ALBERT

Description: Abstract 3050 Approximately 30% of Caucasian and 70% of African-American hematopoietic stem cell transplant (HCT) patients are unable to find an 8/8 HLA matched unrelated donor. Mismatches at HLA-A, B, C, or DRB1 alleles reduce survival. Therefore, identification and avoidance of high-risk allele combinations and the associated amino acid substitutions (AAS) that negatively impact HCT outcomes may increase access to this treatment option and allow safer utilization of HLA mismatched donors. Using random forest (RF) analysis, our group has previously reported the AAS associated with 100 day survival (D100S) in single HLA class I mismatched, DRB1 matched recipient-donor pairs. We now extend that analysis to one year outcomes of overall survival (1y OS), disease free survival (1y DFS), transplant related mortality (1y TRM), and acute graft-versus-host disease (aGvHD) grades III-IV using the same clinical variables (recipient age, disease type, disease status, and gender match) and 389 AAS position and types (AASPT). The AASPT were defined by the HLA locus, amino acid position in the HLA class I protein and the actual AAS, e.g. locus: HLA-C, position: 97, type: tryptophan to arginine = C97_WR. Patients (n=2107) received myeloablative (99%) HCT as treatment for ALL, AML, CML, and MDS in early and intermediate stage of disease between 1988 and 2003. RF analysis, a tree-based method for classification was used to assign an importance score (IS), reflecting the association of each potential predictor variable with the outcome of interest. Logistic regression analyses were performed to determine the magnitude of the effect of each individual AASPT (n=600) relative to 8/8 matched cases (n=1507), adjusted for the four clinical variables. Using the criteria of n≥10, a relatively high IS (≥5) and a highly statistically significant odds ratio (p