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

Nicole Harrison,Birgit Willinger,Christina Forstner,Hildegard Greinix,Heinz Burgmann,Selma Tobudic,Werner Rabitsch,Margit Mitterbauer,Elisabeth Presterl,Peter Kalhs

doi:10.1186/s12879-015-1329-6

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.

Highlights

Allogeneic hematopoietic stem cell transplant (HSCT) recipients experience an increased risk for invasive fungal diseases (IFDs)
Invasive fungal diseases (IFDs) still cause a considerably high mortality among these patients [3], despite the development of new antifungal agents for prophylaxis and treatment [4,5,6,7]. Their epidemiology continues to evolve as new transplantation strategies are implemented and the use of prophylaxis against fungal infections is broadened
The patients’ demographic characteristics, details about the transplantation including donor, type of graft, conditioning regimen, and the post-transplant follow-up including the severity of graft-versus-host disease (GvHD) [17], post-transplant complications as well as the use of prophylaxis and antifungal therapy were entered into a database

Summary

Introduction

Allogeneic hematopoietic stem cell transplant (HSCT) recipients experience an increased risk for invasive fungal diseases (IFDs). Allogeneic hematopoietic stem cell transplant (HSCT) recipients experience an increased risk for opportunistic fungal infections, during aplasia, but for an extended period of time, often enhanced by certain risk factors such as severe graft-versus-host disease (GvHD) [1, 2]. Invasive fungal diseases (IFDs) still cause a considerably high mortality among these patients [3], despite the development of new antifungal agents for prophylaxis and treatment [4,5,6,7]. Their epidemiology continues to evolve as new transplantation strategies are implemented and the use of prophylaxis against fungal infections is broadened. Several risk factors for IFDs have been described, like HLA-mismatched donors, use of cord blood as graft, prolonged severe neutropenia, cytomegalovirus reactivation, severe GvHD, iron overload, intensified immunosuppressive treatment e.g. with highdose steroids, and genetic risk factors such as toll-like receptor polymorphisms [2, 10,11,12,13,14,15,16]

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Discussion

Conclusion