Leukemic Transformation in MPNs a Major Challenge for Clinicians

There is no standard of care treatment option for patients with leukemic transformation in myeloproliferative neoplasms (MPNs), though new approaches may provide practice-changing strategies, according to a case-based review published in the Hospital Physician Hematology-Oncology Board Review Manual (January/February 2018;13[1]:7-22).

Lorenzo Falchi, MD, and Srdan Verstovsek, MD, PhD, University of Texas MD Anderson Cancer Center (Houston, TX) collaborated on a review of the diagnosis criteria, risk stratification, treatment options, and disease evolution of polycythemia vera and essential thrombocythemia. In a subsection of the disease evolution section, Drs Falchi and Verstovsek detail the incidence of leukemic transformation in patients with MPNs.

“The presence of more than 20% of blasts in peripheral blood or bone marrow in a patient with MPN” constitutes a leukemic transformation, they wrote. Up to 10% of patients diagnosed with MPNs may experience leukemic transformation, which may or may not be preceded by a myelofibrosis phase. In the specific instance of extramedullary transformation, a lower percentage of blasts can be seen in the bone marrow compared with the peripheral blood.

As for the pathogenesis of leukemic transformation, Drs Falchi and Verstovsek explain that there may be an association with genetic instability, which may facilitate the acquisition of mutations such as TET2, ASXL1, EZH2 and DNMT3, IDH1/2, and TP53.

The researchers list the clinical risk factors for leukemic transformation, including advanced age, karyotypic abnormalities, prior therapy with alkylating agents or P-32, splenectomy, increased peripheral blood or bone marrow blasts, leukocytosis, anemia, thrombocytopenia, and cytogenetic abnormalities.

While prognosis of leukemic transformation is poor and patient survival rarely exceeds 6 months, there are multiple treatment options for these patients, ranging from low-intensity regimens to aggressive acute myeloid leukemia (AML)-type induction chemotherapy. Nonetheless, there is no standard of care for leukemic transformation in MPN, and no strategy appears clearly superior to the others. Optimal treatment strategy is dependent on individual patient characteristics, researchers explain (ie, hematopoietic stem cell transplantation is effective only in patients with chemosensitive disease and good performance status).

Dr Verstovsek told Journal of Clinical Pathways in a comment that any and all questions related to individual patient treatment strategy should be directed to the NCCN guideline for the management of myelofibrosis. “[This guideline] is up-to-date and should be used as standard-of-care in the US,” he told the journal.

Among the notable experimental approaches to leukemic transformation are hypomethylating agents (eg, decitabine and azacitidine) with or without ruxolitinib, the researchers added. As research in leukemic transformation in MPNs continues to evolve, “novel strategies are needed to improve patients’ outcomes,” they concluded.—Zachary Bessette