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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1425076
Comparison of hematopoietic stem cell transplantation and repeated intensified immunosuppressive therapy as second-line treatment for relapsed/refractory severe aplastic anemia
Provisionally accepted
Lining Zhang
*
Jianping Li
Weiru Liang
*
Xiaoyu Zhang
Shulian Chen
Yuanyuan Shi
Mengze Hao
*
Xiaoli Zhao
Ming Gong
*
Jialin Wei
*
Yi He
*
Erlie Jiang
Mingzhe Han
Fengkui Zhang
*
Sizhou Feng
*- National Clinical Research Center for Hematological Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7) or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CI) of grade II-IV, III-IV acute graft-versus-host disease (GVHD) was 36.1% ± 0.7%, 13.9% ± 0.3% at day +100. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3-, 6-and 12-months (63.9%, 83.3% and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) were similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.
Keywords: Severe aplastic anemia, relapse, Refractory, Hematopoietic Stem Cell Transplantation, immunosuppressive therapy
Received: 29 Apr 2024; Accepted: 29 Jul 2024.
Copyright: © 2024 Zhang, Li, Liang, Zhang, Chen, Shi, Hao, Zhao, Gong, Wei, He, Jiang, Han, Zhang and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lining Zhang, National Clinical Research Center for Hematological Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Weiru Liang, National Clinical Research Center for Hematological Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Mengze Hao, National Clinical Research Center for Hematological Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Ming Gong, National Clinical Research Center for Hematological Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Jialin Wei, National Clinical Research Center for Hematological Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Yi He, National Clinical Research Center for Hematological Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Fengkui Zhang, National Clinical Research Center for Hematological Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Sizhou Feng, National Clinical Research Center for Hematological Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
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