Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation: A study of the North American Marrow Transplant Group

S. N. Wolff, J. Fay, D. Stevens, R. H. Herzig, B. Pohlman, B. Bolwell, J. Lynch, S. Ericson, C. O. Freytes, F. LeMaistre, R. Collins, L. Pineiro, J. Greer, R. Stein, S. A. Goodman, S. Dummer

Research output: Contribution to journalArticle

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Abstract

Systemic fungal infections are a major problem in bone marrow transplant recipients who have prolonged neutropenia or who receive high-dose corticosteroids. Prophylaxis with Fluconazole or low-dose amphotericin B reduces, but does not eliminate these infections. To determine which prophylactic agent is better, we performed a prospective randomized study. Patients undergoing allogeneic (related or unrelated) or autologous marrow or peripheral stem cell transplantation were randomized to receive Fluconazole (400 mg/day p.o. or i.v.) or amphotericin B (0.2 mg/kg/day i.v.) beginning 1 day prior to stem cell transplantation and continuing until recovery of neutrophils to > 500/μl. Patients were removed from their study drug for drug-associated toxicity, invasive fungal infection or suspected fungal infection (defined as the presence of fever > 38°C without positive culture while on broad-spectrum anti-bacterial antibiotics). Proven or suspected fungal infections were treated with high-dose amphotericin B (0.5-0.7 mg/kg/day). Patients were randomized at each institution and stratified for the type of transplant. The primary end-point of the study was prevention of documented fungal infection; secondary endpoints included fungal colonization, drug toxicity, duration of hospitalization, duration of fever, duration of neutropenia, duration and total dose of high-dose amphotericin B and overall survival to hospital discharge. From July 1992 to October 1994, a total of 355 patients entered into the trial with 159 patients randomized to amphotericin B and 196 to Fluconazole. Patient groups were comparable for diagnosis, age, sex, prior antibiotic or antifungal therapy, use of corticosteroids prior to transplantation and total duration of neutropenia. Amphotericin B was significantly more toxic than Fluconazole especially in related allogeneic transplantation where 19% of patients developed toxicity vs 0% of Fluconazole recipients (p < 0.05). Approximately 44% of all patients were removed from prophylaxis for presumed fungal infection. Proven fungal infections occurred in 4.1% and 7.5% of Fluconazole and amphotericin-treated patients, respectively. Proven fungal infections occurred in 9.1% and 14.3% of related allogeneic marrow recipients receiving Fluconazole or amphotericin B, respectively, and 2.1% and 5.6% of autologous marrow recipients receiving Fluconazole or amphotericin B, respectively (P > 0.05). In this prospective trial, low-dose amphotericin B prophylaxis was as effective as Fluconazole prophylaxis, but Fluconazole was significantly better tolerated.

Original languageEnglish (US)
Pages (from-to)853-859
Number of pages7
JournalBone Marrow Transplantation
Volume25
Issue number8
StatePublished - 2000

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Mycoses
Fluconazole
Amphotericin B
Bone Marrow Transplantation
Bone Marrow
Transplants
Neutropenia
Drug-Related Side Effects and Adverse Reactions
Adrenal Cortex Hormones
Fever
Peripheral Blood Stem Cell Transplantation
Antifungal Agents
Poisons
Homologous Transplantation
Stem Cell Transplantation
Hospitalization
Neutrophils
Transplantation
Prospective Studies
Anti-Bacterial Agents

Keywords

  • Amphotericin B
  • Fluconazole
  • Fungal infection prophylaxis

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation : A study of the North American Marrow Transplant Group. / Wolff, S. N.; Fay, J.; Stevens, D.; Herzig, R. H.; Pohlman, B.; Bolwell, B.; Lynch, J.; Ericson, S.; Freytes, C. O.; LeMaistre, F.; Collins, R.; Pineiro, L.; Greer, J.; Stein, R.; Goodman, S. A.; Dummer, S.

In: Bone Marrow Transplantation, Vol. 25, No. 8, 2000, p. 853-859.

Research output: Contribution to journalArticle

Wolff, SN, Fay, J, Stevens, D, Herzig, RH, Pohlman, B, Bolwell, B, Lynch, J, Ericson, S, Freytes, CO, LeMaistre, F, Collins, R, Pineiro, L, Greer, J, Stein, R, Goodman, SA & Dummer, S 2000, 'Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation: A study of the North American Marrow Transplant Group', Bone Marrow Transplantation, vol. 25, no. 8, pp. 853-859.
Wolff, S. N. ; Fay, J. ; Stevens, D. ; Herzig, R. H. ; Pohlman, B. ; Bolwell, B. ; Lynch, J. ; Ericson, S. ; Freytes, C. O. ; LeMaistre, F. ; Collins, R. ; Pineiro, L. ; Greer, J. ; Stein, R. ; Goodman, S. A. ; Dummer, S. / Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation : A study of the North American Marrow Transplant Group. In: Bone Marrow Transplantation. 2000 ; Vol. 25, No. 8. pp. 853-859.
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AU - Herzig, R. H.

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