Research article

Safety and efficacy of a caspofungin-based combination therapy for treatment of proven or probable aspergillosis in pediatric hematological patients

Simone Cesaro¹ , Mareva Giacchino² , Franco Locatelli³ , Monica Spiller¹ , Barbara Buldini³ , Claudia Castellini⁴ , Desireè Caselli⁵ , Eugenia Giraldi⁶ , Fabio Tucci⁷ , Gloria Tridello¹ , Mario Renato Rossi⁸ and Elio Castagnola⁹

¹Pediatric Hematology Oncology, Department of Pediatrics, University of Padua, Italy

²Pediatric Oncology Hematology, Regina Elena Hospital, University of Turin, Italy

³Pediatric Hematology Oncology, IRCCS Policlinico San Matteo, University of Pavia, Italy

⁴Pediatric Hematology Oncology, Sant'Orsola Hospital, University of Bologna, Italy

⁵Pediatric Hematology Oncology, G. Di Cristina ARNAS Hospital, Palermo, Italy

⁶Division of Pediatrics, Hospital of Bergamo, Italy

⁷Pediatric Hematology Oncology, Meyer Hospital, University of Florence, Italy

⁸Clinic of Pediatrics, San Gerardo Hospital, Monza, Italy

⁹Division of Pediatric Infectious Disease, "Giannina Gaslini" Institute, Genua, Italy

author email corresponding author email

BMC Infectious Diseases 2007, 7:28doi:10.1186/1471-2334-7-28

Published:	18 April 2007

Abstract

Background

Fungal infections are diagnosed increasingly often in patients affected by hematological diseases and their mortality has remained high. The recent development of new antifungal drugs gives the clinician the possibility to assess the combination of antifungal drugs with in-vitro or in animal-model synergistic effect.

Methods

We analyzed retrospectively the safety and efficacy of caspofungin-based combination therapy in 40 children and adolescents, most of them were being treated for a malignant disease, who developed invasive aspergillosis (IA) between November 2002 and November 2005.

Results

Thirteen (32.5%) patients developed IA after hematopoietic stem cell transplantation (HSCT), 13 after primary diagnosis, usually during remission-induction chemotherapy, and 14 after relapse of disease. Severe neutropenia was present in 31 (78%) out of the 40 patients. IA was classified as probable in 20 (50%) and documented in 20 (50%) patients, respectively. A favorable response to antifungal therapy was obtained in 21 patients (53%) and the probability of 100-day survival was 70%. Different, though not significant, 100-day survival was observed according to the timing of diagnosis of IA: 51.9% after HSCT; 71.4% after relapse; and 84.6% after diagnosis of underlying disease, p 0.2. After a median follow-up of 0.7 years, 20 patients are alive (50%). Overall, the combination therapy was well tolerated. In multivariate analysis, the factors that were significantly associated to a better overall survival were favorable response to antifungal therapy, p 0.003, and the timing of IA in the patient course of underlying disease, p 0.04.

Conclusion

This study showed that caspofungin-based combination antifungal therapy is an effective therapeutic option also for pediatric patients with IA. These data need to be confirmed by prospective, controlled studies.