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Role of Management Strategies in Reducing Mortality From Invasive Fungal Disease in Children With Cancer or Receiving Hemopoietic Stem Cell Transplant: A Single Center 30-year Experience

Castagnola, Elio MD, PhD*; Bagnasco, Francesca PhD; Amoroso, Loredana MD; Caviglia, Ilaria PhD*; Caruso, Silvia PhD; Faraci, Maura MD§; Calvillo, Michaela MD; Moroni, Cristina MD*; Bandettini, Roberto MD; Cangemi, Giuliana PhD; Magnano, Gian Michele MD**; Buffa, Piero MD††; Moscatelli, Andrea MD‡‡; Haupt, Riccardo MD

The Pediatric Infectious Disease Journal: March 2014 - Volume 33 - Issue 3 - p 233–237
doi: 10.1097/INF.0000000000000101
Original Studies

Background: In the last decades, several diagnostic and therapeutic strategies have been implemented for management of invasive fungal diseases (IFD) in patients with cancer or receiving allogeneic hemopoietic stem cell transplant. Few data are available on their impact on mortality in children.

Methods: All IFD episodes diagnosed at tertiary care center during a 30-year period between 1983 and 2012 were analyzed for 90-day mortality and risk factors. Diagnoses were coded according to international (European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group) criteria. Four treatment eras (1983–1990, 1991–1999, 2000–2005 and 2006–2012) were defined according to availability of diagnostic technologies, new antifungal drugs and use of a diagnostic-driven approach without empiric antifungal therapy.

Results: A total of 198 IFD were diagnosed in 191 patients; 71.2% were proven/probable infections; 39.9% were caused by yeasts and 31.3% by molds. Within 90 days from IFD diagnosis, 58 (30.4%) patients died for a 28.3% cumulative probability of death. A multivariable analysis showed that the highest risk of death was associated with alternative donor-hemopoietic stem cell transplant [hazard ratio (HR): 3.96] and mold etiology (HR: 1.34). The risk of death significantly decreased across the treatment eras, with almost a 3-fold reduced risk for patients diagnosed during the 2006–2012 period (HR: 0.24). Also if the variable year of diagnosis was considered as continuous, the hazard of death significantly decreased by 5% per year (HR: 0.95).

Conclusions: New management strategies resulted in a better prognosis of IFD in children with cancer or hemopoietic stem cell transplant. A diagnostic-driven approach was not associated with an increase in mortality.

From the *Infectious Diseases Unit; Epidemiology and Biostatistics Unit; Oncology Unit; §Hemopoietic Stem Cell Transplant Unit; Hematology Unit; Laboratory of Analysis; **Service of Radiology; ††Surgery Unit; and ‡‡Intensive Care Unit, “Istituto Giannina Gaslini”, Genova, Italy.

Accepted for publication August 23, 2013.

This work was partially supported by: Italian Foundation for Research on Neuroblastoma; Contributi del “Cinque per mille dell’IRPEF-Finanziamento della Ricerca Sanitaria” (5XMILRIC08 DEL. 136/11); Finanziamento della Ricerca Corrente, Ministero della Salute (contributo per la ricerca intramurale; MSALRC DEL. 169/09) and European Network for Cancer Research in Children and Adolescents (ENCCA; FP7 Project number 261474). The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Elio Castagnola, MD, Infectious Diseases Unit, G. “Istituto Giannina Gaslini”, Largo G. Gaslini 5, 16147 Genova, Italy. E-mail:

© 2014 by Lippincott Williams & Wilkins, Inc.