Seifem 2016 Study: Incidence of Probable and Proven Invasive Aspergillosis in Patients with Acute Myeloid Leukemia during Consolidation Therapy

Maria Ilaria Del Principe 1, Roberta di Blasi 2, Luisa Verga 3, Anna Candoni 4, Stelvio Ballanti 5, Leonardo Potenza 6, Chiara Cattaneo 7, Mario Delia 8, Nunzia Decembrino 9, Lorella MA Melillo 10, Carlo Castagnola 11, Gianpaolo Nadali 12, Rosa Fanci 13, Antonella Ferrari 14, Nicola Fracchiolla 15, Enrico Orciuolo 16, Federica Lessi 17, Anna Chierichini 18, Massimo Offidani 19, Marco Picardi 20, Lucia Prezioso 21, Benedetta Rambaldi 22, Francesco Marchesi 23, Ombretta Annibali 24, Daniele Zama 25, Valentina Mancini 26, Prassede Salutari 27, Maria Grazia Garzia 28, Adriana Vacca 29, Simone Cesaro 30, Rosangela Invernizzi 31, Katia Perruccio 32, Maria Enza Mitra 33, Angela Maria Quinto 34, Maria Chiara Tisi 35, Bruno Martino 36, Adriano Venditti 37, Alessandro Busca 38, Franco Aversa 39 and Livio Pagano 2

Author address: 

1Department of Biomedicine and Prevention, University Tor Vergata, Roma, Italy 2Ematologia Policlinico Gemelli, Roma, Italy 3Clinica Ematologica, Ospedale San Gerardo, ASST Monza, Università Milano Bicocca, Milano, Italy 4Division of Hematology and Bone Marrow Transplantation, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy 5Istituto di Ematologia, Università di Perugia,, Perugia, Italy 6Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy 7Department of Hematology, ASST Spedali Civili di Brescia, Brescia, Italy 8Sezione di Ematologia, Dipartimento dell'Emergenza e dei Trapianti d'Organo-Università di Bari, Italia, Bari, Italy 9UOC Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo,, Pavia, Italy 10IRCCS CASA SOLLIEVO DELLA SOFFERENZA, San Giovanni Rotondo, ITA 11Dipartimento Onco-Ematologico Fondazione ICRRS Policlinico San Matteo, Pavia, ITA 12Azienda Ospedaliera Di Verona, Verona, ITA 13Unità Funzionale di Ematologia, Azienda Ospedaliero-Universitaria Careggi e Università di Firenze,, Firenze, Italy 14UOC Ematologia, Ospedale S. Andrea, Università "Sapienza", Rome, ITA 15Oncohaematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italia, Milano, Italy 16Hematology Division, AOUP, Pisa, Italy 17Dipartimento di Medicina - Unità Operativa di Ematologia, Azienda Ospedaliera di Padova, Padova, Italy 18UOC Ematologia, AO San Giovanni Addolorata,, Rome, ITA 19Clinica di Ematologia, Azienda Ospedaliero-Universitaria, Ospedali Riunti di Ancona,, Ancona, Italy 20Dipartimento di Scienze Biomediche Avanzate, Azienda Ospedaliera Universitaria Federico II,, Napoli, Italy 21University of Parma, Parma, ITA 22Cattedra di Ematologia, Unità di Malattie del Sangue e Trapianto di Midollo Osseo, Dipartimento di Scienze Cliniche e Sperimentali, Università di Brescia e ASST Spedali Civili,, Brescia, ITA 23Hematology and Stem Cell Transplant Unit Regina Elena National Cancer Institute Rome, Italia, Roma, ITA 24Italian Multiple Myeloma Network, GIMEMA, Italy 25Pediatric Oncology and Hematology Unit "lalla Ser' gnoli" - Sant'orsola-Malpighi, Bologna, ITA 26Department of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy 27Dipartimento di Ematologia Clinica, Ospedale Santo Spirito,, Pescara, ITA 28UOC Ematologia e Trapianto di cellule staminali, Azienda Ospedale San Camillo,, Roma, Italy 29Divisione Ematologia-CTMO Ospedale Roberto Binaghi,, Cagliari, Italy 30Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy 31Department of Internal Medicine, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy 32Department of Clinical and Experimental Medicine, Perugia, ITA 33Divisione di Ematologia, Policlinico di Palermo, Italia, Palermo, ITA 34UO Ematologia IRCCS Giovanni Paolo II, Bari, Italy 35Department of Cell Therapy and Haematology, San Bortolo Hospital, Vicenza, Italy 36Hematology, "Bianchi Melacrino Morelli", Reggio Calabria, ITA 37Fondazione Policlinico Tor Vergata, Rome, Italy 38Dipartimento di Oncologia e Ematologia, SSD Trapianto Allogenico di Cellule Staminali, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy 39Azienda Ospedaliero-Universitaria di Parma,Hematology, Italy, Parma, Italy


