1
|
Ma L, Zhang Y, Wang T, Cai Y, Yang J, Tong Y, Huang C, Qiu H, Zhou K, Xu X, Niu J, Shen C, Xia X, Wei Y, Shao J, Yang M, Cao J, Song X, Wan L. Epstein-Barr virus reactivation after haplo-peripheral blood stem cell transplantation in patients with hematological malignancies: immune reconstitution and influence on survival. Ther Adv Hematol 2025; 16:20406207251335477. [PMID: 40336916 PMCID: PMC12056333 DOI: 10.1177/20406207251335477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 03/24/2025] [Indexed: 05/09/2025] Open
Abstract
Background Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a common alternative for patients with hematological malignancies. Epstein-Barr virus (EBV) reactivation is a common complication post-transplantation, but its impact on immune reconstitution and survival remains unclear. Objective To compare immune reconstitution and survival between patients with and without EBV reactivation after haplo-HSCT. Design A retrospective study was conducted involving 322 patients aged 18-60 years, diagnosed with hematological malignancies, who underwent haplo-HSCT at our center from January 2018 to December 2021. Methods Data analysis was performed using SPSS (version 24.0) and R4.3.0 software. Statistical methods included Chi-square tests for qualitative variables, independent t tests for continuous variables, Kaplan-Meier method for survival analysis, and logistic regression for risk factor analysis. Results After a median of 58 days posttransplant, 176 patients (54.6%) had EBV reactivation, but only 5 patients developed posttransplant lymphoproliferative disorder. Logistics multivariate analysis showed EBV IgA-negative donor, cytomegalovirus (CMV) reactivation, and graft-versus-host disease (GVHD) prophylaxis with anti-thymocyte globulin (ATG) were independent risk factors of EBV reactivation. Then a risk factor prediction model for EBV reactivation after transplantation was established based on the multivariate regression. The analysis based on the generalized linear mixed model showed dramatic improvements in the reconstitution of CD8+CD45RO+ memory T-cells and CD16+CD56+ NK cells of the EBV-reactivated group. There was no statistical difference in overall survival (p = 0.26), relapse-free survival (p = 0.72), GVHD-relapse free survival (p = 0.44), cumulative incidence of relapse (Gray's test p = 0.72), and transplant-related mortality (Gray's test p = 0.066) between patients with and without EBV reactivation. Conclusion Our study showed EBV IgA-negative donor, CMV reactivation, and GVHD prophylaxis with ATG were independent risk factors of EBV reactivation. Posttransplant EBV reactivation had no significant influence on the outcomes of patients, but its impact on immune reconstitution might be complicated. The predictive model based on the study could direct our attention toward patients at high risk of EBV reactivation.
Collapse
Affiliation(s)
- Ling Ma
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ying Zhang
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ting Wang
- Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, China
| | - Yu Cai
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Yang
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yin Tong
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chongmei Huang
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huiying Qiu
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kun Zhou
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaowei Xu
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiahua Niu
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chang Shen
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xinxin Xia
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu Wei
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Shao
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Yang
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jingjing Cao
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xianmin Song
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Hongkou District, Shanghai 200080, China
| | - Liping Wan
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Hongkou District, Shanghai 200080, China
| |
Collapse
|
2
|
Sanz J, Labopin M, Choi G, Kulagin A, Peccatori J, Vydra J, Reményi P, Versluis J, Rovira M, Blaise D, Labussière-Wallet H, Montoro J, Sica S, Meijer E, Itälä-Remes M, Schaap N, Bulabois CE, Piemontese S, Mohty M, Ciceri F. Younger unrelated donors may be preferable over HLA match in the PTCy era: a study from the ALWP of the EBMT. Blood 2024; 143:2534-2543. [PMID: 38657278 DOI: 10.1182/blood.2023023697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 02/22/2024] [Accepted: 03/02/2024] [Indexed: 04/26/2024] Open
