Iinvasive fungal infections in transplanted patients The “Transnet Experience”

A. Symeonidis

Author address: 

University of Patras Medical School, Patras, Greece


Invasive Fungal infections (IFIs) represent a major cause of non-relapse mortality among patients with hematological malignancies, undergoing conventional or high dose chemotherapy and hematopoietic stem-cell transplantation (HSCT). Well-recognized risk factors for the development of an IFI in these patients are a history of previous IFI, mucosal colonization by fungi, prolonged (>14 days) chemotherapy-induced neutropenia or delayed neutrophil engraftment, profound lymphopenia, previous treatment with purine analogs or ATG, treatment with high doses of corticosteroids, presence of active or relapsed disease, severe mucosal damage, CMV reactivation and extensive chronic GVHD. The majority of IFIs occur within 60 days following HSCT, while invasive aspergillosis (IA) in particular, exhibits a bimodal distribution, with an early peak at about 3 weeks, and a later peak at approximately 3-4 months post transplant. The Transplant Associated Infection Surveillance Network (TransNet) is a prospective surveillance study, collecting data from about 25 transplant centers in the US. The aims of this study are the description of the incidence of IFIs in HSCT and solid organ transplantation (SOT) recipients, and the development of strategies for prevention and early treatment. Only proven and probable IFIs according to EORTC/MSG criteria are included. The study will be conducted in 3 phases over a period of 6 years. Data from an interim analysis, covering a 22- month period (1.3.2001 to 31.12.2002), among 4621 HSCT- and 4110 SOT recipients, revealed 487 cases of IFIs, including 217 (46%) of IA, zygomycosis and other molds; 209 (43%) of invasive candidiasis (IC); 20 (4%) of cryptococcosis (CC); 17 (3%) of endemic mycoses (EM); 13 (2.7%) of other yeasts and 11 (2.3%) of Pneumocystis Carinii Pneumonia (PCP). The widespread use of prophylactic fluconazole has resulted in decreasing rates of IC in HSCT recipients. Indeed, 149 (70%) out of the 212 IFI cases, diagnosed in HSCT recipients, were IA, zygomycosis and infections by other molds. An updated report from TransNet, including 6999 HSCT- and 6474 SOT-recipients, revealed a twice higher rate of IFIs caused by molds, than by yeasts (1.8 versus 0.78/100 person-years, respectively). Aspergillus was the predominant mold, followed by the Zygomycetes, particularly associated with a prior exposure to voriconazole. The cumulative incidence of IA at 12 months was 0.5% after autologous SCT, 2.3% after allogeneic SCT from an HLA-matched related donor, 3.2% after allogeneic SCT from an HLA-mismatched related donor, and 3.9% after transplantation from an unrelated donor. In contrast to previous reports, the incidence at 12 months was similar following myeloablative, or non-myeloablative conditioning before allogeneic SCT (3.1 versus 3.3%). The cumulative incidence of IA at 12 months was 2.4% after lung, 0.8% after heart, 0.3% after liver, and 0.1% after kidney transplantation, figures lower than previously reported. Overall mortality at 3 months was 46% (36% for IC, 60% for IA and other molds) and was significantly higher in HSCT, than in SOT recipients (68% vs. 29%, p

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Full conference title: 

4th Trends in Medical Mycology
    • TIMM 4th (2012)