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

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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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 (2021). https://doi.org/10.1038/s41409-021-01447-y

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