Introduction.During last years, a reduction in invasive aspergillosis (IA) incidence and mortality was observed in acute myeloid leukemia (AML) patients undergoing to induction phase of treatment. Instead, the incidence of IA and the attributable mortality rate (AMR) during the consolidation has not been recently evaluated. It is also uncertain whether posaconazole prophylaxis during induction chemotherapy affects IA on consolidation phase.

Design and Methods. The aim of our study was to evaluate incidence and mortality for IA in AML patients during the consolidation phase. All cases of proven/probable IA observed during consolidation chemotherapy in adult and pediatric patients with AML, who received conventional chemotherapy, between 2011 and 2015 were retrospectively collected in a multicenter study involving 38 Italian hematologic centers. All relevant clinical data were collected in CRFs.

Results. A total of 2556 of AML patients in consolidation phase were registered. A total of 52 patients (2%) developed an IA [13 proven (0,5%) and 39 probable (1.5%)]. Male/female ratio was 33/19, median age was 57 yrs (range 5-79). As a consolidation, all these patients received high/intermediate doses cytarabine, in combination with an anthracycline in 30. Only 21 of 52 (40%) were on antifungal prophylaxis at the time of IA diagnosis: posaconazole in 5 (24%), fluconazole in 6 (28%), itraconazole in 5 (24%), liposomal amphotericin B (L-AmB) in 4 (19%) and voriconazole in 1 (5%). In 2 of 52 IA was a reactivation of an infection diagnosed during induction (Fig.).

Empiric antifungal therapy was initiated in 33 cases (65%) (mainly L-AmB: 24/33, 73%), while the remaining 19 (35%) received a pre-emptive/targeted approach. Fourteen cases switched from L-AmB to voriconazole, so that the most frequently targeted antifungal therapy was voriconazole (29/52, 55%). The median duration of antifungal treatment was 89 days (range 12-700). The overall mortality at day 120 was 19% (10/52), but the AMR was only 3.2% (5/52).

During induction, many patients (85%) received posaconazole as antifungal prophylaxis while the remaining 15% received other antifungals. (Fig.) During consolidation, antifungal prophylaxis was performed in about 50% of the patients. The most commonly used drug was fluconazole. In consideration of the hypothesized long-lasting activity of posaconazole, we also performed an analysis of incidence of IA during consolidation taking into whether or not the patients received posaconazole during induction. Considering the overall population of AMLs treated in consolidation no statistical differences were observed between those receiving in induction posaconazole or other prophylaxis, even if a lower percentage of patients in posaconazole arm developed an IA. (Fig.)

Conclusion. Our study shows that the incidence of IA during the consolidation in patients with AML is low but not absent. Similarly, also the AMR is low, likely due to advances in diagnosis and antifungal therapy. It is still a matter of discussion whether or not prophylaxis is needed in this subset of patients, since these are in remission and often candidates for transplantation. Finally, the long-lasting benefits of posaconazole is not confirmed but it might be correlated to the few cases of IA observed.



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Full conference title: 

59th American Society of Hematology Annual Meeting 2017
    • ASH 59th (2017)