kusuda M, Kameda K, Ugai T, Wada H, Ishihara Y, Kawamura K, Sakamoto K, Sato M, Terasako-Saito K, Kikuchi M, Nakasone H, Kako S, Kanda Y. Delayed platelet recovery after allogeneic hematopoietic stem cell transplantation: Association with chronic graft-versus-host disease and survival outcome. Hematol Oncol 2017; 36:276-284. [DOI: 10.1002/hon.2427] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Accepted: 04/07/2017] [Indexed: 11/05/2022]
Affiliation(s)
- Yu Akahoshi
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Shun-ichi Kimura
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Ayumi Gomyo
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Jin Hayakawa
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Masaharu Tamaki
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Naonori Harada
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Machiko Kusuda
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Kazuaki Kameda
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Tomotaka Ugai
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Hidenori Wada
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Yuko Ishihara
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Koji Kawamura
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Kana Sakamoto
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Miki Sato
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Kiriko Terasako-Saito
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Misato Kikuchi
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Hideki Nakasone
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Shinichi Kako
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
| | - Yoshinobu Kanda
- Division of Hematology, Saitama Medical Center; Jichi Medical University; Saitama Japan
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Collignon A, Calmels B, Harbi S, Fürst S, Granata A, Faucher C, Lemarie C, Weiller PJ, Chabannon C, Blaise D, Devillier R. Impact of CD34-positive cell dose on outcome after peripheral blood stem cell allogeneic transplantation prepared with ATG-based reduced intensity conditioning regimen. Am J Hematol 2017; 92:E57-E59. [PMID: 28133837 DOI: 10.1002/ajh.24661] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Accepted: 01/23/2017] [Indexed: 12/31/2022]
Affiliation(s)
- Aude Collignon
- Department of Hematology; Institut Paoli-Calmettes; Marseille France
- Medical School; Aix-Marseille University; Marseille France
- Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm U1068, CNRS UMR7258, Institut Paoli-Calmettes; Marseille F-13009 France
| | - Boris Calmels
- Cell Therapy Facility, Institut Paoli-Calmettes; Marseille France
- CIC Biothérapies: Inserm CBT-1409; Marseille France
| | - Samia Harbi
- Department of Hematology; Institut Paoli-Calmettes; Marseille France
| | - Sabine Fürst
- Department of Hematology; Institut Paoli-Calmettes; Marseille France
| | - Angela Granata
- Department of Hematology; Institut Paoli-Calmettes; Marseille France
| | - Catherine Faucher
- Department of Hematology; Institut Paoli-Calmettes; Marseille France
| | - Claude Lemarie
- Cell Therapy Facility, Institut Paoli-Calmettes; Marseille France
- CIC Biothérapies: Inserm CBT-1409; Marseille France
| | - Pierre-Jean Weiller
- Department of Hematology; Institut Paoli-Calmettes; Marseille France
- Medical School; Aix-Marseille University; Marseille France
- Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm U1068, CNRS UMR7258, Institut Paoli-Calmettes; Marseille F-13009 France
| | - Christian Chabannon
- Cell Therapy Facility, Institut Paoli-Calmettes; Marseille France
- CIC Biothérapies: Inserm CBT-1409; Marseille France
| | - Didier Blaise
- Department of Hematology; Institut Paoli-Calmettes; Marseille France
- Medical School; Aix-Marseille University; Marseille France
- Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm U1068, CNRS UMR7258, Institut Paoli-Calmettes; Marseille F-13009 France
| | - Raynier Devillier
- Department of Hematology; Institut Paoli-Calmettes; Marseille France
- Medical School; Aix-Marseille University; Marseille France
- Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm U1068, CNRS UMR7258, Institut Paoli-Calmettes; Marseille F-13009 France
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Geerman S, Nolte MA. Impact of T cells on hematopoietic stem and progenitor cell function: Good guys or bad guys? World J Stem Cells 2017; 9:37-44. [PMID: 28289507 PMCID: PMC5329688 DOI: 10.4252/wjsc.v9.i2.37] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Revised: 11/22/2016] [Accepted: 01/14/2017] [Indexed: 02/06/2023] Open
Abstract
When hematopoietic stem and progenitor cells (HSPC) are harvested for transplantation, either from the bone marrow or from mobilized blood, the graft contains a significant number of T cells. It is these T cells that are the major drivers of graft-vs-host disease (GvHD). The risk for GvHD can simply be reduced by the removal of these T cells from the graft. However, this is not always desirable, as this procedure also decreases the engraftment of the transplanted HSPCs and, if applicable, a graft-vs-tumor effect. This poses an important conundrum in the field: T cells act as a double-edged sword upon allogeneic HSPC transplantation, as they support engraftment of HSPCs and provide anti-tumor activity, but can also cause GvHD. It has recently been suggested that T cells also enhance the engraftment of autologous HSPCs, thus supporting the notion that T cells and HSPCs have an important functional interaction that is highly beneficial, in particular during transplantation. The underlying reason on why and how T cells contribute to HSPC engraftment is still poorly understood. Therefore, we evaluate in this review the studies that have examined the role of T cells during HSPC transplantation and the possible mechanisms involved in their supporting function. Understanding the underlying cellular and molecular mechanisms can provide new insight into improving HSPC engraftment and thus lower the number of HSPCs required during transplantation. Moreover, it could provide new avenues to limit the development of severe GvHD, thus making HSPC transplantations more efficient and ultimately safer.
