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Optimizing conditioning regimen with low-dose irradiation or busulfan enables the outcome of transplantation from a 6–7/8 HLA-matched donor comparable to that from an 8/8 HLA-matched unrelated donor in severe aplastic anemia patients under 40 years

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Abstract

With the dramatic improvements in outcomes following alternative donor hematopoietic stem cell transplantation (HSCT), interest in the use of alternative donors in severe aplastic anemia (SAA) is increasing. We conducted a multicenter prospective study to explore the efficiency and safety of upfront HSCT from a 6–8/8 HLA-matched unrelated donor (MUD) or 6–7/8 HLA-matched related donor (MRD) in acquired SAA patients under 40 years. Between August 2014 and July 2017, 115 patients were enrolled, including 48 (41.7%) patients receiving grafts from an 8/8 MUD, 25 (21.7%) from a 6–7/8 MRD, and 42 (36.5%) from a 6–7/8 MUD. The incidence of grade II–IV acute graft-versus-host disease (GVHD) was higher in the 6–7/8 MUD group than in the 8/8 MUD group (42.9% vs. 12.8%, P=0.001). The corresponding incidence in the 6–7/8 MRD group was comparable to that in the 8/8 MUD group (21.7% vs. 12.8%, P=0.332). There was no significant difference in the incidence of chronic GVHD (24.3%, 13.6%, and 17.9%, P=0.676), graft failure (2.4%, 8.0%, and 6.3%, P=0.551), overall survival (85.7%, 96.0%, and 87.5%, P=0.424), and failure-free survival (83.3%, 88.0%, and 83.3%, P=0.885) among the three groups (6–7/8 MUD, 6–7/8 MRD, and 8/8 MUD). In multivariate analysis, conditioning regimen without low-dose irradiation or busulfan was associated with an inferior failure-free survival (HR=2.973, P=0.042). In conclusion, after an intensified conditioning regimen with additional low-dose irradiation or busulfan, the outcome of HSCT from a 6–7/8 MRD or 6–7/8 MUD is comparable to that from an 8/8 MUD.

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Data availability

The datasets generated or analyzed during this study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank all patients and physicians who participated in this study. We also sincerely thank Timothy S. Olson (Transplant Medical Director, Comprehensive Bone Marrow Failure Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA) for his valuable comments.

Funding

This study was supported by grants from the National Natural Science Foundation of China (No. 81970114, J.C.), Shanghai Jiao Tong University School of Medicine (No. DLY201814, J.C.), Shanghai Municipal Administrator of Traditional Chinese Medicine (No. ZY [2018- 2020]-FWTX-3002, J.C.), and Shanghai Municipal Health Commission (No. 20184Y0145, X.Q.).

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Authors and Affiliations

  1. Department of Hematology and Oncology, National Children’s Medical Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China

    Xia Qin, Cheng-Juan Luo & Jing Chen

  2. Department of Pediatric Hematology and Oncology, West China Second University Hospital/West China Women and Children’s Hospital, Sichuan University, Chengdu, China

    Yi-Ping Zhu

  3. Department of Hematology, Guangzhou First People’s Hospital , School of Medicine, South China University of Technology, 1 Panfu Road, Guangzhou, 510180, Guangdong, China

    Ming Zhou & Shun-Qing Wang

  4. Department of Pediatric Hematology and Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

    Ke Huang & Chun Chen

  5. Department of Hematology, Changhai Hospital, Navy Military Medical University, Shanghai, China

    Wei-Ping Zhang

  6. Department of Hematology and Oncology, Beijing JingDu Children’s Hospital, Beijing, China

    Yuan Sun

  7. Department of Hematology and Oncology, BaYi Children’s Hospital, The Seventh Medical Center of PLA General Hospital, Beijing, China

    Rong-Mu Luo

  8. Department of Pediatric Hematology and Oncology, The Sixth Medical Center of PLA General Hospital, Beijing, China

    Xiang-Feng Tang

  9. Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, China

    Ting Yang

  10. Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Xian-Min Song

  11. Department of Hematology and Oncology, Children’s Hospital of Soochow University, Soochow, China

    Shao-Yan Hu

  12. Department of Hematology, Anhui Provincial Hospital, University of Science and Technology of China, Hefei, China

    Zi-Min Sun

  13. Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Jiong Hu

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  1. Xia Qin
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Contributions

X.Q. and Y.P.Z. contributed equally to this work. J.C. and S.Q.W. contributed equally to this work. J.C. and S.Q.W. designed the study; J.C., S.Q.W., X.Q., and Y.P.Z. analyzed the data and wrote the paper; X.Q., Y.P.Z., C.J.L., M.Z., K.H., C.C., W.P.Z., Y.S., R.M.L., X.F.T., T.Y., X.M.S., S.Y.H., Z.M.S., and J.H. collected and assembled the data. All the authors approved the final manuscript.

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Correspondence to Shun-Qing Wang or Jing Chen.

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The study was approved by the local Ethics Committee of Shanghai Children’s Medical Center and was conducted according to the Declaration of Helsinki.

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The authors declare no competing interests.

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Qin, X., Zhu, YP., Luo, CJ. et al. Optimizing conditioning regimen with low-dose irradiation or busulfan enables the outcome of transplantation from a 6–7/8 HLA-matched donor comparable to that from an 8/8 HLA-matched unrelated donor in severe aplastic anemia patients under 40 years . Ann Hematol 100, 2363–2373 (2021). https://doi.org/10.1007/s00277-021-04540-w

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