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15 February 2007

Volume 44, Number 4
Clinical Infectious Diseases 2007;44:531–540
© 2007 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2007/4404-0009$15.00
DOI: 10.1086/510592
MAJOR ARTICLE

Invasive Aspergillosis following Hematopoietic Cell Transplantation: Outcomes and Prognostic Factors Associated with Mortality

Arlo Upton,

Katharine A. Kirby,

Paul Carpenter,

Michael Boeckh, and

Kieren A. Marr

Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington

Background.Invasive aspergillosis (IA) is a leading cause of infection‐related mortality following hematopoietic cell transplantation (HCT). The aim of this study was to determine the probability of survival and prognostic factors associated with outcomes over a long period of time.

Methods.Cases of proven and probable IA diagnosed in HCT recipients at the Fred Hutchinson Cancer Research Center from 1 January 1990 through 31 December 2004 were included. Patient data were collected from a prospectively maintained database and by retrospective clinical chart review. Survival was estimated using Kaplan‐Meier curves, and Cox regression models were used for multivariable analyses.

Results.Four hundred five cases were identified. The probability of survival at 90 days after diagnosis was higher for patients identified as having IA between 2002 and 2004 than for patients whose IA was diagnosed in preceding years (45% vs. 22%; ). Risk factors independently associated with all‐cause mortality include impairment in pulmonary function before HCT, receipt of human leukocyte antigen–mismatched stem cells, neutropenia, elevated bilirubin and creatinine levels, receipt of corticosteroids at 2 mg/kg per day, disseminated and proven IA, and IA occurring >40 days after HCT. Factors associated with a decreased risk of all‐cause mortality included receipt of nonmyeloablative conditioning and peripheral blood stem cells. In a subanalysis of attributable mortality restricted to patients receiving antifungal therapy, receipt of voriconazole was independently associated with protection from IA‐related death.

Conclusions.There has been a significant decrease in mortality in patients with a diagnosis of IA following HCT in recent years, coinciding with multiple changes in transplantation practices, including use of nonmyeloablative conditioning regimens, receipt of peripheral blood stem cells, more prompt diagnosis of IA, and use of voriconazole.

Received 31 July 2006; accepted 19 October 2006; electronically published 9 January 2007.

Reprints or correspondence: Dr. Kieren Marr, Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., D3‐100, Seattle, WA 98109 ().

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