Comparison of T & NK Cell Donor Chimerism & Hematopoietic Engraftment Following Allogeneic Hematopoetic Stem Cell Transplantation in Pediatric Recipients Receiving Bone Marrow (BM) or Umbilical Cord Blood and/or Human Placental Derived Stem Cells (HPDSC)

Abstract

Background: Natural killer (NK) cell allo-reactivity in haploidentical allogeneic hematopoietic cell transplantation (HCT) is associated with lower relapse without greater graft-versus-host disease (GVHD). Dimorphisms of the MHC class I chain-related gene A (MICA) alleles can influence NK cell triggering and T cell modulation. Studies evaluating donorrecipient MICA incompatibilities on outcomes after matched unrelated donor HCT show conflicting results, but its significance is unknown in haploidentical HCT. We hypothesized donor-recipient MICA incompatibilities may influence outcomes in haploidentical HCT. Methods: We conducted a single center, retrospective analysis of all haploidentical HCT for hematologic malignancies in which MICA data was available. Outcomes were compared between those with and without donor-recipient MICA matches with Cox analysis or Fine and Gray regression. A secondary analysis examined dimorphisms at the MICA-129 position, which has been categorized as weak (valine/valine: V/V), mixed (methionine/valine: V/M), or strong (methionine/methionine: M/M) receptor binding affinity. Results: From 2014 -2016, 38 patients underwent a haploidentical HCT, with 14 in the MICA matched cohort and 24 in the MICA mismatched cohort with no significant differences in baseline characteristics. Diagnoses included acute myeloid (N = 17) and lymphoblastic leukemia (N = 7), myelodysplastic syndromes (N = 4), and others (N = 10). Median age at HCT was 51 years (range, 7-72), with 79% Caucasian. Myeloablative HCT was performed in 53% of patients and 55% had a bone marrow graft source. Most patients received tacrolimus and mycophenolate with post-transplant cyclophosphamide as GVHD prophylaxis. There were no differences in HLA disparities between the two groups (P = .64). There was a trend towards greater acute GVHD in the MICA mismatched cohort (HR 3.06, P = .07) ( Figure 1). The MICA mismatched group also had a trend towards a lower risk of relapse mortality (HR .28, P = .06) ( Figure 2). There was no significant difference in relapse-free survival (HR .62, P = .32), nonrelapse mortality (HR 1.52, P = .63), or overall survival (HR .56, P = .24). The most common cause of death was relapse. In secondary analysis examining the MICA-129 genotype, patients with a V/V donor had higher risk of chronic GVHD (P = .006), though sample size was limited to 4 patients. No other outcome differences were seen relative to MICA-129 genotype. Conclusion: We conclude that donor-recipient MICA incompatibility may be associated with a higher incidence of acute GVHD after haploidentical HCT consistent with previous

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“…the T cells, is completely of recipient origin, whereas the others are donor-derived, this is a situation of 'split chimerism'. 9,11 The aim of the work is to study certain number of VNTR to identify their potential value in the detection of chimerism in conventional ablative transplanted patients. Also to demonstrate the value of T-cells subset analysis added to whole blood chimerism in detecting transplantation outcomes.…”