OR26. Investigating the impact of patient’s non-shared HLA-C Allotype expression levels in A 9/10 Single HLA-C mismatched hematopoieticstem cell transplantationsetting using two different HLA-C Expression proxy models

Abstract

Aim Petersdorf et al. reported in 2014 an association between patient high expressed HLA-C (C) allotypes and inferior HSCT outcome using an imputed C-expression model (Apps et al., 2013). This study aims at: a) examining the validity of Apps et al. model in Caucasians by using the same methodology in a sample of 400 healthy German blood donors. b) specifically investigating the effect of patient’s non-shared (PNS) C expression levels on outcome by applying C expression imputed data in a 9/10 HLA C-mismatched HSCT setting. Methods Buffy coats from 400 healthy German blood donors were tested by flow cytometry as previously described (Apps et al., 2013) in order to determine C expression on lymphocytes. With reference to the mean fluorescence intensity (MFI) values measured, C antigens were categorized as high- or low- expressed. In a cohort of 324 single C-mismatched transplant pairs both C expression models were used in order to investigate the impact of high- and low-expressed PNS-C on HSCT outcome. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as outcome endpoints, while statistical significance was set at p 0.05. Results With the exception of HLA-C*15, the two expression models were fully concordant as to the definition of low- and high-expressed C antigens. Analysis of PNS-C expression’s effect on HSCT outcome revealed an unexpected correlation between high expression and better OS (49% vs 33% p = 0.04; HR = 0.43, p = 0.002) due to lower NRM (37% vs 47%, p = 0.02; HR = 0.29, p 0.001). Although similar trends were observed, statistical significance was only met with the Apps et al. model. Death cause analysis revealed a tendency for lower infection-related mortality in the high expressed PNS-C (10% vs 14%), while no differences were observed for GvHD-associated death. Interestingly, overall patient’s C expression had no influence on any outcome endpoint. Conclusions a) HLA-C antigens exhibit similar expression patterns regardless of race. b) The lower OS observed in lower expressed PNS C mismatches may be attributed to inferior infection control and thus higher NRM. Albeit noteworthy, these findings must be confirmed by larger independent cohorts, before definitive conclusions can be drawn.