Relationship of donor age and relationship to outcomes of haploidentical transplantation with posttransplant cyclophosphamide

Abstract

Abstract Allogeneic blood or marrow transplantation (BMT) physicians seek to optimize all possible variables to improve outcomes. Selectable factors include conditioning, graft-versus-host disease (GVHD) prophylaxis, graft source, and donor. Many patients, especially those with eligible haploidentical (haplo) donors, will have multiple donor options. We seek to identify factors to optimize the choice of haplo donors when using posttransplantation cyclophosphamide (PTCy) GVHD prophylaxis. We evaluated the effect of modifiable donor characteristics (donor age and relationship) on outcomes following haplo BMT with a uniform nonmyeloablative conditioning and PTCy. From 2002 to 2017, 889 consecutive adult patients underwent nonmyeloablative haplo BMT with PTCy. Median follow-up among survivors was 2.5 years after BMT. Median recipient age was 59 (range: 18 to 76) years and median donor age was 40 (range: 13 to 79) years. Multivariable analyses demonstrated that increasing donor age by decade was associated with poorer overall survival (hazard ratio [HR], 1.13 [1.05, 1.22; P = .0015]), worse progression-free survival (HR, 1.09 [1.02, 1.16; P = .015]), and a higher risk for grade 2 to 4 and grade 3 to 4 GVHD (1.3 [1.06, 1.61; P = .013]), but not for chronic GVHD (HR, 1.06 [0.94, 1.2]; P = .37). These less-favorable results with older donors were attributable to worse nonrelapse mortality (HR, 1.19 [1.05, 1.34]; P = .006), not relapse. Parents were associated with inferior outcomes compared with sibling donors, whereas no significant differences were observed between parental donors. These data suggest that the youngest, adult-sized donors should be preferred when multiple haplo donors are available.