Myeloid Blastic Transformation of Myeloproliferative Neoplasms – A Review of 113 Cases.
Authors: Noor Syed , Tan Wei , Wilding Gregory , Ford Laurie Ann , Barcos Maurice , Sait Sheila N.J. , Block AnneMarie W. , Thompson James E. , Wang Eunice S. , Wetzler Meir 
Published: October 2019

Abstract
Abstract 3113
Poster Board III-50
Blastic transformation of myeloproliferative neoplasms (MPN) is still poorly understood. Mutations of JAK2V617F were described in the majority of MPN patients but only about half of those undergoing blastic transformation continue to harbor that mutation. We describe a cohort of 23 patients from Roswell Park Cancer Institute (RPCI) and discuss 90 additional cases from the English literature for whom biologic features were described. We also screened our cases for JAK2V617F, JAK2T875N and MPL515L/K. We initially compared our 23 patients to the 90 cases from the literature. Our population had significantly less patients with prior history of polycythemia vera (22% vs. 53%; P<0.0001), shorter time from MPN diagnosis to blastic transformation (<5 years to transformation in 68% vs. 40%; p=0.0296), <3 prior therapies (100% vs. 16%; p<0.0001), more frequent use of hydroxyurea (63% vs. 27%; p=0.0056), less frequent use of alkylating agents (5% vs. 54%; p<0.0001) and more frequent use of erythropoietin (11% vs. 0%; p=0.0332). Detection of normal karyotype at the time of blastic transformation was more common in the RPCI population (35% vs. 7%; p=0.0033). The two populations did not differ in regards to age at diagnosis of MPN or blastic transformation, gender, prior use of interferon or karyotype aberrations. Interestingly, the overall survival of the two cohorts from the time of blastic transformation was similar [3 vs. 5 months; 95% confidence interval (CI) 2 to 5 vs. 3 to 9; p=0.1639]. We therefore looked at the outcome of the entire cohort (n=113). Patients with prior history of essential thrombocythemia survived longer (8.6 months; 95% CI 4.3, 24) than patients with prior history of myelofibrosis (4.5 months; 95% CI 2, 11) or polycythemia vera (3 months; 95% CI 2, 5) (p=0.0224). Further, patients with <3 prior therapies had significantly longer survival (8 vs. 3 months; 95% CI 4 to 11 vs. 2 to 5; p=0.0212). Finally, patients with complex karyotype had significantly shorter survival (3 vs. 5 months; 95% CI 2 to 5 vs. 3 to 10); p=0.0272). No difference in survival was detected based on time from MPN diagnosis to blastic transformation, age, prior hydroxyurea treatment, prior alkylating agents, erythropoietin, or interferon, or presence of non-complex karyotype aberrations. We then evaluated the treatment response among the PRCI patients (n=23). A total of 20/23 patients underwent induction treatment with cytarabine and an anthracycline containing regimens; 12 achieved remission and eight did not. The overall survival of those achieving remission was significantly longer than those who did not [13 vs. 3 months; 95% CI 8 to 25 vs. 2 to 4); p<0.0001]. Three patients underwent an allogeneic transplantation and their survival was significantly longer that those who did not [11 vs. 4 months; 95% CI 8 to 57 vs. 3 to 5; p=0.0119]. Samples were available for eight of the patients at disease transformation; JAK2V617F was detected in two and none had T875N or MPL515K/L. In summary, patients with less than three prior therapies and lack of complex karyotype have longer survival following blastic transformation. Finally, allogeneic transplantation represents the only chance for long term survival in these patients.

Disclosures
No relevant conflicts of interest to declare.