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Salvage haploidentical hematopoietic cell transplantation for graft rejection following a prior haploidentical allograft

Bone Marrow Transplantation volume 52, pages 147–150 (2017)Cite this article

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Allogeneic hematopoietic cell transplantation (HCT) remains the only curative therapy for patients with relapsed/refractory, advanced and high-risk hematological malignancies. Although HLA-identical siblings are currently considered to be the preferred donor source for allogeneic HCT, only 25–30% of patients have such a donor. Alternative donor options include, unrelated donors (URD), umbilical cord blood units and haplotype-mismatched (haplo) related donors. The use of haplo-HCT is increasing based on recent promising results1, 2, 3, 4 and the near-universal availability of this option. However, graft rejection is not uncommon (10–15%) after haplo-HCT and can be life threatening.1 Although second allografts are an accepted strategy after rejection of an HLA-matched allograft,5 there is paucity of data regarding second haplo-HCT in patients experiencing graft rejection after a prior haplo-HCT. In the current study, we report the toxicity and outcomes of salvage haplo-HCT using the post-transplant cyclophosphamide (PT-Cy) platform in five patients experiencing graft rejection after a prior haplo-HCT.

Adult patients with hematological malignancies who received a second salvage haplo-HCT for either primary or secondary graft rejection, following a prior haplo-HCT between January 2012 to January 2016 at our institution were eligible for this study. There were no other graft rejections following haplo-HCT during the era of the report, at our center. Primary graft rejection was defined as the failure to demonstrate donor-derived hematopoiesis after allogeneic HCT (that is, no evidence of donor-cell chimerisms of ⩾5% on unsorted or lineage-specific chimerism analysis (LSCA) at any time point post HCT), whereas complete loss of donor-cell chimerism (that is, <5% donor-cells on chimerism analysis) after demonstrating evidence of donor-derived hematopoiesis was termed secondary graft rejection. Full donor chimerism was defined as the presence of ⩾95% of donor-cells on chimerism testing and mixed donor chimerism was defined as coexistence of recipient and donor hematopoietic cells (ranging from 5 to 94%), following allogeneic HCT.5 Neutrophil recovery was defined as the first of 3 successive days with ANC ⩾500/μL after post-transplantation nadir. Platelet recovery was defined as achieving platelet counts ⩾20 000/μL for the first of 3 successive days, unsupported by transfusion. All recipients of haplo-HCT at our institution are screened for the presence of donor-specific antibodies (DSAs). The method used for detection of DSA in our study was solid-phase HLA antibody identification assays.6 The mean fluorescent intensity (MFI) values provide a relative indication of the strength of the DSAs. The general cutoff value in our laboratory for a positive antibody is an MFI >1000.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

    N Epperla, M Pasquini, K Zellner, S Ramirez, K Bartz, R V Raj, P N Hari & M Hamadani

  2. Department of Medicine, CIBMTR (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI, USA

    M Pasquini, W R Drobyski, J D Rizzo, M M Horowitz, W Saber & M Hamadani

  3. Department of Histocompatibility, Blood Center of Wisconsin, Milwaukee, WI, USA

    K Pierce

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  1. N Epperla
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Correspondence to M Hamadani.

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Epperla, N., Pasquini, M., Pierce, K. et al. Salvage haploidentical hematopoietic cell transplantation for graft rejection following a prior haploidentical allograft. Bone Marrow Transplant 52, 147–150 (2017). https://doi.org/10.1038/bmt.2016.200

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