Prognosis of patients with myeloproliferative neoplasms developing blast phase (MPN-BP) is very poor. Median survival of these patients is about 2-3 months (Cervantes F, Acta Hemathol 1991; Mesa RA, Blood 2005; Kantajian HM, Leukemia 1997; Tam CS, Blood 2008) and nowadays no drug can induce a durable complete response (CR) in patients who are not candidate to BMT. A phase II study (Thepot S., Blood 2010, 116, 3735) recently reported on 54 patients with MPN-BP treated with 5-AZA, showing a median survival of 9 months with an Overall Response Rate (ORR) of 52% (24% complete response).

Material and Methods

To highlight the role of 5-AZA in this subset, we evaluated retrospectively 16 patients (M/F 12/4, median age 63.5 years, range 51 - 81) with MPN-BP according to standard definition (Mascarenhas J et al., Leuk Res. 2012 Dec;36(12):1500-4) treated with 5-AZA in the last 3 years and reported in the database of Gruppo Laziale for the study of Ph- SMPC. Primitive MPN diagnosis was Essential Thrombocythemia in 5 cases, Primary Myelofibrosis in 6, Polycythemia Vera in 1 and MDS/MPN in 4; the JAK-2 V617F mutation was present in 7/14 patients tested (50%); all, but 1, patients received a previous treatment during chronic myeloproliferative phase [12 patients with Hydroxyurea (HU) alone, 1 with HU + Anagrelide, 1 with HU + Pipobroman and 1 with Melphalan + Allogeneic bone marrow transplantation]. Median time from diagnosis to BP evolution was 47 months (range 12 - 317). All patients were treated with 5-AZA at the dosage of 75 mg/m2: as to the schedule, 13 patients received a 7-day schedule and 3 patients a 5-day schedule every 28 days. At the time of evolution, median WBC value was 17.1 x 106/L (range 5.0–89.5), median Hb level 9.9 g/dl (range 6.6–12.7) and median PLT value 155 x 106/L (range 7–434). Two patients died early after 5-AZA initiation from pulmonary fungal infection and respiratory failure respectively, 4 patients had a disease progression, 4 patients a stable disease, 2 patients(14%) had an hematological improvement and 4 pts (28.5%) a complete response after 4, 4, 5, and 12 months; median survival of patients in CR is 19.6 months. The overall survival from BP evolution was 8.1 months (range 1–49.5 months) and 3/4 patients in CR are still alive after 15, 24 and 49.5 months, respectively.

Conclusions

Our data confirm the relative efficacy and safety of 5-AZA in this group of patients with otherwise dismal prognosis, underlining the possible achievement of long-lasting responses in a sizeable portion of them.

Disclosures:

Off Label Use: Bendamustine.

Topics:
azacitidine, myeloproliferative disease, complete remission, anagrelide, bendamustine, blast phase, bone marrow transplantation, allogeneic, brachial plexus neuritis, disease progression, hydroxyurea

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2013 by The American Society of Hematology
2013
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