Abstract
ABSTRACT There is a paucity of information on how to select the most appropriate unrelated donor (UD) in hematopoietic stem cell transplantation (HSCT) using posttransplant cyclophosphamide (PTCy). We retrospectively analyzed the characteristics of 10/10 matched UDs (MUDs) and 9/10 mismatched UDs (MMUDs) that may affect transplant outcomes in patients with acute myeloid leukemia (AML) in first or second complete remission (CR1 or CR2). The primary end point was leukemia-free survival (LFS). Overall, 1011 patients were included with a median age of 54 years (range, 18-77). Donors had a median age of 29 years (range, 18-64); 304 (30%) were females, of which 150 (15% of the whole group) were donors to male recipients, and 621 (61%) were MUDs; 522 (52%) had negative cytomegalovirus (CMV-neg) serostatus, of which 189 (19%) were used for CMV-neg recipients. Donor age older than 30 years had a negative impact on relapse (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.06-1.8), LFS (HR, 1.4; 95% CI, 1.12-1.74), overall survival (HR 1.45; 95% CI, 1.14-1.85) and graft-versus-host disease (GVHD) free, relapse-free survival (HR, 1.29; 95% CI, 1.07-1.56). In addition, CMV-neg donors for CMV-neg recipients were associated with improved LFS (HR, 0.74; 95% CI, 0.55-0.99). The use of MMUD and female donors for male recipients did not significantly impact any transplant outcomes. For patients undergoing HSCT from a UD with PTCy for AML, donor age <30 years significantly improves survival. In this context, donor age might be prioritized over HLA match considerations. In addition, CMV-neg donors are preferable for CMV-neg recipients. However, further research is needed to validate and refine these recommendations.
Collapse
Affiliation(s)
- Jaime Sanz
- Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain; Department de Medicina de la Universitat de València; CIBERONC, Instituto Carlos III, Madrid, Spain
| | - Myriam Labopin
- EBMT Paris Office, Hospital Saint-Antoine, Paris, France
| | - Goda Choi
- University Medical Center Groningen, Groningen, The Netherlands
| | - Alexander Kulagin
- Raisa Memorial Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia
| | - Jacopo Peccatori
- Hematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Jan Vydra
- Institute of Hematology and Blood Transfusion-Prague, Prague, Czech Republic
| | | | | | - Montserrat Rovira
- BMT Unit, Department of Haematology, Institute of Haematology and Oncology, IDIBAPS, Hospital Clinic, Josep Carreras Leukaemia Research Foundation, University of Barcelona, Barcelona, Spain
| | - Didier Blaise
- Programme de Transplantation & Therapie Cellulaire-Marseille, Marseille, France
| | | | - Juan Montoro
- Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain; Department de Medicina de la Universitat de València; CIBERONC, Instituto Carlos III, Madrid, Spain
| | - Simona Sica
- Universita Cattolica del Sacro Cuore, Rome, Italy
| | - Ellen Meijer
- VU University Medical Center, Amsterdam, The Netherlands
| | | | - Nicolaas Schaap
- Radboud University Medical Center, Nijmegen, The Netherlands
| | | | - Simona Piemontese
- Hematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Mohamad Mohty
- Hôpital Saint-Antoine, Sorbonne University, INSERM UMRs 938, Paris, France
| | - Fabio Ciceri
- Hematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute IRCCS, Milano, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| |
Collapse
|
3
|
Chen YF, Li J, Xu LL, Găman MA, Zou ZY. Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities. World J Clin Cases 2023; 11:268-291. [PMID: 36686358 PMCID: PMC9850970 DOI: 10.12998/wjcc.v11.i2.268] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 12/02/2022] [Accepted: 01/05/2023] [Indexed: 01/12/2023] Open
Abstract
As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient's conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and post-transplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.
Collapse
Affiliation(s)
- Yong-Feng Chen
- Department of Basic Medical Sciences, School of Medicine of Taizhou University, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Jing Li
- Department of Histology and Embryology, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Ling-Long Xu
- Department of Hematology, Taizhou Central Hospital, Taizhou 318000, Zhejiang Province, China
| | - Mihnea-Alexandru Găman
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest 050474, Romania
| | - Zhen-You Zou
- Department of Scientific Research,Brain Hospital of Guangxi Zhuang Autonomous Region, Liuzhou 545005, Guangxi Zhuang Autonomous Region, China
| |
Collapse
|