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Impact of mother donor, peripheral blood stem cells and measurable residual disease on outcomes after haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide in children with acute leukaemia

Abstract

Haploidentical hematopoietic-cell transplantation using post-transplant cyclophosphamide(Haplo-PTCy) is a feasible procedure in children with haematologic malignancies. However, data of a large series of children with acute leukaemia(AL) in this setting is missing. We analysed 144 AL Haplo-PTCy paediatric recipients; median age was 10 years. Patients had acute lymphoblastic(ALL; n = 86) or myeloblastic leukaemia(AML; n = 58) and were transplanted in remission(CR1: n = 40; CR2: n = 57; CR3+: n = 27) or relapse (n = 20). Bone marrow was the graft source in 57%; donors were father (54%), mother (35%), or sibling (11%). Myeloablative conditioning was used in 87%. Median follow-up was 31 months. At day +100, cumulative incidence (CI) of neutrophil recovery and acute GVHD (II–IV) were 94% and 40%, respectively. At 2-years, CI of chronic GVHD and relapse, were 31%, 40%, and estimated 2-year overall survival (OS), leukaemia-free survival (LFS) and graft-versus-host-relapse-free survival (GRFS) were 52%, 44% and 34% respectively. For patients transplanted in remission, positive measurable residual disease (MRD) prior to transplant was associated with decreased LFS (p = 0.05) and GRFS (p = 0.003) and increased risk of relapse (p = 0.02). Mother donor was associated with increased risk of chronic GVHD (p = 0.001), decreased OS (p = 0.03) and GRFS (p = 0.004). Use of PBSC was associated with increased risk of chronic GVHD (p = 0.04). In conclusion, achieving MRD negativity pre-transplant, avoiding use of mother donors and PBSC as graft source may improve outcomes of Haplo-PTCy in children with AL.

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Fig. 1: Impact of mother donor vs. non-mother donor.
Fig. 2: Cumulative incidence of relapse by measurable residual disease status at transplant.
Fig. 3: Leukaemia-free survival by status of disease at transplant.

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Acknowledgements

We thank Dr. Giancarlo Fatobene for editing and revising the final version of the manuscript and Dr. Maura Ikoma-Colturato for the definitions of measurable residual disease in this study.

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VR, LJA, AS, VC, VGZ, CCK, SN, RG, JFF, AVM, RT, LD, MPS, LGDJ, NCV, LCBM, VCG, AZ, GL, AAG, NH, MEF and CB were responsible for the study design and conduction, and critically reviewed the manuscript. LJA, AS, VC, VGZ, CCK, SN, RG, JFF, AVM, RT, LD, MPS, LGDJ, NCV, LCBM, VCG, AZ, GL, AAG, NH, and CB were responsible for patient inclusion and local site management. VR, LJA, MEF and CB were responsible for data analyses and writing of the manuscript.

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Correspondence to C. Bonfim.

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Rocha, V., Arcuri, L.J., Seber, A. et al. Impact of mother donor, peripheral blood stem cells and measurable residual disease on outcomes after haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide in children with acute leukaemia. Bone Marrow Transplant (2021). https://doi.org/10.1038/s41409-021-01453-0

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