HLA-haploidentical vs matched unrelated donor transplants with posttransplant cyclophosphamide-based prophylaxis

Abstract

Posttransplant cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis has enabled haploidentical (Haplo) transplantation to be performed with results similar to those after matched unrelated donor (MUD) transplantation with traditional prophylaxis. The relative value of transplantation with MUD vs Haplo donors when both groups receive PTCy/calcineurin inhibitor/mycophenolate GVHD prophylaxis is not known. We compared outcomes after 2036 Haplo and 284 MUD transplantations with PTCy GVHD prophylaxis for acute leukemia or myelodysplastic syndrome in adults from 2011 through 2018. Cox regression models were built to compare outcomes between donor types. Recipients of myeloablative and reduced-intensity regimens were analyzed separately. Among recipients of reduced-intensity regimens, 2-year graft failure (3% vs 11%), acute grades 2 to 4 GVHD (hazards ratio [HR], 0.70; P = .022), acute grades 3 and 4 GVHD (HR, 0.41; P = .016), and nonrelapse mortality (HR, 0.43; P = .0008) were lower after MUD than with Haplo donor transplantation. Consequently, disease-free (HR, 0.74; P = .008; 55% vs 41%) and overall (HR, 0.65; P = .001; 67% vs 54%) survival were higher with MUD than with Haplo transplants. Among recipients of myeloablative regimens, day-100 platelet recovery (95% vs 88%) was higher and grades 3 and 4 acute (HR, 0.39; P = .07) and chronic GVHD (HR, 0.66; P = .05) were lower after MUD than with Haplo donor transplantation. There were no differences in graft failure, relapse, nonrelapse mortality, and disease-free and overall survival between donor types with myeloablative conditioning regimens. These data extend and confirm the importance of donor-recipient HLA matching for allogeneic transplantation. A MUD is the preferred donor, especially for transplantations with reduced-intensity conditioning regimens.

Graphical abstract

Figure 1.

Reduced-intensity regimens: incidence of nonrelapse mortality, relapse, and disease-free and overall survival. (A) Relapse. The 2-year cumulative incidence of relapse was 42% (95% CI, 39-45) for Haplo relative donor (a) and 37% (95% CI, 30-45) for MUD (b) transplants. (B) Nonrelapse mortality. The 2-year cumulative incidence of nonrelapse mortality was 16% (95% CI, 14-19) for Haplo relative donor (a) and 8% (95% CI, 5-13) for MUD (b) transplants. (C) Overall survival. The 2-year probability of overall survival was 54% (95% CI, 51-57) for Haplo relative donor (a) and 67% (95% CI, 60-74) for MUD (b) transplants. (D) Disease-free survival. The 2-year probability of disease-free survival was 41% (95% CI, 38-45) for Haplo relative donor (a) and 55% (95% CI, 47-62) for MUD (b) transplants.

Figure 2.

Myeloablative regimens: incidence of nonrelapse mortality, relapse, and disease-free and overall survival. (A) Relapse. The 1-year cumulative incidence of relapse was 19% (95% CI, 17-22) for Haplo relative donor (a) and 21% (95% CI, 23-41) for MUD (b) transplants. (B) Nonrelapse mortality. The 1-year cumulative incidence of nonrelapse mortality was 15% (95% CI, 13-18) for Haplo relative donor (a) and 15% (95% CI, 8-23) for MUD (b) transplants. (C) Overall survival. The 1-year probability of overall survival was 75% (95% CI, 72-78) for Haplo relative donor (a) and 77% (95% CI, 68-85) for MUD (b) transplants. (D) Disease-free survival. The 1-year probability of disease-free survival was 66% (95% CI, 62-69) for Haplo relative donor (a) and 65% (95% CI, 54-74) for MUD (b) transplants.