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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

Bone Marrow Transplantation volume 56, pages 3042–3048 (2021)Cite this article

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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.

Author information

Authors and Affiliations

  1. Hospital das Clínicas and LIM31, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    V. Rocha & L. C. B. Mariano

  2. Hospital Vila Nova Star, Rede D’Or, São Paulo, Brazil

    V. Rocha

  3. Churchill Hospital, Oxford, United Kingdom

    V. Rocha

  4. Hospital Israelita Albert Eisntein, São Paulo, SP, Brazil

    L. J. Arcuri

  5. Hospital Samaritano, São Paulo, SP, Brazil

    A. Seber & V. C. Ginani

  6. Hospital Fundação Amaral Carvalho, Jau, SP, Brazil

    V. Colturato & M. P. De Souza

  7. Hospital do IOP-GRAACC, São Paulo, SP, Brazil

    V. G. Zecchin

  8. Hospital Infantil Pequeno Príncipe, Curitiba, PR, Brazil

    C. Kuwahara & C. Bonfim

  9. Hospital Nossa Senhora das Graças, Curitiba, PR, Brazil

    S. Nichele & C. Bonfim

  10. Hospital Sao Camilo, São Paulo, SP, Brazil

    R. Gouveia

  11. Instituto do Tratamento do Câncer Infantil, Instituto da Criança da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil

    J. F. Fernandes

  12. Hospital Israelita Albert Einstein, Sao Paulo, SP, Brazil

    J. F. Fernandes & N. Hamerschlak

  13. Hospital da Polícia Militar, Belo Horizonte, MG, Brazil

    A. V. Macedo

  14. Instituto Nacional do Cancer, Rio de Janeiro, RJ, Brazil

    R. Tavares

  15. Serviço de Hematologia Clínica e Transplante de Medula Óssea, Hospital de Clínicas de Porto Alegre -, Porto Alegre, RS, Brasil

    L. Daudt

  16. Paediatric Haematology and Oncology, University of São Paulo, Ribeirão Preto, SP, Brazil

    L. G. Darrigo-Jr

  17. Hospital de Cancer de Barretos, Barretos, SP, Brazil

    N. C. Villela

  18. Hospital Erasto Gaertner, Curitiba, PR, Brazil

    A. Zanette

  19. Hospital de Clínicas – Federal University of Parana, Curitiba, PR, Brazil

    G. Loth & C. Bonfim

  20. Hospital Sírio-Libanês, Sao Paulo, SP, Brazil

    A. A. Gomes

  21. Fred Hutchinson Cancer Research Cancer, Seattle, USA

    M. E. Flowers

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  1. V. Rocha
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on behalf of the Paediatric Working Group and the Brazil-Seattle Consortium Study Group (GEDECO) of the Brazilian Bone Marrow Transplantation Society (SBTMO)

Contributions

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 56, 3042–3048 (2021). https://doi.org/10.1038/s41409-021-01453-0

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