P043 HLA-DPB matching and donor cytomegalovirus positive (CMV+) status: An “unconventional alliance” associated with a decreased relapse incidence in unrelated hematopoietic stem cell transplantation (UHSCT)
2017
Aim While the role of HLA-DPB1 (DP) compatibility in uHSCT regarding graft versus host disease (GVHD)- and graft versus leukaemia (GVL)-effects has been extensively discussed, its interaction with donor CMV status (dCMV), remains elusive. The aim of this study was, to investigate the impact of dCMV status in DP matched (DPM) and mismatched (DPMM) uHSCT. Methods 1749 HSCT transplant (Tx) pairs were DP genotyped with an exon 2 amplicon based NGS approach in order to assess their DP matching status. CMV sero-status as well as clinical data were retrieved from the German Stem Cell Registry. Overall survival (OS), relapse incidence (RI) and chronic GvHD (cGvHD) were defined as endpoints, while statistical significance was set to a p Download high-res image (52KB) Download full-size image Results Data analysis revealed a significantly lower 5y RI in DPM dCMV(+) vs. DPM dCMV(−) Tx (34.6% vs 54.5%, p = 0.01). In DPMM cases, dCMV did not appear to positively influence this endpoint. Furthermore, dCMV(+) appeared to benefit DPM vs. DPMM Tx, as lower cGvHD incidence rates were observed in DPM compared to DPMM cases, yet not in a statistically significant manner (36.3% vs. 44.7%, p = 0.38). This beneficial association between dCMV(+) and DP matching did not appear to significantly influence OS. Our study, although not conclusive, is suggestive of a positive interaction between dCMV positivity and patient-donor DP-Match status as to relapse and cGvHD incidence rates. In a DPM setting, dCMV specific allo-reactive T-cells may account for a more pronounced GvL effect, as their T-cell Receptors are programmed to recognize “self”-DP/viral peptide complexes. Accordingly, in a DPMM setting, a CMV-induced upregulation of DP expression on patients’ non HC’s could lead to higher cGvHD rates via DP-specific CD4 + T-cell alloreactivity. Conclusions In conclusion, our study provides information regarding a possible association between donor CMV status and DP matching in patients undergoing HSCT. Larger cohort studies are needed to confirm these initial findings, before further conclusions can be drawn.
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