TACROLIMUS AND METHOTREXATE FOR THE PROPHYLAXIS OF ACUTE GRAFT-VERSUS-HOST DISEASE IN ALLOGENEIC BONE-MARROW TRANSPLANTATION IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES

We conducted a study to evaluate the efficacy of the combination of ta crolimus and short-course methotrexate for the prevention of acute GVH D in patients with hematologic malignancies, Patients received prepara tive regimens specific for their disease category, Twenty-six out of 2 8 received HLA-identical sibling transplants and the two remaining pat ients received one-antigen mismatched transplants from a family member , With a median follow-up of 14 months, the Kaplan-Meier estimate of e vent-free survival was 50 +/- 9%. The probability of grade II-IV GVHD was 15 +/- 7%, Four patients developed GVHD: two had grade II and one each developed grade III and IV GVHD, Administration of methotrexate w as associated with severe mucositis and there was no correlation betwe en the distribution of the GVHD grade and the cumulative dose of metho trexate given, Thirteen patients have died; nine from transplant-relat ed complications and four from relapse. The major toxicity of tacrolim us was renal, Nine out of 28 patients (32%) developed renal dysfunctio n attributed to tacrolimus, The combination of tacrolimus and methotre xate is an effective regimen for GVHD prophylaxis but associated with significant renal and mucosal toxicity, Further studies of tacrolimus as a single agent or in combination with either steroids or with a low er dose of methotrexate or with other antiproliferative drugs to modif y the adverse events may improve the therapeutic index of this useful and promising agent.