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Moaveni AK, Seyed Taher SF, Ghavamzadeh A, Hamidieh AA, Kajbafzadeh AM. The potential of uroflowmetry to predict and detect hemorrhagic cystitis following hematopoietic stem cell transplantation. J Pediatr Urol 2025; 21:426-433. [PMID: 39603892 DOI: 10.1016/j.jpurol.2024.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 09/28/2024] [Accepted: 11/05/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND Hemorrhagic cystitis (HC) is a serious complication following hematopoietic stem cell transplantation (HSCT) associated with significant morbidity and mortality. Early identification of at-risk patients and prompt diagnosis are crucial for effective management. This prospective cohort study evaluated the potential of uroflowmetry as a predictive tool for detecting HC in pediatric HSCT patients. METHODS Thirty-one children who underwent allogeneic HSCT were enrolled. Uroflowmetry was performed on admission (Day 0), post-HSCT Day 1 and Day 15, and at HC onset. Uroflowmetric parameters, including maximum flow rate (Qmax), average flow rate (Qavg), voided volume (VV), and flow curve shape, were compared between HC and non-HC patients. RESULTS The incidence of HC within 100 days post-HSCT was 58 %, with a mean onset time of 35 days. At baseline (Day 0), HC patients had significantly lower Qmax (12.5 vs. 17.8 mL/s), Qavg (6.8 vs. 9.5 mL/s), and VV (185 vs. 245 mL) compared to non-HC patients (all p < 0.05). Age-stratified analysis revealed the observation of these differences across all age groups. At HC onset, compared to Day 0, patients experienced a significant decrease in Qmax (8.7 vs. 12.5 mL/s) and Qavg (4.2 vs. 6.8 mL/s) (both p < 0.05). Flow curve analysis demonstrated a shift from bell-shaped to interrupted curves in HC patients over time. CONCLUSIONS Uroflowmetry can potentially predict and detect HC in pediatric HSCT patients. Lower baseline uroflowmetric parameters may identify patients at higher risk for HC, while a significant decrease in these parameters from baseline may indicate HC onset. Uroflowmetry is a simple, non-invasive tool that can be performed at home and monitored remotely, facilitating early detection and intervention for HC in this population.
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Affiliation(s)
- Amir Kian Moaveni
- Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Farshad Seyed Taher
- Hematology, Oncology, and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ardeshir Ghavamzadeh
- Hematology, Oncology, and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Ali Hamidieh
- Pediatric Cell and Gene Therapy Research Centre, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Abdol-Mohammad Kajbafzadeh
- Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
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Qu Y, Zhao P, Ding X, Qiao X, Wang L, Li Y. Hyperbaric oxygen therapy improves the efficacy of conventional supportive treatment for late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Hematology 2024; 29:2356307. [PMID: 38776234 DOI: 10.1080/16078454.2024.2356307] [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: 08/25/2023] [Accepted: 05/12/2024] [Indexed: 05/24/2024] Open
Abstract
OBJECTIVE This study aims to investigate the efficacy and safety of hyperbaric oxygen therapy (HBOT) in the treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. METHODS This retrospective analysis included 16 patients with late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation between 2016 and 2022. Among them, 8 patients received HBOT in addition to conventional treatment, while the other 8 received only conventional treatment. The clinical efficacy and safety of HBOT were evaluated by comparing the Numeric Rating Scale pain scores and clinical grades of hematuria before and after treatment, reflecting the patients' urinary pain and hematuria status. RESULTS The patients were divided into two groups based on whether they received HBOT. The group that received HBOT (n = 8) had a shorter duration of illness compared to the non-HBOT group (n = 8) (p < 0.05). The time for the NRS to decrease to below 2 was also shorter in the HBOT group. Furthermore, the patients who received HBOT did not experience any significant adverse reactions. CONCLUSION The combination of conventional treatment and hyperbaric oxygen therapy (HBOT) has been shown to improve symptoms such as urinary pain, frequency, urgency, and hematuria in patients with late-onset hemorrhagic cystitis after transplantation. This approach has been proven to be safe and effective.
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Affiliation(s)
- Yiwen Qu
- Medical Science Center of Qingdao University, Qingdao, Shandong, People's Republic of China
- Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, Shandong, People's Republic of China
| | - Peng Zhao
- Medical Science Center of Qingdao University, Qingdao, Shandong, People's Republic of China
- Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, Shandong, People's Republic of China
| | - Xiaojie Ding
- Medical Science Center of Qingdao University, Qingdao, Shandong, People's Republic of China
- Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, Shandong, People's Republic of China
| | - Xiansen Qiao
- Medical Science Center of Qingdao University, Qingdao, Shandong, People's Republic of China
- Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, Shandong, People's Republic of China
| | - Ling Wang
- Medical Science Center of Qingdao University, Qingdao, Shandong, People's Republic of China
- Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, Shandong, People's Republic of China
| | - Ying Li
- Medical Science Center of Qingdao University, Qingdao, Shandong, People's Republic of China
- Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, Shandong, People's Republic of China
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Khudari RA, Doba D, Esmandar A, Kheder M. Treatment outcome at the pediatric stem cell transplantation center in Syria: A single-center experience. Pediatr Transplant 2024; 28:e14789. [PMID: 38808750 DOI: 10.1111/petr.14789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 04/09/2024] [Accepted: 05/08/2024] [Indexed: 05/30/2024]
Abstract
BACKGROUND Hematopoietic stem cell transplantation (HSCT) is a therapeutic approach known for its high success rates in treating various hematologic malignancies, hemoglobinopathies, immune deficiencies, and other disorders. Notably, pediatric HSCT commenced in Syria in 2021 amidst the prevailing crisis. This study aims to assess the demographic and clinical profiles of pediatric patients who underwent stem cell transplantation and to analyze treatment outcomes at Syria's inaugural pediatric HSCT center. METHODS This study is a single-center retrospective analysis of 25 pediatric patients who underwent HSCT underage of 14 years in the National Stem Cell Center (HAYAT) in Damascus within the period 2021-2023. The databases were created based on data that were collected from patient medical records. RESULTS In autologous patients, transplant-related mortality (TRM) was 0%, with 4 (57%) experiencing disease relapse, resulting in the death of one patient. Additionally, 3 (42.8%) of patients remain alive under second-line management. The overall survival rate was 6 (85.7%), and the disease-free survival rate was 16 (88%). In allogeneic patients, TRM was 5.5% (1/18). One allogeneic patient experienced disease relapse and subsequently died. The overall survival rate and disease-free survival rate were 16 (88%). CONCLUSIONS The objective of this study was to assess the outcomes of pediatric HSCT patients who have undergone transplantation thus far. Given the recent initiation of pediatric stem cell transplantation in Syria, our dataset provides a basis for comparison with international hematopoietic stem cell transplantation centers regarding treatment complications and outcomes, notwithstanding the challenges and crises faced within our country.
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Affiliation(s)
- Rawan Al Khudari
- Department of Pediatrics, Faculty of Medicine, Children's University Hospital, Damascus University, Damascus, Syria
| | - Dalal Doba
- Department of Laboratory, Laboratory in Tishreen Military Hospital, HSCT Laboratory in the National Stem Cell Center (HAYAT), Children's University Hospital, Damascus, Syria
| | - Amjad Esmandar
- Department of Hematology, BMT Technology in Tishreen Military Hospital, Damascus, Syria
| | - Maged Kheder
- Pediatrics Hematopoietic Stem Cell Transplantation Center, National Stem Cell Center (HAYAT), Faculty of Medicine, Children's University Hospital, Damascus University, Damascus, Syria
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Ersoy GZ, Bozkurt C, Aksoy BA, Öner ÖB, Aydoğdu S, Çipe F, Sütçü M, Özkaya O, Fışgın T. Evaluation of the risk factors for BK virus-associated hemorrhagic cystitis in pediatric bone marrow transplantation patients: Does post-transplantation cyclophosphamide increase the frequency? Pediatr Transplant 2023; 27:e14364. [PMID: 35851981 DOI: 10.1111/petr.14364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/31/2022] [Accepted: 07/04/2022] [Indexed: 01/24/2023]
Abstract
BACKGROUND BKV-HC is one of the most significant complications of HSCT. This retrospective study aimed to determine the frequency of BKV-HC in pediatric patients undergoing HSCT, detect the associated risk factors for the development of BKV-HC, and explore the effects of post-transplantation Cy use. METHODS Three hundred twenty-seven patients (girls: 121, boys: 206) were analyzed according to sex, conditioning regimen, transplantation type, donor relatedness, stem cell source, the presence and grade of aGVHD, CMV co-existence, and Cy use. RESULTS Multivariate analysis confirmed the prognostic importance of age (OR: 4.865), TBI use, the presence of aGVHD (OR: 2.794), CMV coinfection (OR: 2.261), and Cy use (OR: 27.353). A statistically significant difference was found between the mean BKV-HC follow-up times compared with post-transplantation Cy intake (p < .001). The BKV-HC rate increased as the number of risk factors of the patient increased. CONCLUSION BKV-HC is an essential complication of HSCT primarily associated with Cy use, the presence of aGVHD, and donor relatedness. The present study shows that the use of Cy in the post-transplantation period further increases BKV-HC risk in pediatric patients, regardless of dose.
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Affiliation(s)
- Gizem Zengin Ersoy
- Altınbaş University Medical Park Bahçelievler Hospital Pediatric Hematology Oncology & Pediatric Bone Marrow Transplantation Unit, İstanbul, Turkey
| | - Ceyhun Bozkurt
- Medical Park Bahçelievler Hospital Pediatric Hematology Oncology & Pediatric Bone Marrow Transplantation Unit, İstinye University Pediatric Hematology Oncology, Istanbul, Turkey
| | - Basak Adakli Aksoy
- Altınbaş University Medical Park Bahçelievler Hospital Pediatric Hematology Oncology & Pediatric Bone Marrow Transplantation Unit, İstanbul, Turkey
| | - Özlem Başoğlu Öner
- Altınbaş University Medical Park Bahçelievler Hospital Pediatric Hematology Oncology & Pediatric Bone Marrow Transplantation Unit, İstanbul, Turkey
| | - Selime Aydoğdu
- Umraniye Research & Training Hospital Pediatric Hematolgy & Oncology Department, Medical Sciences University, Istanbul, Turkey
| | - Funda Çipe
- Altınbaş University Medical Park Bahçelievler Hospital Pediatric Allergy-Immunology & Pediatric Bone Marrow Transplantation Unit, İstanbul, Turkey
| | - Murat Sütçü
- İstinye University Pediatric Infectious Diseases, Istanbul, Turkey
| | - Ozan Özkaya
- İstinye University Pediatric Nephrology, Istanbul, Turkey
| | - Tunç Fışgın
- Altınbaş University Medical Park Bahçelievler Hospital Pediatric Hematology Oncology & Pediatric Bone Marrow Transplantation Unit, İstanbul, Turkey
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Rostami T, Aghabeigi S, Kiumarsi A, Kasaeian A, Parizi MK, Mirhosseini A, Rostami MR, Babakhani D, Tavakoli F, Janbabai G, Mousavi SA. Incidence of hemorrhagic cystitis following unmanipulated peripheral blood stem cell transplantation in acute Leukemia: A retrospective single-center risk factor analysis. J Pediatr Urol 2023; 19:54.e1-54.e8. [PMID: 36443142 DOI: 10.1016/j.jpurol.2022.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 10/19/2022] [Accepted: 11/06/2022] [Indexed: 11/13/2022]
Abstract
BACKGROUND Hemorrhagic cystitis (HC) is an important adverse event experienced after hematopoietic stem cell transplantation (HSCT). Severe HC could lead to significant morbidity, prolonged hospitalization with increased health-care costs, and may cause considerable mortality. OBJECTIVES In order to investigate the influence of different contributing factors other than BK viruria on HC occurrence in a homogenous population, we retrospectively analyzed the potential risk factors. STUDY DESIGN We conducted a retrospective study among 200 patients (median age 12.4 years, IQR: 7.9-16.1) with acute leukemia who received peripheral blood allogenic HSCT after radiation-free myeloablative conditioning regimen, in pediatric cell therapy department of Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Tehran, Iran, between December 2014 and December 2021. Associations between risk factors and outcomes were examined by univariable and multivariable logistic regression models. RESULTS A total of 46 patients (23%) had developed HC during the study period. The median onset of HC was 29 (IQR: 24-37) days post-transplant, and it persisted for a median of 33 (7-270) days. The incidence of HC in our patients was estimated to be 3 in 1000 cases (95% CI: 2-4). The results of multivariable logistic model shows that the chance of HC in T-cell acute lymphoblastic leukemia (ALL) compared to B-cell All is nearly five times more (OR = 4.88; 95%CI: (1.51-15.78), P = 0.008). The incidence of HC in patients who underwent HSCT from haploidentical donors was significantly higher than full matched donors (P < 0.001). Undergoing transplant from a matched unrelated and haploidentical donor both augment the chance of HC in about six times more than matched related donors (OR = 6.36; 95%CI: (1.58-25.49), P = 0.009 and OR = 5.7; 95%CI: (1.83-17.75), P = 0.003, respectively). In patients who developed HC compared to non-HC group, overall survival was much worse (P < 0.001). DISCUSSION Most studies have failed to demonstrate any relationship between late-onset HC and the dose of cyclophosphamide. In our study, although the dose of cyclophosphamide was similar in HSCT from MRD and MUD, the hazard of HC incidence was significantly higher in the latter group. This could be accredited to ATG, as in patients in the MRD group who had not received any ATG, the incidence of HC was much lower than the patients who had underwent HSCT from MUD or haploidentical donor group. CONCLUSIONS Patients with T-cell ALL and those who under haploidentical HSCT had the highest incidence of HC.
