Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty-seven patients undergoing bone marrow transplantation were randomly assigned to receive either cyclosporin A (CsA, n = 26) or methotrexate, followed by rescue with folinic acid (MTX + FA, n = 31) as prophylaxis for graft-versus-host disease (GVHD). All patients but one receiving CsA had evidence of sustained engraftment, and there was no difference between the two groups on the day in which marrow engraftment was documented. Oropharyngeal mucositis was of similar incidence and severity in the two groups. In contrast, patients receiving CsA showed higher renal and hepatic toxicity rates than those treated with MTX + FA. Severe-to-moderate acute GVHD (grades II-IV) was documented in 12 patients receiving CsA and in 12 treated with MTX + FA. The cumulative incidence of this complication was similar in both groups (46.1% and 38.7%). Similarly, there was no difference in the incidence of chronic GVHD. The leukemic relapse rates were also comparable, as well as the estimated probability of survival, which was 55% in patients treated with MTX + FA and 41% in those who were given CsA. We conclude that MTX + FA is as effective as CsA in the prevention of GVHD, with the additional advantage of reduced renal and hepatic toxicities.
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PMID:Cyclosporin A versus methotrexate, followed by rescue with folinic acid as prophylaxis of acute graft-versus-host disease after bone marrow transplantation. 264 54

Grades 2-4 acute graft-versus-host disease (GVHD) occurs in approximately 35% of matched, related donor (MRD) allogeneic hematopoietic cell transplantation (HCT) recipients. We sought to determine if the combination of tacrolimus and sirolimus (Tac/Sir) was more effective than tacrolimus and methotrexate (Tac/Mtx) in preventing acute GVHD and early mortality after allogeneic MRD HCT in a phase 3, multicenter trial. The primary end point of the trial was to compare 114-day grades 2-4 acute GVHD-free survival using an intention-to-treat analysis of 304 randomized subjects. There was no difference in the probability of day 114 grades 2-4 acute GVHD-free survival (67% vs 62%, P = .38). Grades 2-4 GVHD was similar in the Tac/Sir and Tac/Mtx arms (26% vs 34%, P = .48). Neutrophil and platelet engraftment were more rapid in the Tac/Sir arm (14 vs 16 days, P < .001; 16 vs 19 days, P = .03). Oropharyngeal mucositis was less severe in the Tac/Sir arm (peak Oral Mucositis Assessment Scale score 0.70 vs 0.96, P < .001), but otherwise toxicity was similar. Chronic GVHD, relapse-free survival, and overall survival at 2 years were no different between study arms (53% vs 45%, P = .06; 53% vs 54%, P = .77; and 59% vs 63%, P = .36). Based on similar long-term outcomes, more rapid engraftment, and less oropharyngeal mucositis, the combination of Tac/Sir is an acceptable alternative to Tac/Mtx after MRD HCT. This study was funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; and the trial was registered at www.clinicaltrials.gov as #NCT00406393.
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PMID:Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT. 2498 4