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Reduced-intensity stem cell transplantation for acute myeloid leukemia with fludarabine-based conditioning with intravenous busulfan versus melphalan

Bone Marrow Transplantation volume 55, pages 1955–1965 (2020)Cite this article

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Abstract

Reduced-intensity conditioning (RIC) has been facilitating allogeneic hematopoietic cell transplantation (allo-HCT) for patients originally considered ineligible for HCT with myeloablative conditioning. Fludarabine (Flu) with reduced doses of busulfan (Bu) (Flu + Bu) and Flu with reduced doses of melphalan (Mel) (Flu + Mel) are widely used RIC regimens for acute myeloid leukemia (AML). A nationwide retrospective study comparing clinical outcomes of adult patients with AML receiving first allo-HCT after RIC between 2001 and 2010 was performed. Cumulative incidences of relapse were not significantly different among the Flu + ivBu-based (FBiv), Flu + poBu-based (FBpo), and Flu + Mel-based (FM) groups (p = 0.29). Non-relapse mortality (NRM) was significantly lower in patients receiving FBiv compared with FBpo (p = 0.003) and FM (p < 0.001). On multivariate analysis, there was no significant difference in overall survival, but FM was associated with a significantly lower risk of relapse (hazard ratio (HR) = 0.65, 95% confidence interval (CI): 0.50–0.85, p = 0.002), higher NRM (HR = 1.60, 95% CI: 1.10–2.33, p = 0.013) and better leukemia-free survival (HR = 0.77, 95% CI: 0.63–0.95, p = 0.015) compared with FBiv. These results suggest that Flu + Mel has a more intense disease control potential and Flu + ivBu is less toxic than the other. Both RIC regimens provide similar survival outcomes and are effective and useful regimens for patients with AML who received allo-HCT.

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Fig. 1: Adjusted probabilities of leukemia-free and overall survival for all patients according to conditioning regimen.
Fig. 2: Cumulative incidence of relapse according to conditioning regimen, stratified by disease status at transplant.
Fig. 3: Cumulative incidence of non-relapse mortality according to conditioning regimen, stratified by disease status at transplant.

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Acknowledgements

The authors would like to acknowledge all of the HCT recipients, donors, and their families, all of the HCT teams in Japan, and the members of the adult AML working group of the Japan Society for Hematopoietic Cell Transplantation.

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Authors and Affiliations

  1. Department of Hematology, St. Luke’s International Hospital, Tokyo, Japan

    Takuya Yamashita

  2. Division of Hematology, Department of Internal Medicine, Aichi Medical University Hospital, Aichi, Japan

    Akiyoshi Takami

  3. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital, Tokyo, Japan

    Naoyuki Uchida

  4. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    Takahiro Fukuda

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

    Tetsuya Eto

  6. Department of Hematology, Hokkaido University Hospital, Sapporo, Japan

    Souichi Shiratori

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

    Shuichi Ota

  8. Department of Hematology, Tenri Hospital, Tenri, Japan

    Takashi Akasaka

  9. Department of Hematology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

    Shigesaburo Miyakoshi

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

    Tadakazu Kondo

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

    Michihiro Hidaka

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

    Junya Kanda

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

    Yoshiko Atsuta

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

    Yoshiko Atsuta

  15. Department of Clinical Oncology and Hematology, The Jikei University School of Medicine, Tokyo, Japan

    Shingo Yano

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Yamashita, T., Takami, A., Uchida, N. et al. Reduced-intensity stem cell transplantation for acute myeloid leukemia with fludarabine-based conditioning with intravenous busulfan versus melphalan. Bone Marrow Transplant 55, 1955–1965 (2020). https://doi.org/10.1038/s41409-020-0856-y

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