PB1726 DOUBLE FLUDARABINE‐BASED INDUCTION AND INFECTIVE RISK: THE BOLOGNA EXPERIENCE.
Authors: C. Sartor, S. De Polo, R.E. Lewis, G. Marconi, M. Abbenante, J. Nanni, A. Talami, M. Olivi, L. Bertamini, S. Ragaini, S. Paolini, S. Parisi, G. Cristiano, M. Ottaviani, L. Bandini, M.C. Fontana, G. Martinelli, A. Curti, C. Papayannidis, M. Cavo, M. Stanzani
Journal: HemaSphere (2019)

Background: “3+7” represents the current standard of care for acute myeloid leukemia (AML). Fludarabine‐based regimens have limited application due to the absence of survival benefit and prolonged hematological toxicity after 2 nd cycle. Infections in neutropenic patients represent an important cause of mortality and morbidity. Aims: To analyze the infective risk associated with intensive chemotherapy based on double‐FLAI induction. Methods: We retrospectively collected data of 40 consecutive adult patients with newly diagnosed AML treated with FLAI‐5 induction therapy (Fludarabine IV 25 mg/sqm/die days 1‐5, Cytarabine IV 2000 mg/sqm/die days 1‐5 and Idarubicin 10 mg/sqm/die on days 1, 3 and 5). Patients in complete remission (CR) proceeded to second FLAI‐5 followed by allogeneic transplant or chemotherapy consolidation. The incidence and type of infective events were collected in 36/40 patients. Patients were compared with a historical court of 39 patients treated with non‐fludarabine based induction. MRD was assessed by qRT‐PCR or WT1 gene expression. Data were harmonized using RedCap custom eCRFs. Results: Forty patients received FLAI‐5 from August 2015 to December 2018. Median age at diagnosis was 53 years (range 19‐66). According to NCCN‐2016 stratification criteria 12/40 (30%) patients were favorable, 10/40 (25%) intermediate and 17/40 (42.5%) high risk; one patient wasn’t evaluable. Thirty‐five patients (87.5%) achieved a CR after induction, 4 (10%) patients were refractory and 1 patient (2.5%) died during induction. Twenty‐nine of 40 patients were evaluable for MRD analysis and 15/29 (52%) patients achieved MRD negativity. Twenty‐two of the 35 patients in CR proceeded to 2 nd FLAI‐5 chemotherapy regimen. At induction, patients recovered from neutropenia (ANC&gt; 500 x 10 9 /L) after 21.5 days (range 13‐32) from the end of chemotherapy and reached platelet &gt; 20 x 10 9 /L after a median of 16 days (range 10‐33). Patients spent a median of 33 nights in hospital (range 14‐61; historical control 35 nights, range 31‐42; p = ns). After 2 nd cycle, median days for ANC and platelet recovery were 29 and 26 (range 16‐45 and 13‐60 respectively, historical control for ANC recovery 20 days, range 18‐25; p = 0.001). Median patients’ hospitalization was 39 nights (range 26‐55; historical control 32.5 nights, range 24‐47; p = 0.003). Patients and historical controls received same antimicrobial prophylaxis in induction and experienced respectively 33/36 (91.7%) and 36/39 (92.3%) infective events. Patients had a higher number of infections of unknown origin (15/33 vs 6/36, p. 002), and lower incidence of Gram‐positive isolates (4/12 vs 15/22, p = 0.002). Any‐mould infection rate was comparable in the two groups. Twenty‐seven of 36 patients and 22/39 controls proceeded to consolidation chemotherapy. Antimould prophylaxis was different, with patients receiving mainly posaconazole 17/27 (63 %), fluconazole 5/27 (18.5%), itraconazole 4/27 (14.8%) and voriconazole 1/27 (3.7%); while controls received posaconazole 4/22 (18.2%) fluconazole 5/22 (22.7%), itraconazole 12/22 (54.5%) and voriconazole 1/22 (4.5%). Twenty‐two of 27 patients (81.5%) and 17/22 (77.3%) in controls had an infection. Three patients of 27 had a probable mould infection and 1 possible, compared to 1 proven mould infection and 1 possible in the 22 controls (any‐mould infection 4/27 vs 2/22). Summary/Conclusion: In our experience FLAI‐5 is associated with high CR rates, but prolonged neutropenia and hospitalization after 1 st consolidation. However, this doesn’t translate in a higher infection risk in this set of patients.