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Chen Y, Xu LP, Liu KY, Chen H, Chen YH, Zhang XH, Wang Y, Wang FR, Han W, Wang JZ, Yan CH, Huang XJ. Higher dose of CD34+ peripheral blood stem cells is associated with better survival after haploidentical stem cell transplantation in pediatric patients. Clin Transplant 2016; 31. [PMID: 27888540 DOI: 10.1111/ctr.12880] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/08/2016] [Indexed: 01/25/2023]
Abstract
Haploidentical stem cell transplantation (SCT) is increasingly used to treat pediatric patients with malignant or nonmalignant hematological disorders. The CD34+ dose of bone marrow or peripheral blood stem cells (PBSCs) has been shown to be an important determinant of the transplant outcome in adults under various preparative regimens. However, knowledge of the effect of the CD34+ dose in pediatric haploidentical SCT is limited. We analyzed the data of 348 pediatric patients (aged 2-18 years) with acute or chronic leukemia, myelodysplastic syndrome (MDS), and other hematological disorders that received a transplant between 2002 and 2012. The results of multivariate analysis showed that PBSC CD34+ counts greater than 1.01 × 106 kg-1 improved platelet engraftment, improved overall survival, and reduced nonrelapse mortality. In contrast, a higher PBSC CD34+ dose did not affect the incidence of acute or chronic graft-versus-host disease, including engraftment syndrome. These data suggest that a PBSC CD34+ dose greater than 1.01 × 106 kg-1 is optimal for pediatric haploidentical SCT.
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Affiliation(s)
- Yao Chen
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Lan-Ping Xu
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Kai-Yan Liu
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Huan Chen
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Yu-Hong Chen
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Xiao-Hui Zhang
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Yu Wang
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Feng-Rong Wang
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Wei Han
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Jing-Zhi Wang
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Chen-Hua Yan
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Xiao-Jun Huang
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China.,Peking-Tsinghua Center for Life Sciences, Beijing, China
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Dufort G, Castillo L, Pisano S, Castiglioni M, Carolina P, Andrea I, Simon E, Zuccolo S, Schelotto M, Morosini F, Pereira I, Amarillo P, Silveira A, Guerrero L, Ferreira V, Tiscornia A, Mezzano R, Lemos F, Boggia B, Quarnetti A, Decaro J, Dabezies A. Haploidentical hematopoietic stem cell transplantation in children with high-risk hematologic malignancies: outcomes with two different strategies for GvHD prevention. Ex vivo T-cell depletion and post-transplant cyclophosphamide: 10 years of experience at a single center. Bone Marrow Transplant 2016; 51:1354-1360. [DOI: 10.1038/bmt.2016.161] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Revised: 03/26/2016] [Accepted: 05/01/2016] [Indexed: 11/09/2022]
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Martin PS, Li S, Nikiforow S, Alyea EP, Antin JH, Armand P, Cutler CS, Ho VT, Kekre N, Koreth J, Luckey CJ, Ritz J, Soiffer RJ. Infused total nucleated cell dose is a better predictor of transplant outcomes than CD34+ cell number in reduced-intensity mobilized peripheral blood allogeneic hematopoietic cell transplantation. Haematologica 2016; 101:499-505. [PMID: 26768686 DOI: 10.3324/haematol.2015.134841] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Accepted: 01/04/2016] [Indexed: 01/01/2023] Open
Abstract
