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Myeloablative intravenous busulfan-containing regimens for allo-HSCT in AML or MDS patients over 54 years old: combined results of three phase II studies

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Abstract

An optimal pretransplant conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in older adults has not been established. Three prospective multicenter phase II studies were conducted, in which 142 patients older than 54 years (median age, 61 years; range 55–70 years) with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) received a myeloablative dose of intravenous busulfan (ivBu, 12.8 mg/kg) along with fludarabine (180 mg/m2) ± low dose total body irradiation for allo-HSCT between September 2009 and February 2013. A total of 103 AML and 39 MDS patients including 21 related bone marrow (BM) or peripheral blood (PB), 50 unrelated BM, and 71 unrelated cord blood (UCB) transplantation were enrolled. Grade 3 or greater toxicities were observed in 105 patients. Neutrophil engraftment was achieved in 70 out of the 71 related PB/BM or unrelated BM recipients, and 61 out of the 71 UCB recipients. The cumulative incidence rates of relapse and non-relapse mortality after 2 years were 24.0 and 24.1%, respectively. The overall and event-free survival rates at 2 years were 53.3 and 47.4%, respectively. The myeloablative dose of ivBu was well tolerated without increased toxicity-related mortality in older adults who underwent allo-HSCT with any donor source.

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Acknowledgements

The authors thank all physicians, nurses, pharmacists, and support personnel in the participating institutes for their care of patients in this study. The authors also thank the staff members of the JSCT office for outstanding data management. This work was supported by Grants from the Research Foundation for Community Medicine. The ivBu PK study was supported by Grants from the Japanese Ministry of Health, Labour and Welfare (H22-018).

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Authors and Affiliations

  1. Department of Hematology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan

    Naoyuki Uchida & Shuichi Taniguchi

  2. Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyoto, Japan

    Kana Matsumoto & Kunihiko Morita

  3. Department of Hematology, Saiseikai Maebashi Hospital, Gunma, Japan

    Toru Sakura

  4. Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan

    Michihiro Hidaka

  5. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan

    Toshihiro Miyamoto & Koichi Akashi

  6. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan

    Tetsuya Eto

  7. Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan

    Yoshinobu Maeda

  8. Department of Hematology, Hyogo Cancer Center, Hyogo, Japan

    Tohru Murayama

  9. Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan

    Naohito Fujishima

  10. Department of Hematology, National Kyushu Medical Center, Fukuoka, Japan

    Goichi Yoshimoto

  11. Department of Research and Development of Next Generation Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan

    Junji Kishimoto

  12. Department of Hematology, Faculty of Medicine, Hokkaido University, Hokkaido, Japan

    Takanori Teshima

  13. Division of Hematology and Oncology, St. Luke’s International Hospital, Tokyo, Japan

    Takuya Yamashita & Shin-ichiro Mori

  14. Department of Hematology, Karatsu Higashimatsuura Medical Association, Saga, Japan

    Mine Harada

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  1. Naoyuki Uchida
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for the Japan Study Group for Cell Therapy, Transplantation (JSCT)

Contributions

NU, TM, TT, ST, TY, S-IM, and MH designed the clinical protocol; KM and KM designed the PK protocol and did measurement and analysis of serum concentration of ivBu; JK conducted the statistical analysis; NU, TS, MH, TM, TE, YM, TM, NF, and GY enrolled and cared for the patients; NU and MH supervised the overall conduction of the study; NU and KM wrote the manuscript; KA and MH critically reviewed the manuscript and all authors approved the final manuscript.

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Correspondence to Naoyuki Uchida.

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Uchida, N., Matsumoto, K., Sakura, T. et al. Myeloablative intravenous busulfan-containing regimens for allo-HSCT in AML or MDS patients over 54 years old: combined results of three phase II studies. Int J Hematol 112, 510–523 (2020). https://doi.org/10.1007/s12185-020-02941-7

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