Treatment of patients in the plethoric phase of the disease is aimed at ameliorating symptoms and decreasing the risk of thrombosis or bleeding by reducing the blood counts. This is accomplished by myelosuppressive drugs and, additionally in some patients, phlebotomies, platelet-reducing agents, or pegylated interferon-α therapy.
Treatment should be individualized according to risk factors:
— High risk: patients with previous thrombosis and/or transient ischemic attacks
— Intermediate risk: patients older than 60 years of age
— Low risk: remaining patients
High-risk and intermediate-risk patients require interferon or other myelosuppressive therapy.
Absolute leukocyte count correlates with thrombotic complications; this laboratory parameter is now evaluated in the therapeutic decision-making process as are additional risk factors, including hypertension, smoking, and diabetes.
— Myelosuppressive therapy decreases blood counts, decreases risk of vascular events, ameliorates symptoms, and increases overall sense of well-being. Although there is also the clinical impression that it increases a patient’s long-term survival, there are no clinical studies to document this.
— At present, hydroxyurea at doses of 500 to 2500 mg daily is the preferred treatment.
— Hydroxyurea’s suppressive effect is of short duration. Thus, continuous rather than intermittent therapy is required. Because it is short acting, it is relatively safe to use; even when excessive marrow suppression occurs, the blood counts rise within a few days of decreasing the dose or stopping the drug.
— Because it is not an alkylating agent, hydroxyurea has less potential for causing leukemic transformation.
— Busulfan (Myleran) or P32 may be used in selected cases.
— This technique is best used in conjunction with myelosuppression; it is also used as the initial treatment by some physicians.
— Phlebotomy alone is recommended for low-risk disease. Most patients of average size can tolerate initial phlebotomy of 450 to 500 mL about every 4 days until the target hemoglobin level is reached.
— Phlebotomy contributes to iron deficiency. Iron supplementation is counterproductive and may result in rapid reappearance of polycythemia, but a short course of oral iron therapy is often helpful in amelioration of fatigue.
— Alone, phlebotomy is associated with a higher incidence of thrombotic events, especially in older patients, those with a high phlebotomy requirement, and those with a prior thrombotic event.
Summary of therapeutic approach for patients not participating in clinical trials:
— Myelosuppression with hydroxyurea daily, both as initial therapy (1500 mg qd) and long-term treatment (500 to 2000 mg qd), aiming to maintain hemoglobin, neutrophil, and platelet counts at low-normal levels. In addition, some patients require the use of phlebotomies and/or anagrelide to maintain the hemoglobin and platelet levels in normal ranges.
— Aspirin at a dose 80 to 100 mg daily is given to all patients without histories of major bleeding or gastric intolerance and when platelet count is not over 1000 × 109/L.
— Allopurinol for elevated uric acid levels and medication to control pruritus are used when required.
— Judicious phlebotomies with isovolemic replacement in patients with hematocrits greater than 55% (some recommend keeping hematocrit at < 45% for men and < 43% for women) and in patients who report immediate improvement of symptoms after phlebotomy. Symptoms that may be related to hyperviscosity are headaches, difficulty concentrating, and fatigue.
— Pegylated interferon preparations are being used increasingly, with excellent results reported in pilot studies.
— JAK2 tyrosine kinase inhibitors have been shown effective and are recommended for hydroxyurea intolerant or refractory disease.