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Deng L, Yu X, Song X, Guan R, Li W, Liu X, Shao Y, Hou Y, Zhao Y, Wang J, Liu Y, Xiao Q, Xin B, Zhou F. The prophylactic application of low-dose rabbit antithymocyte globulin in matched siblings HSCT with high-risk factors for graft-versus-host disease. Transpl Immunol 2024; 87:102131. [PMID: 39307438 DOI: 10.1016/j.trim.2024.102131] [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: 08/01/2024] [Revised: 09/13/2024] [Accepted: 09/19/2024] [Indexed: 09/27/2024]
Abstract
Relapse and graft-versus-host disease (GVHD) are currently the predominant causes of mortality post allogeneic hematopoietic stem cell transplantation (allo-HSCT). The contentious use of antithymocyte globulin (ATG) for preventing GVHD in matched sibling HSCT scenarios has been a topic of significant debate. A retrospective analysis was conducted on matched sibling HSCT cases with high-risk factors for GVHD in our center from January 2018 to June 2023. Our assessment revealed that the group administered with ATG exhibited a 30 % incidence of acute GVHD (aGVHD), in contrast to 81.8 % in the non-ATG cohort (P = 0.037) among matched sibling HSCT cases with high GVHD risk factors. Furthermore, chronic GVHD (cGVHD) occurred in 20 % of the ATG group and 72.7 % of the non-ATG group (P = 0.03). Notably, the administration of ATG did not significantly impact disease relapse (p = 0.149), infection rates (p = 0.64), granulocyte recovery time (p = 0.15), platelet recovery time (p = 0.12), overall survival (p = 0.889), or disease-free survival time (p = 0.787). The use of rabbit antithymocyte globulin (r-ATG) at a 5 mg/kg dosage demonstrated a notable reduction in aGVHD and cGVHD incidences within sibling matched HSCT cases with high-risk factors for GVHD, without increasing rates of disease recurrence or infections. These findings highlight the potential benefit of using low-dose r-ATG in high-risk of GVHD sibling matched allogeneic HSCTs, although further validation with a larger cohort is necessary.
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Affiliation(s)
- Lei Deng
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
| | - Xiaolin Yu
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
| | - Xiaocheng Song
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
| | - Rui Guan
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
| | - Wenjun Li
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
| | - Ximing Liu
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
| | - Yan Shao
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
| | - Yixi Hou
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
| | - Yuerong Zhao
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
| | - Jing Wang
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
| | - Yue Liu
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
| | - Qianqian Xiao
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
| | - Bo Xin
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
| | - Fang Zhou
- Department of Hematology, The 960th Hospital of The Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China.
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Yue K, Gao H, Liang S, Wu N, Cheng C, Xu LP, Zhang XH, Wang Y, Cheng Y, Huang XJ, Liu J. Improved Vδ2 + T cells recovery correlates to reduced incidences of mortality and relapse in acute myeloid leukemia after hematopoietic transplantation. Ann Hematol 2023; 102:937-946. [PMID: 36763109 DOI: 10.1007/s00277-023-05125-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 02/01/2023] [Indexed: 02/11/2023]
Abstract
Acute myeloid leukemia (AML) patients can benefit from allogeneic hematopoietic cell transplantation (alloHCT) and achieve long-term remission. Recovery of T cell quantity and quality is critical to reduce the incidences of life-threatening complications after alloHCT. Although the general recovery level of γδ T cells is recognized to be associated with outcomes of patients who suffered from various hematological diseases and received alloHCT, the correlation between γδ T cell subsets and the prognosis in AML patients following transplantation remains to be investigated. In the current study, the recoveries of T cell subpopulations in 103 AML patients were dissected at different time points after haploidentical HCT (haploHCT). Statistical analyses showed that the absolute number of Vδ2+ T cells on day 90 was an independent risk factor for predicting 2-year OS in AML patients following haploHCT. The survival advantage from the improved recovery of day-90 Vδ2+ T cells was attributed to reducing the infection-related mortality. Consistently, lower 2-year non-relapse mortality was found in recipients with higher day-90 levels of Vδ2+ T cells. Notably, day-270 Vδ2+ T cell numbers reversely correlated to both 2-year and 5-year probabilities of relapse in this scenario. These results highlighted the significant correlation of Vδ2+ T cells recovery with long-term survival and relapse after alloHCT, suggesting that Vδ2+ T cells-based immune strategies may help control infectious complications and leukemia recurrence in AML patients.
