The T-Cell Epitope (TCE) Algorithm for Classifying HLA-DPB1 Mismatches Does Not Predict Clinical Outcomes in HSCT

A number of reports suggested the relevance of HLA-DPB1 matching for the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). An algorithm for determining DPB1 mismatch permissiveness based on T-Cell Epitopes (TCE) has been proposed (Zino et al, Blood 2004). According to this algorithm, all DPB1 alleles are categorized in 3 (TCE3) or 4 (TCE4) groups based on antigenicity. Accordingly DPB1 mismatches are classified as permissive; non-permissive in GvHD; or non-permissive in HvG direction.ObjectiveTo determine whether TCE classification is associated with HSCT outcomes. The outcomes considered in this analysis are failure to engraft, acute GvHD, chronic GvHD, and overall survival.MethodsWe analyzed 144 unrelated donor (≥ 7/8 allele matches at A, B, C, DRB1) allogeneic transplants performed in our center between 1999-2009. HLA-DPB1 mismatches were assessed using both TCE3 and TCE4 versions of the algorithm. Recursive partitioning analysis with a log-rank splitting method was used to categorize TCE variables into groups that best predict each outcome. Cox proportional hazards analysis was used to identify prognostic factors for each outcome.ResultsGraft failure was significantly highest among recipient with permissive DPB1 mismatches (AHR 9.87, 95% CI 1.21-80.3, P = 0.03) compared to recipients of zero mismatched, GvHD non-permissive, and HvG nonpermissive DPB1 mismatched donors. Acute GvHD was significantly higher in all DPB1 mismatches regardless of TCE classification (AHR 1.93, 95% CI 1.11-3.34, P = 0.02) compared zero DPB1 mismatch. There was no significant association between TCE classification and chronic GvHD, or overall survival.ConclusionOur results indicate an increased risk of acute GvHD in association with DPB1 mismatch regardless of the TCE classification. TCE classification did not correlate with any transplant outcome considered in our cohort. This analysis does not support the clinical relevance of ranking DPB1 mismatches based on the TCE algorithm. A number of reports suggested the relevance of HLA-DPB1 matching for the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). An algorithm for determining DPB1 mismatch permissiveness based on T-Cell Epitopes (TCE) has been proposed (Zino et al, Blood 2004). According to this algorithm, all DPB1 alleles are categorized in 3 (TCE3) or 4 (TCE4) groups based on antigenicity. Accordingly DPB1 mismatches are classified as permissive; non-permissive in GvHD; or non-permissive in HvG direction. ObjectiveTo determine whether TCE classification is associated with HSCT outcomes. The outcomes considered in this analysis are failure to engraft, acute GvHD, chronic GvHD, and overall survival. To determine whether TCE classification is associated with HSCT outcomes. The outcomes considered in this analysis are failure to engraft, acute GvHD, chronic GvHD, and overall survival. MethodsWe analyzed 144 unrelated donor (≥ 7/8 allele matches at A, B, C, DRB1) allogeneic transplants performed in our center between 1999-2009. HLA-DPB1 mismatches were assessed using both TCE3 and TCE4 versions of the algorithm. Recursive partitioning analysis with a log-rank splitting method was used to categorize TCE variables into groups that best predict each outcome. Cox proportional hazards analysis was used to identify prognostic factors for each outcome. We analyzed 144 unrelated donor (≥ 7/8 allele matches at A, B, C, DRB1) allogeneic transplants performed in our center between 1999-2009. HLA-DPB1 mismatches were assessed using both TCE3 and TCE4 versions of the algorithm. Recursive partitioning analysis with a log-rank splitting method was used to categorize TCE variables into groups that best predict each outcome. Cox proportional hazards analysis was used to identify prognostic factors for each outcome. ResultsGraft failure was significantly highest among recipient with permissive DPB1 mismatches (AHR 9.87, 95% CI 1.21-80.3, P = 0.03) compared to recipients of zero mismatched, GvHD non-permissive, and HvG nonpermissive DPB1 mismatched donors. Acute GvHD was significantly higher in all DPB1 mismatches regardless of TCE classification (AHR 1.93, 95% CI 1.11-3.34, P = 0.02) compared zero DPB1 mismatch. There was no significant association between TCE classification and chronic GvHD, or overall survival. Graft failure was significantly highest among recipient with permissive DPB1 mismatches (AHR 9.87, 95% CI 1.21-80.3, P = 0.03) compared to recipients of zero mismatched, GvHD non-permissive, and HvG nonpermissive DPB1 mismatched donors. Acute GvHD was significantly higher in all DPB1 mismatches regardless of TCE classification (AHR 1.93, 95% CI 1.11-3.34, P = 0.02) compared zero DPB1 mismatch. There was no significant association between TCE classification and chronic GvHD, or overall survival. ConclusionOur results indicate an increased risk of acute GvHD in association with DPB1 mismatch regardless of the TCE classification. TCE classification did not correlate with any transplant outcome considered in our cohort. This analysis does not support the clinical relevance of ranking DPB1 mismatches based on the TCE algorithm. Our results indicate an increased risk of acute GvHD in association with DPB1 mismatch regardless of the TCE classification. TCE classification did not correlate with any transplant outcome considered in our cohort. This analysis does not support the clinical relevance of ranking DPB1 mismatches based on the TCE algorithm.