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  • Review Article
  • Published:

Modern approaches to HLA-haploidentical blood or marrow transplantation

Nature Reviews Clinical Oncology volume 13, pages 10–24 (2016)Cite this article

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An Erratum to this article was published on 31 December 2015

Key Points

  • HLA-haploidentical allogeneic blood or bone-marrow transplantation (haploBMT) has historically been associated with poor outcomes, owing to high rates of graft failure and graft-versus-host disease (GVHD)

  • Several transplantation platforms have been developed that successfully overcome these historical barriers to haploBMT; three main approaches have been used extensively to conduct haploBMT procedures in patients

  • T-cell depletion with 'megadose' CD34+ cells results in exceptionally low rates of GVHD, but is associated with poor T-cell function and thus high nonrelapse mortality (NRM), predominantly owing to infection

  • The GIAC protocol, which involves in vivo modulation of T-cell-replete allografts, produces essentially universal engraftment with limited relapse and favourable survival, albeit with high rates of GVHD, particularly chronic GVHD

  • Use of high-dose, post-transplantation cyclophosphamide after T-cell-replete allografting results in low rates of GVHD and NRM and favourable immune reconstitution, with somewhat higher rates of relapse, particularly after reduced-intensity conditioning

  • No standard-of-care currently exists, as no completed prospective randomized studies have, thus far, compared any of these haploBMT approaches with each other or with transplantation approaches using other donor types

Abstract

Allogeneic blood or bone-marrow transplantation (alloBMT) is a potentially curative treatment for a variety of haematological malignancies and nonmalignant diseases. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with alloBMT using other donors. Although only approximately one-third of patients have an HLA-matched sibling, nearly all patients have HLA-haploidentical related donors. Early studies using HLA-haploidentical alloBMT resulted in unacceptably high rates of graft rejection and graft-versus-host disease (GVHD), leading to high nonrelapse mortality and consequently poor survival. Several novel approaches to HLA-haploidentical alloBMT have yielded encouraging results with high rates of successful engraftment, effective GVHD control and favourable outcomes. In fact, outcomes of several retrospective comparative studies seem similar to those seen using other allograft sources, including those of HLA-matched-sibling alloBMT. In this Review, we provide an overview of the three most-developed approaches to HLA-haploidentical alloBMT: T-cell depletion with 'megadose' CD34+ cells; granulocyte colony-stimulating factor-primed allografts combined with intensive pharmacological immunosuppression, including antithymocyte globulin; and high-dose, post-transplantation cyclophosphamide. We review the preclinical and biological data supporting each approach, results from major clinical studies, and completed or ongoing clinical studies comparing these approaches with other alloBMT platforms.

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Figure 1: HLA-haploidentical donors.
Figure 2: Components of each transplantation platform.

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  1. Sidney Kimmel Comprehensive Cancer Center, 1650 Orleans Street, Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA

    Christopher G. Kanakry, Ephraim J. Fuchs & Leo Luznik

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Kanakry, C., Fuchs, E. & Luznik, L. Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev Clin Oncol 13, 10–24 (2016). https://doi.org/10.1038/nrclinonc.2015.128

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