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Affiliation(s)
- Keli Yue
- Peking University People's Hospital, Peking University Institute of Hematology, 11 Xizhimen South Street, Beijing, 100044, China
- National Clinical Research Center for Hematologic Disease, Beijing, China
- Beijing Key laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Haitao Gao
- Peking University People's Hospital, Peking University Institute of Hematology, 11 Xizhimen South Street, Beijing, 100044, China
- National Clinical Research Center for Hematologic Disease, Beijing, China
- Beijing Key laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Shuang Liang
- Peking University People's Hospital, Peking University Institute of Hematology, 11 Xizhimen South Street, Beijing, 100044, China
- National Clinical Research Center for Hematologic Disease, Beijing, China
- Beijing Key laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
| | - Ning Wu
- Peking University People's Hospital, Peking University Institute of Hematology, 11 Xizhimen South Street, Beijing, 100044, China
- National Clinical Research Center for Hematologic Disease, Beijing, China
- Beijing Key laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Cong Cheng
- Peking University People's Hospital, Peking University Institute of Hematology, 11 Xizhimen South Street, Beijing, 100044, China
- National Clinical Research Center for Hematologic Disease, Beijing, China
- Beijing Key laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Lan-Ping Xu
- Peking University People's Hospital, Peking University Institute of Hematology, 11 Xizhimen South Street, Beijing, 100044, China
- National Clinical Research Center for Hematologic Disease, Beijing, China
- Beijing Key laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Xiao-Hui Zhang
- Peking University People's Hospital, Peking University Institute of Hematology, 11 Xizhimen South Street, Beijing, 100044, China
- National Clinical Research Center for Hematologic Disease, Beijing, China
- Beijing Key laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Yu Wang
- Peking University People's Hospital, Peking University Institute of Hematology, 11 Xizhimen South Street, Beijing, 100044, China
- National Clinical Research Center for Hematologic Disease, Beijing, China
- Beijing Key laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Yifei Cheng
- Peking University People's Hospital, Peking University Institute of Hematology, 11 Xizhimen South Street, Beijing, 100044, China
- National Clinical Research Center for Hematologic Disease, Beijing, China
- Beijing Key laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Xiao-Jun Huang
- Peking University People's Hospital, Peking University Institute of Hematology, 11 Xizhimen South Street, Beijing, 100044, China
- National Clinical Research Center for Hematologic Disease, Beijing, China
- Beijing Key laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
| | - Jiangying Liu
- Peking University People's Hospital, Peking University Institute of Hematology, 11 Xizhimen South Street, Beijing, 100044, China.
- National Clinical Research Center for Hematologic Disease, Beijing, China.
- Beijing Key laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
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Serroukh Y, Hébert J, Busque L, Mercier F, Rudd CE, Assouline S, Lachance S, Delisle JS. Blasts in context: the impact of the immune environment on acute myeloid leukemia prognosis and treatment. Blood Rev 2023; 57:100991. [PMID: 35941029 DOI: 10.1016/j.blre.2022.100991] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 06/22/2022] [Accepted: 07/13/2022] [Indexed: 01/28/2023]
Abstract
Acute myeloid leukemia (AML) is a cancer that originates from the bone marrow (BM). Under physiological conditions, the bone marrow supports the homeostasis of immune cells and hosts memory lymphoid cells. In this review, we summarize our present understanding of the role of the immune microenvironment on healthy bone marrow and on the development of AML, with a focus on T cells and other lymphoid cells. The types and function of different immune cells involved in the AML microenvironment as well as their putative role in the onset of disease and response to treatment are presented. We also describe how the immune context predicts the response to immunotherapy in AML and how these therapies modulate the immune status of the bone marrow. Finally, we focus on allogeneic stem cell transplantation and summarize the current understanding of the immune environment in the post-transplant bone marrow, the factors associated with immune escape and relevant strategies to prevent and treat relapse.