Mobilized peripheral blood is the most common graft source for allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning. In assessing the effect of donor cell dose and graft composition on major transplant outcomes in the reduced-intensity setting, prior studies focused primarily on CD34(+)cell dose and reported conflicting results, especially in relation to survival end-points. While the impact of total nucleated cell dose has been less frequently evaluated, available studies suggest higher total nucleated cell dose is associated with improved survival outcomes in the reduced-intensity setting. In order to further explore the relationship between CD34(+)cell dose and total nucleated cell dose on reduced-intensity transplant outcomes, we analyzed the effect of donor graft dose and composition on outcomes of 705 patients with hematologic malignancies who underwent reduced-intensity peripheral blood stem cell transplantation at the Dana Farber Cancer Institute from 2000 to 2010. By multivariable analysis we found that higher total nucleated cell dose (top quartile; ≥10.8 × 10(10)cells) was associated with improved overall survival [HR 0.69 (0.54-0.88),P=0.0028] and progression-free survival [HR 0.68 (0.54-0.85),P=0.0006]. Higher total nucleated cell dose was independently associated with decreased relapse [HR 0.66 (0.51-0.85),P=0.0012] and increased incidence of chronic graft-versus-host disease [HR 1.4 (1.12-1.77),P=0.0032]. In contrast, higher doses of CD34(+)cells (top quartile; ≥10.9 × 10(6)/kg) had no significant effect on graft-versus-host disease or survival outcomes. These data suggest total nucleated cell dose is a more relevant prognostic variable for reduced-intensity transplant outcomes than the more commonly studied CD34(+)cell dose.
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Affiliation(s)
- Paul S Martin
- Fred Hutchinson Cancer Research Center and University of Washington School of Medicine, Seattle, WA, USA
| | - Shuli Li
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Sarah Nikiforow
- Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA
| | - Edwin P Alyea
- Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA
| | - Joseph H Antin
- Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA
| | - Philippe Armand
- Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA
| | - Corey S Cutler
- Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA
| | - Vincent T Ho
- Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA
| | - Natasha Kekre
- Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA
| | - John Koreth
- Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA
| | - C John Luckey
- Department of Pathology, University of Virginia, Charlottesville, VA, USA
| | - Jerome Ritz
- Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA
| | - Robert J Soiffer
- Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA
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Reshef R, Huffman AP, Gao A, Luskin MR, Frey NV, Gill SI, Hexner EO, Kambayashi T, Loren AW, Luger SM, Mangan JK, Nasta SD, Richman LP, Sell M, Stadtmauer EA, Vonderheide RH, Mick R, Porter DL. High Graft CD8 Cell Dose Predicts Improved Survival and Enables Better Donor Selection in Allogeneic Stem-Cell Transplantation With Reduced-Intensity Conditioning. J Clin Oncol 2015; 33:2392-8. [PMID: 26056179 DOI: 10.1200/jco.2014.60.1203] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
PURPOSE To characterize the impact of graft T-cell composition on outcomes of reduced-intensity conditioned (RIC) allogeneic hematopoietic stem-cell transplantation (alloHSCT) in adults with hematologic malignancies. PATIENTS AND METHODS We evaluated associations between graft T-cell doses and outcomes in 200 patients who underwent RIC alloHSCT with a peripheral blood stem-cell graft. We then studied 21 alloHSCT donors to identify predictors of optimal graft T-cell content. RESULTS Higher CD8 cell doses were associated with a lower risk for relapse (adjusted hazard ratio [aHR], 0.43; P = .009) and improved relapse-free survival (aHR, 0.50; P = .006) and overall survival (aHR, 0.57; P = .04) without a significant increase in graft-versus-host disease or nonrelapse mortality. A cutoff level of 0.72 × 10(8) CD8 cells per kilogram optimally segregated patients receiving CD8(hi) and CD8(lo) grafts with differing overall survival (P = .007). Donor age inversely correlated with graft CD8 dose. Consequently, older donors were unlikely to provide a CD8(hi) graft, whereas approximately half of younger donors provided CD8(hi) grafts. Compared with recipients of older sibling donor grafts (consistently containing CD8(lo) doses), survival was significantly better for recipients of younger unrelated donor grafts with CD8(hi) doses (P = .03), but not for recipients of younger unrelated donor CD8(lo) grafts (P = .28). In addition, graft CD8 content could be predicted by measuring the proportion of CD8 cells in a screening blood sample from stem-cell donors. CONCLUSION Higher graft CD8 dose, which was restricted to young donors, predicted better survival in patients undergoing RIC alloHSCT.
