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Comparison of fludarabine, a myeloablative dose of busulfan, and melphalan vs conventional myeloablative conditioning regimen in patients with relapse and refractory acute myeloid leukemia in non-remission status

Bone Marrow Transplantation volume 56, pages 2302–2304 (2021)Cite this article

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The prognosis of refractory and relapsed acute myeloid leukemia (R/R AML) is dismal with the 2-year overall survival (OS) being ~20% [1]. Salvage chemotherapy alone offers almost no chance for cure, and allogeneic hematopoietic stem cell transplantation (HSCT) is required to achieve a cure [2, 3].

Conditioning regimens prior to HSCT play an important role in eliminating tumor cells and suppressing host immune cells. Cyclophosphamide plus total body irradiation and a myeloablative dose of intravenous busulfan plus cyclophosphamide are regarded as standard conditioning regimens (conventional myeloablative conditioning regimen, cMAC) for patients with R/R AML in non-remission status by default [4]. Because of a low survival rate due to a high relapse rate even with the standard conditioning regimen, several conditioning strategies are being investigated [5, 6]. Among these regimens, a myeloablative conditioning regimen consisting of fludarabine, a myeloablative dose of intravenous busulfan, and melphalan (Flu/Bu4/Mel) was first established in Japan for R/R AML patients who received cord blood transplants [6]. Subsequent research revealed that treatment with Flu/Bu4/Mel resulted in a better 5-year OS compared to fludarabine and a myeloablative dose of busulfan, which is an alternative standard conditioning regimen [7].

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Fig. 1: Transplant outcomes in a propensity score-matched cohort.

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Acknowledgements

The authors thank all the physicians and data managers of the centers, who contributed to the collection of data on transplantation to Japanese Data Center for Hematopoietic Cell Transplantation and the Transplant Registry Unified Management Program 2. We would like to express our gratitude to the Japan Society of Clinical Research for their dedicated support.

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Authors and Affiliations

  1. Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan

    Yoshimitsu Shimomura

  2. Center for Community-based Healthcare Research and Education, Shimane University, Shimane, Japan

    Masahiko Hara

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

    Shigeki Hirabayashi & Tadakazu Kondo

  4. Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan

    Shohei Mizuno

  5. Department of hematology, Toranomon Hospital, Tokyo, Japan

    Naoyuki Uchida

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

    Junichi Mukae

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

    Toshiro Kawakita

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

    Takahiro Fukuda

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

    Yoshinobu Kanda

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

    Shuichi Ota

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

    Yukiyasu Ozawa

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

    Tetsuya Eto

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

    Yumiko Maruyama

  14. Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan

    Masatsugu Tanaka

  15. Department of Hematology, Imamura General Hospital, Kagoshima, Japan

    Nobuaki Nakano

  16. Preparation Department, Japanese Red Cross Kinki Block Blood Center, Osaka, Japan

    Takafumi Kimura

  17. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    Tatsuo Ichinohe

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

    Yoshiko Atsuta

  19. Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yoshiko Atsuta

  20. Department of Hematology and Cell Therapy, Aichi Cancer Center, Aichi, Japan

    Masamitsu Yanada

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  1. Yoshimitsu Shimomura
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  2. Masahiko Hara
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Correspondence to Yoshimitsu Shimomura.

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Shimomura, Y., Hara, M., Hirabayashi, S. et al. Comparison of fludarabine, a myeloablative dose of busulfan, and melphalan vs conventional myeloablative conditioning regimen in patients with relapse and refractory acute myeloid leukemia in non-remission status. Bone Marrow Transplant 56, 2302–2304 (2021). https://doi.org/10.1038/s41409-021-01380-0

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