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 Marr, Kristy Seidel, Monica A. Slavin, Raleigh A. Bowden, H. Gary Schoch, Mary E D Flowers, Lawrence Corey, Michael Boeckh

Research output: Contribution to journalArticle

Abstract

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. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)2055-2061
Number of pages7
JournalBlood
Volume96
Issue number6
StatePublished - Sep 15 2000
Externally publishedYes

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Transplants
Fluconazole
Candidiasis
Randomized Controlled Trials
Bone Marrow
Placebos
Blood
Graft vs Host Disease
Invasive Candidiasis
Grafts
Survival
Incidence
Transplant Recipients
Allografts
Cause of Death
Arm
Infection

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Marr, Kieren; Seidel, Kristy; Slavin, Monica A.; Bowden, Raleigh A.; Gary Schoch, H.; Flowers, Mary E D; Corey, Lawrence; Boeckh, Michael.

In: Blood, Vol. 96, No. 6, 15.09.2000, p. 2055-2061.

Research output: Contribution to journalArticle

Marr, Kieren ; Seidel, Kristy ; Slavin, Monica A. ; Bowden, Raleigh A. ; Gary Schoch, H. ; Flowers, Mary E D ; Corey, Lawrence ; Boeckh, Michael. / 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. In: Blood. 2000 ; Vol. 96, No. 6. pp. 2055-2061.
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abstract = "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. (C) 2000 by The American Society of Hematology.",
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AU - Slavin, Monica A.

AU - Bowden, Raleigh A.

AU - Gary Schoch, H.

AU - Flowers, Mary E D

AU - Corey, Lawrence

AU - Boeckh, Michael

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