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Affiliation(s)
- Ran Reshef
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
| | - Austin P Huffman
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Amy Gao
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Marlise R Luskin
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Noelle V Frey
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Saar I Gill
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Elizabeth O Hexner
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Taku Kambayashi
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Alison W Loren
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Selina M Luger
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - James K Mangan
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Sunita D Nasta
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Lee P Richman
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Mary Sell
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Edward A Stadtmauer
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Robert H Vonderheide
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Rosemarie Mick
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - David L Porter
- All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
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41
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Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Total Body Irradiation-Based Myeloablative Haploidentical Stem Cell Transplantation Is a Safe and Effective Alternative to Unrelated Donor Transplantation in Patients Without Matched Sibling Donors. Biol Blood Marrow Transplant 2015; 21:1299-307. [PMID: 25797174 DOI: 10.1016/j.bbmt.2015.03.003] [Citation(s) in RCA: 125] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Accepted: 03/06/2015] [Indexed: 12/14/2022]
Abstract
We enrolled 30 patients on a prospective phase II trial utilizing a total body irradiation (TBI)-based myeloablative preparative regimen (fludarabine 30 mg/m2/day × 3 days and TBI 150 cGy twice per day on day -4 to -1 [total dose 1200 cGy]) followed by infusion of unmanipulated peripheral blood stem cells from a haploidentical family donor (haplo). Postgrafting immunosuppression consisted of cyclophosphamide 50 mg/kg/day on days 3 and 4, mycophenolate mofetil through day 35, and tacrolimus through day 180. Median patient age was 46.5 years (range, 24 to 60). Transplantation diagnosis included acute myelogenous leukemia (n = 16), acute lymphoblastic leukemia (n = 6), chronic myelogenous leukemia (n = 5), myelodysplastic syndrome (n = 1), and non-Hodgkin's lymphoma (n = 2). Using the Dana Farber/Center for International Blood and Marrow Transplant Research/Disease Risk Index (DRI), patients were classified as low (n = 4), intermediate (n = 12), high (n = 11), and very high (n = 3) risk. All patients engrafted with a median time to neutrophil and platelet recovery of 16 and 25 days, respectively. All evaluable patients achieved sustained complete donor T cell and myeloid chimerism by day +30. Acute graft-versus-host disease (GVHD) grades II to IV and III and IV was seen in 43% and 23%, respectively. The cumulative incidence of chronic GVHD was 56% (severe in 10%). After a median follow-up of 24 months, the estimated 2-year overall survival (OS), disease-free survival (DFS), nonrelapse mortality, and relapse rate were 78%, 73%, 3%, and 24%, respectively. Two-year DFS and relapse rate in patients with low/intermediate risk disease was 100% and 0%, respectively, compared with 39% and 53% for patients with high/very high risk disease. When compared with a contemporaneously treated cohort of patients at our institution receiving myeloablative HLA-matched unrelated donor (MUD) transplantation (acute myelogenous leukemia [n = 17], acute lymphoblastic leukemia [n = 15], chronic myelogenous leukemia [n = 7], myelodysplastic syndrome [n = 7], non-Hodgkin lymphoma [n = 1], chronic lymphoblastic leukemia [n = 1]), outcomes were statistically similar, with 2-yr OS and DFS being 78% and 73%, respectively after haplo transplantation versus 71% and 64%, respectively, after MUD transplantation. In patients with DRI low/intermediate risk disease, 2-yr DFS was superior after haplo compared with MUD transplantations (100% versus 74%, P = .032), whereas there was no difference in DFS in patients with high/very high risk disease (39% versus 37% for haplo and MUD respectively, P = .821). Grade II to IV acute GVHD was seen less often after haplo compared with MUD transplantation (43% versus 63%, P = .049), as was moderate-to-severe chronic GVHD (22% versus 58%, P = .003). Myeloablative haplo transplantation using this regimen is a valid option for patients with advanced hematologic malignancies who lack timely access to a conventional donor. Outcomes appear at least equivalent to those seen in contemporaneous patients who underwent transplantation from MUD.
