HLA-C Mismatch without Impact on Outcome after Allogeneic HSCT

In the present retrospective study we analysed 382 patients undergoing HSCT between 1995 and 2011. Of these 115 patients received an HLA-C mm HSCT and 266 received an HLA-C matched graft. Only patients with malignant disease were included in the analysis with no significant differences between patients with HLA-C matched or mm donors. Median age was 42 (<1-68) versus 41 (<1-65) years in the matched and mm groups respectively. Early/late disease was 119/147 and 51/64, respectively (ns). Reduced intensity conditioning was given to 100 patients (38%) among HLA-C matched patients compared to 42 (37%) in the HLA-C mm group. Myeloablative conditioning was similar in both groups. Female donor to male recipient was given to 20 (8%) in the matched group versus 19 (17%) in the mm group. Bone marrow was used as stem cell source in 74 (28%) patients in the HLA-C matched group compared to 45 (39%) in the mm group (ns). The remaining patients received PBSC in each group. Median CD34 cell dose (x106/kg) was 7.2 (0.2-56.4) versus 7.1 (0.3-28.7), respectively. GVHD prophylaxis consisted of CsA + MTX in 84% versus 85% of the patients in each group. ATG was given to all patients before HSCT.

In the present material graft failure (GF) occurred in 9 (3.4%) in HLA-C matched group compared to 7 (6.1%) in the mm group (ns). In multivariate analysis for GF, major AB0 mismatch (p=0.03), RIC (p=0.01) and female donor to male recipient (p=0.002) were significant risk factors. HLA-C mm was not found to be significant (p=0.71). Neither had HLA-C mm any impact on mortality. Significant factors associated to mortality in multivariate analysis were: disease stage (p<0.001), year of HSCT (p=0.015) and donor age (p<0.001). For acute GVHD grades II-IV CsA+MTX (p<0.001) and RIC (p<0.001) decreased the risk whereas the use of PBSC (p=0.016) increased the risk. HLA-C matched patients compared to HLA-C mm showed no statistical difference regarding TRM, RFS, mortality, acute GVHD grades II-IV and relapse incidence. We also analysed MFI for all HLA-C alleles which showed no significant correlation to outcome.

In conclusion, in the present study we find no negative impact of HLA-C mismatch on outcome after HSCT.