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FK506 in combination with methotrexate for the prevention of graft-
versus-host disease after marrow transplantation from matched unrelated
donors
RA Nash, LA Pineiro, R Storb, HJ Deeg, WE Fitzsimmons, T Furlong, JA Hansen, T Gooley, RM Maher, P Martin, PA McSweeney, KM Sullivan, C Anasetti and JW Fay
Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
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 unrelated
donors was evaluated in a single-arm Phase II study conducted at two
centers. Forty-three patients, 15 to 54 (median 41) years of age, were
transplanted for hematologic malignancies. Thirty-seven of 43 evaluable
patients had evidence of sustained marrow engraftment. Five patients died
before day 17 after transplantation. The median time to an absolute
neutrophil count of > 0.5 x 10(5)/L was 21 (range, 14 to 30) days.
Nephrotoxicity (serum creatinine concentration > 2 mg/dL or doubling of
baseline) occurred in 32 patients (74% cumulative incidence during the
first 100 days after transplant). Other adverse effects included
hypertension (n = 27), hyperglycemia (n = 27), neurotoxicity (n = 9) and
thrombotic thrombocytopenic purpura (n = 2). Severe veno- occlusive disease
of the liver occurred in 9 (21%) of the 43 patients. Eighteen patients
(42%) developed grades II to IV acute GVHD and five (12%) developed grades
III to IV acute GVHD. Twelve of 25 evaluable patients developed extensive
chronic GVHD within 1 year of marrow transplantation resulting in an
estimate of the probability of developing this complication of 48%. The
cumulative incidence of transplant-related mortality during 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 transplantation from unrelated
donors. Further studies comparing the combination of FK506 and MTX with
cyclosporine and MTX for the prevention of acute GVHD are warranted.
Volume 88,
Issue 9,
pp. 3634-3641,
11/01/1996
Copyright © 1996 by The American Society of Hematology
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