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Affiliation(s)
- Scott R Solomon
- Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia.
| | - Connie A Sizemore
- Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia
| | - Melissa Sanacore
- Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia
| | - Xu Zhang
- Department of Mathematics and Statistics, Georgia State University, Atlanta, Georgia
| | - Stacey Brown
- Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia
| | - H Kent Holland
- Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia
| | - Lawrence E Morris
- Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia
| | - Asad Bashey
- Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia
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Remberger M, Törlén J, Ringdén O, Engström M, Watz E, Uhlin M, Mattsson J. Effect of Total Nucleated and CD34(+) Cell Dose on Outcome after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 2015; 21:889-93. [PMID: 25662230 DOI: 10.1016/j.bbmt.2015.01.025] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Accepted: 01/26/2015] [Indexed: 12/16/2022]
Abstract
During more recent years only few studies have analyzed the effect of total nucleated cell (TNC) and CD34(+) cell dose in allogeneic hematopoietic stem cell transplantation (HSCT). A single-center analysis included 544 patients, 227 with a sibling donor and 317 with an unrelated donor. Most patients (n = 292) were treated with myeloablative conditioning, whereas the remaining patients (n = 252) received reduced-intensity conditioning. Bone marrow (BM) (n = 121) and peripheral blood stem cell (PBSC) grafts (n = 423) were analyzed separately. Median TNC and CD34(+) cell dose was 3.2 × 10(8)/kg versus 11.6 × 10(8)/kg in BM and 3.9 × 10(6)/kg versus 8.1 × 10(6)/kg in PBSC. In the BM group we found a higher TNC and CD34(+) cell dose was associated with a faster neutrophil engraftment (P < .001 and P = .02). In the PBSC group we found patients given a very high (≥11 × 10(6)/kg) CD34(+) cell dose had decreased rates of survival (P = .001) and increased relapse (P = .02). A high CD34(+) cell dose correlated with faster platelet engraftment (P < .01). In HSCT using PBSCs, the CD34(+) cell doses should be kept below 11 × 10(6)/kg but over 2.5 × 10(6)/kg.
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Affiliation(s)
- Mats Remberger
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden.
| | - Johan Törlén
- Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Olle Ringdén
- Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Mats Engström
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Emma Watz
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Michael Uhlin
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Jonas Mattsson
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden
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Flommersfeld S, Sohlbach K, Jaques G, Bein G, Hoffmann J, Kostrewa P, Sachs UJ. Collection of peripheral blood progenitor cells on Day 4 is feasible and effective while reducing granulocyte-colony-stimulating factor exposure to healthy donors. Transfusion 2015; 55:1269-74. [DOI: 10.1111/trf.13002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Revised: 11/18/2014] [Accepted: 11/28/2014] [Indexed: 11/28/2022]
Affiliation(s)
| | - Kristina Sohlbach
- Department of Hematology, Oncology, and Immunology; University Hospital Giessen and Marburg, Marburg Campus; Marburg Germany
| | - Gabriele Jaques
- Department of Hematology, Oncology, and Immunology; University Hospital Giessen and Marburg, Marburg Campus; Marburg Germany
| | - Gregor Bein
- Institute for Clinical Immunology and Transfusion Medicine; Justus Liebig University; Giessen Germany
| | - Jörg Hoffmann
- Department of Hematology, Oncology, and Immunology; University Hospital Giessen and Marburg, Marburg Campus; Marburg Germany
| | - Philippe Kostrewa
- Department of Hematology, Oncology, and Immunology; University Hospital Giessen and Marburg, Marburg Campus; Marburg Germany
| | - Ulrich J. Sachs
- Center for Transfusion Medicine and Hemotherapy
- Institute for Clinical Immunology and Transfusion Medicine; Justus Liebig University; Giessen Germany
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Detrait MY, Morisset S, Peffault de Latour R, Yakoub-Agha I, Crocchiolo R, Tabrizi R, Bay JO, Chevalier P, Barraco F, Raus N, Vigouroux S, Magro L, Mohty M, Milpied N, Blaise D, Socié G, Michallet M. Pre-transplantation risk factors to develop sclerotic chronic GvHD after allogeneic HSCT: A multicenter retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). Bone Marrow Transplant 2014; 50:253-8. [DOI: 10.1038/bmt.2014.244] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Revised: 08/02/2014] [Accepted: 09/17/2014] [Indexed: 12/11/2022]
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45
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Impact of CD34+ cell dose in children who receive unrelated PBSCT with in vivo T-cell depletion for hematologic malignancies. Bone Marrow Transplant 2014; 50:68-73. [PMID: 25265463 DOI: 10.1038/bmt.2014.202] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Revised: 07/07/2014] [Accepted: 07/28/2014] [Indexed: 11/09/2022]
Abstract