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Affiliation(s)
- Yasmina Serroukh
- Centre de recherche de l'Hôpital Maisonneuve-Rosemont, 5415 Boul. de L'Assomption, Montréal, Canada; Erasmus Medical center Cancer Institute, University Medical Center Rotterdam, Department of Hematology, Rotterdam, the Netherlands; Department of Medicine, Université de Montréal, Montreal, Canada; Institute for Hematology-Oncology, Transplantation, Cell and Gene Therapy, Hôpital Maisonneuve-Rosemont, Montreal, Canada.
| | - Josée Hébert
- Centre de recherche de l'Hôpital Maisonneuve-Rosemont, 5415 Boul. de L'Assomption, Montréal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada; Institute for Hematology-Oncology, Transplantation, Cell and Gene Therapy, Hôpital Maisonneuve-Rosemont, Montreal, Canada; The Quebec Leukemia Cell Bank, Canada
| | - Lambert Busque
- Centre de recherche de l'Hôpital Maisonneuve-Rosemont, 5415 Boul. de L'Assomption, Montréal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada; Institute for Hematology-Oncology, Transplantation, Cell and Gene Therapy, Hôpital Maisonneuve-Rosemont, Montreal, Canada
| | - François Mercier
- Division of Hematology and Experimental Medicine, Department of Medicine, McGill University, 3755 Côte-Sainte-Catherine Road, Montreal, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Côte-Sainte-Catherine Road, Montreal, Canada
| | - Christopher E Rudd
- Centre de recherche de l'Hôpital Maisonneuve-Rosemont, 5415 Boul. de L'Assomption, Montréal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada; Institute for Hematology-Oncology, Transplantation, Cell and Gene Therapy, Hôpital Maisonneuve-Rosemont, Montreal, Canada
| | - Sarit Assouline
- Division of Hematology and Experimental Medicine, Department of Medicine, McGill University, 3755 Côte-Sainte-Catherine Road, Montreal, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Côte-Sainte-Catherine Road, Montreal, Canada
| | - Silvy Lachance
- Department of Medicine, Université de Montréal, Montreal, Canada; Institute for Hematology-Oncology, Transplantation, Cell and Gene Therapy, Hôpital Maisonneuve-Rosemont, Montreal, Canada
| | - Jean-Sébastien Delisle
- Centre de recherche de l'Hôpital Maisonneuve-Rosemont, 5415 Boul. de L'Assomption, Montréal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada; Institute for Hematology-Oncology, Transplantation, Cell and Gene Therapy, Hôpital Maisonneuve-Rosemont, Montreal, Canada
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Deng DX, Fan S, Zhang XH, Xu LP, Wang Y, Yan CH, Chen H, Chen YH, Han W, Wang FR, Wang JZ, Pei XY, Chang YJ, Liu KY, Huang XJ, Mo XD. Immune Reconstitution of Patients Who Recovered From Steroid-Refractory Acute Graft-Versus-Host Disease After Basiliximab Treatment. Front Oncol 2022; 12:916442. [PMID: 35936697 PMCID: PMC9351448 DOI: 10.3389/fonc.2022.916442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 06/15/2022] [Indexed: 11/18/2022] Open
Abstract
We aimed to identify the characteristics of immune reconstitution (IR) in patients who recovered from steroid-refractory acute graft-versus-host disease (SR-aGVHD) after basiliximab treatment. A total of 179, 124, 80, and 92 patients were included in the analysis for IR at 3, 6, 9, and 12 months, respectively, after haploidentical donor hematopoietic stem cell transplantation (HID HSCT). We observed that IR was fastest for monocytes and CD8+ T cells, followed by lymphocytes, CD3+ T cells, and CD19+ B cells and slowest for CD4+ T cells. Almost all immune cell subsets recovered comparably between patients receiving <5 doses and ≥5 doses of basiliximab. Most immune cell subsets recovered comparably between SR-aGVHD patients who recovered after basiliximab treatment and event-free HID HSCT recipients. Patients who recovered from SR-aGVHD after basiliximab treatment experienced satisfactory IR, which suggested that basiliximab may not have prolonged the negative impact on IR in these patients.
