Initial therapy of acute graft-versus-host disease with low-dose prednisone does not compromise patient outcomes

Abstract

We hypothesized that initial treatment of acute graft-versus-host disease (GVHD) with low-dose glucocorticoids (prednisone-equivalent dose of 1 mg/kg per day) instead of standard-dose glucocorticoids (prednisone-equivalent dose of 2 mg/kg per day) does not compromise major transplantation outcomes. We retrospectively analyzed outcomes among 733 patients who received transplants between 2000 and 2005 according to initial treatment with low-dose (n=347) versus standard-dose (n=386) systemic glucocorticoids. The mean cumulative prednisone-equivalent doses at day 100 after starting treatment were 44 and 87 mg/kg for patients given low-dose and standard-dose glucocorticoids, respectively. Adjusted outcomes between the groups given low-dose versus standard-dose glucocorticoids were not statistically significantly different: overall mortality (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.9-1.4), relapse (HR, 1.22; 95% CI, 0.9-1.7), nonrelapse mortality (HR, 1.06; 95% CI, 0.8-1.5). The small number of patients with grades III/IV acute GVHD at onset precluded definitive conclusions for this subgroup. In multivariate analysis, the risks of invasive fungal infections (HR, 0.59; 95% CI, 0.3-1.0) and the duration of hospitalization (odds ratio, 0.62; 95% CI, 0.4-0.9) were reduced in the low-dose prednisone group. We conclude that initial treatment with low-dose glucocorticoids for patients with grades I-II GVHD did not compromise disease control or mortality and was associated with decreased toxicity.

Figure 1

Cumulative use of glucocorticoids among patients given either low-dose glucocorticoids (prednisone-equivalent dose of 1 mg/kg per day; dashed line) or standard-dose glucocorticoids (prednisone-equivalent dose 2 mg/kg per day; solid line) for initial treatment of acute GVHD. In this analysis, follow-up was censored when patients returned to the care of the referring physicians.

Figure 2

Major transplantation outcomes for patients with acute GVHD given either low-dose glucocorticoids (prednisone-equivalent dose of 1 mg/kg per day; dashed line) or standard-dose glucocorticoids (prednisone-equivalent dose of 2 mg/kg per day; solid line) for initial treatment of acute GVHD. Cumulative incidence of NRM (A) and recurrent malignancy (B), and Kaplan-Meier estimates of overall survival (C).

Figure 3

Cumulative incidence of secondary therapy among patients with acute GVHD initially given either low-dose glucocorticoids (prednisone-equivalent dose of 1 mg/kg per day) or standard-dose glucocorticoids (prednisone-equivalent dose of 2 mg/kg per day). (Left panel) Nonglucocorticoid secondary therapy. (Right panel) Increased glucocorticoid dose or nonglucocorticoid secondary therapy.

Figure 4

Cumulative incidence of invasive fungal infections among patients given either low-dose glucocorticoids (prednisone-equivalent dose of 1 mg/kg per day; dashed line) or standard-dose glucocorticoids (prednisone-equivalent dose of 2 mg/kg per day; solid line) for initial treatment of acute GVHD.