PBSCs are increasingly being chosen as the mode of donation among unrelated donors. Pediatric patients, in particular, may receive very high CD34(+) and CD3(+) doses during unrelated PBSCT. In this work, we analyzed survival and GVHD outcomes in a cohort of 81 children who received unrelated PBSCT with uniform antithymocyte globulin (ATG)-based in vivo T-cell depletion for treatment of hematologic malignancy, with emphasis on the impact of cell dose on transplant outcomes. EFS was 61.5±5.6%, with higher CD34(+) dose (>10.0 × 10(6)/kg) and lower patient risk status predicting improved survival in multivariate study. Cumulative incidence of relapse was 30.2±5.2%; a low CD34(+) dose was the only significant factor for relapse. Neither CD34(+) nor CD3(+) dose was a significant determinant of acute or chronic GVHD. Importance of CD34(+) dose was reaffirmed in a subcohort of younger patients who received greater median cell doses than the overall cohort. In summary, for children who received unrelated PBSCT with ATG-based T-cell depletion for treatment of hematologic malignancy, the CD34(+) dose was the most important factor for relapse and EFS, and neither the CD34(+) nor the CD3(+) dose influenced incidence of acute or chronic GVHD.
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46
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Duong HK, Savani BN, Copelan E, Devine S, Costa LJ, Wingard JR, Shaughnessy P, Majhail N, Perales MA, Cutler CS, Bensinger W, Litzow MR, Mohty M, Champlin RE, Leather H, Giralt S, Carpenter PA. Peripheral blood progenitor cell mobilization for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2014; 20:1262-73. [PMID: 24816581 DOI: 10.1016/j.bbmt.2014.05.003] [Citation(s) in RCA: 164] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 05/01/2014] [Indexed: 02/03/2023]
Abstract
Peripheral blood progenitor cell mobilization practices vary significantly among institutions. Effective mobilization regimens include growth factor alone, chemotherapy and growth factor combined, and, more recently, incorporation of plerixafor with either approach. Many institutions have developed algorithms to improve stem cell mobilization success rates and cost-effectiveness. However, an optimal stem cell mobilization regimen has not been defined. Practical guidelines are needed to address important clinical questions, including which growth factor is optimal, what chemotherapy and dose is most effective, and when to initiate leukapheresis. We present recommendations, based on a comprehensive review of the literature, from the American Society of Blood and Marrow Transplantation.
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Affiliation(s)
- Hien K Duong
- Department of Blood and Marrow Transplant, Blood and Marrow Transplant Program, Cleveland Clinic Foundation, Cleveland, Ohio.
| | - Bipin N Savani
- Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Ed Copelan
- Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North Carolina
| | - Steven Devine
- Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio
| | - Luciano J Costa
- Division of Hematology and Oncology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - John R Wingard
- Division of Hematology/Oncology, University of Florida Health Cancer Center, Gainesville, Florida
| | - Paul Shaughnessy
- Department of Adult Bone Marrow Transplant, Texas Transplant Institute, San Antonio, Texas
| | - Navneet Majhail
- Department of Blood and Marrow Transplant, Blood and Marrow Transplant Program, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Miguel-Angel Perales
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, and Weill Cornell Medical College, New York, New York
| | - Corey S Cutler
- Department of Hematologic Oncology, Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - William Bensinger
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Mark R Litzow
- Division of Hematology, Division of Palliative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Mohamad Mohty
- Department of Haematology, Saint Antoine Hospital, Paris, France
| | - Richard E Champlin
- Department of Stem Cell Transplantation, M.D. Anderson Cancer Center, Houston, Texas
| | - Helen Leather
- Division of Hematology/Oncology, University of Florida Health Cancer Center, Gainesville, Florida
| | - Sergio Giralt
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, and Weill Cornell Medical College, New York, New York
| | - Paul A Carpenter
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
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47
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Törlén J, Ringdén O, Le Rademacher J, Batiwalla M, Chen J, Erkers T, Ho V, Kebriaei P, Keever-Taylor C, Kindwall-Keller T, Lazarus HM, Laughlin MJ, Lill M, O'Brien T, Perales MA, Rocha V, Savani BN, Szwajcer D, Valcarcel D, Eapen M. Low CD34 dose is associated with poor survival after reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant 2014; 20:1418-25. [PMID: 24892261 PMCID: PMC4127369 DOI: 10.1016/j.bbmt.2014.05.021] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Accepted: 05/22/2014] [Indexed: 10/25/2022]
Abstract
