FK506 IN COMBINATION WITH METHOTREXATE FOR THE PREVENTION OF GRAFT-VERSUS-HOST DISEASE AFTER MARROW TRANSPLANTATION FROM MATCHED UNRELATED DONORS

The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus -host disease (GVHD) after marrow transplantation from HLA-matched unr elated donors was evaluated in a single-arm Phase II study conducted a t two centers. forty-three patients, 15 to 54 (median 41) years of age , were transplanted for hematologic malignancies. Thirty-seven of 43 e valuable patients had evidence of sustained marrow engraftment. Five p atients died before day 17 after transplantation. The median time to a n absolute neutrophil count of >0.5x10(9)/L was 21 (range, 14 to 30) d ays. Nephrotoxicity (serum creatinine concentration >2 mg/dL or doubli ng of baseline) occurred in 32 patients (74% cumulative incidence duri ng the first 100 days after transplant). Other adverse effects include d hypertension (n=27), hyperglycemia (n=27), neurotoxicity (n=9) and t hrombotic thrombocytopenic purpura (n=2). Severe veno-occlusive diseas e of the liver occurred in 9 (21%) of the 43 patients. Eighteen patien ts (42%) developed grades II to IV acute GVHD and five (12%) developed grades III to IV acute GVHD. Twelve of 25 evaluable patients develope d extensive chronic GVHD within 1 year of marrow transplantation resul ting in an estimate of the probability of developing this complication of 48%. The cumulative incidence of transplant-related mortality duri ng the first 100 days was 37%. Kaplan-Meier estimates of disease-free survival at 2 years for good-risk, poor-risk, and all patients were 65 %, 4%, and 32%, respectively. FK506 in combination with a short course of MTX appears active in preventing acute GVHD after marrow transplan tation from unrelated donors. Further studies comparing the combinatio n of FK506 and MTX with cyclosporine and MTX for the prevention of acu te GVHD are warranted. (C) 1996 by The American Society of Hematology.