P042 Impact of minor HLA allelic mismatches on outcomes of hematopoietic cell transplants

Abstract

Aim The risk of graft failure or graft-versus-host disease (GvHD) after Hematopoietic cell transplantation (HCT) strictly depends the degree of matching of histocompatibility antigens between the donor and recipient. In some cases due to rare HLA alleles or clinical emergency, it is difficult or even impossible to find a perfectly matched donor. HLA minor (allelic) mismatched (MM) donors (for example, B∗35:02 vs B∗35:05) have been shown to be an option for such patients. The goal of this study was to retrospectively analyze how class I minor MM HLA affect HCT outcomes. Methods The study population included 18 adult patients with a variety of hematological diseases who underwent HCT from 2001 through 2011 using unrelated donors with MM at class I HLA region. The control group included 55 patients transplanted within the same period of time who received 10/10 (HLA-A, -B, -C, -DR, -DQB1) matched HCTs. The groups were matched according to sex, age, diagnosis and pre-transplant protocol. High resolution HLA typing was performed using sequence based typing. The variables tested included total number of amino acid substitutions (AAS), locations of the AAS ( α helix or β strand), affected pockets (A, B, C, D, E, F), TCR or peptide binding sites, and dissimilarity score (DSS). These parameters were estimated using the HISTOCHECK computer algorithm. Statistical analysis comparing HLA matching parameters with the incidence of acute (a) and chronic (c) GvHD was done by ANOVA. Results All donor-recipient combinations were allele matched for DRB1 and DQB1 loci. Allelic MM transplants with a non-myeloablative preparative regimen was associated with a higher incidence of cGvHD (p = 0.009) Allelic MM at any class I locus was associated with increased risk of grade III-IV aGvHD (p = 0.0425). Variables predictive of any grade aGvHD were AAS in any HLA pocket but C (p Conclusions AAS in peptide binding pockets in the setting of HLA class I MM donor-recipient combinations are at higher risk for GvHD and as such provide additional insight into donor search strategies.