Reduced-intensity conditioning/nonmyeloablative conditioning regimens are increasingly used in allogeneic hematopoietic cell transplantation (HCT). Reports have shown CD34(+) dose to be important for transplantation outcome using myeloablative conditioning. The role of CD34(+) dose of peripheral blood progenitor cells (PBPC) has not been previously analyzed in a large population undergoing reduced-intensity conditioning/nonmyeloablative HCT. We studied 1054 patients, ages 45 to 75 years, with acute myeloid leukemia or myelodysplastic syndrome who underwent transplantation between 2002 and 2011. Results of multivariate analysis showed that PBPC from HLA-matched siblings containing <4 × 10(6) CD34(+)/kg was associated with higher nonrelapse mortality (hazard ratio [HR], 2.03; P = .001), overall mortality (HR, 1.48; P = .008), and lower neutrophil (odds ratio [OR], .76; P = .03) and platelet (OR, .76; P = .03) recovery. PBPC from unrelated donors with CD34(+) dose < 6 × 10(6) CD34(+)/kg was also associated with higher nonrelapse (HR, 1.38; P = .02) and overall mortality (HR, 1.20; P = .05). In contrast to reports after myeloablative HCT, CD34(+) dose did not affect relapse or graft-versus-host disease with either donor type. An upper cell dose limit was not associated with adverse outcomes. These data suggest that PBPC CD34(+) doses >4 × 10(6) CD34(+)/kg and >6 × 10(6) CD34(+)/kg are optimal for HLA-matched sibling and unrelated donor HCT, respectively.
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Affiliation(s)
- Johan Törlén
- Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Olle Ringdén
- Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden; Division of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden
| | - Jennifer Le Rademacher
- Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Minoo Batiwalla
- Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland
| | - Junfang Chen
- Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Tom Erkers
- Division of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden
| | - Vincent Ho
- Department of Hematologic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Partow Kebriaei
- Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas
| | - Carolyn Keever-Taylor
- Division of Hematology & Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Tamila Kindwall-Keller
- Division of Hematology/Oncology, University of Virginia Health System, Charlottesville, Virginia
| | - Hillard M Lazarus
- Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio
| | - Mary J Laughlin
- Stem Cell Therapeutics Program, Novartis Pharmaceuticals Inc, East Hanover, New Jersey
| | - Michael Lill
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - Tracey O'Brien
- Centre for Children's Cancer & Blood Disorders, Sydney Children's Hospital, Sydney, NSW, Australia
| | - Miguel-Angel Perales
- Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Vanderson Rocha
- Department of Clinical Haematology, Churchill Hospital, Oxford University Hospital, Oxford, United Kingdom
| | - Bipin N Savani
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - David Szwajcer
- Department of Hematology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - David Valcarcel
- Department of Hematology, Hospital Vall d'Hebron, Barcelona, Spain
| | - Mary Eapen
- Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Hematology & Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
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48
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Ceberio I, Devlin SM, Sauter C, Barker JN, Castro-Malaspina H, Giralt S, Ponce DM, Lechner L, Maloy MA, Goldberg JD, Perales MA. Sirolimus, tacrolimus and low-dose methotrexate based graft-versus-host disease prophylaxis after non-ablative or reduced intensity conditioning in related and unrelated donor allogeneic hematopoietic cell transplant. Leuk Lymphoma 2014; 56:663-70. [PMID: 24913499 DOI: 10.3109/10428194.2014.930851] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Encouraging results have been reported with sirolimus, tacrolimus and low-dose methotrexate after non-myeloablative allogeneic hematopoietic cell transplant. We conducted a retrospective analysis of 71 patients with lymphoid malignancies treated with this prophylaxis regimen after non-myeloablative or reduced intensity allogeneic hematopoietic cell transplant. Grafts were human leukocyte antigen (HLA)-matched related in 29 (41%), matched unrelated in 36 (51%) and 9/10 HLA-matched unrelated in six (8%) patients. The regimen was well tolerated and over 90% of patients completed the planned treatment. The cumulative incidences of 1-year grade B-D and C-D acute graft-versus-host disease (GVHD) were 0.28 (95% confidence interval [CI], 0.18-0.39) and 0.07 (95% CI, 0.03-0.15), respectively, and of 1- and 2-year chronic GVHD (National Institutes of Health criteria) in 70 evaluable patients were 0.15 (95% CI, 0.08-0.24) and 0.33 (95% CI, 0.22-0.44), respectively. The median day of onset of acute GVHD was 123 days (range, 17-268 days). Peri-transplant rituximab or anti-thymocyte globulin did not affect GVHD. The cumulative incidence of 1-year non-relapse mortality and relapse were 4% and 20%, respectively. With a median follow-up of 3.5 (range: 0.18-5.1) years, overall survival and progression-free survival at 2 years were 82% and 66%, respectively. This GVHD regimen results in a low incidence and severity of acute and chronic GVHD after reduced intensity and non-myeloablative allogeneic hematopoietic cell transplant for lymphoid malignancies. The study also highlights the incidence of late onset acute GVHD in non-myeloablative/reduced intensity conditioning, and the contribution of the new GVHD staging system that more accurately reflects clinical outcomes.
