Chronic graft vs. host disease following post-transplant cyclophosphamide (PTCy) based prophylaxis vs. non-PTCy...

Chronic GVHD is less frequent after post-transplant cyclophosphamide (PTCy)-based prophylaxis, but its clinical characteristics and outcomes compared with chronic GVHD following non-PTCy approaches remain understudied. We addressed this through a single-center retrospective study of 1,534 consecutive adult transplants (PTCy: n = 477; non-PTCy: n = 1,057) using matched related or matched/mismatched unrelated donors. The cumulative incidence of NIH moderate/severe chronic GVHD was significantly lower after PTCy (17% v 46%; P < .001). Among chronic GVHD-affected patients (PTCy: n = 163; non-PTCy: n = 656), chronic GVHD after PTCy involved fewer organ sites, had lower severity scores, and less NIH moderate/severe disease overall. However, this profile did not translate into improved survival. Univariate analysis demonstrated higher non-relapse mortality (24-month NRM: 22% v 13%; P = .014) for the PTCy group, while on multivariate analysis 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 following chronic GVHD diagnosis was comparable to that observed after non‑PTCy prophylaxis approaches. Multicenter validation of these findings and novel strategies to mitigate non-relapse mortality in chronic GVHD are warranted.