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Affiliation(s)
- Tahereh Rostami
- Department of Pediatric Cell Therapy, Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Sohrab Aghabeigi
- Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Azadeh Kiumarsi
- Department of Pediatric Cell Therapy, Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Amir Kasaeian
- Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran; Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mehdi Kardoust Parizi
- Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Urology, Medical University of Vienna, Vienna, Austria.
| | - Amirhosein Mirhosseini
- Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Mohammad Reza Rostami
- Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Davoud Babakhani
- Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Farnaz Tavakoli
- Department of Nephrology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
| | - Ghasem Janbabai
- Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Seied Asadollah Mousavi
- Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
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Yuan H, Chen G, Qu J, Yang R, Muhashi M, Aizezi G, Jiang M. Clinical study of late-onset hemorrhagic cystitis after allo-HSCT without in vitro T-cell depletion. Medicine (Baltimore) 2022; 101:e32130. [PMID: 36550833 PMCID: PMC9771304 DOI: 10.1097/md.0000000000032130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
This study is to investigate the hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) without in vitro T-cell depletion. Patients receiving allo-HSCT in 2019 were enrolled. The occurrence and clinical characteristics of HC after HLA-identical HSCT and haploidentical HSCT were retrospectively analyzed. BK, JC, cytomegalovirus, and other viruses were monitored when HC occurred. Conventional HC treatment was performed. Additionally, 5 cases of severe refractory HC were treated with adipose-derived mesenchymal stem cell (ADSC) besides conventional HC treatment. Totally, 54 patients with allo-HSCT were enrolled, including 12 cases with HLA-identical HSCT and 42 cases with haploidentical HSCT. Among them, 17 developed late-onset HC (LOHC). There was no early-onset HC. The median onset time was 33.5 (9-189) days, with a median duration of 19 (5-143) days. There were 8 cases of grade III HC and 2 cases of grade IV HC. The cumulative incidence of LOHC in 54 patients was 29.6%, and the cumulative incidence of LOHC in 42 patients with haploidentical HSCT was 40.5%. The 1-year expected progression-free survival (PFS) of 26 patients without HC was 86.6%, and the 1-year expected PFS of 16 HC patients was 74.5%. However, there was no statistically significant difference (P = .326). The urine BK virus of 14 patients was positive, with the lowest of 1.98 × 105 copies/mL, and the highest of 8.96 × 105 copies/mL. For the 5 patients with severe refractory HC, the lowest infusion dose of ADSC was 0.9 × 106/kg and the highest was 1.4 × 106/kg. All 5 patients were cured. The incidence of LOHC is higher after haploidentical HSCT. LOHC is positively correlated with urine BK virus. LOHC has no obvious effect on the overall PFS of patients. ADSC infusion has a good therapeutic effect on severe and prolonged LOHC.
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Affiliation(s)
- Hailong Yuan
- Hematology Center, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Gang Chen
- Hematology Center, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Jianhua Qu
- Hematology Center, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Ruixue Yang
- Hematology Center, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Maria Muhashi
- Hematology Center, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Gulibadanmu Aizezi
- Hematology Center, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Ming Jiang
- Hematology Center, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi, Xinjiang Uygur Autonomous Region, China
- * Correspondence: Ming Jiang, Hematology Center, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, No.137, Liyushan South Road, Urumqi 830054, Xinjiang Uygur Autonomous Region, China (e-mail: )
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Yuan H, Chen G, Xu J, Yang R, Muhashi M, Aizezi G, Jiang M. Incidence of late-onset hemorrhagic cystitis and its effect on PFS in acute leukemia patients after haplo-PBSCT: The 5-year single-center data. Front Oncol 2022; 12:913802. [PMID: 35912244 PMCID: PMC9334683 DOI: 10.3389/fonc.2022.913802] [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: 04/06/2022] [Accepted: 06/28/2022] [Indexed: 12/02/2022] Open
Abstract
We conducted a single-center 5-year retrospective study on the occurrence of hemorrhagic cystitis (HC) and its effect on survival after haploid high-dose peripheral blood stem cell transplantation (haplo-PBSCT) in patients with acute leukemia. We retrospectively analyzed 153 patients with acute leukemia who were treated with non-in vitro T-cell depleted haplo-PBSCT and myeloablative conditioning regimen. All patients were followed up for more than 180 days after transplantation. HC occurrence and its effect on long-term progression free survival (PFS) were retrospectively analyzed. Totally, 64 out of 153 patients had late onset HC (LOHC). No early onset HC occurred. The median onset time was 38.5 (17-163) days after transplantation. The cumulative incidence of LOHC was 41.8%. The cumulative incidence of LOHC in patients under 27 years old (50.0%) and in ALL patients (54.1%) was significantly higher than that in patients over 27 years old (34.5%) and in AML patients (36.9%), respectively. The cumulative incidence of mild LOHC was 44.2% and that of severe LOHC was 28.6%. However, urine copies of BK virus were not related to LOHC duration. There was no significant difference in 3-year expected PFS between AML and ALL patients with and without LOHC, or between LOHC duration more than and less than 38.5 days (P>0.05). Conclusively, LOHC incidence is higher in patients under 27 years old and in ALL patients. LOHC occurrence is related to urine BK virus copy, but not blood BK virus load. LOHC duration and severity has no significant effect on PFS.
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Yuan H, Chen G, Qu J, Yang R, Muhashi M, Aizezi G, Jiang M. Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT. Open Med (Wars) 2021; 16:1493-1502. [PMID: 34703902 PMCID: PMC8494146 DOI: 10.1515/med-2021-0368] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 08/12/2021] [Accepted: 09/02/2021] [Indexed: 01/17/2023] Open
Abstract
Introduction This study is to investigate the effect of late-onset hemorrhagic cystitis (LOHC) on progression-free survival (PFS) of patients after haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). Methods This retrospective study enrolled 74 patients with hematological malignancies treated with a myeloablative conditioning regimen and haplo-PBSCT. The effect of LOHC on PFS was studied in terms of HC occurrence, grade, disease type, duration, onset time, gender, and age. Results There were 28 patients with LOHC, and no case was with early-onset HC. The cumulative incidence of LOHC was 37.8% (95% CI: 26.9–48.7%). The 2-year expected PFS of 74 patients and 34 AML patients was not significantly different between LOHC patients and patients without HC (P > 0.05). Among 27 ALL patients, the 2-year expected PFS of LOHC patients was 75%, significantly higher than patients without HC (54.2%) (P < 0.05). The 2-year expected PFSs of patients with mild LOHC and severe LOHC were 69.8 and 77.8%, respectively (P > 0.05). Similarly, the onset time, duration, age, and gender of LOHC patients did not show significant effects on PFS (P > 0.05). Conclusions After haplo-PBSCT, LOHC has a significant effect on the PFS of ALL patients. The HC grade, duration, onset time, gender, and age have no significant effect on PFS.
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Affiliation(s)
- Hailong Yuan
- Hematology Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi 830054, China
| | - Gang Chen
- Hematology Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi 830054, China
| | - Jianhua Qu
- Hematology Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi 830054, China
| | - Ruixue Yang
- Hematology Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi 830054, China
| | - Maria Muhashi
- Hematology Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi 830054, China
| | - Gulibadanmu Aizezi
- Hematology Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi 830054, China
| | - Ming Jiang
- Hematology Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, No. 137 Liyushan South Road, Urumqi 830054, China
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Pretransplant BK Virus-Specific T-Cell-Mediated Immunity and Serotype Specific Antibodies May Have Utility in Identifying Patients at Risk of BK Virus-Associated Haemorrhagic Cystitis after Allogeneic HSCT. Vaccines (Basel) 2021; 9:vaccines9111226. [PMID: 34835157 PMCID: PMC8625163 DOI: 10.3390/vaccines9111226] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/15/2021] [Accepted: 10/18/2021] [Indexed: 11/17/2022] Open
Abstract
BK polyomavirus (BKPyV) persists lifelong in renal and urothelial cells with asymptomatic urinary shedding in healthy individuals. In some immunocompromised persons after transplantation of hematopoietic stem cells (HSCT), the BKPyV high-rate replication is associated with haemorrhagic cystitis (HC). We tested whether the status of BKPyV immunity prior to HSCT could provide evidence for the BKPyV tendency to reactivate. We have shown that measurement of pretransplant anti-BKPyV 1 and 4 IgG levels can be used to evaluate the HC risk. Patients with anti-BKPyV IgG in the range of the 1st-2nd quartile of positive values and with positive clinical risk markers have a significantly increased HC risk, in comparison to the reference group of patients with "non-reactive" anti-BKPyV IgG levels and with low clinical risk (LCR) (p = 0.0009). The predictive value of pretransplant BKPyV-specific IgG was confirmed by determination of genotypes of the shed virus. A positive predictive value was also found for pretransplant T-cell immunity to the BKPyV antigen VP1 because the magnitude of IFN-γ T-cell response inversely correlated with posttransplant DNAuria and with HC. Our novel data suggest that specific T-cells control BKPyV latency before HSCT, and in this way may influence BKPyV reactivation after HSCT. Our study has shown that prediction using a combination of clinical and immunological pretransplant risk factors can help early identification of HSCT recipients at high risk of BKPyV disease.
