The Experience of Gruppo Laziale for the Study of Ph-, Chronic Myeloproliferative Syndromes in the Treatment of Myeloproliferative Neoplasms in Blastic Phase with Azacytidine

Prognosis of patients with myeloproliferative neoplasms developing blast phase (MPN-BP) is very poor with a median survival of about 2-3 months; nowadays, no treatment can induce a durable complete response (CR) in patients who are not candidate to BMT. Very recently, a possible role of azacytidine (AZA) was reported in these patients, but there is still a lack of data as to its efficacy; to address this issue, we evaluated retrospectively 19 patients (M/F 15/4 F, median age 71.3 years, interquartile range (IQR) 64.5 – 77.7] with MPN-BP treated with AZA and collected in the database of our cooperative group. The primary MPN diagnosis was Essential Thrombocythemia in 6 cases (31,6%), Policythemia Vera in 3 (15,8%), Primary Myelofibrosis in 7 (36,8%) and MDS/MPN in 3 (15,8%); the JAK-2 V617F mutation was present in 11/17 patients tested (64.7%). All but 1 patient received previous chemotherapies during chronic phase. Median time from diagnosis to BP evolution was 52.6 months (IQR 11.2 – 181.8). All patients were treated with AZA at the standard dosage of 75 mg/m²: 16 patients received a 7-day schedule and 3 a 5-day schedule every 28 days. Two patients died early after 5-AZA initiation for pulmonary fungal infection and respiratory failure respectively, 4 patients had a disease progression, 4 patients maintained stable disease, 3 patients had a hematological improvement, 1 patient achieved partial response and 5 patients (26.3%) a CR after 4, 4, 4, 5, and 12 months. The median cumulative survival from BP evolution was 9.9 months (95%CI 6.7 – 13.1).A comparison with the historical cohort of 72 patients of our database presenting MPN-BP and treated with approaches other than AZA (median cumulative survival 3.1 months, 95%CI 1.1 – 5.1) showed a significant advantage for patients treated with AZA (p= 0.02). Our data confirm the relative good efficacy and safety of AZA in this group of patients with otherwise dismal prognosis, underlining the possible achievement of long-lasting responses in a sizeable portion of them.