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.

Incidence and risk factors of post-engraftment invasive fungal disease in adult allogeneic hematopoietic stem cell transplant recipients receiving oral azoles prophylaxis

“…For these reasons, our overall 1-year CI of 11% cannot be compared with other studies reporting late or very-late IFD incidence after alloSCT (ranging from 7 to 10%). [3][4][5]11 Concerning the type and timing of IFD, we found that, as in previous studies, Aspergillus spp. was the most frequent isolate and the lungs were the most common site, 18 and that the CI of IFD increased during the first year with a gradual decline of episodes until 5 years after SCT.…”

“…1,5 In addition, we found that post-engraftment IFD was associated with several risk factors that have been previously related with early or overall IFD, such as older age, delayed neutrophil engraftment, previous SCT, HLA mismatch and non PBSCT. 3,4 Our data suggest that ATG-containing regimens could increase the risk of IFD, which is in line with other studies reporting ex vivo T-cell depletion using Cl of IFD alemtuzumab as a risk factor for IFD. 25 Unfortunately, we did not evaluate other potential risk factors such as iron overload and lymphocyte counts in the PB.…”

“…However, despite the knowledge of several post-engraftment risk factors associated with late IFD (for example, corticosteroid therapy and GVHD), considered as a guide for risk-adapted antifungal prophylaxis, the usefulness of such prophylaxis beyond the alloSCT engraftment is still controversial. [8][9][10] There are a few studies specifically analyzing the epidemiology and risk factors for IFD after engraftment in alloSCT adult recipients [3][4][5]11 and the potential impact of antifungal prophylaxis in this setting.…”

Invasive fungal infection in allogeneic hematopoietic stem cell transplant recipients: single center experiences of 12 years

“…Candida is the most common pathogen of early IFI, while mold is the most common pathogen of late IFI. In patients who also developed GVHD, IFI may occur at three to six months and even later (Koldehoff and Zakrzewski, 2005;Garcia-Vidal et al, 2008). Our data demonstrate that the median time for the development of ICI is earlier than that for IMI (140 d vs. 243 d, P<0.05), reflecting the fact that mold infections are more common in the late period after HSCT.…”

Fungal Infections in Transplant and Oncology Patients

“…Host (e.g., older age) and transplant variables (e.g., human leukocyte antigen mis-match) tend to influence IFI risk early while complications of the transplant procedure (e.g., GVHD and cytomegalovirus [CMV] disease) tend to predominate later [1,2,5,68]. Certain biological factors such as malnutrition, iron overload, diabetes mellitus, and cytopenias are influential throughout the post transplant course [79]. Risk factors specific to early onset IA have been identified as aplastic anemia, myelodysplastic syndrome, cord-blood transplantation, delayed neutrophil engraftment, and CMV disease.…”