hematology and oncology
Polycythemia Vera
Treatment of Polycythemia Vera
Phlebotomy Possiblyaspirintherapy Possibly targeted therapy withruxolitinibor pegylated interferon Therapy must be individualized according to age, sex, medical status, clinical manifestations, and hematologic findings ( Treatment references ). However, previous criteria used to stratify treatment by high- or low-risk classification such as age and extreme thrombocytosis (1,000,000/mcL [1000 Although very high leukocyte counts (>30,000/mcL [>30×109/L]) have been correlated with disease acceleration, there is no evidence that lowering the leukocyte count with chemotherapy prolongs survival. In fact, the polycythemia vera hematopoietic stem cell is resistant to conventional chemotherapy, and lowering the leukocyte or platelet count to normal does not prevent thrombosis if the red cell mass is not normalized by phlebotomy. 42% in women. A randomized controlled trial showed that patients randomized to a hematocrit < 45% had a significantly lower rate of cardiovascular death and thrombosis than did those with a target hematocrit of 45 to 50% ( Treatment references ). In pregnancy, the hematocrit level should be lowered to Initially, 500 mL of blood is removed every other day. Less blood is removed (ie, 200 to 300 mL twice a week) from older patients and from patients with cardiac or cerebrovascular disorders. Once the hematocrit is below the target value, it is checked monthly and maintained at this level by additional phlebotomies as needed. If necessary, intravascular volume can be maintained with crystalloid or colloid solutions. Platelets may increase as a result of phlebotomy, but this increase is small and transient, and a gradual increase in the platelet count as well as the leukocyte count is a feature of polycythemia vera and requires no therapy in patients without symptoms. In patients treated only with phlebotomy, the phlebotomy requirement will eventually diminish. This is not a sign of marrow failure (ie, the so-called spent phase) but rather is due to an expansion of plasma volume. A new class of agents, hepcidin mimetics such as rusfertide, is being studied ( Treatment references ). These agents are used to prevent iron absorption, which is increased in polycythemia vera. They may obviate the need for additional phlebotomy once body iron stores are depleted by phlebotomy. Aspirinalleviates symptoms of microvascular events. Thus, patients who have erythromelalgia, ocular migraine, or transient ischemic attacks should be givenaspirin81 to 100 mg orally once a day unless contraindicated (eg, because of acquired von Willebrand disease); higher doses may be required but clearly increase the risk of hemorrhage.Aspirindoes not reduce the incidence of macrovascular events and thus is not indicated in patients with polycythemia vera (in the absence of other indications) who do not have symptoms, particularly in patients>65 years of age. Numerous studies have shown that many previously used myelosuppressive treatments, includinghydroxyurea, radioactive phosphorus, and alkylating agents such asbusulfanandchlorambucil, do not reduce incidence of thrombosis and fail to improve survival over appropriate phlebotomy because the affected hematopoietic stem cell is resistant to them. Agents such aschlorambucil,busulfan, radioactive phosphorus, andhydroxyureacan increase the incidence of acute leukemia and solid tumors; these agents are not recommended except in special circumstances.Hydroxyureashould be prescribed only by specialists familiar with its use and monitoring. If intervention other than phlebotomy is necessary (eg, because of symptoms or thrombotic events), pegylated interferon orruxolitinibis preferred.Anagrelidehas been used to control the platelet count but has both cardiac and renal toxicity and can cause anemia. ( Treatment references ) specifically target the affected hematopoietic stem cells but not normal stem cells. These medications are usually well tolerated and are effective in controlling pruritus and excessive blood production as well as in reducing spleen size. demonstrated better molecular response as well as superior complete remission and event-free survival rates as compared with best supportive care ( Treatment references ). It is not necessary to lower the white blood cell or platelet count to normal in patients without symptoms. Hyperuricemiashould be treated withallopurinol300 mg orally once a day if it causes symptoms or if patients are receiving simultaneous myelosuppressive therapy. Pruritusmay be managed with antihistamines but is often difficult to control;ruxolitiniband interferon are effective.Cholestyramine,cyproheptadine,cimetidine,paroxetine, or PUVA light therapy may also be successful. After bathing, the skin should be dried gently. 1.Spivak JL: How I treat polycythemia vera.Blood134(4):341–352, 2019. doi:10.1182/blood.2018834044 2.Marchioli R, Finazzi G, Specchia G, et al: Cardiovascular events and intensity of treatment in polycythemia vera.N Engl J Med368:22–33, 2013. 3.Handa S, Ginzburg Y, Hoffman R, Kremyanskaya M: Hepcidin mimetics in polycythemia vera: resolving the irony of iron deficiency and erythrocytosis.Curr Opin Hematol30(2):45–52, 2023. doi:10.1097/MOH.0000000000000747 4.Gisslinger H, Klade C, Georgiev P, et al:Ropeginterferon alfa-2bversus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study [published correction appears inLancet Haematol2020 Feb 25;:].Lancet Haematol7(3):e196–e208, 2020. doi:10.1016/S2352-3026(19)30236-4 5.Harrison CN, Nangalia J, Boucher R, et al:RuxolitinibVersus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial.J Clin Oncol41(19):3534–3544, 2023. doi:10.1200/JCO.22.01935 