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Stem cell transplantation

Is there a stronger graft-versus-leukemia effect using HLA-haploidentical donors compared with HLA-identical siblings?

Leukemia volume 30, pages 447–455 (2016)Cite this article

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Abstract

Haploidentical hematopoietic stem cell transplants (HSCTs) are increasingly used, but it is unknown whether they have a stronger graft-versus-leukemia (GVL) effect. We analyzed 10 679 acute leukemia patients who underwent HSCT from an HLA-matched sibling donor (MSD, n=9815) or a haploidentical donor (⩾2 HLA-antigen disparity, n=864) between 2007 and 2012, reported to the European Group for Blood and Marrow Transplantation. In a Cox regression model, acute and chronic graft-versus-host disease (GVHD) was added as time-dependent variables. There was no difference in probability of relapse between recipients of haploidentical and MSD grafts. Factors of importance for relapse after T-cell-replete grafts included remission status at HSCT, Karnofsky score ⩽80, acute GVHD of grade II or higher and chronic GVHD (P<10−5). Patients with post-transplant cyclophosphamide (n=194) had similar outcome as other T-cell-replete haploidentical transplants (n=369). Non-relapse mortality was significantly higher in the haploidentical group compared with that in MSD patients (P<10−5). Leukemia-free survival was superior in the MSD patients receiving T-cell-replete (P<10−5) or T-cell-depleted grafts (P=0.0006). The risk of relapse was the same in acute leukemia patients who received haploidentical donor grafts as in those given MSD transplants, suggesting a similar GVL effect.

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Acknowledgements

We thank Inger Holmström for expert preparation of this manuscript. We also thank Prof. JV de Melo (University of Adelaide, Adelaide, SA, Australia) for critical reading of the manuscript. We acknowledge all the EBMT centers for reporting to the EBMT database, which made this analysis possible. A list of contributing centers is given in Supplementary 1 of this article. The study was supported by funding from EBMT. OR was supported by grants from the Swedish Cancer Society (CAN2013/671), the Swedish Research Council (K2014-64X-05971-34-4), the Children's Cancer Foundation (PR2013-0045), the Cancer Society in Stockholm (111293) and Karolinska Institutet.

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Author notes

  1. A Nagler and M Mohty: Shared senior authorship.

Authors and Affiliations

  1. Division of Therapeutic Immunology, F79, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

    O Ringdén

  2. Department of Hematology, EBMT-ALWP Office and University Pierre and Marie Curie, Hospital Saint Antoine, Paris, France

    M Labopin, A Nagler & M Mohty

  3. Hospital San Raffaele, Milano, Italy

    F Ciceri

  4. Dipartimento di Medicina Clinical e Sperimentale, Sezione di Ematologia, Università di Perugia Ospedale Santa Maria della Misericordia, Perugia, Italy

    A Velardi

  5. Department of Haematology II, Ospedale San Martino, Genova, Italy

    A Bacigalupo

  6. Rome Transplant Network, 'Tor Vergata' University of Rome, Stem Cell Transplant Unit Policlinico Universitario Tor Vergata, Rome, Italy

    W Arcese

  7. Tehran University of Medical Sciences, Shariati Hospital Hematology, Oncology and BMT Research Center, Tehran, Iran

    A Ghavamzadeh

  8. Centre Pierre et Marie Curie, Service Hématologie Greffe de Moëlle, Alger, Algeria

    R M Hamladji

  9. II Medizinische Klinik, Klinikum Augsburg, Augsburg, Germany

    C Schmid

  10. Chaim Sheba Medical Center, Tel-Hashomer, Israel

    A Nagler

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for the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

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Correspondence to O Ringdén.

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Ringdén, O., Labopin, M., Ciceri, F. et al. Is there a stronger graft-versus-leukemia effect using HLA-haploidentical donors compared with HLA-identical siblings?. Leukemia 30, 447–455 (2016). https://doi.org/10.1038/leu.2015.232

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