title: A prospective, randomized study of empirical antifungal therapy for the treatment of chemotherapy-induced febrile neutropenia in children.
abstract: Given that the rationale for empirical antifungal therapy in neutropenic children is limited and based on adult patient data, we performed a prospective, randomized, controlled trial that evaluated 110 neutropenic children with persistent fever. Those at high risk for invasive fungal infections (IFI) received caspofungin (Arm C) or liposomal amphotericinB (Arm B); those with a lower risk were randomized to receive Arm B, C, or no antifungal treatment (Arm A). Complete response to empirical antifungal therapy was achieved in 90/104 patients (86·5%): 48/56 at high risk (85·7%) [88·0% in Arm B; 83·9% in Arm C (P = 0·72)], and 42/48 at low risk (87·5%) [87·5% in control Arm A, 80·0% Arm B, 94·1% Arm C; (P = 0·41)]. None of the variables tested by multiple logistic regression analysis showed a significant effect on the probability to achieve complete response. IFI was diagnosed in nine patients (8·2%, 95% confidence interval, 3·8-15·0). This randomized controlled study showed that empirical antifungal therapy was of no advantage in terms of survival without fever and IFI in patients aged <18 years and defined with low risk of IFI. Higher risk patients, including those with relapsed cancer, appear to be the target for empirical antifungal therapy during protracted febrile neutropenia.
authors.affiliation: Department Paediatric Haematology Oncology, Azienda Ospedaliero-Universitaria Meyer, Firenze, Italy.
authors.forename: Désirée
authors.initials: D
authors.lastname: Caselli
authors.affiliation: Oncoematologia Pediatrica, Dipartimento di Pediatria, Università di Padova, Padova, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Cesaro
authors.affiliation: Paediatric Haematology and Oncology Unit, G. Di Cristina Children's Hospital, Palermo, Italy.
authors.forename: Ottavio
authors.initials: O
authors.lastname: Ziino
authors.affiliation: Dipartimento di Scienze Statistiche e Matematiche Silvio Vianelli, Palermo, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Ragusa
authors.affiliation: Dipartimento di Scienze Statistiche e Matematiche Silvio Vianelli, Palermo, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontillo
authors.affiliation: Oncoematologia Pediatrica, Dipartimento di Pediatria, Università di Padova, Padova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pegoraro
authors.affiliation: Dipartimento Biomedicina Età Evolutiva, U.O Pediatrica I Policlinico, Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Santoro
authors.affiliation: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Zanazzo
authors.affiliation: Dipartimento di Oncologia, A.O.R.N. Santobono - Pausilipon, Napoli, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Poggi
authors.affiliation: Dip. Scienze Pediatriche e dell'Adolescenza, Ospedale Infantile Regina Margherita, Torino, Italy.
authors.forename: Mareva
authors.initials: M
authors.lastname: Giacchino
authors.affiliation: Ospedale Bambino Gesù, Roma, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Livadiotti
authors.affiliation: Clinica Pediatrica, Oncologia ed Ematologia Lalla Seràgnoli, Policlinico Sant'Orsola Malpighi, Bologna, Italy.
authors.forename: Fraia
authors.initials: F
authors.lastname: Melchionda
authors.affiliation: Dipartimento di Scienze Statistiche e Matematiche Silvio Vianelli, Palermo, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Chiodi
authors.affiliation: Department Paediatric Haematology Oncology, Azienda Ospedaliero-Universitaria Meyer, Firenze, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use; D000935:Antifungal Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000077336:Caspofungin; D002648:Child; D002675:Child, Preschool; D054714:Echinocandins / Q000627:therapeutic use; D005260:Female; D005335:Fever of Unknown Origin / Q000188:drug therapy* / Q000382:microbiology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007223:Infant; D007902:Length of Stay / Q000706:statistics & numerical data; D055666:Lipopeptides; D008297:Male; D009181:Mycoses / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy* / Q000382:microbiology; D009894:Opportunistic Infections / Q000139:chemically induced / Q000188:drug therapy; D018579:Patient Selection; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D054714:Echinocandins; D055666:Lipopeptides; C068538:liposomal amphotericin B; D000666:Amphotericin B; D000077336:Caspofungin