Maria Ilaria Del Principe1, Giulia Dragonetti2, Luisa Verga3, Anna Candoni4, Francesco Marchesi5, Chiara Cattaneo6, Mario Delia7, Leonardo Potenza8, Francesca Farina9, Stelvio Ballanti10, Nunzia Decembrino11, Carlo Castagnola12, Gianpaolo Nadali13, Rosa Fanci14, Enrico Orciulo15, Barbara Veggia16, Massimo Offidani17, Lorella Melillo18, Sara Manetta19, Mario Tumbarello20, Adriano Venditti1, Alessandro Busca19, Franco Aversa21, Livio Pagano2. 1. Cattedra di Ematologia, Dipartimento di Biomedicina e Prevenzione, Università degli Studi di Roma 'Tor Vergata', Roma, Italy. 2. Istituto di Ematologia, Fondazione Policlinico Universitario A. Gemelli-IRCCS-Università Cattolica del Sacro Cuore, Roma, Italy. 3. Clinica Ematologica, Ospedale San Gerardo, ASST Monza, Università Milano Bicocca, Milano, Italy. 4. Clinica di Ematologia e Unità di terapie Cellulari 'Carlo Melzi'-Azienda Sanitaria-Universitaria, Integrata, Udine, Italy. 5. Haematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Roma, Italy. 6. Divisione di Ematologia, ASST-Spedali Civili di Brescia, Brescia, Italy. 7. Sezione di Ematologia, Dipartimento dell'Emergenza e dei Trapianti d'Organo-Università di Bari, Bari, Italy. 8. UOC Ematologia, Dipartimento di Scienze Mediche e Chirurgiche Materno infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italy. 9. IRCCS Ospedale San Raffaele, Milano, Italy. 10. Istituto di Ematologia, Università di Perugia, Perugia, Italy. 11. UOC Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 12. Dipartimento Onco-Ematologico Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 13. Unità Operativa Complessa di Ematologia, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy. 14. Unità Funzionale di Ematologia, Azienda Ospedaliero-Universitaria Careggi e Università di Firenze, Firenze, Italy. 15. Dipartimento di Oncologia, Trapianti e Tecnologie Avanzate, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 16. UOC Ematologia, AO San Giovanni Addolorata, Roma, Italy. 17. Clinica di Ematologia, Azienda Ospedaliero-Universitaria, Ospedali Riunti di Ancona, Ancona, Italy. 18. Divisione di Ematologia, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. 19. Stem Cell Transplant Centre, AOU Citta' della Salute e della Scienza, Torino, Italy. 20. Istituto di Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli-IRCCS-Università Cattolica del Sacro Cuore, Roma, Italy. 21. Dipartimento di Medicina Interna, Università di Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Abstract
BACKGROUND: We evaluated the incidence of proven/probable invasive aspergillosis (IA) and the role of antifungal prophylaxis (AP) in a 'real-life' setting of patients with AML receiving intensive consolidation therapy. METHODS: Cases of IA, observed during consolidation in adult/paediatric patients with AML between 2011 and 2015, were retrospectively collected in a multicentre Italian study. RESULTS: Of 2588 patients, 56 (2.2%) developed IA [43 probable (1.7%) and 13 proven (0.5%)]. IA was diagnosed in 34 of 1137 (2.9%) patients receiving no AP and in 22 of 1451 (1.5%) who were given AP (P = 0.01). Number-needed-to-treat calculation indicates that, on average, 71 patients should have received AP (instead of no AP) for one additional patient to not have IA. Initial antifungal therapy was 'pre-emptive' in 36 (64%) patients and 'targeted' in 20 (36%) patients. A good response to first-line therapy was observed in 26 (46%) patients, mainly those who received AP [16 of 22 (73%) versus 10 of 34 (29%); P = 0.001]. The overall mortality rate and the mortality rate attributable to IA by day 120 were 16% and 9%, respectively. In multivariate analysis, age ≥60 years (OR = 12.46, 95% CI = 1.13-136.73; P = 0.03) and high-dose cytarabine treatment (OR = 10.56, 95% CI = 1.95-116.74; P = 0.04) independently affected outcome. CONCLUSIONS: In our experience, AP appears to prevent IA from occurring during consolidation. However, although the incidence of IA was low, mortality was not negligible among older patients. Further prospective studies should be carried out particularly in elderly patients treated with high-dose cytarabine to confirm our data and to identify subsets of individuals who may require AP.
BACKGROUND: We evaluated the incidence of proven/probable invasive aspergillosis (IA) and the role of antifungal prophylaxis (AP) in a 'real-life' setting of patients with AML receiving intensive consolidation therapy. METHODS: Cases of IA, observed during consolidation in adult/paediatric patients with AML between 2011 and 2015, were retrospectively collected in a multicentre Italian study. RESULTS: Of 2588 patients, 56 (2.2%) developed IA [43 probable (1.7%) and 13 proven (0.5%)]. IA was diagnosed in 34 of 1137 (2.9%) patients receiving no AP and in 22 of 1451 (1.5%) who were given AP (P = 0.01). Number-needed-to-treat calculation indicates that, on average, 71 patients should have received AP (instead of no AP) for one additional patient to not have IA. Initial antifungal therapy was 'pre-emptive' in 36 (64%) patients and 'targeted' in 20 (36%) patients. A good response to first-line therapy was observed in 26 (46%) patients, mainly those who received AP [16 of 22 (73%) versus 10 of 34 (29%); P = 0.001]. The overall mortality rate and the mortality rate attributable to IA by day 120 were 16% and 9%, respectively. In multivariate analysis, age ≥60 years (OR = 12.46, 95% CI = 1.13-136.73; P = 0.03) and high-dose cytarabine treatment (OR = 10.56, 95% CI = 1.95-116.74; P = 0.04) independently affected outcome. CONCLUSIONS: In our experience, AP appears to prevent IA from occurring during consolidation. However, although the incidence of IA was low, mortality was not negligible among older patients. Further prospective studies should be carried out particularly in elderly patients treated with high-dose cytarabine to confirm our data and to identify subsets of individuals who may require AP.