The Impact of Isolated HLA-DQB1 Mismatch and Donor Age in Unrelated Donor Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide.

In unrelated donor hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (PTCy), the clinical relevance and interplay between an isolated HLA-DQB1 mismatch and donor age remain unclear. We conducted a single-center retrospective analysis of 988 consecutive patients with hematologic malignancies undergoing a first unrelated donor HCT with PTCy prophylaxis between 2017 and 2024. We compared outcomes among recipients of 10/10 matched unrelated donors (MUD) (10/10-MUD; n = 854), 8/8 MUD with an isolated HLA-DQB1 mismatch (n = 47), and 7/8 mismatched unrelated donors (7/8-MMUD, n = 87). Multivariable analyses were performed using Cox proportional hazards models for cause-specific hazards for outcomes with competing risks. Outcomes included overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), relapse, and acute and chronic graft-versus-host disease (GVHD), adjusting for relevant covariates. In multivariable analysis, there was no statistically significant difference in OS, PFS, NRM, or relapse between the three donor groups. Compared to the 10/10 MUD group, the adjusted hazard ratio (HR) for OS was 1.10 (95% CI, 0.75 to 1.61, P = .64) in the 7/8-MMUD group and 0.84 (95% CI, 0.48 to 1.48, P = .55) in the DQB1 mismatch group. Similarly, for NRM (P = .69), adjusted HRs were 1.24 (95% CI, 0.73 to 2.11) for 7/8-MMUD and 0.92 (95% CI, 0.45 to 1.89) for DQB1 mismatch. For relapse (P = .46), HRs were 0.79 (95% CI, 0.46 to 1.34) and 0.72 (95% CI, 0.34 to 1.53), respectively. Chronic GVHD risk was not significantly different (P = .21), with HRs of 1.53 (95% CI, 0.85 to 2.76) for 7/8-MMUD and 0.61 (95% CI, 0.23 to 1.64) for DQB1 mismatch. Acute GVHD risks, however, differed. The 7/8-MMUD group had a significantly higher risk of grade III to IV acute GVHD (HR = 2.91; 95% CI, 1.43 to 5.92; P = .003), whereas the DQB1 mismatch group had an increased risk of grade II to IV acute GVHD (HR = 1.63; 95% CI, 0.98 to 2.71; P = .062), though this did not reach statistical significance. Donor age, analyzed as a continuous variable, was not a significant predictor of OS, PFS, NRM, relapse, grade III to IV acute GVHD, or chronic GVHD but was associated with an increased risk of grade II to IV acute GVHD (HR = 1.02 per year; 95% CI, 1.00 to 1.03; P = .011). In this single-center study, we found no significant survival detriment associated with an isolated HLA-DQB1 mismatch, a 7/8 mismatch, or increased donor age in the PTCy setting. While a 7/8 mismatch was a significant risk factor for severe acute GVHD, and older donor age for grade II to IV acute GVHD, the impact of a DQB1 mismatch on GVHD remains uncertain. These preliminary data suggest that PTCy may mitigate the historical risks of these donor characteristics, though validation in larger cohorts is essential.