Acute GVHD in AML and MDS Patients Receiving Matched Related Donor (MRD) Reduced-Intensity Conditioning Allogeneic Hematopoietic Progenitor Cell Transplant (RIC-AHPCT) Correlates with Major Histocompatibility Complex Class I-Related Molecule A (MICA) Gene Polymorphisms,

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).