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Clinical Trial
. 2017 Dec;102(12):2125-2133.
doi: 10.3324/haematol.2017.171157. Epub 2017 Sep 29.

Steroid treatment of acute graft- versus-host disease grade I: a randomized trial

Andrea Bacigalupo  1 , Giuseppe Milone  2 , Alessandra Cupri  2 , Antonio Severino  3 , Franca Fagioli  4 , Massimo Berger  4 , Stella Santarone  5 , Patrizia Chiusolo  6 , Simona Sica  6 , Sonia Mammoliti  7 , Roberto Sorasio  8 , Daniela Massi  9 , Maria Teresa Van Lint  10 , Anna Maria Raiola  10 , Francesca Gualandi  10 , Carmine Selleri  11 , Maria Pia Sormani  12 , Alessio Signori  12 , Antonio Risitano  13 , Francesca Bonifazi  14 ; Gruppo Italiano Trapianto di Midollo Osseo (GITMO)
Affiliations
Clinical Trial

Steroid treatment of acute graft- versus-host disease grade I: a randomized trial

Andrea Bacigalupo et al. Haematologica. 2017 Dec.

Abstract

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 grade II-IV GvHD was 50% in the observation arm 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 9%). In multivariate analysis, an early interval between transplant and randomization (<day +20) was the only negative predictor of grade III-IV GvHD. 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 five years, non-relapse mortality was 20% versus 26% (P=0.2), relapse-related mortality 25% versus 21%, and actuarial survival was 51% versus 41% (P=0.3) in the observation and treatment arms, respectively. 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, steroid treatment of acute grade I GvHD 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 developing infections and have more adverse events. (Trial registered as EUDTRACT 2008-000413-29).

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Figures

Figure 1.
Figure 1.
Study outline. Patients randomized to the observation (n=85) or treatment (n=86) arms all went forward for analysis. Two patients were not evaluable because essential data were missing (1 observation arm; 1 treatment arm). 6MPred: 6 mthylprednisolone; FU: follow up.
Figure 2.
Figure 2.
Cumulative incidence of grade II–IV acute graft-versus-host disease (GvHD) in patients allocated to no treatment (observation) or treatment with prednisolone 1 mg/kg (treatment).
Figure 3.
Figure 3.
Cumulative incidence of grade III–IV acute graft-versus-host disease (GvHD) in patients allocated to no treatment (observation) or treatment with prednisolone 1 mg/kg (treatment).
Figure 4.
Figure 4.
Comparable cumulative incidence of non-relapse mortality (NRM) in the two randomization groups.
Figure 5.
Figure 5.
Comparable cumulative incidence of relapse-related death (RRD) in the two randomization groups.
Figure 6.
Figure 6.
Comparable 5-year overall survival (OS) in the two randomization groups.
See this image and copyright information in PMC

References

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