Myeloid blastic transformation of myeloproliferative neoplasms—A review of 112 cases

Abstract

Blastic transformation of myeloproliferative neoplasms (MPN) is still poorly understood. We describe a cohort of 23 Roswell Park Cancer Institute (RPCI) patients and 89 additional cases from the English literature for whom biologic features were described. We initially compared our 23 patients to the 89 cases from the literature. Our population had significantly less patients with prior history of polycythemia vera (PV), shorter time from MPN diagnosis to blastic transformation, <3 prior therapies, more frequent use of hydroxyurea and erythropoietin and less frequent use of alkylating agents. Interestingly, the overall survival of the two cohorts from the time of blastic transformation was similar. We therefore looked at the outcome of the entire cohort (n=112). Patients with prior history of essential thrombocythemia survived longer than patients with prior history of myelofibrosis or PV. Further, patients with <3 prior therapies, those who lacked complex karyotype and those <60 year old at MPN diagnosis had significantly longer survival. Among the PRCI population, 20/23 patients underwent induction treatment with cytarabine and an anthracycline containing regimens; 12 achieved remission and their overall survival was significantly longer than those who did not. Three patients underwent an allogeneic transplantation and their survival was significantly longer than those who did not. Patients with <3 prior therapies, those who lack complex karyotype and those <60 at MPN diagnosis have longer survival following blastic transformation. Finally, allogeneic transplantation represents the only chance for long-term survival in these patients.

Treatment outcomes following leukemic transformation in Philadelphia-negative myeloproliferative neoplasms

“…Data pertaining to the prognostic value of cytogenetics in this patient population are limited, with alterations of chromosome 17 and the number of cytogenetic abnormalities having been shown to predict survival in separate reports. 2,4 In the present study, both were associated with poor prognosis, as was the broader MRC category of adverse cytogenetics. Although prognostic factors identified within the whole cohort of patients provide some value, this group was comprised of individuals treated with regimens ranging from strict supportive care to HCT.…”

“…Transformation to acute myeloid leukemia (AML) occurs in ;5% to 10% of cases after 10 y and is associated with exceptionally poor prognosis. [1][2][3][4][5] At present, our understanding of the optimal treatment strategy for patients who undergo leukemic transformation (LT; also referred to as MPN-blast phase 5 ) is limited. In a retrospective analysis of 91 patients with AML arising from myelofibrosis, the median survival from the time of LT was 2.6 mo.…”

A Phase I Study of Topotecan, Carboplatin and the PARP Inhibitor Veliparib in Acute Leukemias, Aggressive Myeloproliferative Neoplasms, and Chronic Myelomonocytic Leukemia

“…Despite advances in the treatment of acute myeloid leukemia (AML) (1), certain groups of AML patients, including the elderly, those with therapy-associated disease, and patients with prior chronic myelomonocytic leukemia (CMML) or myeloproliferative neoplasms (MPNs) have a particularly poor response to conventional cytarabine/anthracycline-based therapy and have an unmet clinical need (2-4). For example, patients with AML that arises in the setting of prior myelofibrosis with myeloid metaplasia have a 41% response rate (all regressing to prior chronic phase MPN and not meeting conventional CR criteria for AML) with conventional therapy but only a 9% 1-year survival (5).…”

The promise of Janus kinase inhibitors in the treatment of hematological malignancies

“…JAK2 mutations are rare in AML, but the majority of AMLs have activated STAT3 and/or STAT5, which may be due to aberrations in signaling molecules upstream of STAT, such as FLT3 [70]. However, AML is a common complication stemming from MPNs [71]. The efficacy of ruxolitinib in treating relapsed/refractory AML and ALL was studied in a Phase II trial.…”