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Olson A, Lin R, Marin D, Rafei H, Bdaiwi MH, Thall PF, Basar R, Abudayyeh A, Banerjee P, Aung FM, Kaur I, Abueg G, Rao S, Chemaly R, Mulanovich V, Al-Atrash G, Alousi AM, Andersson BS, Anderlini P, Bashir Q, Castro KM, Daher M, Galvan IM, Hosing C, Im JS, Jones RB, Kebriaei P, Khouri I, Mehta R, Molldrem J, Nieto Y, Oran B, Popat U, Qazilbash M, Rondon G, Saini N, Spencer B, Srour S, Washington D, Barnett M, Champlin RE, Shpall EJ, Rezvani K. Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation. J Clin Oncol 2021; 39:2710-2719. [PMID: 33929874 PMCID: PMC10166368 DOI: 10.1200/jco.20.02608] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 01/06/2021] [Accepted: 03/17/2021] [Indexed: 02/06/2023] Open
Abstract
PURPOSE BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option. METHODS We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed. RESULTS Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement. CONCLUSION Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.
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Affiliation(s)
- Amanda Olson
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ruitao Lin
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - David Marin
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Hind Rafei
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Mustafa H. Bdaiwi
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Peter F. Thall
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Rafet Basar
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ala Abudayyeh
- Division of Internal Medicine, Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Pinaki Banerjee
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Fleur M. Aung
- Department of Laboratory Medicine, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Indresh Kaur
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Glorette Abueg
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Sheetal Rao
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Roy Chemaly
- Department of Infectious Disease, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Victor Mulanovich
- Department of Infectious Disease, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Gheath Al-Atrash
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Amin M. Alousi
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Borje S. Andersson
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Paolo Anderlini
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Qaiser Bashir
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Karla M. Castro
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - May Daher
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Isabel M. Galvan
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Chitra Hosing
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jin S. Im
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Roy B. Jones
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Partow Kebriaei
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Issa Khouri
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Rohtesh Mehta
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jeffrey Molldrem
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Yago Nieto
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Betul Oran
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Uday Popat
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Muzaffar Qazilbash
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Gabriela Rondon
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Neeraj Saini
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Bryan Spencer
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Samer Srour
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Dominique Washington
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Melissa Barnett
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Richard E. Champlin
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Elizabeth J. Shpall
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Katayoun Rezvani
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
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Slack D, Ray S, Lee B, Sastry J. An Unusual Cause of Hemorrhagic Cystitis in a Teenager With Medulloblastoma. J Pediatr Hematol Oncol 2021; 43:e861-e863. [PMID: 32925398 DOI: 10.1097/mph.0000000000001949] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 08/24/2020] [Indexed: 11/26/2022]
Abstract
Hemorrhagic cystitis is a life-threatening condition in which the transitional epithelium and blood vessels of the bladder necrose leading to severe hematuria, abdominal pain, and voiding lower urinary tract symptoms. Etiology includes chemotherapy (cyclophosphamide, ifosfamide, busulfan), radiotherapy, or infectious agents. We present a pediatric case of a 15-year-old boy with medulloblastoma who developed hemorrhagic cystitis following cisplatin chemotherapy. All other causes were ruled out and it is therefore likely that the agent, in this case, was cisplatin, which has never had hemorrhagic cystitis reported as a side effect. We also suggest a mechanism for urothelial injury centered around OCT-2 receptors.
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Affiliation(s)
| | - Satyajit Ray
- Department of Paediatric Oncology, Schiehallion Unit
| | - Boma Lee
- Departments of Paediatric Urology
| | - Jairam Sastry
- Paediatric Oncology, Royal Hospital for Children Glasgow, Glasgow, UK
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12
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Cassani A, Marchioni M, Silletta F, D'orta C, Primiceri G, Rizzoli A, Di Gregorio P, Verna S, Natale A, Santarone S, Berardinelli F, Schips L. Efficacy and safety of intravesical fibrin glue instillation for management of patients with refractory hemorrhagic cystitis: 12-months results. A promising therapy for hemorrhagic cystitis. ACTA ACUST UNITED AC 2021; 93:200-205. [PMID: 34286556 DOI: 10.4081/aiua.2021.2.200] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 03/10/2021] [Indexed: 11/22/2022]
Abstract
OBJECTIVES Fibrin glue (FG) endo-vesical application seems to be a promising therapy for hemorrhagic cystitis (HC). We aimed to evaluate efficacy and safety of FG instillation in patients with HC. METHODS Patients with HC not responsive to conventional treatments (bladder irrigation, catheterization, blood transfusions, hyperhydration and endoscopic coagulation) were treated with FG endo-vesical instillation (April 2017- December 2018). FG was prepared from 120 mL of patient blood with the Vivostat® system. After standard cystoscopy, bladder was insufflated with carbon dioxide (CO2) according to bladder compliance and autologous FG was applied to bladder wall and bleeding sites. RESULTS Ten patients included with grade 2 or higher HC secondary to bone marrow graft for hematological diseases (30%) or to actinic cystitis caused by prostate cancer radiotherapy (RT) (70%). The median HC onset time after RT was 4.8 (IQR 3.9- 6.3) years and 35 (IQR 27.5-62.5) days after hematopoietic stem cell transplantation (HSCT). Five patients had a complete response after one treatment, three patients had clinical response (grade < 2 hematuria, amelioration of symptoms), one of them required catheterization and bladder irrigation. One patient required a second instillation of FG achieving a clinical response. No adverse events related to the procedure were recorded, however one patient died for causes not related to the procedure. Median Interstitial Cystitis Symptoms Index was 13.0 (IQR 11.0-15.0) pre-operatively and 4.0 (IQR 2.0-5.0) post-operatively. CONCLUSIONS Our study showed that, even in hematological patients, autologous FG instillation maybe a safe, repeatable and effective treatment modality in patients with refractory HC.
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Affiliation(s)
- Alessandra Cassani
- "G. D'Annunzio" University of Chieti, Dept. of Medical, Oral and Biotechnological Sciences, "SS. Annunziata" Hospital, Urology Unit, Chieti, Italy; ASL Abruzzo 2, Department of Urology, Chieti.
| | - Michele Marchioni
- "G. D'Annunzio" University of Chieti, Dept. of Medical, Oral and Biotechnological Sciences, "SS. Annunziata" Hospital, Urology Unit, Chieti, Italy; ASL Abruzzo 2, Department of Urology, Chieti.
| | - Francesco Silletta
- "G. D'Annunzio" University of Chieti, Dept. of Medical, Oral and Biotechnological Sciences, "SS. Annunziata" Hospital, Urology Unit, Chieti, Italy; ASL Abruzzo 2, Department of Urology, Chieti.
| | - Carlo D'orta
- "G. D'Annunzio" University of Chieti, Dept. of Medical, Oral and Biotechnological Sciences, "SS. Annunziata" Hospital, Urology Unit, Chieti, Italy; ASL Abruzzo 2, Department of Urology, Chieti.
| | - Giulia Primiceri
- "G. D'Annunzio" University of Chieti, Dept. of Medical, Oral and Biotechnological Sciences, "SS. Annunziata" Hospital, Urology Unit, Chieti, Italy; ASL Abruzzo 2, Department of Urology, Chieti.
| | - Ambra Rizzoli
- "G. D'Annunzio" University of Chieti, Dept. of Medical, Oral and Biotechnological Sciences, "SS. Annunziata" Hospital, Urology Unit, Chieti, Italy; ASL Abruzzo 2, Department of Urology, Chieti.
| | - Patrizia Di Gregorio
- "SS. Annunziata" Hospital, Chieti, Italy; ASL Abruzzo 2, Servizio di Medicina Trasfusionale ed Ematologia Aziendale Ospedaliero - Centro Emofilia 52, Chieti.
| | - Sandra Verna
- "SS. Annunziata" Hospital, Chieti, Italy; ASL Abruzzo 2, Servizio di Medicina Trasfusionale ed Ematologia Aziendale Ospedaliero - Centro Emofilia 52, Chieti.
| | - Annalisa Natale
- Santo Spirito Hospital, Pescara, Department of Hematology, Bone Marrow Transplant Center, Pescara.
| | - Stella Santarone
- Santo Spirito Hospital, Pescara, Department of Hematology, Bone Marrow Transplant Center, Pescara.
| | - Francesco Berardinelli
- "G. D'Annunzio" University of Chieti, Dept. of Medical, Oral and Biotechnological Sciences, "SS. Annunziata" Hospital, Urology Unit, Chieti, Italy; ASL Abruzzo 2, Department of Urology, Chieti.
| | - Luigi Schips
- "G. D'Annunzio" University of Chieti, Dept. of Medical, Oral and Biotechnological Sciences, "SS. Annunziata" Hospital, Urology Unit, Chieti, Italy; ASL Abruzzo 2, Department of Urology, Chieti.
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Prospective analysis of BKV hemorrhagic cystitis in children and adolescents undergoing hematopoietic cell transplantation. Ann Hematol 2021; 100:1283-1293. [PMID: 33661334 PMCID: PMC8043890 DOI: 10.1007/s00277-021-04454-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 02/07/2021] [Indexed: 12/11/2022]
Abstract
BK virus is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic cell transplantation (HCT). Viruses can be found in urine and serum samples of immunocompromised patients. Malignant diseases, age, cell source, day of granulocyte reconstitution, conditioning regimen, or use of total body irradiation may play an important role in BKV epidemiology, development of hemorrhagic cystitis course, and outcome. The aim of this study was to evaluate the incidence, clinical course, and risk factors for BKV-HC in children undergoing HCT. A total number of 133 patients who were prospectively tested for BKV colonization/infection were enrolled into this multicenter analysis. Episodes of BKV-HC occurred in 36/133 (27%) enrolled subjects. In a univariate analysis for BKV-HC incidence, the following factors were significant: age >5 years, peripheral blood transplantation, matched unrelated donor (MUD) transplantation, busulfan-cyclophosphamide-melphalan conditioning regimen, and acute myeloblastic leukemia (AML) diagnosis. Presence of acute graft-versus-host disease (aGVHD) in liver and gut GVHD was a significant risk factor of BKV-HC. No BKV-attributed deaths were reported. In multivariate analysis, the incidence of HC was significantly higher in patients with AML, age >5 years, MUD transplants, and children with GVHD. HC is a frequent complication after HCT among children causes prolonged hospitalization but rarely contributes to death. We identified risk factors of BKV-HC development in children, with focus on aGVHD: we concluded that excessive immune reaction connected with GVHD and immunosuppression drugs might play a pivotal role in the development of BKV-HC.
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Superselective Vesical Artery Embolization for Intractable Hemorrhagic Cystitis Following Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Study in 26 Patients. Cardiovasc Intervent Radiol 2021; 44:943-951. [PMID: 33608760 DOI: 10.1007/s00270-021-02786-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 01/23/2021] [Indexed: 10/22/2022]
Abstract
PURPOSE To evaluate the safety and efficacy of superselective vesical artery embolization (SVAE) in the treatment of intractable hemorrhagic cystitis (HC) following hematopoietic stem cell transplantation (HSCT). METHODS From January 2010 to December 2018, 26 patients with hematologic malignancy who underwent SVAE for treatment of intractable HC following HSCT were retrospectively reviewed. SVAE was performed with 300-500 μm gelatin-sponge particles initially. Technical success was defined as achieving bilateral SVAE for all the prominent vesical arteries. Therapeutic efficacy was defined as: Complete response (CR): macroscopic hematuria completely disappeared on more than 2 consecutive days after SVAE; Partial response (PR): macroscopic hematuria reduced after SVAE or briefly disappeared after SVAE but reappeared soon within 2 days; No response: no response to SVAE or hematuria aggravated after SVAE; Recurrence: macroscopic hematuria relapsed on follow-up after achieving an initial CR. Adverse events were also registered. RESULTS There was a mean follow-up of 11.4 months (range, 0.5-83.7). The mean interval for the onset of HC after HSCT was 39.7 ± 19.0 days, and mean duration of hematuria before embolization was 14.9 ± 15.7 days. SVAE was technically successful in all patients. After embolization, macroscopic hematuria regressed within 48 h for all patients. The mean urine erythrocyte counts dropped from 14,213.2 ± 20,999.0/uL before SVAE to 6072.9 ± 12,720.7/uL on 3d after SVAE (P = 0.002) and 3720.2 ± 8988.9/uL on 7 d after SVAE (P = 0.001), respectively. Hematuria completely disappeared prior to discharge in 23 (88.5%) patients (including 20 with one embolization and 3 with 2 embolizations) and remainder 3 patients had PR. No major procedure-related complications were noted, except for post-embolization syndrome in 8 patients, which resolved with symptomatic treatment. On follow-up monthly, hematuria recurrence was seen in 4/23 patients (17.4%) and was managed conservatively in 2 patients and with repeat embolization in the remainder 2 patients. CONCLUSION For fragile patients with hematologic malignancy, SVAE is safe and effective to treat HC following HSCT, even though repeat embolization may be required to achieve a sustained complete remission of the hematuria.
