Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prophylaxis of acute graft-versus-host disease

N Engl J Med. 1993 Oct 21;329(17):1225-30. doi: 10.1056/NEJM199310213291703.


Background: Acute graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation remains a serious problem. In a clinical trial, we tested the combination of cyclosporine and prednisone with and without methotrexate for the prevention of GVHD.

Methods: One hundred fifty patients with either acute leukemia in first complete remission, chronic myelogenous leukemia in first chronic phase, or lymphoblastic lymphoma in first complete remission were enrolled in the study. All the patients were given fractionated total-body irradiation (1320 cGy) and etoposide (60 mg per kilogram of body weight) in preparation for transplantation, and received bone marrow from genotypically histocompatible donors. To prevent GVHD, they were randomly assigned to prophylactic treatment with either cyclosporine, methotrexate, and prednisone or cyclosporine and prednisone without methotrexate. All the patients received standardized supportive care after transplantation, including intravenous gamma globulin.

Results: Patients receiving cyclosporine, methotrexate, and prednisone had a significantly lower incidence of acute GVHD of grades II to IV (9 percent) than those receiving cyclosporine and prednisone (23 percent, P = 0.02). Multivariate regression analysis demonstrated that an increased risk of acute GVHD was associated with an elevated serum creatinine concentration (P = 0.006) and treatment with cyclosporine and prednisone alone (P = 0.02). The lower incidence of acute GVHD was not associated with a higher rate of relapse of leukemia or lymphoma. There was no significant difference in disease-free survival at three years between the two treatment groups (64 percent with the three-drug regimen vs. 59 percent with the two-drug regimen, P = 0.57).

Conclusions: The combination of cyclosporine, methotrexate, and prednisone was more effective in preventing acute GVHD of grades II to IV than was the combination of cyclosporine and prednisone without methotrexate.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chi-Square Distribution
  • Child
  • Child, Preschool
  • Chronic Disease
  • Cyclosporine / therapeutic use
  • Drug Administration Schedule
  • Female
  • Graft vs Host Disease / prevention & control*
  • Humans
  • Infant
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Prednisone / therapeutic use
  • Recurrence
  • Regression Analysis
  • Treatment Outcome


  • Cyclosporine
  • Prednisone
  • Methotrexate