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Affiliation(s)
- Dao-Xing Deng
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Shuang Fan
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Xiao-Hui Zhang
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Lan-Ping Xu
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Yu Wang
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Chen-Hua Yan
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Huan Chen
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Yu-Hong Chen
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Wei Han
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Feng-Rong Wang
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Jing-Zhi Wang
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Xu-Ying Pei
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Ying-Jun Chang
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Kai-Yan Liu
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Xiao-Jun Huang
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
- Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiao-Dong Mo
- Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
- Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, Beijing, China
- *Correspondence: Xiao-Dong Mo,
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Takahashi T, Prockop SE. T-cell depleted haploidentical hematopoietic cell transplantation for pediatric malignancy. Front Pediatr 2022; 10:987220. [PMID: 36313879 PMCID: PMC9614427 DOI: 10.3389/fped.2022.987220] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 09/20/2022] [Indexed: 11/13/2022] Open
Abstract
Access to allogenic hematopoietic cell transplantation (HCT), a potentially curative treatment for chemotherapy-resistant hematologic malignancies, can be limited if no human leukocyte antigen (HLA) identical related or unrelated donor is available. Alternative donors include Cord Blood as well as HLA-mismatched unrelated or related donors. If the goal is to minimize the number of HLA disparities, partially matched unrelated donors are more likely to share 8 or 9 of 10 HLA alleles with the recipient. However, over the last decade, there has been success with haploidentical HCT performed using the stem cells from HLA half-matched related donors. As the majority of patients have at least one eligible and motivated haploidentical donor, recruitment of haploidentical related donors is frequently more rapid than of unrelated donors. This advantage in the accessibility has historically been offset by the increased risks of graft rejection, graft-versus-host disease and delayed immune reconstitution. Various ex vivo T-cell depletion (TCD) methods have been investigated to overcome the immunological barrier and facilitate immune reconstitution after a haploidentical HCT. This review summarizes historical and contemporary clinical trials of haploidentical TCD-HCT, mainly in pediatric malignancy, and describes the evolution of these approaches with a focus on serial improvements in the kinetics of immune reconstitution. Methods of TCD discussed include in vivo as well as ex vivo positive and negative selection. In addition, haploidentical TCD as a platform for post-HCT cellular therapies is discussed. The present review highlights that, as a result of the remarkable progress over half a century, haploidentical TCD-HCT can now be considered as a preferred alternative donor option for children with hematological malignancy in need of allogeneic HCT.
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Affiliation(s)
- Takuto Takahashi
- Pediatric Stem Cell Transplantation, Boston Children's Hospital/Dana-Farber Cancer Institute, Boston, MA, United States.,Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis, MN, United States
| | - Susan E Prockop
- Pediatric Stem Cell Transplantation, Boston Children's Hospital/Dana-Farber Cancer Institute, Boston, MA, United States
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Compagno F, Basso S, Panigari A, Bagnarino J, Stoppini L, Maiello A, Mina T, Zelini P, Perotti C, Baldanti F, Zecca M, Comoli P. Management of PTLD After Hematopoietic Stem Cell Transplantation: Immunological Perspectives. Front Immunol 2020; 11:567020. [PMID: 33042147 PMCID: PMC7526064 DOI: 10.3389/fimmu.2020.567020] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 08/18/2020] [Indexed: 01/07/2023] Open
Abstract
Post-transplant lymphoproliferative disorders (PTLDs) are life-threatening complications of iatrogenic immune impairment after allogeneic hematopoietic stem cell transplantation (HSCT). In the pediatric setting, the majority of PTLDs are related to the Epstein-Barr virus (EBV) infection, and present as B-cell lymphoproliferations. Although considered rare events, PTLDs have been increasingly observed with the widening application of HSCT from alternative sources, including cord blood and HLA-haploidentical stem cell grafts, and the use of novel agents for the prevention and treatment of rejection and graft-vs.-host disease. The higher frequency initially paralleled a poor outcome, due to limited therapeutic options, and scarcity of controlled trials in a rare disease context. In the last 2 decades, insight into the relationship between EBV and the immune system, and advances in early diagnosis, monitoring and treatment have changed the approach to the management of PTLDs after HSCT, and significantly ameliorated the prognosis. In this review, we summarize literature on the impact of combined viro-immunologic assessment on PTLD management, describe the various strategies for PTLD prevention and preemptive/curative treatment, and discuss the potential of novel immune-based therapies in the containment of this malignant complication.
