Polycythemia Vera and Essential Thrombocythemia: Current Management
Clinical risk factors for leukemic transformation include 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. Hydroxyurea, interferon, and ruxolitinib have not been shown to have leukemogenic potential thus far. Prognosis of leukemic transformation is uniformly poor and patient survival rarely exceeds 6 months.
There is no standard of care for leukemic transformation of MPN (MPN-LT). Treatment options range from low-intensity regimens to more aggressive AML-type induction chemotherapy. No strategy appears clearly superior to others.128 Hematopoietic stem cell transplantation is the only therapy that provides clinically meaningful benefit to patients,129 but it is applicable only to a minority of patients with chemosensitive disease and good performance status.130 Notable experimental approaches to MPN–LT include hypomethylating agents, such as decitabine131 or azacitidine,132 with or without ruxolitinib.133-135
Conclusion
PV and ET are rare, chronic myeloid disorders. Patients typically experience a long clinical course and enjoy near-normal quality of life if properly managed. The 2 most important life-limiting complications of PV and ET are thrombohemorrhagic events and myelofibrosis/AML transformation. Vascular events are at least in part preventable with counseling on risk factors, phlebotomy (for patients with PV), antiplatelet therapy, and cytoreduction with hydroxyurea, IFNs, or anagrelide (for patients with ET). In addition, ruxolitinib was recently approved for PV patients after hydroxyurea failure. PV/ET transformation in myelofibrosis or AML is part of the natural history of the disease and no therapy has been shown to prevent it. Treatment follows recommendations set forth for PMF and AML, but results are generally poorer and novel strategies are needed to improve patients’ outcomes.
