Abstract

Abstract 4072

Donor immune effector cells including T and NK cells have been implicated in the development of GVHD after AHPCT. MICA is a ligand recognized by the activating receptor NKG2D that is expressed on the surface of NK, NKT, CD8+ and TCRγδ+ T cells. Allelic variants of MICA due to a single amino acid substitution at position 129 in the alpha2 domain have been reported to result in large differences in NKG2D binding. MICA alleles with a methionine (M) or valine (V) have been classified as having strong or weak binding affinity for NKG2D, respectively. It has been suggested that these variable affinities affect thresholds of NK cell triggering and T cell modulation. Homozygosity of V alleles (VV) has been associated with chronic GVHD (Boukouaci et al. Blood 2009;114:5216–5224). However, the effect of such polymorphisms on outcomes after RIC-AHPCT is not clear. We studied 31 patients (20 AML and 11 MDS) who had MRD RIC-AHPCT with fludarabine/low-dose TBI conditioning. All patients received peripheral blood stem cells and GVHD prophylaxis consisted of a calcineurin inhibitor and mycophenolate. Genotyping was performed retrospectively on patients' DNA samples by rSSOP to determine MICA 129 dimorphisms and they were then categorized as having VV (n=12), MV (n=17) or MM (n=2) dimorphisms. Post-transplant outcomes were compared between patients with VV (weak) vs. VM/MM (mixed/strong binding affinities). Outcomes were estimated using the cumulative incidence method and compared between groups with the Pepe-Mori test. Patients in the VV group had significantly less grade 3–4 acute GVHD (0 vs. 26%, respectively, p=0.022) and a trend to less chronic GVHD (8 vs. 37%, respectively, p=0.07) than the VM/MM group (see Figures).

There were no differences between these groups regarding pre-transplant patient characteristics, CD34+/TNC doses, neutrophil or platelet engraftment, CMV/other infections, relapse, relapse mortality, non-relapse mortality, relapse-free or overall survival. We conclude that assessment of MICA gene polymorphisms in MRD RIC-AHPCT patients may have important implications for predicting GVHD. Those with a MICA dimorphism indicating weak binding affinity (VV) for the NKG2D activating receptor may have less alloreactive recipient immune effector cells that decrease the risk of developing GVHD. Further investigation of this observation with larger study populations is warranted.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.