A randomized trial comparing prednisone with antithymocyte globulin/prednisone as an initial systemic therapy for moderately severe acute graft-versus-host disease

Glucocorticoids remain the standard approach to initial systemic management of acute graft-versus-host disease (aGVHD). For patients refractory to ste roids, antithymocyte globulin (ATG) is frequently used as salvage therapy. We decided to test whether the combination of corticosteroids and equine AT G would improve the outcome of initial management of aGVHD, especially in h igh-risk patients such as recipients of unrelated donor (URD) transplants. One hundred patients with grade II. to TV aGVHD having undergone a related or URD marrow transplant were enrolled in the study. Of the patients, 46 we re randomly assigned to therapy with prednisone (60 mg/m(2) per day x 7 day s) and 50 received ATG/prednisone (15 mg/kg ATG bid plus 20 mg/m(2) prednis one bid x 5 days, each followed by an 8-week prednisone taper). An intent-t o-treat analysis of the overall response at day 42 revealed equivalent comp lete plus partial response rates of 76% in both the prednisone and ATG/pred nisone therapy groups (P > .80). In univariate analysis, patient age, donor type, site of involvement, or aGVHD stage did not influence overall respon se to therapy (all P > .2). When treatment arms were studied separately, no single clinical feature predicted outcome in either group. Complications w ere more frequent in the ATG/prednisone arm; patients experienced more infe ctions with cytomegalovirus (44% versus 22%; P = .02) and more frequent pne umonitis, both infectious and noninfectious (50% versus 24%; P < .01). Epst ein-Barr virus lymphoproliferative disease was uncommon (4 cases) and compa rable in both arms (P = .35). There was no significant difference in surviv al at day 100, 6 months, and 2 years between the 2 treatment arms. The more intensive immunosuppressive combination of ATG/prednisone failed to improv e control of aGVHD and may have affected survival by causing more infectiou s complications. Combination therapy with ATG should thus be reserved as se cond-line therapy in the management of aGVHD.