Impact of Invasive Aspergillosis occuring during remission-induction therapy on outcome of Acute Myeloid Leukemia (SEIFEM 2012B Study).

A. Candoni1 , F. Farina2 , K. Perruccio3 , R. Di Blasi4 , M. Criscuolo4 , C. Cattaneo5 , M. Delia6 , D. Lazzarotto1 , M.V. Dubbini1 , G. Dragonetti4 , R. Fanci7 , B. Martino8 , M.I. Del Principe9 , L. Potenza10, N. Vianelli11, A. Chierichini12, M. Garzia13, G. Nadali14, L. Verga15, A. Busca16, L. Pagano4

Author address: 

1University Hospital, Asuiud, Division of Hematology and Stem Cells Transplantation, Udine, Italy, 2 IRCCS San Raffaele, Milan, Italy, 3Division of Pediatric Hematology, University Hospital of Perugia, Perugia, Italy, 4Division of Hematology, IRCCS A Gemelli-University CSR, Rome, Italy, 5Division of Hematology, Spedali Civili, Brescia, Brescia, Italy, 6Division of Hematology, University of Bari, Bari, Italy, 7Division of Hematology, University of Firenze, Firenze, Italy, 8Division of Hematology, Hospital B. Melacrino Morelli, Reggio Calabria, Reggio Calabria, Italy, 9Division of Hematology, University "Tor Vergata" , Rome, Rome, Italy, 10Division of Hematology, University of Modena and Reggio Emilia, Modena, Italy, 11Division of Hematology, University of Bologna, Bologna, Italy, 12Division of Hematology, San Giovanni Addolorata Hospital, Rome, Rome, Italy, 13Division of Hematology, San Camillo Hospital, Rome, Rome, Italy, 14Division of Hematology, University of Verona, Verona, Italy, 15Division of Hematology, San Gerardo Hospital, Monza, Monza, Italy, 16Division of Hematology, AOU Citta della Salute e della Scienza, Torino, Turin, Italy


Objectives: Acute myeloid leukemia (AML) patients are at high risk of invasive aspergillosis (IA) and required a mould active antifungal prophylaxis during induction chemotherapy (CHT). Although IA risk factors have been identified, few data are available on impact of IA, occurring during first remission induction phase, on overall AML outcome.

Methods: The primary endpoint of this prospective, multicentric, case-control study, was to evaluate if IA, occurring during first remission-induction CHT, can affect treatment schedule and, consequently, patient overall survival (OS). We identified 40 AML patients (cases) who developed IA during induction phase, 31 probable (67%) and 9 proven (33%) IA. These cases were matched with a control group (80 AML) without IA, balanced according to age, type of induction CHT, AML characteristics and cytogenetic-molecular risk factors. The overall response rate to induction CHT was the same in the 2 groups.

Results: In the 40 cases with AI, the overall response rate (ORR) to antifungal treatment was favorable (ORR 80%) but it was significantly affected by the achievement of leukemia complete remission (CR) with induction CHT. In fact, in cases with AML responsive to induction CHT, complete responses of IA to antifungal therapy were 96% compared to 21% in cases of AML not responsive to induction CHT (p <0.0001). The adherence to schedule and full doses of CHT was reported in 35% of cases (14/40) and in 76% of controls (61/80) (p = 0.0001). After induction CHT a significant higher number of cases (15/40; 37.5%) compared to controls (21/80; 26%) could not receive additional cycles of CHT (p = 0.01). The IFI related mortality was 22.5%. Comparing OS of 40 cases with the OS of the 80 controls, the median OS of cases was significantly worse with a difference of 12.3 months (12.1 vs 24.4 months, p = 0.04-Figure 1A). However, the occurrence of IA during induction phase did not have a significant impact on the OS of cases who achieved a CR with induction CHT which are able to proceed, despite the IA, with their intensive therapeutic program, achieving the same OS as the control group with an AML in CR (p = ns-Figure 1B). 

Conclusion: These data showed that IAs during induction CHT can delay the subsequent therapeutic program and has a significant impact on OS of AML, specifically in those patients with IA occurring during induction phase who did not achieved a CR of AML with the first course of CHT (Figure 1C).


abstract No: 


Full conference title: 

9th Trends in Medical Mycology Conference 2019
    • TIMM (2019)