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Atilla E, Ateş C, Uslu A, Ataca Atilla P, Dolapçı I, Tekeli A, Topçuoğlu P. Prospective Analysis of Hemorrhagic Cystitis and BK Viremia in Allogeneic Hematopoietic Stem Cell Transplantation. Turk J Haematol 2020; 37:186-192. [PMID: 31852035 PMCID: PMC7463211 DOI: 10.4274/tjh.galenos.2019.2019.0296] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 12/18/2019] [Indexed: 02/07/2023] Open
Abstract
Objective BK virus (BKV) infection has been shown to be related to hemorrhagic cystitis (HC) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). There are conflicting data regarding the association between BKV titers in plasma and clinical disease as well as the risk factors for BKV-related HC. Our aim is to study the risk factors and relationship with plasma BK viral load for development of HC in a prospective analysis. Materials and Methods We prospectively evaluated 59 patients who received allo-HSCT between 2014 and 2016 by quantitative BK virus polymerase chain reaction (PCR) (Altona Diagnostics, Germany) from blood samples at days 0, 30, 60, and 90 after allo-HSCT. The patients were monitored for signs and symptoms of HC. Results HC was diagnosed in 22 patients (37%) at a mean of 100 days (range: 0-367 days). In multivariate analysis, the usage of cyclophosphamide (sub-distribution hazard ratio [sdHR]: 7.82, confidence interval [CI]: 1.375-39.645, p=0.02), reactivated CMV (sdHR: 6.105, CI: 1.614-23.094, p=0.008), and positive BKV viremia (sdHR: 2.15, CI: 1.456-22.065, p=0.01) significantly increased the risk of developing HC. Patients with higher viral loads at day 30 and day 60 were diagnosed with more severe HC (p<0.001). Median BK viral loads of >101.5 copies/mL at day 0 (sensitivity 0.727, specificity 0.875), >98.5 copies/mL at day 30 (sensitivity 0.909, specificity 0.875), and >90.0 copies/mL at day 60 (sensitivity 0.909, specificity 0.875) were indicative of HC. Conclusion Our study showed that administration of cyclophosphamide, CMV reactivation, and BK virus positivity were associated with HC. Plasma BK virus PCR titers at days 0, 30, and 60 after transplant were sensitive tools for predicting clinically proven HC.
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Affiliation(s)
- Erden Atilla
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Can Ateş
- Van Yüzüncü Yıl University Faculty of Medicine, Department of Biostatistics, Van, Turkey
| | - Atilla Uslu
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Pınar Ataca Atilla
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Istar Dolapçı
- Ankara University Faculty of Medicine, Department of Microbiology, Ankara, Turkey
| | - Alper Tekeli
- Ankara University Faculty of Medicine, Department of Microbiology, Ankara, Turkey
| | - Pervin Topçuoğlu
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
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Shaikh H, Bakalov V, Shaikh S, Khattab A, Sadashiv S. Coincident remission of ankylosing spondylitis after autologous stem cell transplantation for multiple myeloma. J Oncol Pharm Pract 2020; 27:232-234. [PMID: 32493162 DOI: 10.1177/1078155220927750] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Ankylosing spondylitis is an autoimmune disease with chronic inflammation of the spine and sacroiliac joints that is commonly treated with immunosuppressants including disease-modifying antirheumatic drugs and anti-tumor necrosis factor alpha therapy. CASE REPORT A 75-year-old female with active ankylosing spondylitis on treatment with etanercept was referred to us for newly diagnosed IgG kappa free light chain multiple myeloma. After failing induction with revlimid, bortezomib, and dexamethasone, she was initiated on carfilzomib. Following the achievement of adequate response to induction, she underwent an autologous hematopoietic stem cell transplant selected for CD34+ cells with melphalan 200mg/m2 conditioning regimen. Given high-risk cytogenetics, i.e. monosomy 17 (17p) and hypodiploidy, she received two cycles of carfilzomib consolidation post-transplant. The patient tolerated the transplant well with successful engraftment and achieved complete remission of multiple myeloma with no detectable M spike, negative immunofixation study, and normalization of light chain ratio. While being off etanercept since the transplant, she noticed complete relief from joint pains related to her ankylosing spondylitis without a need to use the pain-relieving medications.Management and outcome: The patient has sustained remission of ankylosing spondylitis for two years post-transplant without flares or symptoms. She continues to remain off immunosuppressants. DISCUSSION Although our patient had a coincident and unprecedented resolution of ankylosing spondylitis after receiving the hematopoietic stem cell transplant, this case consolidates the idea of transplant as a potential treatment option for ankylosing spondylitis and other rheumatological conditions.
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Affiliation(s)
- Hira Shaikh
- Department of Hematology-Oncology, University of Cincinnati Medical Center, Cincinnati, USA
| | - Veli Bakalov
- Department of Hematology-Oncology, University of Cincinnati Medical Center, Cincinnati, USA
| | - Soorih Shaikh
- Department of Hematology-Oncology, University of Cincinnati Medical Center, Cincinnati, USA
| | - Ahmed Khattab
- Department of Hematology-Oncology, University of Cincinnati Medical Center, Cincinnati, USA
| | - Santhosh Sadashiv
- Department of Internal Medicine, 6596Allegheny Health Network, Pittsburgh, USA
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Retrospective Evaluation Of Children After Stem Cell Transplantation: Single Center Experience. JOURNAL OF CONTEMPORARY MEDICINE 2019. [DOI: 10.16899/jcm.605404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Chang J, Hsiao M, Blodget E, Akhtari M. Increased risk of 100-day and 1-year infection-related mortality and complications in haploidentical stem cell transplantation. J Blood Med 2019; 10:135-143. [PMID: 31191064 PMCID: PMC6526927 DOI: 10.2147/jbm.s201073] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 03/27/2019] [Indexed: 11/23/2022] Open
Abstract
Background: While haploidentical transplantation has led to the near-universal availability of donors, several challenges for this form of transplant still exist. This study sought to investigate the rates of infection-related mortality and other complications following haploidentical vs nonhaploidentical transplant. Methods: We conducted a retrospective cohort study in adults with various malignant and benign hematological conditions who underwent allogeneic hematopoietic stem cell transplantation from 2011 to 2018. One hundred-day and 1-year overall survival were defined as survival from the time of transplant until 100 days or 1 year later. Results: A total of 187 patients were included in this study, with 45 (24.1%) receiving transplants from haploidentical donors and 142 (75.9%) from nonhaploidentical donors. There were similar rates of acute graft-versus-host disease (GVHD) (40% vs 38% in haploidentical vs nonhaploidentical recipients, P=0.86) and chronic GVHD (44.4% vs 43.7%, P=1). Rates of 100-day and 1-year infection-related mortality were significantly higher in the haploidentical group compared to the nonhaploidentical group (8.9% vs 1.4% at 100 days, P=0.03, and 15.9% vs 3.8% at 1 year, P=0.01). There were also higher rates of cytomegalovirus infections (59.1% vs 23.8%, P<0.01), BK virus-associated hemorrhagic cystitis (40.9% vs 8.4%, P<0.01), and BK viremia (15.9% vs 0.8%, P<0.01) in haploidentical recipients. Conclusions: Despite the use of identical antimicrobial prophylactic and treatment agents, haploidentical recipients were found to have significantly increased rates of 100-day and 1-year infection-related mortality as well as several other infectious complications.
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Affiliation(s)
- Jeremy Chang
- Department of Internal Medicine, Los Angeles County and University of Southern California, Los Angeles, CA, USA
| | - Mindy Hsiao
- Department of Hematology/Oncology, Norris Comprehensive Cancer Center, Los Angeles, CA, USA
| | - Emily Blodget
- Division of Infectious Diseases, University of Southern California, Los Angeles, USA
| | - Mojtaba Akhtari
- Department of Hematology/Oncology, Norris Comprehensive Cancer Center, Los Angeles, CA, USA
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Nathan S, Ustun C. Complications of Stem Cell Transplantation that Affect Infections in Stem Cell Transplant Recipients, with Analogies to Patients with Hematologic Malignancies. Infect Dis Clin North Am 2019; 33:331-359. [PMID: 30940464 DOI: 10.1016/j.idc.2019.01.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
This article discusses the complications of hematopoietic stem cell transplantion (HSCT) that affect infections in HSCT recipients, with analogies to patients with hematologic malignancies. Mucositis, with mucosal barrier disruption, is common and increases the risk of gram-positive and anaerobic bacterial, and fungal infections, and can evolve to typhlitis. Engraftment syndrome; graft-versus-host disease, hepatic sinusoidal obstruction syndrome; and posterior reversible encephalopathy syndrome can affect the infectious potential either directly from organ dysfunction or indirectly from specific treatment. Pulmonary infections can predispose to life threatening complications including diffuse alveolar hemorrhage, idiopathic pulmonary syndrome, bronchiolitis obliterans syndrome, and bronchiolitis obliterans with organizing pneumonia.
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Affiliation(s)
- Sunita Nathan
- Section of Bone Marrow Transplant and Cellular Therapy, Division of Hematology, Oncology and Cell Therapy, Rush University Medical Center, 1725 West Harrison Street, Suite 809, Chicago, IL 60612, USA
| | - Celalettin Ustun
- Section of Bone Marrow Transplant and Cellular Therapy, Division of Hematology, Oncology and Cell Therapy, Rush University Medical Center, 1725 West Harrison Street, Suite 809, Chicago, IL 60612, USA.
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20
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Xie YX, Wang Y, Huang XJ, Xu LP, Zhang XH, Liu KY, Yan CH, Wang FR, Sun YQ, Kong J, Gao YQ, Shi HY, Liu DP, Cheng YF. [Clinical analysis of hemorrhagic cystitis in children and adolescents with hematological diseases post haplo-hematopoietic stem cell transplantation]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2018; 39:833-838. [PMID: 30369205 PMCID: PMC7348279 DOI: 10.3760/cma.j.issn.0253-2727.2018.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Indexed: 11/09/2022]
Abstract
Objective: To investigate the incidence and clinical features to probe the risk factors of hemorrhagic cystitis (HC) in children and adolescents with hematological diseases post haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Medical records of 62 children and 27 adolescents with hematological diseases treated with haplo-HSCT between 2015 and 2016 were analyzed. Results: Of 89 cases (56 boys and 33 girls) , 44 patients were diagnosed with ALL, 33 AML, 3 AHL and 9 MDS. HC occurred in 32 of the 89 patients with an incidence of 36%, including 6 with grade Ⅰ, 16 with grade Ⅱ, 8 with grade Ⅲ, 2 with grade Ⅳ HC, respectively. The median time of HC onset was 25 days (range 2-55 days) after haplo-HSCT with the median duration as 19 days (range 3-95 days) , all of them were cured. The incidence of HC was lower in the group of children than that in the group of adolescents (27.4% vs 55.6%, χ(2)=6.466, P<0.05) , and the incidence of HC was higher in the group of patients who were ≥5 years old than that in the group of patients who were <5 years old (0 vs 34%, χ(2)=4.043, P<0.05) . Conclusion: HC is one of common complications in children and adolescents with hematological diseases post haplo-HSCT, older age was associated with increased mortality.
