Incidence of Infectious Complications in MDS/AML Patients Treated with Azacitidine By the Italian Cooperative Groups Gruppo Romano MDS (GROM) and Basilicata MDS Registry

• Published in: Blood 2014-12, Vol.124 (21), p.3265-3265
• Main Authors: Voso, Maria Teresa, Niscola, Pasquale, Piciocchi, Alfonso, Pagano, Livio, Maurillo, Luca, Musto, Pellegrino, Fianchi, Luana, Mansueto, Giovanna, Aloe-Spiriti, Antonietta, Buccisano, Francesco, Venditti, Adriano, Tendas, Andrea, Mancini, Stefano, Piccioni, Anna Lina, Andriani, Alessandro, Latagliata, Roberto, Alimena, Giuliana, Filardi, Nunzio, Fragasso, Alberto, Tafuri, Agostino, Fenu, Susanna, Breccia, Massimo
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V124.21.3265.3265

Azacitidine (AZA) is the standard of care for higher-risk myelodysplastic syndromes (MDS). Cytopenias are a major problem during the first treatment cycles due to MDS itself and to the mechanism of action of the drug, which includes not only demethylation, but also cytotoxicity and apoptosis. We evaluated the incidence of infectious complication during AZA treatment in 200 “real life” patients, collected retrospectively by the italian cooperative groups Gruppo Romano MDS (GROM) and Basilicata MDS Registry. Patients gave informed consent and the study was approved by the Ethycal Committes of partecipating Centers. Patient started AZA between 3/2006 and 3/2014. Median age at treatment start was 71 years (range 33-93 yrs, 66 females, 134 males). There were 182 MDS (up to 20% BM-Blasts) and 18 AML (median BM-blasts 23%, range 21-60% BM-blasts). In MDS, IPSS stratification (n=178) was: low: 4%, Int-1: 19%, Int-2: 60%, high 17%, and according to R-IPSS (n=123 pts): low: 4%, intermediate: 20%, high: 51%, very-high: 20%. MDS-specific comorbidity index (MDS-CI) was available for 154 patients: 50 patients were classified as low-risk (0), 85 as intermediate (1-2), and 19 as high risk (>2). Azacitidine was started at a median of 1.4 months from initial diagnosis. One-hundred-sixty-six patients received AZA at the standard dose of 75 mg/sqm (7 days continuously: 22%, 5-2-2 days: 64%, 6-1-1: 4%) while 34 patients received AZA at 50 mg/sqm for 5- 7 days. Response, according to IWG 2006 criteria, was evaluable in 188 patients: 27 obtained complete remission (CR, 14%), marrow CR was achieved in 6 (3%), partial remission (PR) in 30 (16%), hematological improvement (HI) in 40 (21%), disease was reported stable (SD) in 54 (29%), whereas 31 patients presented progressive disease (16%). A median of 10 (range 1-62) cycles of AZA were delivered. Probability of response was independent from age, IPSS, IPSS-R, MDS-CI, and was associated to a shorter time from diagnosis to therapy initiation (p=0.04) and to the 75 mg/sqm through 7 days vs 50 mg/sqm through 5 -7 days schedule (60 vs 30% CR/PR/HI, p=0.007). With a median follow-up of 14.8 months (range 0-100 months), 57 patients are alive, resulting into a median overall survival of 17.2 months. IPSS and MDS-CI did not predict survival, while grouping according to IPSS-R was associated to a significantly different survival probability (p=0.0007). Across delivery of a total of 1547 AZA cycles, 213 (13%) febrile events were recorded. Fe