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Blood, 15 September 2000, Vol. 96, No. 6, pp. 2055-2061
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Prolonged fluconazole prophylaxis is associated with persistent
protection against candidiasis-related death in allogeneic marrow
transplant recipients: long-term follow-up of a randomized,
placebo-controlled trial
Kieren A. Marr,
Kristy Seidel,
Monica A. Slavin,
Raleigh A. Bowden,
H. Gary Schoch,
Mary E. D. Flowers,
Lawrence Corey, and
Michael Boeckh
From the Fred Hutchinson Cancer Research Center and the
University of Washington, Seattle, WA.
Two randomized, placebo-controlled trials previously showed that
fluconazole (400 mg/d) administered prophylactically decreases the
incidence of candidiasis in blood and marrow transplant (BMT) recipients. However, there exists conflicting data regarding the optimal duration of fluconazole administration, specifically whether prophylaxis through acute graft-versus-host disease (GVHD) results in
improved survival in allograft recipients. Reported here are the
results of long-term follow-up and a detailed analysis of invasive candidiasis and candidiasis-related death in 300 patients who received fluconazole (400 mg/d) or placebo for 75 days
after BMT at the Fred Hutchinson Cancer Research Center. Patients in both treatment arms were compared for survival, causes of death, and
the incidence of invasive fungal infections early (less than 110 days)
and late (more than 110 days) after BMT. After 8 years of follow-up,
survival is significantly better in fluconazole recipients compared
with placebo recipients (68 of 152 vs 41 of 148, P = .0001). The overall incidence of invasive candidiasis was increased in patients who received placebo compared with
fluconazole (30 of 148 vs 4 of 152, P < .001). More
patients who received placebo died with candidiasis early (13 of 148 vs
1 of 152, P = .001) and late (8 of 96 vs 1 of 121, P = .0068) after BMT. The incidence of severe GVHD
involving the gut was higher in patients who did not receive
fluconazole (20 of 143 vs 8 of 145, P = .02), and fewer
patients who received fluconazole died with this complication. Thus,
administration of fluconazole (400 mg/d) for 75 days after BMT appears
to be associated with decreased gut GVHD, a persistent protection
against disseminated candidal infections and candidiasis-related death,
resulting in an overall survival benefit in allogeneic BMT recipients.

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