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Affiliation(s)
- Y X Xie
- Institute of Hematology, People's Hospital, Peking University, Beijing 100044, China
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21
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Copelan OR, Oberlin DT. Hemorrhagic Cystitis: Brighter Days Ahead. Biol Blood Marrow Transplant 2018; 24:1773-1774. [PMID: 30021128 DOI: 10.1016/j.bbmt.2018.07.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 07/10/2018] [Indexed: 10/28/2022]
Affiliation(s)
| | - Daniel T Oberlin
- Department of Urology, University of Southern California School of Medicine, Glendale, California.
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22
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Jiang Y, Fang X, Sui X, Liu X, Li Y, Wang X, Xu H, Zhang L, Wang X. Comparison of Different Conditioning Regimens of Haploidentical Hematopoietic Stem Cell Transplant in Patients With Acute Myeloid Leukemia. EXP CLIN TRANSPLANT 2018; 16:736-744. [PMID: 29790457 DOI: 10.6002/ect.2017.0100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES We evaluated the safety and efficacy of 2 conditioning regimens (busulfan/fludarabine vs modified busulfan/cyclophosphamide) in patients with acute myeloid leukemia undergoing haploidentical hematopoietic stem cell transplant. MATERAILS AND METHODS Twenty patients with primary acute myeloid leukemia had been randomized into busulfan/fludarabine and modified busulfan/cyclophosphamide groups. We retrospectively compared hematopoietic engraftment, regimen-related toxicity, graft-versus-host disease, transplant-related mortality, leukemia-free survival, and overall survival between the groups. RESULTS All patients achieved engraftment with 100% donor chimerism. The median times for the neutrophil and platelet engraftment in the busulfan/fludarabine and modified busulfan/cyclophosphamide groups were 14.1 versus 14.3 days and 12.7 versus 12.2 days, respectively. Significantly lower incidences of pretreatment toxicity, blood transfusion, and virus activation were observed in the busulfan/fludarabine group. Acute grade 1 graft-versus-host-disease developed in all patients, which was successfully controlled with methylprednisolone. There were no significant differences in engraftment, graft-versus-host disease, leukemia-free survival, and overall survival between groups. Both of these conditioning regimens achieved stable engraftment. Regimen-related toxicity in the busulfan/fludarabine group was well tolerated compared with that in the modified busulfan/cyclophosphamide group, without an increase in relapse rate. CONCLUSIONS Our results demonstrated that myeloablative busulfan/fludarabine might be a highly effective and low-toxicity alternative for patients with acute myeloid leukemia.
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Affiliation(s)
- Yujie Jiang
- From the Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
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23
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Foster JH, Cheng WS, Nguyen NY, Krance R, Martinez C. Intravesicular cidofovir for BK hemorrhagic cystitis in pediatric patients after hematopoietic stem cell transplant. Pediatr Transplant 2018; 22:e13141. [PMID: 29388318 DOI: 10.1111/petr.13141] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/28/2017] [Indexed: 12/11/2022]
Abstract
BK virus hemorrhagic cystitis is a complication of HCST. Response to IV cidofovir is unpredictable, and treatment carries risk of toxicity. We report the largest series of pediatric patients with BKHC after HSCT successfully treated with intravesicular cidofovir. There was no significant decrease in urine or plasma BK PCR. There was significant decrease in pain score on days 3 and 7, with associated decrease in morphine use. No patients experienced toxicities associated with IV cidofovir. Intravesicular cidofovir appears to be safe and effective for symptomatic treatment of BKHC in pediatric patients after HSCT.
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Affiliation(s)
- Jennifer H Foster
- Baylor College of Medicine, Houston, TX, USA.,Texas Children's Hospital, Houston, TX, USA
| | | | | | - Robert Krance
- Baylor College of Medicine, Houston, TX, USA.,Texas Children's Hospital, Houston, TX, USA
| | - Caridad Martinez
- Baylor College of Medicine, Houston, TX, USA.,Texas Children's Hospital, Houston, TX, USA
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24
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Atilla E, Yalciner M, Atilla PA, Ates C, Bozdag SC, Yuksel MK, Toprak SK, Gunduz M, Ozen M, Akan H, Demirer T, Arslan O, Ilhan O, Beksac M, Ozcan M, Gurman G, Topcuoglu P. Is cytomegalovirus a risk factor for haemorrhagic cystitis in allogeneic haematopoietic stem cell transplantation recipients? Antivir Ther 2018; 23:647-653. [DOI: 10.3851/imp3252] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2018] [Indexed: 10/28/2022]
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25
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Uppugunduri CRS, Storelli F, Mlakar V, Huezo-Diaz Curtis P, Rezgui A, Théorêt Y, Marino D, Doffey-Lazeyras F, Chalandon Y, Bader P, Daali Y, Bittencourt H, Krajinovic M, Ansari M. The Association of Combined GSTM1 and CYP2C9 Genotype Status with the Occurrence of Hemorrhagic Cystitis in Pediatric Patients Receiving Myeloablative Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation. Front Pharmacol 2017; 8:451. [PMID: 28744217 PMCID: PMC5504863 DOI: 10.3389/fphar.2017.00451] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Accepted: 06/22/2017] [Indexed: 12/01/2022] Open
Abstract
Hemorrhagic cystitis (HC) is one of the complications of busulfan-cyclophosphamide (BU-CY) conditioning regimen during allogeneic hematopoietic stem cell transplantation (HSCT) in children. Identifying children at high risk of developing HC in a HSCT setting could facilitate the evaluation and implementation of effective prophylactic measures. In this retrospective analysis genotyping of selected candidate gene variants was performed in 72 children and plasma Sulfolane (Su, water soluble metabolite of BU) levels were measured in 39 children following treatment with BU-CY regimen. The cytotoxic effects of Su and acrolein (Ac, water soluble metabolite of CY) were tested on human urothelial cells (HUCs). The effect of Su was also tested on cytochrome P 450 (CYP) function in HepaRG hepatic cells. Cumulative incidences of HC before day 30 post HSCT were estimated using Kaplan–Meier curves and log-rank test was used to compare the difference between groups in a univariate analysis. Multivariate Cox regression was used to estimate hazard ratios with 95% confidence intervals (CIs). Multivariate analysis included co-variables that were significantly associated with HC in a univariate analysis. Cumulative incidence of HC was 15.3%. In the univariate analysis, HC incidence was significantly (p < 0.05) higher in children older than 10 years (28.6 vs. 6.8%) or in children with higher Su levels (>40 vs. <11%) or in carriers of both functional GSTM1 and CYP2C9 (33.3 vs. 6.3%) compared to the other group. In a multivariate analysis, combined GSTM1 and CYP2C9 genotype status was associated with HC occurrence with a hazards ratio of 4.8 (95% CI: 1.3–18.4; p = 0.02). Ac was found to be toxic to HUC cells at lower concentrations (33 μM), Su was not toxic to HUC cells at concentrations below 1 mM and did not affect CYP function in HepaRG cells. Our observations suggest that pre-emptive genotyping of CYP2C9 and GSTM1 may aid in selection of more effective prophylaxis to reduce HC development in pediatric patients undergoing allogeneic HSCT. Article summary: (1) Children carrying functional alleles in GSTM1 and CYP2C9 are at high risk for developing hemorrhagic cystitis following treatment with busulfan and cyclophosphamide based conditioning regimen. (2) Identification of children at high risk for developing hemorrhagic cystitis in an allogeneic HSCT setting will enable us to evaluate and implement optimal strategies for its prevention. Trial registration: This study is a part of the trail “clinicaltrials.gov identifier: NCT01257854.”
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Affiliation(s)
- Chakradhara Rao S Uppugunduri
- Onco-Hematology Unit, Geneva University Hospital, Department of PediatricsGeneva, Switzerland.,CANSEARCH Research Laboratory, Department of Pediatrics, Faculty of Medicine, University of GenevaGeneva, Switzerland
| | - Flavia Storelli
- Clinical Pharmacology and Toxicology Service, Geneva University HospitalGeneva, Switzerland
| | - Vid Mlakar
- Onco-Hematology Unit, Geneva University Hospital, Department of PediatricsGeneva, Switzerland.,CANSEARCH Research Laboratory, Department of Pediatrics, Faculty of Medicine, University of GenevaGeneva, Switzerland
| | - Patricia Huezo-Diaz Curtis
- Onco-Hematology Unit, Geneva University Hospital, Department of PediatricsGeneva, Switzerland.,CANSEARCH Research Laboratory, Department of Pediatrics, Faculty of Medicine, University of GenevaGeneva, Switzerland
| | - Aziz Rezgui
- CHU Sainte-Justine Research Center, Charles-Bruneau Cancer Center, MontrealQC, Canada
| | - Yves Théorêt
- Clinical Pharmacology Unit, CHU Sainte-Justine, MontrealQC, Canada
| | - Denis Marino
- CANSEARCH Research Laboratory, Department of Pediatrics, Faculty of Medicine, University of GenevaGeneva, Switzerland
| | | | - Yves Chalandon
- Division of Hematology, Department of Medical Specialties, Geneva University HospitalGeneva, Switzerland
| | - Peter Bader
- Division for Stem Cell Transplantation and Immunology, University Hospital FrankfurtFrankfurt, Germany
| | - Youssef Daali
- Clinical Pharmacology and Toxicology Service, Geneva University HospitalGeneva, Switzerland
| | - Henrique Bittencourt
- Department of Pediatrics, Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, MontrealQC, Canada
| | - Maja Krajinovic
- CHU Sainte-Justine Research Center, Charles-Bruneau Cancer Center, MontrealQC, Canada.,Clinical Pharmacology Unit, CHU Sainte-Justine, MontrealQC, Canada.,Department of Pediatrics, Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, MontrealQC, Canada
| | - Marc Ansari
- Onco-Hematology Unit, Geneva University Hospital, Department of PediatricsGeneva, Switzerland.,CANSEARCH Research Laboratory, Department of Pediatrics, Faculty of Medicine, University of GenevaGeneva, Switzerland
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26
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Dosin G, Aoun F, El Rassy E, Assi T, Lewalle P, Blanc J, van Velthoven R, Bron D. Viral-induced Hemorrhagic Cystitis After Allogeneic Hematopoietic Stem Cell Transplant. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2017; 17:438-442. [DOI: 10.1016/j.clml.2017.05.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Revised: 02/28/2017] [Accepted: 05/04/2017] [Indexed: 10/19/2022]
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27
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Vigil D, Konstantinov NK, Barry M, Harford AM, Servilla KS, Kim YH, Sun Y, Ganta K, Tzamaloukas AH. BK nephropathy in the native kidneys of patients with organ transplants: Clinical spectrum of BK infection. World J Transplant 2016; 6:472-504. [PMID: 27683628 PMCID: PMC5036119 DOI: 10.5500/wjt.v6.i3.472] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 08/25/2016] [Accepted: 09/08/2016] [Indexed: 02/05/2023] Open
Abstract
Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy (BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research.
