Superior Outcomes with Matched Unrelated Donors Compared with One Human Leukocyte Antigen Mismatched Related Donors In Allogeneic Hematopoietic Stem Cell Transplantation

Abstract 907 Most candidates for hematopoietic stem cell transplantation lack a human leukocyte antigen (HLA)-identical sibling donor; however, many patients may have a related donor with whom they are mismatched at one antigen/allele. It is not known whether such a match is preferable to a matched unrelated donor (MUD). We hypothesized that, in transplantation using related donors, adding a single HLA antigen/allele mismatch, identified through high resolution HLA typing at HLA-A, -B, -C, -DRB1 and -DQB1, would be associated with worse outcomes than transplantation using matched unrelated donors. Patients and Methods: To test this hypothesis, we analyzed outcomes (survival, relapse, non-relapse mortality) of 367 patients who received transplants from either a 10/10 MUD (n=318) or a one-antigen/allele mismatched related donor (MRD) by 7/8 HLA typing (n=49) treated during the same period of time (1995-2009) at our institution. All patients had intermediate/high-resolution HLA typing at all 5 loci either prospectively or retrospectively, if treated after or before year 2002. Of the 49 patients treated with mismatched related donors, 28 patients (57%) had one antigen/allele mismatched at HLA class I or II loci (or 9/10), 18 patients (37%) had 2 alleles mismatched (or 8/10), and 3 patients (6%) had 3 alleles mismatched (or 7/10). From the 28 patients with a one-allele mismatch, 24 had class I mismatches at either HLA-A or -B loci, and 4 had class II mismatches at either HLA-DR or -DQ loci. Characteristics between the MUD group and 9/10 MRD group were similar [median age 53 vs. 47 years (p=0.08); AML/MDS diagnosis 84% vs. 82% (p=0.5); active disease at transplant 59% vs. 57% (p=0.9); myeloablatie conditioning 63% vs. 75% (p=0.2); bone marrow stem cells 58% vs. 70% (p=0.2); pentostatin use 14% vs. 11% (p=0.4); median year of transplant 2006 vs. 2004, respectively] except more patients in the MUD group received ATG (96% vs. 68%, p=0.02). Results: Outcomes at 3-years were analyzed for the 28 consecutive patients who had received a transplant from a 9/10 MRD based on 5-loci (including -DQB1) HLA typing. Graft failure was more common in patients treated from 9/10 related donors than from MUD. The incidences of primary and secondary graft failure for the 9/10 MRD were 7% and 14%, respectively, whereas none of the MUD transplant recipients had either primary or secondary graft failure (p= 0.02). Cumulative incidence of progression was 40% vs. 25% (p=0.02, HR 1.9, CI 1.1–3.9), non-relapse mortality 40% vs. 26% (p=0.05, HR 1.9, CI 1.0–3.6) and grade II-IV a GVHD was 27% vs. 38% (p=0.4, HR 0.7, CI 0.3–2.5) for the two groups, respectively. Median survival was 6 months for the 9/10 MRD vs. 18 months for the MUD group. The overall survival and progression-free survival rates were 19% and 45% (p=0.007, HR 1.8, CI 1.2–2.9) and 19% vs. 42% (p=0.006, HR1.8, CI 1.2–2.9), respectively. Outcomes for 9/10 MRD transplant patients with class I mismatches (n=24) were significantly worse than outcomes in those with MUD transplants (n=318). The 2-year actuarial OS rate was 27% for the 9/10 MRD and 48% for the MUD transplant group (HR 1.9; 95% CI 1.1 – 3.1; p=0.01). Conclusion: These results indicate that transplant outcomes for patients treated from a one-antigen/allele mismatch related donor are significantly worse than from a MUD, primarily due to increased non-relapse mortality. Patients receiving transplants form a 9/10 related donors, at least with a class I mismatch, should be treated on investigational protocols. Disclosures: No relevant conflicts of interest to declare.