Newer approaches to control alloreactivity may produce similar transplant outcomes using HLA-mismatched donors versus HLA-matched unrelated donors. However, prospective comparisons are lacking. BMT CTN 1702 used a donor search prognosis score to assign patients without matched sibling donors, to transplant using an 8/8 HLA-matched unrelated donor (MUD) or the center's preference of haploidentical-related (HAPLO), mismatched unrelated (MMUD), or umbilical cord blood (UCB) donors. Outcomes using MUD were compared to HAPLO, MMUD and UCB while adjusting for relevant covariates. Patients (n=1179) (93% adults) underwent transplantation with a MUD (n=772), HAPLO (n=254), MMUD (n=112) and UCB (n=41) at a median of 3.7, 3.4, 3.9 and 3.8 months from enrollment. Post-transplant cyclophosphamide (PTCy) was used in 23.9%, 83.9%, 65.2% and 0% of MUD, HAPLO, MMUD and UCB HCT. In multivariate analysis, compared to MUD, survival after HCT was significantly lower for patients receiving UCB (HR 2.65, p0.001) but not statistically different for HAPLO and MMUD HCT recipients (HR 1.08 and 1.18). The risk of relapse was not significantly different by donor type, but treatment-related mortality (TRM) (HR 3.31, p0.001) and disease-free survival (DFS) (HR 1.99, p=0.002) were inferior for UCB but not different for HAPLO and MMUD than MUD. In PTCy patients, HAPLO and MMUD were associated with increased grade 3/4 acute GVHD (HR 2.39, p=0.017 and 2.53, p=0.038) and chronic GVHD (HR 1.71 each, p=0.028 and 0.080) than MUD, but other outcomes were not different. HAPLO or MMUD may effectively be used to expedite transplantation when finding MUD is unlikely. NCT03904134
Bashey et al. (Fri,) studied this question.