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28
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Comparable outcomes between younger (⩽40 years) and older (>40 years) adult patients with severe aplastic anemia after HLA-matched sibling stem cell transplantation using fludarabine-based conditioning. Bone Marrow Transplant 2016; 51:1456-1463. [DOI: 10.1038/bmt.2016.171] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 04/21/2016] [Accepted: 05/18/2016] [Indexed: 01/21/2023]
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29
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Peterson L, Ostermann H, Fiegl M, Tischer J, Jaeger G, Rieger CT. Reactivation of polyomavirus in the genitourinary tract is significantly associated with severe GvHD and oral mucositis following allogeneic stem cell transplantation. Infection 2016; 44:483-90. [PMID: 26792012 DOI: 10.1007/s15010-016-0872-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Accepted: 01/04/2016] [Indexed: 12/16/2022]
Abstract
PURPOSE BK-virus and JC-virus are the most common polyomaviridae associated with hemorrhagic cystitis in the allogeneic transplant setting. Hemorrhagic cystitis and symptomatic viruria caused by these viruses are a major cause of morbidity in patients undergoing allogeneic stem cell transplantation. METHODS We performed a retrospective evaluation on a highly uniform study population of 73 patients receiving allogeneic stem cell transplantation. Patients were treated according to the FLAMSA-RIC-protocol, and were examined for the incidence of BK-/JC-viruria and late-onset BK-positive hemorrhagic cystitis within a two-year period. RESULTS The occurrence of BK-viruria was correlated with published risk factors (acute GvHD, oral mucositis, donor type, conditioning, age, gender). Thirty patients (41 %) were found to excrete either BK-virus (n = 17), JC-virus (n = 3) or both (n = 10), of whom 18 patients (60 %) developed higher-grade hemorrhagic cystitis as opposed to none in the virus-negative control group. Higher grade GvHD (grade B-D) was more common in patients with viruria (p = 0.013) and also more common in patients with manifest hemorrhagic cystitis (p = 0.048). Similarly, oral mucositis was associated both with viruria (p = 0.014) and hemorrhagic cystitis (p = 0.005). Manifest cystitis but not viruria was significantly associated with male gender (p = 0.016). No significant correlation was found with age, conditioning with busulfane vs total body irradiation or related vs unrelated donor. CONCLUSIONS Severe GvHD and oral mucositis are significantly associated with reactivation of polyomaviridae in the genitourinary-tract already at the level of asymptomatic viruria.
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Affiliation(s)
- Lisa Peterson
- Department of Internal Medicine III, University of Munich, Munich, Germany
| | - Helmut Ostermann
- Department of Internal Medicine III, University of Munich, Munich, Germany
| | - Michael Fiegl
- Department of Internal Medicine III, University of Munich, Munich, Germany
| | - Johanna Tischer
- Department of Internal Medicine III, University of Munich, Munich, Germany
| | - Gundula Jaeger
- Max-von-Pettenkofer-Institut, University of Munich, Munich, Germany
| | - Christina T Rieger
- Department of Internal Medicine III, University of Munich, Munich, Germany. .,Internistische Lehrpraxis der LMU Germering, Ludwig-Maximilians-University Munich, Munich, Germany.
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30
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Raup VT, Potretzke AM, Manley BJ, Brockman JA, Bhayani SB. Hemorrhagic Cystitis Requiring Bladder Irrigation is Associated with Poor Mortality in Hospitalized Stem Cell Transplant Patients. Int Braz J Urol 2016; 41:1126-31. [PMID: 26742970 PMCID: PMC4756938 DOI: 10.1590/s1677-5538.ibju.2014.0655] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Accepted: 06/17/2015] [Indexed: 11/24/2022] Open
Abstract
Purpose: To evaluate the overall prognosis of post-stem cell transplant inpatients who required continuous bladder irrigation (CBI) for hematuria. Materials and Methods: We performed a retrospective analysis of adult stem cell transplant recipients who received CBI for de novo hemorrhagic cystitis as inpatients on the bone marrow transplant service at Washington University from 2011-2013. Patients who had a history of genitourinary malignancy and/or recent surgical urologic intervention were excluded. Multiple variables were examined for association with death. Results: Thirty-three patients met our inclusion criteria, with a mean age of 48 years (23-65). Common malignancies included acute myelogenous leukemia (17/33, 57%), acute lymphocytic leukemia (3/33, 10%), and peripheral T cell lymphoma (3/33, 10%). Median time from stem cell transplant to need for CBI was 2.5 months (0 days-6.6 years). All patients had previously undergone chemotherapy (33/33, 100%) and 14 had undergone prior radiation therapy (14/33, 42%). Twenty-eight patients had an infectious disease (28/33, 85%), most commonly BK viremia (19/33, 58%), cytomegalovirus viremia (17/33, 51%), and bacterial urinary tract infection (8/33, 24%). Twenty-two patients expired during the same admission as CBI treatment (22/33 or 67% of total patients, 22/28 or 79% of deaths), with a 30-day mortality of 52% and a 90-day mortality of 73% from the start of CBI. Conclusions: Hemorrhagic cystitis requiring CBI is a symptom of severe systemic disease in stem cell transplant patients. The need for CBI administration may be a marker for mortality risk from a variety of systemic insults, rather than directly attributable to the hematuria.
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Affiliation(s)
- Valary T Raup
- Division of Urology, Washington University School of Medicine, Washington, DC, USA
| | - Aaron M Potretzke
- Division of Urology, Washington University School of Medicine, Washington, DC, USA
| | - Brandon J Manley
- Division of Urology, Washington University School of Medicine, Washington, DC, USA
| | - John A Brockman
- Division of Urology, Washington University School of Medicine, Washington, DC, USA
| | - Sam B Bhayani
- Division of Urology, Washington University School of Medicine, Washington, DC, USA
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31
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Aitken SL, Zhou J, Ghantoji SS, Kontoyiannis DP, Jones RB, Tam VH, Chemaly RF. Pharmacokinetics and safety of intravesicular cidofovir in allogeneic HSCT recipients. J Antimicrob Chemother 2015; 71:727-30. [PMID: 26612873 DOI: 10.1093/jac/dkv393] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Accepted: 10/21/2015] [Indexed: 01/27/2023] Open
Abstract
OBJECTIVES The objective of this study was to evaluate the pharmacokinetics and safety of cidofovir administered via the intravesicular route to patients with haemorrhagic cystitis following allogeneic HSCT (allo-HSCT). METHODS Patients with gross haematuria and confirmed BK or adenovirus viruria following allo-HSCT were prospectively enrolled in an open-label pharmacokinetic study (ClinicalTrials.gov registration: NCT01816646). Three hours after an oral probenecid dose (2 g), cidofovir (2.5-5 mg/kg in 50-100 mL of normal saline) was given via a transurethral catheter for up to 2 h of dwell time. Serial plasma samples were obtained over 24 h and assayed for cidofovir concentrations using LC-MS/MS. A custom pharmacokinetic model with a time-limited absorption compartment was fitted to the concentration-time profile of each patient. Systemic drug exposure was expressed as AUC0-24, by integrating the best-fit profile with respect to time. RESULTS Six subjects (mean ± SD age = 38 ± 21 years) with baseline serum creatinine <1.4 mg/dL were enrolled. Mean values for volume of distribution, clearance and elimination half-life were 19.5 L, 5.6 L/h and 2.8 h, respectively. Compared with the reported AUC0-24 for an equivalent intravenous dose, intravesicular instillation of cidofovir resulted in 1%-74% of the corresponding systemic exposure. Owing to primarily lower abdominal pain, only two patients were able to tolerate a 2 h dwell time. One patient developed a >50% increase in serum creatinine within 7 days of administration. CONCLUSIONS Intravesicular administration of cidofovir resulted in highly variable systemic exposures. The safety and efficacy of intravesicular cidofovir should be further evaluated before routine use.
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Affiliation(s)
- Samuel L Aitken
- Division of Pharmacy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0090, Houston, TX 77030, USA Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, 1441 Moursund St., Houston, TX 77030, USA
| | - Jian Zhou
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, 1441 Moursund St., Houston, TX 77030, USA
| | - Shashank S Ghantoji
- Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1460, Houston, TX 77030, USA
| | - Dimitrios P Kontoyiannis
- Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1460, Houston, TX 77030, USA
| | - Roy B Jones
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0423, Houston, TX 77030, USA
| | - Vincent H Tam
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, 1441 Moursund St., Houston, TX 77030, USA
| | - Roy F Chemaly
- Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1460, Houston, TX 77030, USA
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32
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Ruggeri A, Roth-Guepin G, Battipaglia G, Mamez AC, Malard F, Gomez A, Brissot E, Belhocine R, Vekhoff A, Lapusan S, Isnard F, Legrand O, Gozlan J, Boutolleau D, Ledraa T, Labopin M, Rubio MT, Mohty M. Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients. Transpl Infect Dis 2015; 17:822-30. [PMID: 26354178 DOI: 10.1111/tid.12455] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Revised: 08/13/2015] [Accepted: 08/18/2015] [Indexed: 01/28/2023]
Abstract
BACKGROUND Hemorrhagic cystitis (HC) is a common complication after hematopoietic allogeneic stem cell transplantation (HSCT) associated with intensity of the conditioning regimen, cyclophosphamide (Cy) therapy, and BK polyomavirus (BKPyV) infection. METHODS We analyzed 33 consecutive haploidentical (haplo) HSCT recipients transplanted for hematologic diseases. Eleven patients had a previous transplant. Median follow-up was 11 months. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine + mycophenolate mofetil and post-HSCT Cy. RESULTS Thirty-two of 33 patients achieved neutrophil recovery. Cumulative incidence (CI) of platelet recovery was 65%. CI grade II-IV acute GVHD was 44%. Twenty patients developed HC in a median time of 38 days. CI of HC at day 180 was 62%. BKPyV was positive in blood and urine of 91% of patients at HC onset. HC resolved in 18/20 patients. Factors associated with HC were previous transplant (P = 0.01) and occurrence of cytomegalovirus reactivation before HC (P = 0.05). Grade II-IV acute GVHD was not associated with HC (P = 0.62). CI of day 180 viral infections was 73%. Two-year overall survival (OS) was 50%; HC did not impact OS (P = 0.29). CONCLUSION The incidence of HC after haplo with post-HSCT Cy is high and is associated with morbidity, especially in high-risk patients such as those with a previous transplant history and with impaired immune reconstitution.
