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Fludarabine/busulfan versus busulfan/cyclophosphamide as myeloablative conditioning for myelodysplastic syndrome: a propensity score-matched analysis

Bone Marrow Transplantation volume 56, pages 3008–3015 (2021)Cite this article

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Abstract

Myeloablative conditioning with fludarabine/busulfan (Flu/Bu4) prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) is effective for acute myeloid leukemia. However, the effectiveness of Flu/Bu4 for myelodysplastic syndrome (MDS) remains poorly understood. Therefore, we retrospectively analyzed nationwide registry data in Japan from 2006 to 2018 and compared transplant outcomes of adult MDS patients receiving Flu/Bu4 and busulfan/cyclophosphamide (Bu4/Cy) using propensity score (PS) matching. The primary endpoint was overall survival (OS). Among 2,482 MDS patients, 153 patients were assigned each to the Flu/Bu4 and Bu4/Cy groups. The 3-year OS rates were 52.7% (95% confidence interval [CI], 43.8–60.8%) and 49.5% (95% CI, 40.8–57.6%) in the Flu/Bu4 and Bu4/Cy group, respectively (P = 0.548). The 3-year progression-free survival (P = 0.858), the cumulative incidence of relapse (P = 0.536), and cumulative incidence of non-relapse mortality (P = 0.684) were not significantly different between the two groups. According to the findings of subgroup analyses, no patient had a favorable OS when using either of the two regimens. In conclusion, although our PS-matched cohort mainly comprised older patients who had a low hematopoietic cell transplantation-comorbidity index and low-risk disease status, Flu/Bu4 could be an alternative to Bu4/Cy for MDS patients prior to allo-HSCT.

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Fig. 1: A flow chart of patient selection and study design.
Fig. 2: Transplant outcomes of the Flu/Bu4 and Bu4/Cy groups.
Fig. 3: Forest plot of hazard ratios (HRs) for overall survival (OS) in the subgroup analyses.

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Acknowledgements

The authors are grateful to all physicians and staff at the transplant centers who contributed to the collection of data for the Transplant Registry Unified Management Program of the Japan Society of Hematopoietic Cell Transplantation.

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Authors and Affiliations

  1. Division of Stem Cell and Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Shuhei Kurosawa

  2. Department of Haematology, Kobe City Hospital Organization Kobe City Medical Centre General Hospital, Kobe, Japan

    Yoshimitsu Shimomura

  3. Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan

    Hidehiro Itonaga

  4. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Yuho Najima & Takeshi Kobayashi

  5. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Yukiyasu Ozawa

  6. Division of Hematology, Jichi Medical University, Shimotsuke, Japan

    Yoshinobu Kanda

  7. Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan

    Shinichi Kako

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

    Toshiro Kawakita

  9. Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan

    Ken-ichi Matsuoka

  10. Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan

    Yumiko Maruyama

  11. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan

    Shuichi Ota

  12. Department of Hematology, Shinshu University School of Medicine, Matsumoto, Japan

    Hideyuki Nakazawa

  13. Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan

    Kazunori Imada

  14. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Junya Kanda

  15. Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan

    Takahiro Fukuda & Jun Aoki

  16. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

    Yoshiko Atsuta

  17. Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yoshiko Atsuta

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  1. Shuhei Kurosawa
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Contributions

S Kurosawa and YS designed the research, organized the project, analyzed the data, and wrote the manuscript. HI, YN, and JA critically reviewed the analyzed data and manuscript. All authors contributed to data collection and approved the final version.

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Correspondence to Shuhei Kurosawa.

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Kurosawa, S., Shimomura, Y., Itonaga, H. et al. Fludarabine/busulfan versus busulfan/cyclophosphamide as myeloablative conditioning for myelodysplastic syndrome: a propensity score-matched analysis. Bone Marrow Transplant 56, 3008–3015 (2021). https://doi.org/10.1038/s41409-021-01447-y

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