Comparable outcomes of haploidentical transplant with TBF conditioning versus matched unrelated donor with fludarabine/busulfan conditioning for acute myeloid leukemia

Abstract

We compared transplant outcomes of 708 acute myeloid leukemia (AML) patients receiving haploidentical allogeneic hematopoietic-cell transplantation using thiotepa/busulfan/fludarabine (TBF) conditioning with posttransplant cyclophosphamide (ptCy), to 2083 patients receiving matched unrelated donor (MUD) transplantation using fludarabine/busulfan (FB) conditioning and in vivo T-cell depletion. For intermediate cytogenetic risk AML transplanted in first complete remission (CR1), multivariate analysis revealed that haplo-TBF significantly increased nonrelapse mortality (NRM) (HR 2.1; p = 0.0006) but did not affect relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS), or graft-versus-host disease-free, relapse-free survival (GRFS). For high cytogenetic risk AML transplanted in CR1, haplo-TBF significantly increased NRM (HR = 2.7; p = 0.02), decreased RI (HR = 0.45; p = 0.03) but had no influence on LFS, OS, or GRFS. For AML transplanted in CR2, haplo-TBF significantly increased NRM (HR = 2.36; p = 0.008), decreased RI (HR = 0.38; p = 0.005), but had no influence on LFS, OS, or GRFS. Finally, for AML patients transplanted with active disease, haplo-TBF had no influence on transplant outcomes. In conclusion, compared to MUD-FB, haplo-TBF increased NRM, reduced RI in high-risk AML in CR, resulting in similar LFS, OS, and GRFS. These results comparing two different approaches support the use of a haploidentical family donor for high-risk AML patients lacking a matched sibling donor.

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Fig. 1: Transplant outcomes for intermediate-risk AML patients transplanted in CR1.
Fig. 2: Transplant outcomes for high-risk AML patients transplanted in CR1.
Fig. 3: Transplant outcomes for AML patients transplanted in CR2.
Fig. 4: Transplant outcomes for AML patients transplanted with active disease.

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Acknowledgements

AB and MM proposed the study, interpreted the data, and wrote the manuscript. ML helped with the design and was responsible for statistical analysis. All other authors reported updated patient data and read and commented on the manuscript. All authors proofread the manuscript and agreed on the data presented.

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Correspondence to Ali Bazarbachi or Mohamad Mohty.

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AB received honorarium from Jazz, Adienne, and Sanofi. MM received honorarium from Jazz, Riemser, and Sanofi. EA reports personal fees from Novartis, Jazz Pharmaceuticals, Bluebird Bio, Roche, Celgene, Vertex Pharmaceuticals, and CRISPR Therapeutics all outside the submitted work. All remaining authors do not have any conflicts of interest.

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Bazarbachi, A., Labopin, M., Blaise, D. et al. Comparable outcomes of haploidentical transplant with TBF conditioning versus matched unrelated donor with fludarabine/busulfan conditioning for acute myeloid leukemia. Bone Marrow Transplant (2020). https://doi.org/10.1038/s41409-020-01074-z

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