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Affiliation(s)
- A Ruggeri
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.,INSERM, UMRs 938, Paris, France
| | - G Roth-Guepin
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.,Service d'Hématologie, CHU Nancy, Nancy, France
| | - G Battipaglia
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.,Ematologia, Università Federico II di Napoli, Naples, Italy
| | - A-C Mamez
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France
| | - F Malard
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.,INSERM, UMRs 938, Paris, France
| | - A Gomez
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France
| | - E Brissot
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.,INSERM, UMRs 938, Paris, France.,Université Pierre & Marie Curie, Paris, France
| | - R Belhocine
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France
| | - A Vekhoff
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France
| | - S Lapusan
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France
| | - F Isnard
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France
| | - O Legrand
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France
| | - J Gozlan
- Service de Virologie, Hôpital Saint Antoine, AP-HP, Paris, France
| | - D Boutolleau
- Service de Virologie, Hôpitaux Universitaires Pitié-Salpêtrière, AP-HP, Paris, France
| | - T Ledraa
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France
| | - M Labopin
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.,Université Pierre & Marie Curie, Paris, France
| | - M-T Rubio
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.,INSERM, UMRs 938, Paris, France
| | - M Mohty
- Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.,INSERM, UMRs 938, Paris, France.,Université Pierre & Marie Curie, Paris, France
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Lunde LE, Dasaraju S, Cao Q, Cohn CS, Reding M, Bejanyan N, Trottier B, Rogosheske J, Brunstein C, Warlick E, Young JAH, Weisdorf DJ, Ustun C. Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: risk factors, graft source and survival. Bone Marrow Transplant 2015; 50:1432-7. [PMID: 26168069 PMCID: PMC5343753 DOI: 10.1038/bmt.2015.162] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2014] [Revised: 04/14/2015] [Accepted: 04/18/2015] [Indexed: 01/16/2023]
Abstract
Although hemorrhagic cystitis (HC) is a common complication of allogeneic hematopoietic cell transplantation (alloHCT), its risk factors and effects on survival are not well known. We evaluated HC in a large cohort (n=1321, 2003-2012) receiving alloHCT from all graft sources, including umbilical cord blood (UCB). We compared HC patients with non-HC (control) patients and examined clinical variables at HC onset and resolution. Of these 1321 patients, 219 (16.6%) developed HC at a median of 22 days after alloHCT. BK viruria was detected in 90% of 109 tested HC patients. Median duration of HC was 27 days. At the time of HC diagnosis, acute GVHD, fever, severe thrombocytopenia and steroid use were more frequent than at the time of HC resolution. In univariate analysis, male sex, age <20 years, myeloablative conditioning with cyclophosphamide and acute GVHD were associated with HC. In multivariate analysis, HC was significantly more common in males and HLA-mismatched UCB graft recipients. Severe grade HC (grade III-IV) was associated with increased treatment-related mortality but not with overall survival at 1 year. HC remains hazardous and therefore better prophylaxis, and early interventions to limit its severity are still needed.
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Affiliation(s)
- Laura E. Lunde
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Sandhyarani Dasaraju
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Qing Cao
- Masonic Cancer Center, Biostatistics & Bioinformatic Core, Fairview Health Services, Minneapolis, MN, USA
| | - Claudia S. Cohn
- Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Fairview Health Services, Minneapolis, MN, USA
| | - Mark Reding
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Nelli Bejanyan
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Bryan Trottier
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - John Rogosheske
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Claudio Brunstein
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Erica Warlick
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Jo Anne H. Young
- Division of Infectious Disease, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Daniel J. Weisdorf
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Celalettin Ustun
- Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
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Safety and feasibility of romiplostim treatment for patients with persistent thrombocytopenia after allogeneic stem cell transplantation. Bone Marrow Transplant 2015; 50:1574-7. [DOI: 10.1038/bmt.2015.182] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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35
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Abudayyeh A, Abdelrahim M. Current Strategies for Prevention and Management of Stem Cell Transplant-Related Urinary Tract and Voiding Dysfunction. CURRENT BLADDER DYSFUNCTION REPORTS 2015. [DOI: 10.1007/s11884-015-0289-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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36
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A Rare Case of Hemorrhagic Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Patient. Indian J Hematol Blood Transfus 2015; 32:196-200. [PMID: 27408390 DOI: 10.1007/s12288-015-0530-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Accepted: 03/10/2015] [Indexed: 10/23/2022] Open
Abstract
Post bone marrow transplant patients are susceptible to atypical infections, especially viral pathogens. The risk increases many folds in cases of allogeneic transplantation, which also receive GVHD prophylaxis. Viral pathogens like cytomegalovirus and herpes are the common ones encountered during follow-up period. However, in recent times there have been reports of a variety of disease manifestations of rare viruses like polyoma virus and adenovirus. These viral infections may play a crucial role in morbidity and mortality in immunocompromised patients. We hereby elaborate the follow-up course of a 36-year-old post allogeneic transplant patient of acute myeloid leukemia who developed adenovirus related haemorrhagic cystitis. Treatment with oral ribavirin lead to dramatic improvement in symptomatology within a week. This cases re-emphasizes the fact that after ruling out the commoner pathogens, it's of utmost importance to strongly consider the atypical pathogens in such cases.
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37
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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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38
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Han SB, Cho B, Kang JH. BK virus-associated hemorrhagic cystitis after pediatric stem cell transplantation. KOREAN JOURNAL OF PEDIATRICS 2014; 57:514-9. [PMID: 25653684 PMCID: PMC4316594 DOI: 10.3345/kjp.2014.57.12.514] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Accepted: 10/08/2014] [Indexed: 02/08/2023]
Abstract
Hemorrhagic cystitis is a common stem cell transplantation-related complication. The incidence of early-onset hemorrhagic cystitis, which is related to the pretransplant conditioning regimen, has decreased with the concomitant use of mesna and hyperhydration. However, late-onset hemorrhagic cystitis, which is usually caused by the BK virus, continues to develop. Although the BK virus is the most common pathogenic microorganism of poststem cell transplantation late-onset hemorrhagic cystitis, pediatricians outside the hemato-oncology and nephrology specialties tend to be unfamiliar with hemorrhagic cystitis and the BK virus. Moreover, no standard guidelines for the early diagnosis and treatment of BK virus-associated hemorrhagic cystitis after stem cell transplantation have been established. Here, we briefly introduce poststem cell transplantation BK virus-associated hemorrhagic cystitis.
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Affiliation(s)
- Seung Beom Han
- Department of Pediatrics, The Catholic University of Korea College of Medicine, Seoul, Korea. ; The Vaccine Bio Research Institute, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Bin Cho
- Department of Pediatrics, The Catholic University of Korea College of Medicine, Seoul, Korea. ; The Catholic Blood and Marrow Transplantation Center, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jin Han Kang
- Department of Pediatrics, The Catholic University of Korea College of Medicine, Seoul, Korea. ; The Vaccine Bio Research Institute, The Catholic University of Korea College of Medicine, Seoul, Korea
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39
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Tirindelli MC, Flammia GP, Bove P, Cerretti R, Cudillo L, De Angelis G, Picardi A, Annibali O, Nobile C, Cerchiara E, Dentamaro T, De Fabritiis P, Lanti A, Ferraro AS, Sergi F, Di Piazza F, Avvisati G, Arcese W. Fibrin Glue Therapy for Severe Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 2014; 20:1612-7. [DOI: 10.1016/j.bbmt.2014.06.018] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Accepted: 06/13/2014] [Indexed: 11/15/2022]
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40
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Zaleska-Dorobisz U, Biel A, Sokołowska-Dąbek D, Olchowy C, Łasecki M. Ultrasonography in the diagnosis of hemorrhagic cystitis - a complication of bone marrow transplantation in pediatric oncology patients. J Ultrason 2014; 14:258-72. [PMID: 26675710 PMCID: PMC4579689 DOI: 10.15557/jou.2014.0026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Revised: 11/08/2013] [Accepted: 11/13/2013] [Indexed: 11/22/2022] Open
Abstract
Objective The aim of this study was to evaluate the usefulness of ultrasonography in the diagnosis of hemorrhagic cystitis following bone marrow transplantation in children. Material and methods The study involved an analysis of clinical material and the results of imaging tests performed in 334 patients who underwent hematopoietic cell transplantation. Ultrasonographic findings in 42 patients with hemorrhagic cystitis were analyzed in detail. The ultrasound images served to assess the severity of hemorrhagic cystitis and the results were compared with the clinical assessment of the disease on the Droller scale, as well as the laboratory and endoscopic tests. Results In the studied group of patients hemorrhagic cystitis following allogeneic transplantation was diagnosed in 12.5% cases. 73.8% patients received transplants from unrelated donors, 26.2% – from compatible siblings. The study revealed a higher incidence of hemorrhagic cystitis in children above 10 years of age. Grade 3 according to the Droller was diagnosed in 42.9%, grade 2 – in 30.9%, grade 4 – in 14.3%, and grade 1 – in 11.9% patients. The number of ultrasound examinations depended on the clinical symptoms, severity, duration and co-occurrence of other complications following the transplantation and was within the 1–15 range (average: 4.6). Grades 3 and 4 were related to the poor clinical condition of the patients and to their longer hospitalization. During this period there was an increased risk of renal malfunction and acute renal failure, post-inflammatory narrowing of the ureters, hydronephrosis, and in grade 4 the fibrosis of the bladder with reduced bladder capacity. Analyses demonstrated a significant correlation between the ultrasound image of the bladder wall and the clinical severity. Conclusions Ultrasound with Doppler options remains the primary diagnostic tool in the evaluation of hemorrhagic cystitis, and is useful in terms of its diagnosis, determination of the severity, and monitoring of the treatment.
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Affiliation(s)
- Urszula Zaleska-Dorobisz
- Division of General and Pediatric Radiology, Department of Radiology, Wrocław Medical University, Wrocław, Poland
| | - Anna Biel
- Division of General and Pediatric Radiology, Department of Radiology, Wrocław Medical University, Wrocław, Poland
| | - Dąbrówka Sokołowska-Dąbek
- Division of General and Pediatric Radiology, Department of Radiology, Wrocław Medical University, Wrocław, Poland
| | - Cyprian Olchowy
- Division of General and Pediatric Radiology, Department of Radiology, Wrocław Medical University, Wrocław, Poland
| | - Mateusz Łasecki
- Division of General and Pediatric Radiology, Department of Radiology, Wrocław Medical University, Wrocław, Poland
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41
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The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD. Bone Marrow Transplant 2014; 49:1528-34. [PMID: 25111517 DOI: 10.1038/bmt.2014.181] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2014] [Revised: 06/16/2014] [Accepted: 06/18/2014] [Indexed: 01/13/2023]
Abstract
Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic SCT (allo-HSCT). Several risk factors have been suggested including BU-containing myeloablative conditioning, unrelated donors and GVHD, but these have not been consistently reported. We conducted a retrospective study including 339 allo-HSCT recipients between 2009 and 2012. Of 339 patients, 79 (23.3%) developed HC with 2-year cumulative incidence of 24.0% (95% confidence interval, 19.4-28.9). The median onset time was 45 days (range, 16-430) after allo-HSCT. Sixty-two patients (84%) out of 74 evaluated for urine BK virus PCR testing showed a positive result (mean 2.0 × 10(10) copies of DNA per mL). In univariate analysis, myeloablative conditioning, HLA-mismatched donor, CMV viremia and acute GVHD (aGVHD) grade 3-4 were significantly associated with the risk of HC. Multivariate analysis confirmed all associating factors identified in univariate analysis except for HLA-mismatched donor: myeloablative conditioning (hazard ratio (HR) 2.63, P=0.003), CMV viremia (HR 1.88, P=0.014) and aGVHD grade 3-4 (HR 1.71, P=0.029). HC did not affect OS or non-relapse mortality. Symptomatic HC is a frequent complication following allo-HSCT, with a 2-year cumulative incidence of 24.0%. Three clinical factors associated with HC were identified including myeloablative conditioning, CMV viremia and severe aGVHD.
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42
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Hosokawa K, Yamazaki H, Nakamura T, Yoroidaka T, Imi T, Shima Y, Ohata K, Takamatsu H, Kotani T, Kondo Y, Takami A, Nakao S. Successful hyperbaric oxygen therapy for refractory BK virus-associated hemorrhagic cystitis after cord blood transplantation. Transpl Infect Dis 2014; 16:843-6. [PMID: 25040402 DOI: 10.1111/tid.12266] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2013] [Revised: 02/20/2014] [Accepted: 04/21/2014] [Indexed: 11/30/2022]
Abstract
BK virus-associated hemorrhagic cystitis (BKV-HC) is a common and major cause of morbidity in recipients of allogeneic hematopoietic stem cell transplantation. A 32-year-old woman developed severe BKV-HC on day 24 after cord blood transplantation (CBT). Despite supportive therapies - such as hyperhydration, forced diuresis, and urinary catheterization - macroscopic hematuria and bladder irritation persisted for over a month. Hyperbaric oxygen (HBO) therapy at 2.1 atmospheres for 90 min per day was started on day 64 after CBT. Macroscopic hematuria resolved within a week, and microscopic hematuria was no longer detectable within 2 weeks. Hematuria did not recur after 11 sessions of HBO therapy, and no significant side effects were observed during or after treatment. HBO therapy could thus be useful in controlling refractory BKV-HC after CBT.
