Case-Based Review

Polycythemia Vera and Essential Thrombocythemia: Current Management

2018 January/February;13(1):7-22

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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.