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Comparative analysis of reduced toxicity conditioning regimens between fludarabine plus melphalan and fludarabine plus busulfex in adult patients with acute lymphoblastic leukemia

Bone Marrow Transplantation volume 59, pages 1413–1422 (2024)Cite this article

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Abstract

Reduced-toxicity conditioning (RTC) regimens aim to mitigate regimen-related toxicity while maintaining anti-leukemic efficacy in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed outcomes of RTC regimens utilizing melphalan versus intravenous busulfan combined with fludarabine in adult acute lymphoblastic leukemia (ALL) patients. A retrospective analysis was conducted with 149 consecutive adult ALL patients (median age 51, range 18–60) in remission undergoing allo-HSCT. Patients received either fludarabine 150 mg/BSA plus 2 days of melphalan 70 mg/BSA (FM140, n = 76) from 2009 to 2015 or fludarabine plus 3 days of busulfan 3.2 mg/kg (FB9.6, n = 73) from 2016 to 2021. At 5 years post-HSCT, FM140 demonstrated superior disease-free survival (53.4% vs. 30.5%, p = 0.007) and lower cumulative relapse (27.4% vs. 46.8%, p = 0.026) than FB9.6. Five-year overall survival and non-relapse mortality did not significantly differ. FM140 exhibited a higher incidence of acute graft-versus-host disease (GVHD) grades II-IV (49.3% vs. 30.3%, p = 0.016), though rates of acute GVHD grades III-IV and chronic GVHD were similar. Multivariate analysis identified Philadelphia chromosome and minimal residual disease positive status, and FB9.6 conditioning as predictors of increased relapse and poorer disease-free survival. FM140 RTC regimen displayed significantly reduced relapse and superior disease-free survival compared to FB9.6 in ALL patients undergoing allo-HSCT, highlighting its current clinical utility.

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Fig. 1: Survival outcomes according to RTC regimens (FM140 vs. FB9.6).
Fig. 2: The cumulative incidence of graft-versus-host disease in FM140 and FB9.6 group.
Fig. 3: Post-transplant immune reconstitution in FM140 and FB9.6 group.

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Data availability

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

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Acknowledgements

We thank all patients and their families for their participation in the trial.

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  1. These authors contributed equally: Jaehyun Ahn, Jae-Ho Yoon.

Authors and Affiliations

  1. College of Medicine, The Catholic University of Korea, Seoul, Korea

    Jaehyun Ahn

  2. Department of Hematology, Catholic Hematology Hospital and Leukemia Research Institute, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Jae-Ho Yoon, Daehun Kwag, Gi June Min, Sung-Soo Park, Silvia Park, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho & Seok Lee

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Contributions

JA and JHY conceptualized and designed the study, contributed to statistical analysis and data interpretation, and wrote the manuscript as a first author. DHK, GJM, SSP, SP, SEL, BSC, KSE, YJK, HJK, CKM, SGC, provided patients and reviewed this manuscript; SL designed and conducted the study, provided patients and materials, analyzed data, and wrote the manuscript; and all authors reviewed and gave final approval of the manuscript.

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This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of the Catholic University of Korea (reference number: KC24RISI0192). Written informed consent was obtained from all participants.

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Ahn, J., Yoon, JH., Kwag, D. et al. Comparative analysis of reduced toxicity conditioning regimens between fludarabine plus melphalan and fludarabine plus busulfex in adult patients with acute lymphoblastic leukemia. Bone Marrow Transplant 59, 1413–1422 (2024). https://doi.org/10.1038/s41409-024-02363-7

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