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Total body irradiation plus fludarabine versus busulfan plus fludarabine as a myeloablative conditioning for adults with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation. A study on behalf of the Acute Leukemia Working Party of the EBMT

Abstract

Cyclophosphamide is frequently substituted with fludarabine (Flu) in conditioning regimens before allogeneic hematopoietic cell transplantation (allo-HCT). We aimed to compare retrospectively, total body irradiation (12 Gy) plus Flu (FluTBI12) versus busulfan (Bu) plus Flu (FB4) as a myeloablative conditioning before allo-HCT in patients with acute myeloid leukemia (AML). Out of 3203 patients who met the inclusion criteria, 109 patients treated with FluTBI12 and 213 treated with FB4 were included in a final matched-pair analysis. In both groups, median patient age was 41 years, first or second complete remission (CR1/CR2) proportion was 78%/22%, allo-HCT from an unrelated donor was performed in 78% of patients. The probabilities of leukemia-free survival and overall survival at 2 years in FluTBI12 and FB4 groups were 65% vs. 60% (p = 0.64) and 70% vs. 72% (p = 0.87), respectively. The cumulative incidence of relapse was 19% vs. 29% (p = 0.11), while non-relapse mortality was 16% vs. 11%, respectively (p = 0.13). There were no statistical differences in both acute and chronic graft-versus-host disease (GVHD) incidence. The probability of GVHD-free, relapse-free survival (GRFS) was 49% for both groups. FluTBI12 and FB4 are comparable myeloablative regimens before allo-HCT in AML patients transplanted in CR1 and CR2.

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Fig. 1: Graft versus host disease (GVHD) in FluTBI12 and FB4 group.
Fig. 2: Results of allo-HCT in FluTBI12 and FB4 group.

Data availability

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

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Acknowledgements

We sincerely thank the centers of the EBMT for contributing patient information and data collection.

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RS and SG interpreted results and wrote the manuscript. ML performed the statistical analysis. RS, SG, TS, NK, MA, BS, AS, RMH, VP, AB, IYA, AR, HO, JS, AN, and MM provided patient data and reviewed the final version of the manuscript. SG, BS, AS, AN, and MM designed the study and interpreted the results.

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Correspondence to Ryszard Swoboda.

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Swoboda, R., Labopin, M., Giebel, S. et al. Total body irradiation plus fludarabine versus busulfan plus fludarabine as a myeloablative conditioning for adults with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation. A study on behalf of the Acute Leukemia Working Party of the EBMT. Bone Marrow Transplant (2022). https://doi.org/10.1038/s41409-022-01882-5

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