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The Impact of Mold Infections after Allogeneic Transplantation

Track: Poster Abstracts
Saturday, March 1, 2014, 6:45 PM-7:45 PM
Longhorn Hall E (Exhibit Level 1) (Gaylord Texan)
Tracey L. Churay , Adult Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI
Holly A. Justman , Adult Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI
Nancy L. Skurka , Adult Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI
Gregory Yanik, MD , Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI
Steven C. Goldstein, MD , Adult Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI
Attaphol Pawarode, MD , Adult Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI
John Magenau, M.D. , Adult Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI
Daniel R. Couriel, MD , Adult Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI
Introduction: Fungi are among the most common microbes encountered by mammalian hosts and a major cause of morbidity and mortality of allogeneic hematopoietic stem cell transplantation (HSCT). Both innate and adaptive immunity prevent invasive fungal infections (IFI), and are impaired after HSCT. Due to Candida prophylaxis, Aspergillus and other molds are emerging as one of the main causes of non-relapse mortality (NRM) after allogeneic HSCT. In this study, we retrospectively evaluated the incidence of IFI and their impact on the outcomes of allogeneic HSCT.

Methods: The data was obtained from University of Michigan Blood and Marrow Transplant Program database under an IRB-approved protocol. We included only proven and probable fungal infections, defined according EORTC/MSG criteria (CID 2008; June 15;46 (12):1813).

Results: A total of 50 IFI were diagnosed in 542 patients between 2007 and 2012, 76% (n=37) due to mold mostly represented by Aspergillus (n=24, 63%), followed by Zygomyces and Rhizopus. Only 3/37 infections were diagnosed in 2012, probably reflecting more consistent prophylaxis against mold during this period. The CI of mold infections was 6.6% (95% CI 5-10%) and 10.4% (95% CI 8-14%) at 1 and 2 years respectively, with a median time to infection of 194 days (9-644). The median prednisone dose was 15 mg at the time of diagnosis, with a median duration of therapy of 124 days (0-1757). Mold infections were significantly more common in patients with a history of acute GVHD (aGVHD, CI at 1y 10.3% vs. 0.2%, HR=6.2, p=0.0001), but not in those with chronic GVHD (cGVHD, CI at 1y 5.4 vs. 7.7%, HR=0.7, p=0.2). The case fatality rate of mold infections was high at 83.3%, and they were associated with a substantial increase in NRM both in aGVHD (70 vs. 34% at 2 ys, HR=2.6, 1.68-4.1) and cGVHD (43% vs. 15% at 2y, HR=4, 2.2-7.5). After adjusting for other HSCT-related factors, mold infections persisted as an independent risk factor for NRM for patients with both aGVHD (HR=2.78, 1.7-4.4) and cGVHD (HR=4, 2-7).

Conclusions: Mold infections are emerging as a major cause of infection-related mortality, with a very high case fatality rate and a significant impact on NRM in patients with aGVHD and cGVHD. Our data further supports the need for anti-mold prophylaxis in high-risk populations.

Disclosures:
D. R. Couriel, Merck, Speaker: Advisory Board, Consultancy and Honoraria
Therakos, None: Consultancy and Honoraria
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