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    ABSTRACT: Objective: Fungal infection is a significant problem, causing of infective deaths of leukemic patients. The situation in developing countries is not well documented. The purpose of this study was characterizing IFD by analyzing data retrospectively to determine the incidence, predisposing factors, diagnostic methods, efficacy of treatment, and the outcome in pediatric patients with hematological disorders. Materials and Methods: There were 160 children with leukemia (22 AML, 129 ALL) and 9 with aplastic anemia (AA). The diagnostic criteria for IFD were defined according to the EORTC/MSG, 2008. IFD was classified as proven or probable. Empiric antifungal treatment with L-AmB was commenced by day 5-7 of persistent fever. Patients with invasive aspergillosis (IA) who were refractory to primary treatment were commenced on voriconazole (VCZ). Salvage therapy as combination of VCZ and caspofungin was given to those with progressive infection. Results: The incidence of IFD was found 23 (14.3%). 19 with leukemia (14 ALL, 5 AML) and 4 with aplastic anemia were diagnosed as IFD. IA was the dominant cause of infection (n=17) and the rest (n: 6) had candidiasis. Ten children had “proven” infection and 13 children were defined as “probable”. The most frequent site of infection was lungs. In our series, the most frequently used diagnostic methods were clinical findings (100%) and radiologic methods (84%). The success rate of treatment for candidiasis and IA were found 60%, 71% respectively. IFD related death rate was found 30%.Conclusion: IFD is still a major morbidity and mortality reason in children with hematologic disorders. However, the availability of new antifungal treatments and diagnostic tests will improve the survival rates in these children.
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    ABSTRACT: Invasive fungal infections (IFI) are a major cause of infection-related mortality during induction chemotherapy of acute leukemia (AL) patients. Data on antifungal prophylaxis (AFP) in children are limited by retrospective design, small sample size, and variability of chemotherapy phases having different risk of IFI. There are no data comparing voriconazole versus amphotericin B (AmB) as AFP in either adult/pediatric AL. The objectives of this study were to compare efficacy and toxicity of AmB and voriconazole as AFP in pediatric AL patients. As a pilot study, total 100 children (≤15 y) with denovo acute myeloid leukemia and acute lymphoblastic leukemia were randomized to either oral voriconazole or low dose intravenous AmB as AFP during induction chemotherapy. Failure of prophylaxis occurred in 14/50 patients in voriconazole arm (1 proven mucormycosis, 1 possible IFI, 11 empirical antifungal therapy, and 1 withdrawal owing to hepatotoxicity) and 17/50 patients in AmB arm (3 possible IFI, 13 empirical antifungal therapy, and 1 withdrawal owing to difficult venous access) (P=0.66). Of the 29 patients who had failure of prophylaxis unrelated to drug toxicity, computed tomography of the chest showed infiltrates in 10 patients with 3/12 in voriconazole arm and 7/16 in AmB arm (P=0.43). Drug-related serious adverse events were 6% versus 30% in voriconazole and AmB arms, respectively (P<0.01). Further, total number of toxicities per patient in AmB arm were significantly higher as compared with voriconazole arm (P<0.0001). This is the first randomized study comparing voriconazole with AmB in pediatric AL patients as AFP during induction chemotherapy; our results showed that oral voriconazole seems to be comparable with AmB with less toxicity and more convenience. (ClinicalTrials.gov identifier: NCT00624143).
    Journal of Pediatric Hematology/Oncology 12/2011; 33(8):e333-41. DOI:10.1097/MPH.0b013e3182331bc7 · 0.96 Impact Factor
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    ABSTRACT: Introduction Invasive fungal infections (IFI) are serious complications of chemotherapy-induced immunosuppression of children treated in hematology/oncology pediatric unit. The incidence of those complications is known to be particularly high among children treated for acute myeloid leukemia (AML). Methods In this retrospective and multicenter study, all children with an invasive fungal infection (defined according to the EORTC/MSG criteria) during their chemotherapy treatment according to ELAM 02 protocol from 2005 to 2011 were included. Patients were treated in Hematology/Oncology centers of the SFCE (Société française de lutte contre les cancers et leucémies de l’enfant et de l’adolescent). No prophylactic antifungal therapy was recommended. Results Twenty-six cases of IFI occurred (incidence of 6.7%). The median age was 12 years. There were 15 aspergillosis, nine candidiasis and two mucormycosis. Twelve IFI were defined as proven, six probable and eight possible. Most of them occurred during the intensive phase of treatment and located in the lung. In a comparative analysis with the non-IFI group, no risk factor was demonstrated. All children were treated by new antifungal drugs and the therapeutic strategies were studied. With a median follow-up of 34 months, 10 patients died; among them, two deaths were directly attributable to the IFI. There was no significant difference concerning overall survival and event-free survival between the group with and without IFI. Conclusion Recommendations for the management of IFI in pediatric oncology patients have been published but prospective and multicenter pediatrics studies are still necessary to improve preventive strategies, early diagnosis and treatment of IFI in this population.
    12/2013; 1(s 3–4):130–138. DOI:10.1016/j.oncohp.2013.10.005