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Affiliation(s)
- Izaskun Ceberio
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center , New York, NY , USA
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49
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Maie K, Fuji S, Tajima K, Tatsuno M, Yamagata S, Takahashi N, Ueda R, Hashimoto H, Takano K, Inoue Y, Ito A, Hayashi Y, Okinaka K, Kurosawa S, Kim SW, Tanosaki R, Heike Y, Yamashita T, Fukuda T. A higher number of infused CD34(+) cells has a positive impact on the clinical outcome after related PBSC transplantation. Bone Marrow Transplant 2014; 49:1113-5. [PMID: 24797181 DOI: 10.1038/bmt.2014.94] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- K Maie
- 1] Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan [2] Department of Hematology, University of Tsukuba, Tsukuba, Japan
| | - S Fuji
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - K Tajima
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - M Tatsuno
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - S Yamagata
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - N Takahashi
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - R Ueda
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - H Hashimoto
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - K Takano
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - Y Inoue
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - A Ito
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - Y Hayashi
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - K Okinaka
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - S Kurosawa
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - S-W Kim
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - R Tanosaki
- Department of Blood Transfusion and Cellular Therapy, National Cancer Center Hospital, Tokyo, Japan
| | - Y Heike
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - T Yamashita
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - T Fukuda
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
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50
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Servais S, Porcher R, Xhaard A, Robin M, Masson E, Larghero J, Ribaud P, Dhedin N, Abbes S, Sicre F, Socié G, Peffault de Latour R. Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors. Haematologica 2013; 99:519-26. [PMID: 24241489 DOI: 10.3324/haematol.2013.089979] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. In this retrospective single center study of 442 patients with hematologic malignancies, we analyzed prognostic factors for long-term survival after peripheral blood stem cell transplantation from HLA-matched related or unrelated donors. To account for disease/status heterogeneity, patients were risk-stratified according to the Disease Risk Index. Five-year overall survival was similar after transplants with matched related and unrelated donors (45% and 46%, respectively; P=0.49). Because donor age ≥60 years impacted outcome during model building, we further considered 3 groups of donors: matched unrelated (aged <60 years by definition), matched related aged <60 years and matched related aged ≥60 years. In multivariate analysis, the donor type/age group and the graft CD34(+) and CD3(+) cell doses impacted long-term survival. Compared with matched unrelated donor transplant, transplant from matched related donor <60 years resulted in similar long-term survival (P=0.67) while transplant from matched related donor ≥60 years was associated with higher risks for late mortality (hazard ratio (HR) 4.41; P=0.006) and treatment failure (HR: 6.33; P=0.009). Lower mortality risks were observed after transplant with CD34(+) cell dose more than 4.5×10(6)/kg (HR: 0.56; P=0.002) and CD3(+) cell dose more than 3×10(8)/kg (HR: 0.61; P=0.01). The Disease Risk Index failed to predict survival. We built an "adapted Disease Risk Index" by modifying risks for myeloproliferative neoplasms and multiple myeloma that improved stratification ability for progression-free survival (P=0.04) but not for overall survival (P=0.82).
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