Impact of cyclosporine and methylprednisolone dose used for prophylaxis and therapy of graft-versus-host disease on survival and relapse after allogeneic bone marrow transplantation

In order to determine whether doses of cyclosporine and methylprednisolone used for prophylaxis and therapy of acute graft-versus-host disease (GVHD) have any influence on relapse and survival following allogeneic bone marrow transplantation (BMT), we studied 176 adult patients with hematologic mali gnancies, who underwent a first allogeneic transplant from an HLA-identical sibling donor. Two methods of management of acute GVHD used in two differe nt centers were compared: group I included 62 patients who had 'standard' m anagement of GVHD including prophylaxis with 1-3 mg/kg/day of cyclosporine and treatment with 2 mg/kg/day of methylprednisolone when acute GVHD develo ped; group II included 114 patients who received 'intensive' management of GVHD including prophylaxis with 5 mg/kg/day of cyclosporine and treatment w ith high-dose methylprednisolone (8-20 mg/kg/day for 3 days) at the onset o f GVHD, The overall incidence of GVHD was the same in both groups. However, acute GVHD was more severe in group I than in group II (P < 0.0001), with consequently less resolution of GVHD after treatment in group I (61%) than in group LI (80%) (P = 0.06). Overall survival and disease-free survival (D FS) did not differ between the two groups. However, actuarial risk of disea se relapse was significantly higher in group II than in group I (36% vs 17% , P = 0.02). In a multivariate analysis taking into account known factors i nfluencing GVHD and relapse, only type of GVHD management and age were sign ificantly predictive for the occurrence of GVHD, while only type of GVHD ma nagement and pathology other than chronic myeloid leukemia (CML) were predi ctive for relapse, This study demonstrates that intensity of GVHD prophylax is and therapy can influence the graft-versus-leukemia effect by decreasing severity of GVHD but at the price of increasing relapse rate post transpla nt.