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Affiliation(s)
- Francesca Compagno
- Pediatric Hematology/Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
| | - Sabrina Basso
- Pediatric Hematology/Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
- Cell Factory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
| | - Arianna Panigari
- Pediatric Hematology/Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
| | - Jessica Bagnarino
- Pediatric Hematology/Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
- Cell Factory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
| | - Luca Stoppini
- Pediatric Hematology/Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
- Cell Factory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
| | - Alessandra Maiello
- Pediatric Hematology/Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
- Cell Factory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
| | - Tommaso Mina
- Pediatric Hematology/Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
| | - Paola Zelini
- Pediatric Hematology/Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
- Cell Factory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
| | - Cesare Perotti
- Immunohematology and Transfusion Service, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
| | - Fausto Baldanti
- Virology Service, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Marco Zecca
- Pediatric Hematology/Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
| | - Patrizia Comoli
- Pediatric Hematology/Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
- Cell Factory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
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7
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Dessie G, Derbew Molla M, Shibabaw T, Ayelign B. Role of Stem-Cell Transplantation in Leukemia Treatment. Stem Cells Cloning 2020; 13:67-77. [PMID: 32982314 PMCID: PMC7493021 DOI: 10.2147/sccaa.s262880] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 07/25/2020] [Indexed: 12/12/2022] Open
Abstract
Stem cells (SCs) play a major role in advanced fields of regenerative medicine and other research areas. They are involved in the regeneration of damaged tissue or cells, due to their self-renewal characteristics. Tissue or cells can be damaged through a variety of diseases, including hematologic and nonhematologic malignancies. In regard to this, stem-cell transplantation is a cellular therapeutic approach to restore those impaired cells, tissue, or organs. SCs have a therapeutic potential in the application of stem-cell transplantation. Research has been focused mainly on the application of hematopoietic SCs for transplantation. Cord blood cells and human leukocyte antigen-haploidentical donors are considered optional sources of hematopoietic stem-cell transplantation. On the other hand, pluripotent embryonic SCs and induced pluripotent SCs hold promise for advancement of stem-cell transplantation. In addition, nonhematopoietic mesenchymal SCs play their own significant role as a functional bone-marrow niche and in the management of graft-vs-host disease effects during the posttransplantation process. In this review, the role of different types of SCs is presented with regard to their application in SC transplantation. In addition to this, the therapeutic value of autologous and allogeneic hematopoietic stem-cell transplantation is assessed with respect to different types of leukemia. Highly advanced and progressive scientific research has focused on the application of stem-cell transplantation on specific leukemia types. We evaluated and compared the therapeutic potential of SC transplantation with various forms of leukemia. This review aimed to focus on the application of SCs in the treatment of leukemia.
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Affiliation(s)
- Gashaw Dessie
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Meseret Derbew Molla
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Tewodros Shibabaw
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Birhanu Ayelign
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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Eisfeld C, Eßeling E, Wullenkord R, Khandanpour C, Reusch J, Mikesch JH, Reicherts C, Kerkhoff A, Schliemann C, Kessler T, Mesters RM, Berdel WE, Lenz G, Stelljes M. Long-term survival and polyclonal immunoglobulin reconstitution after allogeneic stem cell transplantation in multiple myeloma. Ann Hematol 2020; 99:1907-1915. [PMID: 32444892 PMCID: PMC7340674 DOI: 10.1007/s00277-020-04068-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 04/28/2020] [Indexed: 01/19/2023]
Abstract
Despite significant progress made in the treatment of patients with multiple myeloma (MM) in the last decade, for patients with early relapse or rapidly progressing high-risk disease, allogeneic hematopoietic stem cell transplantation (SCT) might be an option leading to long-term survival. Here, we retrospectively analyzed the outcomes of 90 MM patients who received allogeneic SCT in our center between 1999 and 2017. We specifically assessed the association of impaired humoral immune reconstitution, referred to as immunoparesis, and post-transplant survival. Sixty-four patients received allogeneic SCT in relapse following 2–7 lines of therapy; 26 patients received upfront tandem autologous-allogeneic SCT. With a median follow-up of 76 months, OS and PFS were 52.6% (95% CI 42.9–64.3) and 36.4% (95% CI 27.6–47.9) at 2 years and 38.6% (95% CI 29.2–51.1) and 25.3% (95% CI 17.5–36.4) at 5 years, respectively. Receiving more than two therapy lines prior to transplantation was an independent risk factor for OS (HR 3.68, 95% CI 2.02–6.70) and PFS (HR 3.69, 95% CI 2.09–6.50). In a landmark analysis at day 200, prolonged immunoparesis was associated with reduced OS (HR 3.22, 95% CI 1.14–9.11). Allogeneic stem cell transplantation offers an additional treatment element that may lead to long-term remission in selected patients with poor prognosis, probably exploiting graft-versus-myeloma effects. Immunoparesis could potentially serve as an indicator for impaired survival following allogeneic transplantation, an observation to be further studied prospectively.
