Incidence and characteristics of invasive fungal diseases in allogeneic hematopoietic stem cell transplant recipients: a retrospective cohort study

Abstract

BackgroundAllogeneic hematopoietic stem cell transplant (HSCT) recipients experience an increased risk for invasive fungal diseases (IFDs).MethodsThis retrospective cohort study at the Medical University of Vienna aspired to assess the incidence, characteristics and the outcome of IFDs as well as the associated risk factors in a setting where only 43 % of patients were given systemic antifungal prophylaxis during aplasia. IFDs were classified as probable or proven according to the EORTC/MSG consensus group. All adult patients (n = 242) receiving an allogeneic HSCT at the University Hospital of Vienna from January 2009 to December 2013 were enrolled.ResultsThe primary outcome of this study was the one-year incidence for IFDs after HSCT, which was 10.3 % (25/242). Overall 28 patients experienced an IFD – 20 probable and 8 proven – with invasive aspergillosis being the predominant IFD (n = 18), followed by invasive candidiasis (n = 7) and pneumocystis pneumonia (n = 3). Patients with an IFD were more likely to be admitted to an intensive care unit (64 % versus 12 %, p < 0.0001) and had a significantly higher mortality in the first year after HSCT (48 % versus 25 %, p = 0.02). Multivariate regression analysis revealed that intensified immunosuppressive therapy (high-dose cortisone and basiliximab or etanercept) because of severe graft-versus-host disease (adjusted odds ratio (AOR) 3.6, p = 0.01) and transplant-associated microangiopathy (AOR 3.7, p = 0.04) were associated with an increased risk for IFD, while antifungal prophylaxis given during aplasia and post-engraftment was associated with a decreased risk (AOR 0.3, p = 0.02).ConclusionsWe documented a one-year incidence for IFDs of 10.3 % and no selection of rare pathogens at a centre with moderate use of antifungal prophylaxis. Intensified immunosuppressive therapy and transplant-associated microangiopathy were significant risk factors for IFDs.

Noncanonical Fungal Autophagy Inhibits Inflammation in Response to IFN-γ via DAPK1

“…Although aspergillosis remains a major cause of morbidity and mortality in CGD patients (Marciano et al., 2015), it is a much more common problem in hematopoietic stem cell transplantation (HSCT) patients (Harrison et al., 2015). We therefore assessed the impact of DAPK1 in this setting by analyzing five DAPK1 SNPs in a cohort of HSCT patients.…”

Surveillance for azoles resistance in Aspergillus spp. highlights a high number of amphotericin B‐resistant isolates

“…These ubiquitous opportunistic pathogens are responsible for one of the highest mortality rates among patients with fungal infections. Over 30 million people worldwide are estimated to be at risk of invasive aspergillosis (IA) each year, especially individuals with impaired immune function, those with low numbers of neutrophils, solid organ transplant recipients and patients on immunosuppressive therapies . Over 200 000 patients develop IA annually, with A. fumigatus the most common species isolated in patients, followed by Aspergillus flavus …”

Fungal Pneumonia in Patients with Hematologic Malignancy and Hematopoietic Stem Cell Transplantation

“…T cell depleted HSCT and use of anti-thymocyte globulin place patients at high risk. Radiation, corticosteroids, cyclosporine, azathioprine, tacrolimus, cytotoxic purine analogs (e.g., fludarabine), nucleoside analogue (e.g., cytarabine, gemcitabine, 5-FU), certain monoclonal antibodies (e.g., alemtuzumab), and TNF antagonists can cause profound depletion and dysfunction of T cells that can last many months after treatment is completed 5,13,17,29,30,40–42 . Moreover, patients with Hodgkin’s disease, T-cell lymphoma, and some leukemias have disease-impaired cell mediated immunity even in the absence of cytotoxic therapy 43 , possibly due to microenvironment immunosuppressive or exhaustion mechanisms 44,45 .…”