Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: biological risk factors for infection according to time after transplantation

Abstract

Background: Invasive mold infections (IMIs) are common in individuals who have undergone hematopoietic stem cell transplantation (HSCT). We sought to determine clinical and biological risk factors for different IMIs during each period (early and late) after allogeneic HSCT.

Methods: Cases of proven and probable IMI diagnosed in HSCT recipients at the Fred Hutchinson Cancer Research Center (Seattle, WA) from 1 January 1998 through 31 December 2002 were included. Survival was estimated with Kaplan-Meier curves, and Cox regression models were used for multivariable analyses.

Results: During the study period, 1248 patients underwent allogeneic HSCT; 163 (13.1%) received a diagnosis of probable or proven IMI. The majority of cases were caused by Aspergillus species (88%). The incidence of IMI caused by other molds remained low (<2%) over the 4-year study period. Risk factors for IMI early after HSCT and late after HSCT differed, with host variables (age) and transplant variables (human leukocyte antigen match) predominating as early risk factors and other clinical complications (graft-versus-host disease and cytomegalovirus disease) predominating later. Biological risk factors that were important during all periods included multiple cytopenias (neutropenia, lymphopenia, and monocytopenia) and iron overload.

Conclusions: Risk factors for invasive aspergillosis after allogeneic HSCT are multifactorial and differ according to timing after HSCT. Increased attention should be placed on understanding the immunopathogenesis of fungal disease after HSCT.

Figure 1

One-year cumulative incidence of invasive mold infections (IMIs) among hematopoietic stem cell transplant recipients at Fred Hutchinson Cancer Research Center (Seattle, WA), 1998−2002. Day 0 is the day of receipt of stem cells.

Figure 2

One-year cumulative incidence of invasive mold infections (IMIs) caused by molds other than Aspergillus species, among hematopoietic stem cell transplant recipients at Fred Hutchinson Cancer Research Center (Seattle, WA), 1998−1999 and 2000−2002. Day 0 is the day of receipt of stem cells.

Figure 3

Timing of invasive mold infections (IMIs). Early IMI refers to infection diagnosed from day 0 through day 40; late IMI refers to infection diagnosed from day 41 through day 100; very late IMI refers to infection diagnosed after day 100.