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Affiliation(s)
- Christine Eisfeld
- Department of Medicine A, University Hospital Münster, Münster, Germany
| | - Eva Eßeling
- Department of Medicine A, University Hospital Münster, Münster, Germany
| | - Ramona Wullenkord
- Department of Medicine A, University Hospital Münster, Münster, Germany
| | - Cyrus Khandanpour
- Department of Medicine A, University Hospital Münster, Münster, Germany
| | - Julia Reusch
- Department of Medicine A, University Hospital Münster, Münster, Germany
| | | | | | - Andrea Kerkhoff
- Department of Medicine A, University Hospital Münster, Münster, Germany
| | | | - Torsten Kessler
- Department of Medicine A, University Hospital Münster, Münster, Germany
| | - Rolf M Mesters
- Department of Medicine A, University Hospital Münster, Münster, Germany
| | - Wolfgang E Berdel
- Department of Medicine A, University Hospital Münster, Münster, Germany
| | - Georg Lenz
- Department of Medicine A, University Hospital Münster, Münster, Germany
| | - Matthias Stelljes
- Department of Medicine A, University Hospital Münster, Münster, Germany.
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9
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Baumeister SHC, Rambaldi B, Shapiro RM, Romee R. Key Aspects of the Immunobiology of Haploidentical Hematopoietic Cell Transplantation. Front Immunol 2020; 11:191. [PMID: 32117310 PMCID: PMC7033970 DOI: 10.3389/fimmu.2020.00191] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 01/24/2020] [Indexed: 12/27/2022] Open
Abstract
Hematopoietic stem cell transplantation from a haploidentical donor is increasingly used and has become a standard donor option for patients lacking an appropriately matched sibling or unrelated donor. Historically, prohibitive immunological barriers resulting from the high degree of HLA-mismatch included graft-vs.-host disease (GVHD) and graft failure. These were overcome with increasingly sophisticated strategies to manipulate the sensitive balance between donor and recipient immune cells. Three different approaches are currently in clinical use: (a) ex vivo T-cell depletion resulting in grafts with defined immune cell content (b) extensive immunosuppression with a T-cell replete graft consisting of G-CSF primed bone marrow and PBSC (GIAC) (c) T-cell replete grafts with post-transplant cyclophosphamide (PTCy). Intriguing studies have recently elucidated the immunologic mechanisms by which PTCy prevents GVHD. Each approach uniquely affects post-transplant immune reconstitution which is critical for the control of post-transplant infections and relapse. NK-cells play a key role in haplo-HCT since they do not mediate GVHD but can successfully mediate a graft-vs.-leukemia effect. This effect is in part regulated by KIR receptors that inhibit NK cell cytotoxic function when binding to the appropriate HLA-class I ligands. In the context of an HLA-class I mismatch in haplo-HCT, lack of inhibition can contribute to NK-cell alloreactivity leading to enhanced anti-leukemic effect. Emerging work reveals immune evasion phenomena such as copy-neutral loss of heterozygosity of the incompatible HLA alleles as one of the major mechanisms of relapse. Relapse and infectious complications remain the leading causes impacting overall survival and are central to scientific advances seeking to improve haplo-HCT. Given that haploidentical donors can typically be readily approached to collect additional stem- or immune cells for the recipient, haplo-HCT represents a unique platform for cell- and immune-based therapies aimed at further reducing relapse and infections. The rapid advancements in our understanding of the immunobiology of haplo-HCT are therefore poised to lead to iterative innovations resulting in further improvement of outcomes with this compelling transplant modality.
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Affiliation(s)
- Susanne H C Baumeister
- Division of Pediatric Hematology-Oncology, Boston Children's Hospital, Boston, MA, United States.,Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Benedetta Rambaldi
- Harvard Medical School, Boston, MA, United States.,Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, United States.,Bone Marrow Transplant Unit, Clinical and Experimental Sciences Department, ASST Spedali Civili, University of Pavia, Brescia, Italy
| | - Roman M Shapiro
- Harvard Medical School, Boston, MA, United States.,Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, United States
| | - Rizwan Romee
- Harvard Medical School, Boston, MA, United States.,Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, United States
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