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Affiliation(s)
- K Hosokawa
- Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
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43
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BK Virus and Its Role in Hematopoietic Stem Cell Transplantation: Evolution of a Pathogen. Curr Infect Dis Rep 2014; 16:417. [PMID: 24942378 DOI: 10.1007/s11908-014-0417-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
We reviewed the literature regarding disease induced by BK virus (BKV) in the hematopoietic stem cell transplant (HSCT) population, particularly hemorrhagic cystitis (HC) and nephritis. The association between BKV and HC has been reported over the past four decades. BKV has been clinically implicated and widely accepted as an etiologic agent of HC and nephritis in HSCT and nephropathy in renal transplant patients. We discuss the potential benefit of early initiation of therapy in patients who fail supportive care alone as well as the different treatment strategies for HC induced by BKV. Treatments that have been used such as cidofovir and leflunomide are accompanied by risks, and the benefits are not as concrete as with other viral illness in the HSCT population.
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44
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Satyanarayana G, Marty FM, Tan CS. The polyomavirus puzzle: is host immune response beneficial in controlling BK virus after adult hematopoietic cell transplantion? Transpl Infect Dis 2014; 16:521-31. [PMID: 24834968 DOI: 10.1111/tid.12233] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Revised: 01/22/2014] [Accepted: 02/08/2014] [Indexed: 12/14/2022]
Abstract
BK virus (BKV), a ubiquitous human polyomavirus, usually does not cause disease in healthy individuals. BKV reactivation and disease can occur in immunosuppressed individuals, such as those who have undergone renal transplantation or hematopoietic cell transplantation (HCT). Clinical manifestations of BKV disease include graft dysfunction and failure in renal transplant recipients; HCT recipients frequently experience hematuria, cystitis, hemorrhagic cystitis (HC), and renal dysfunction. Studies of HCT patients have identified several risk factors for the development of BKV disease including myeloablative conditioning, acute graft-versus-host disease, and undergoing an umbilical cord blood (uCB) HCT. Although these risk factors indicate that alterations in the immune system are necessary for BKV pathogenesis in HCT patients, few studies have examined the interactions between host immune responses and viral reactivation in BKV disease. Specifically, having BKV immunoglobulin-G before HCT does not protect against BKV infection and disease after HCT. A limited number of studies have demonstrated BKV-specific cytotoxic T cells in healthy adults as well as in post-HCT patients who had experienced HC. New areas of research are required for a better understanding of this emerging infectious disease post HCT, including prospective studies examining BK viruria, viremia, and their relationship with clinical disease, a detailed analysis of urothelial histopathology, and laboratory evaluation of systemic and local cellular and humoral immune responses to BKV in patients receiving HCT from different sources, including uCB and haploidentical donors.
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Affiliation(s)
- G Satyanarayana
- Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Division of Infectious Disease, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA; Center for Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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45
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Qian L, Shen J, Zhao D, Pan S. Successful treatment of hemorrhagic cystitis after HLA-mismatched allogeneic hematopoietic stem cell transplantation by hyperbaric oxygen. Transplantation 2014; 97:e41-e42. [PMID: 24686429 DOI: 10.1097/tp.0000000000000049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Liren Qian
- 1 Department of Haematology Navy General Hospital Fucheng Road, Beijing People's Republic of China 2 Department of Hyperbaric Oxygen Navy General Hospital Fucheng Road, Beijing People's Republic of China
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46
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High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2014; 49:664-70. [PMID: 24488049 DOI: 10.1038/bmt.2013.235] [Citation(s) in RCA: 107] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2013] [Revised: 09/26/2013] [Accepted: 11/23/2013] [Indexed: 11/08/2022]
Abstract
BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P=0.028), unrelated donor (P=0.0178), stem cell source (P=0.0001), HLA mismatching (P=0.0022) and BU in conditioning regimen (P=0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P=0.0005) and peripheral blood stem cells (P=0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P=0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (P<0.0001), more RBC (P=0.0003) and platelet transfusions (P<0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at \[euro]2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.
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47
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BK virus disease after allogeneic stem cell transplantation: a cohort analysis. Biol Blood Marrow Transplant 2014; 20:564-70. [PMID: 24462984 DOI: 10.1016/j.bbmt.2014.01.014] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Accepted: 01/15/2014] [Indexed: 11/21/2022]
Abstract
The clinical epidemiology of BK virus (BKV) disease after allogeneic hematopoietic stem cell transplantation (HSCT) is not well defined. We evaluated 491 patients transplanted from January 2010 to December 2011 at a single transplant center to assess incidence, severity, and risk factors for BKV disease after HSCT. BKV disease was defined as BKV detection in urine by PCR testing in association with genitourinary symptoms without other concurrent genitourinary conditions. BKV disease occurred in 78 patients (15.9%), for an incidence rate of .47/1000 patient-days (95% confidence interval [CI], .37 to .59); BKV disease was considered severe in 27 patients (5.5%). In multivariate Cox modeling, time-dependent acute graft-versus-host disease (aGVHD) grades II to IV (adjusted hazard ratio [aHR] 4.25; 95% CI, 2.51 to 7.21), cord blood HSCT (aHR 2.28; 95% CI, 1.01 to 5.15), post-transplant mycophenolate use (aHR 3.31; 95% CI, 1.83 to 5.99), and high-dose cyclophosphamide conditioning (aHR 2.34, 95% CI 1.45 to 3.77) were significant predictors of BKV disease. Time-dependent aGVHD grades III to IV (aHR 10.5; 95% CI, 4.44 to 25.0) and cord blood HSCT (aHR 5.40; 95% CI, 1.94 to 15.0) were independent risk factors for severe BKV disease. BKV disease is common and is associated with significant and prolonged morbidity after HSCT. Prospective studies are needed to better define the morbidity of post-HSCT BKV disease and inform the design of prophylaxis and treatment trials.
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Riachy E, Krauel L, Rich BS, McEvoy MP, Honeyman JN, Boulad F, Wolden SL, Herr HW, La Quaglia MP. Risk Factors and Predictors of Severity Score and Complications of Pediatric Hemorrhagic Cystitis. J Urol 2014; 191:186-92. [DOI: 10.1016/j.juro.2013.08.007] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/05/2013] [Indexed: 10/26/2022]
Affiliation(s)
- Edward Riachy
- Pediatric Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Lucas Krauel
- Pediatric Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Barrie S. Rich
- Pediatric Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Maureen P. McEvoy
- Pediatric Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Joshua N. Honeyman
- Pediatric Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Farid Boulad
- Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Suzanne L. Wolden
- Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Harry W. Herr
- Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Michael P. La Quaglia
- Pediatric Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
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Han TT, Xu LP, Liu DH, Liu KY, Fu HX, Zhao XY, Zhao XS, Huang XJ. Cytomegalovirus is a potential risk factor for late-onset hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation. Am J Hematol 2014; 89:55-61. [PMID: 24009106 DOI: 10.1002/ajh.23584] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2013] [Revised: 08/21/2013] [Accepted: 08/24/2013] [Indexed: 11/07/2022]
Abstract
Late-onset hemorrhagic cystitis (LOHC) is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is primarily associated with viral infection. We prospectively quantified cytomegalovirus (CMV), BK virus (BKV), and adenovirus in urine and plasma using Q-RT-PCR in 50 consecutive patients to define the relationship between virus and LOHC. Of the 50 patients, 21 developed LOHC at a median of 29 days (range 4-64 days), with a cumulative incidence of 42% (±7.1%). The cumulative incidence of LOHC on day 100 in patients with and without CMV viremia (prior to or at the onset of LOHC) were 56.3% (±8.9%) and 16.7% (±9.1%) (P = 0.018), respectively, and it was 59.3% (±9.8%) and 21.7% (±8.8%) in patients with and without CMV viruria (prior to or at the onset of LOHC) (P = 0.021), respectively. The cumulative incidence of LOHC was also higher in patients with a plasma BKV load increased ≥3 log10 or with a urine BKV load increased ≥4 log10 than those without the increase (P < 0.001). Only one patient with LOHC was tested positive for ADV. Both the univariate and multivariate analyses showed that CMV viremia (HR = 3.461, 95% CI: 1.005-11.922, P = 0.049) and a plasma BKV load that was increased ≥3 log10 (HR = 10.705, 95%CI: 2.469-46.420, P = 0.002) were independent risk factors for the development of LOHC. We conclude that both CMV viremia and an increase of plasma BKV are independent risk factors for LOHC. And the role of CMV viremia was firstly demonstrated.
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Affiliation(s)
- Ting-Ting Han
- Peking University People's Hospital; Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation; Beijing 100044 P.R. China
| | - Lan-Ping Xu
- Peking University People's Hospital; Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation; Beijing 100044 P.R. China
| | - Dai-Hong Liu
- Peking University People's Hospital; Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation; Beijing 100044 P.R. China
| | - Kai-Yan Liu
- Peking University People's Hospital; Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation; Beijing 100044 P.R. China
| | - Hai-Xia Fu
- Peking University People's Hospital; Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation; Beijing 100044 P.R. China
| | - Xiang-Yu Zhao
- Peking University People's Hospital; Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation; Beijing 100044 P.R. China
| | - Xiao-Su Zhao
- Peking University People's Hospital; Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation; Beijing 100044 P.R. China
| | - Xiao-Jun Huang
- Peking University People's Hospital; Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation; Beijing 100044 P.R. China
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50
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Anoop P, Shaw BE, Riley U, Ethell ME, Taj M, Lancaster DL, Atra A, Saso R, Littlewood S, Mohammed K, Davies F, Treleaven J, Morgan GJ, Potter MN. Clinical profile and outcome of urotheliotropic viral haemorrhagic cystitis following haematopoietic stem cell transplantation: a 7-year tertiary centre analysis. Hematology 2013; 16:213-20. [DOI: 10.1179/102453311x13025568941763] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
Affiliation(s)
- Parameswaran Anoop
- Department of Haematology
- Department of Paediatric Haemato-OncologyRoyal Marsden Hospital NHS Foundation Trust, Sutton, Surrey, UK
| | - Bronwen E Shaw
- Department of Haematology
- Anthony Nolan TrustUCL Cancer Centre, London, UK
| | - Unell Riley
- Department of MicrobiologyRoyal Marsden Hospital NHS Foundation Trust, Sutton, Surrey, UK
| | - Mark E Ethell
- Department of Haematology
- Department of Paediatric Haemato-OncologyRoyal Marsden Hospital NHS Foundation Trust, Sutton, Surrey, UK
| | - Mary Taj
- Department of Paediatric Haemato-OncologyRoyal Marsden Hospital NHS Foundation Trust, Sutton, Surrey, UK
| | - Donna L Lancaster
- Department of Paediatric Haemato-OncologyRoyal Marsden Hospital NHS Foundation Trust, Sutton, Surrey, UK
| | - Ayad Atra
- Department of Paediatric Haemato-OncologyRoyal Marsden Hospital NHS Foundation Trust, Sutton, Surrey, UK
| | | | | | | | - Faith Davies
- Department of Haematology
- Institute of Cancer ResearchSutton, Surrey, UK
| | | | - Gareth J Morgan
- Department of Haematology
- Institute of Cancer ResearchSutton, Surrey, UK
| | - Mike N Potter
- Department of Haematology
- Department of Paediatric Haemato-OncologyRoyal Marsden Hospital NHS Foundation Trust, Sutton, Surrey, UK
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