Chronic graft-versus-host disease after PTCy-based prophylaxis vs non-PTCy prophylaxis

Abstract Chronic graft-versus-host disease (GVHD) is less frequent after posttransplant cyclophosphamide (PTCy)–based prophylaxis, but its clinical characteristics and outcomes compared with chronic GVHD after non-PTCy approaches remain understudied. We addressed this through a single-center retrospective study of 1534 consecutive adult transplant recipients (PTCy, n = 477; non-PTCy, n = 1057) who received grafts from matched related or matched/mismatched unrelated donors. The cumulative incidence of National Institutes of Health (NIH) moderate/severe chronic GVHD was significantly lower after PTCy (17% vs 46%; P< .001). Among patients with chronic GVHD (PTCy, n = 163; non-PTCy, n = 656), chronic GVHD after PTCy involved fewer organ sites, had lower severity scores, and had less NIH moderate/severe disease overall. However, this profile did not translate into improved survival. Univariate analysis demonstrated higher nonrelapse mortality (NRM; 24-month NRM, 22% vs 13%; P = .014) for the PTCy group, whereas multivariate analysis showed that NRM was associated with increased age, NIH overall moderate/severe chronic GVHD severity, prior grade III/IV acute GVHD, reduced platelet count, and increased bilirubin. Chronic GVHD after PTCy was associated with increased infectious complications despite reduced immunosuppressive (IS) therapy and higher rates of complete IS discontinuation. Overall, PTCy-based prophylaxis was associated with a lower incidence and severity of chronic GVHD, and after adjustment for established prognostic factors, mortality after chronic GVHD diagnosis was comparable to that observed with non-PTCy prophylaxis approaches. Multicenter validation of these findings and novel strategies to mitigate NRM in chronic GVHD are warranted.