Fagioli, Sorasio, Santarone, Fagioli, Gualandi, Mammoliti, van Lint, Sica, Sica, Sorasio, Milone, Sormani, Gualandi, Milone, Chiusolo, Risitano, Selleri, Massi, Bacigalupo, Santarone, Selleri, Bonifazi, Crupi, Mammoliti, Chiusolo, Sormani, Severino, Raiola, Berger, Raiola, Massi, Bonifazi, Risitano, Bacigalupo, Severino, Signori
Patients with acute graft versus host disease (GvHD) grade I, were randomized, to an observation arm (n=85) or to a treatment arm (n=86), consisting of 6-methylprednisolone 1 mg/kg/day , after stratification for age and donor type. The primary end point was development of grade II-IV GvHD. The cumulative incidence of GvHD grade II-IV, was 50% in the observation and 33% in the treatment arm (p=0.005). However, grade III-IV GvHD was comparable (13% vs 10% respectively; p=0.6), and this was true for sibling and alternative donor transplants. Moderate/severe chronic GvHD was also comparable (17% vs 19%). In multivariate analysis, an early interval between transplant and randomization (< day +20) , was the only negative predictor of GvHD grade III-IV .Patients in the observation arm had less infectious bacterial episodes (12 vs 25, p=0.04), less severe infectious fungal episodes (0 vs 3; p=0.04), and less severe adverse events (3 vs 11 p=0.07). At 5 years, non relapse mortality was 20% (observation) vs 26% (treatment) (p=0.2), relapse related death 25% vs 21%, and actuarial survival was 51% vs 41% respectively (p=0.3). In multivariate analysis, advanced disease phase, older age and an early onset of GvHD, were significant negative predictors of survival, independent of the randomization arm. In conclusion, steroids treatment of acute GvHD grade I prevents progression to grade II but not to grade III-IV GvHD, and there is no effect on non relapse mortality and survival; patients treated with steroids, are at a higher risk of develping infections and have more adverse events. (This trial is registered as EUDTRACT 2008-000413-29).