Lack of Effective Strategies for Myeloproliferative Neoplasms Represents Unmet Need

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A recent review examined the current evidence regarding risk factors, molecular characterization, and treatment options for myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) represent a heterogenous group of disorders of the hematopoietic stem cell, with a high risk of evolution into acute myeloid leukemia (AML). Prognosis is poor, with a medium overall survival ranging from 2.6 to 7 months. A recent review examined the current evidence regarding risk factors, molecular characterization, and treatment options.

The major causes of morbidity and mortality are usually thrombohemorrhagic events and less frequently infectious complications, and/or transformation to blast phase, often termed secondary AML or blast-phase MPN (MPN-BP). The term MPN-BP has been proposed by the International Working Group for Myelofibrosis Research and Treatment to reflect the occurrence of leukemic transformation in the classical BCR-ABL1—negative MPNs.

Currently, there is no standard of care for managing the blast phase of these diseases; no treatment has consistently led to prolonged survival and/or hematological remission apart from an allogeneic stem cell transplant, the authors wrote.

The frequency of leukemic evolution varies according to the subtype of MPN. It is highest in primary myelofibrosis (PMF), where it is estimated to be approximately 10% to 20% at 10 years, followed by polycythemia vera, with a risk of 2.3% at 10 years and 7.9% at 20 years. AML transformation in essential thrombocythemia is considered relatively rare.


Different factors are associated with leukemic evolution in MPN, but generally include advanced age, leukocytosis, exposure to myelosuppressive therapy, cytogenetic abnormalities, and increased number of mutations in genes associated with myeloid neoplasms.

Independent risk factors for leukemic transformation in PMF include peripheral blood (PB) blast greater than 3% and platelet count less than 100 x 109 L. Other proposed risk factors include increased serum interleukin 8, or C-reactive protein levels, age older than 65 years, and PB blast count greater than 1%.

Unfavorable karyotype and thrombocytopenia were also identified as being the most important risk factors for leukemic evolution in PMF.

Regarding biological risk factors, a complex/monosomal karyotype is one important risk factor, as a favorable karyotype is infrequent in MPN-BP. In addition, several recurrent gene mutations, including those involving epigenetic modifiers and spliceosome machinery, are involved in this phase of the disease. Using a candidate gene approach, 5 mutated genes including ASXL1, SRSF2, EZH2, IDH1, and IDH2, were associated with shorter overall survival and leukemia-free survival, defining a high-molecular risk category.

MPN-BP represents an area of urgent clinical need, the researchers said. Conventional antileukemic therapy has limited efficacy in patients with BCR-ABL1—negative MPNs in accelerated or blast phase of the disease. Currently, stem cell therapy is the best option, but it first requires intensive chemotherapy to reduce the disease burden to become eligible. In most patients, advanced age and significant comorbidities disqualifies them from a transplant.

Effectively targeted chemotherapeutic agents that are currently available include 2 hypomethylating agents: 5-azacytidine (azacytidine) and 5-aza-2' deoxycitidine (decitabine).

Among future therapies, the researchers called CPX-351 (Vyxeos), a liposome formulation of cytarabine and daunorubicin, promising. It is approved for treatment of therapy-related or secondary AML.

The researchers said participation of patients in clinical trials should be strongly encouraged.


Iurlo A, Cattaneo D, Gianelli U. Blast transformation in myeloproliferative neoplasms: risk factors, biological findings, and targeted therapeutic options [published online April 13, 2019]. Int J Mol Sci. doi: 10.3390/ijms20081839.