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HLA disparity is not inconsequential in peripheral blood T-replete haploidentical hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 51, pages 1275–1278 (2016)Cite this article

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By depleting proliferating alloreactive donor and host T cells, high-dose post-transplant cyclophosphamide (PT-Cy) has made haploidentical hematopoietic cell transplantation (haplo-HCT) a viable treatment option for most transplant-eligible patients who lack a fully histocompatible related or unrelated donor.1, 2, 3 In haplo-HCT at least one haplotype is shared between the donor and recipient, although an additional one or more loci on the unshared haplotype may happen to be similar. Given the increasing use of haplo-HCT, an important question is whether the degree of HLA disparity affects transplant outcomes. Specifically, considering HLA-A, -B, -C and -DRB1 loci, are the outcomes of haplo-HCT with less-than-one haplotype mismatch (that is, 1–3 antigen mismatches) different from one-haplotype mismatch (that is, 4 antigen mismatches) transplants? Two recent studies showed that in the setting of haplo-HCT using marrow (with PT-Cy) or combined marrow and blood (using anti-thymocyte globulin but not PT-Cy) as the graft source, there was no association between the degree of HLA disparity and the incidence of acute GvHD grade II–IV.4, 5 However, it is currently unknown whether the same is true in the setting of haplo-HCTs using peripheral blood as the graft source. Importantly, although PT-Cy seems to be able to counter the negative effects of HLA disparities when using marrow products, the substantially (fivefold or higher) larger number of T cells in peripheral blood grafts may limit the ability of PT-Cy in equalizing GvHD incidence and survival irrespective of donor–recipient HLA disparities. The purpose of the present retrospective cohort study was to address this knowledge gap.

After approval by our Institutional Review Board, we reviewed the medical records of all patients with AML who underwent a T-replete haplo-HCT (defined as the presence of one shared haplotype and at least one mismatched antigen on the other haplotype) at our institution between January 2010 and October 2015. Patients with a history of prior allogeneic HCT were not included. All patients received granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood grafts. Molecular typing was an allele or allele group level for HLA-A, -B, -C and -DRB1. HLA mismatch in the GvH (host-versus-graft (HvG)) direction was defined by the presence of host (donor) antigens or alleles not shared by the donor (host). A total of 58 patients were eligible for our analysis (baseline characteristics are shown in Table 1). Patients were classified into two groups: 1–3 antigen mismatches (n=19) vs 4 antigen mismatches (n=39). The groups were similar in all studied baseline characteristics (age, sex, cytogenetic risk, pre-HCT disease status, conditioning intensity, CMV serostatus, ABO match, T-cell dose, donor–recipient relationship, female-to-male transplants, hematopoietic cell transplantation comorbidity index and donor age), except the interval between AML diagnosis and transplant. Specifically, this interval was more frequently longer than 6 months among those with 1–3 vs 4 antigen mismatches (58% vs 23%, respectively; P=0.017). With patients classified according to their GvH-direction antigen mismatches (0–3 vs 4 antigen mismatches), the groups were similar in all studied baseline characteristics except patient age. Specifically, patients in the 4 antigen mismatch group were significantly older than those with 0–3 antigen mismatches (median 59 (range: 27–72) vs 53 (19–73) years, respectively; P=0.026). Finally, with patients classified according to their HvG-direction antigen mismatches (0–3 vs 4 antigen mismatches), the groups were similar in all studied baseline characteristics except patient CMV serostatus. Specifically, patients with 0–3 antigen mismatches were significantly more frequently CMV seropositive than those with 4 antigen mismatches (73% vs 44%, respectively; P=0.03).

Table 1 Patient characteristics
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Acknowledgements

AR is supported by the National Institutes of Health UL1 TR000448 grant (Center for Advancing Translational Sciences/Washington University Institute of Clinical and Translational Sciences).

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  1. Division of Oncology, BMT and Leukemia Section, Washington University School of Medicine, St Louis, MO, USA

    A Rashidi, J F DiPersio, P Westervelt, C N Abboud, M A Schroeder, I Pusic, A F Cashen, T A Fehniger & R Romee

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  1. A Rashidi
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Correspondence to R Romee.

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Rashidi, A., DiPersio, J., Westervelt, P. et al. HLA disparity is not inconsequential in peripheral blood T-replete haploidentical hematopoietic stem cell transplantation. Bone Marrow Transplant 51, 1275–1278 (2016). https://doi.org/10.1038/bmt.2016.117

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