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Loss of the mismatched human leukocyte antigen haplotype in two acute myelogenous leukemia relapses after haploidentical bone marrow transplantation with post-transplantation cyclophosphamide

Leukemia volume 30, pages 2102–2106 (2016)Cite this article

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Modern approaches to human leukocyte antigen (HLA)-haploidentical (haplo) blood or marrow transplantation (BMT), such as the use of high-dose post-transplantation cyclophosphamide (PTCy), have resulted in low incidence of graft failure, graft-versus-host disease (GVHD) and nonrelapse mortality, making its safety comparable to HLA-matched unrelated donor BMT.1, 2 Thus, the potentially curative option of BMT has become a reality to the vast majority of patients. However, post-transplant relapse remains the most common cause of treatment failure. To design effective relapse prevention and treatment strategies, we must understand the mechanisms of relapse after the increasingly utilized haplo BMT with PTCy platform.3

HLA complex-mediated presentation of cellular antigens is required for effective T-cell-dependent tumor recognition and cytotoxicity. Cancer cells may downregulate HLA expression to evade T-cell surveillance.4 Although HLA loss occurs in 70–90% of certain untreated solid tumors,5, 6 it is rare in leukemia at presentation.7 However, it has been identified as a mechanism of leukemia immune escape after haplo BMT, occurring in ~33% of acute myelogenous leukemia (AML) relapses.8, 9 Investigators at the San Raffaele Scientific Institute first described acquired uniparental disomy of chromosome 6p, as a mechanism of genomic HLA loss and evolution in AML patients relapsing after haplo BMT using peripheral blood stem cells (PBSCs) grafts.10 They hypothesized that HLA loss may reflect alloimmune pressure mediated by donor T cells toward the HLA mismatches and later identified that active disease at the time of transplant, higher graft T-cell dose, younger patient age and occurrence of chronic GVHD may represent risk factors.8

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Acknowledgements

This study was supported by National Institutes of Health grants P01 CA015396 and P30 CA006973.

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Author notes

  1. S R McCurdy and B S Iglehart: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    S R McCurdy, H A Knaus, L Luznik & I Gojo

  2. Department of Medicine, Immunogenetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    B S Iglehart, A M Jackson & M S Leffell

  3. Department of Pathology, Cytogenetics and Microarray Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    D A Batista

  4. Division of Molecular Pathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    C D Gocke

  5. Department of Pathology, Cancer Cytogenetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Y Ning

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  1. S R McCurdy
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Correspondence to I Gojo.

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McCurdy, S., Iglehart, B., Batista, D. et al. Loss of the mismatched human leukocyte antigen haplotype in two acute myelogenous leukemia relapses after haploidentical bone marrow transplantation with post-transplantation cyclophosphamide. Leukemia 30, 2102–2106 (2016). https://doi.org/10.1038/leu.2016.144

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