The proposed revised World Health Organization criteria for the diagnosis of polycythemia vera (p. vera) requires two major criteria and one minor criterion or the first major criterion together with two minor criteria.
- Hemoglobin of more than 18.5 g/dL in men, 16.5 g/dL in women, or elevated red cell mass greater than 25% above mean normal predicted value.
- Presence of JAK2 617V greater than F or other functionally similar mutations, such as the exon 12 mutation of JAK2.
- Bone marrow biopsy showing hypercellularity with prominent erythroid, granulocytic, and megakaryocytic proliferation.
- Serum erythropoietin level below normal range.
- Endogenous erythroid colony formation in vitro.
- Oxygen saturation with arterial blood gas greater than 92%.
- Thrombocytosis (>400,000 platelets/mm3).
- Leukocytosis (>12,000/mm3).
- Leukocyte alkaline phosphatase (>100 units in the absence of fever or infection).
There is no staging system for this disease.
Patients have an increased risk of cardiovascular and thrombotic events and transformation to acute myelogenous leukemia or primary myelofibrosis.[5-7] Age older than 65 years, leukocytosis, and a history of vascular events (bleeding or thrombosis) are associated with a poor prognosis.[5,8,9]
The primary therapy for p. vera includes intermittent, chronic phlebotomy to maintain the hematocrit below 45%, and this recommendation has been confirmed in a randomized, prospective trial, which demonstrated lower rates of cardiovascular death and major thrombosis using this hematocrit target.[10,11] The target level for women may need to be lower (e.g., hematocrit <40%), but there are no empiric data to confirm this recommendation.
Complications of phlebotomy include:
- Progressive and sometimes extreme thrombocytosis and symptomatology related to chronic iron deficiency, including pica, angular stomatitis, and glossitis.
- Dysphagia that is the result of esophageal webs (very rare).
- Possibly muscle weakness.
(Refer to the PDQ summary on Oral Complications of Chemotherapy and Head/Neck Radiation for more information.)
In addition, progressive splenomegaly or pruritus not controllable by antihistamines may persist despite control of the hematocrit by phlebotomy. (Refer to the PDQ summary on Pruritus for more information.) If phlebotomy becomes impractical, hydroxyurea or interferon-alpha can be added to control the disease.
The Polycythemia Vera Study Group randomly assigned more than 400 patients to phlebotomy (target hematocrit <45), radioisotope phosphorous-32 (2.7 mg/m2 administered intravenously every 12 weeks as needed), or chlorambucil (10 mg administered by mouth daily for 6 weeks, then given daily on alternate months). The median survival for the phlebotomy group (13.9 years) and the radioisotope phosphorous-32 group (11.8 years) was significantly better than that of the chlorambucil group (8.9 years), primarily because of excessive late deaths from leukemia or other hematologic malignancies.[Level of evidence: 1iiA] Because of these concerns, many clinicians use hydroxyurea for patients who require cytoreductive therapy that is caused by massive splenomegaly, a high phlebotomy requirement, or excessive thrombocytosis.
In a pooled analysis of 16 different trials, interferon-alpha therapy resulted in avoidance of phlebotomy in 50% of patients, with 80% of patients experiencing marked reduction of splenomegaly.[Level of evidence: 3iiiDiv] Interferon posed problems of cost, side effects, and parenteral route of administration, but no cases of acute leukemia were seen in this analysis. When patients are poorly compliant with phlebotomy or issues of massive splenomegaly, leukocytosis, or thrombocytosis supervene, treatment with interferon or pegylated interferon is considered for patients younger than 50 years (who are more likely to tolerate the side effects and benefit from a lack of transformation to leukemia), while hydroxyurea is considered for patients older than 50 years.[2,15]
In a Cochrane review of two randomized studies of 630 patients with no clear indication or contraindication for aspirin, those receiving 100 mg of aspirin versus placebo had reduction of fatal thrombotic events, but this benefit was not statistically significant (odds ratio, 0.20; 95% CI, .03–1.14). A retrospective review of 105 patients who underwent surgery documented 8% thromboembolism and 7% major hemorrhage with prior cytoreduction by phlebotomy and postoperative subcutaneous heparin in one half of the patients.
Guidelines based on anecdotal reports have been developed for the management of pregnant patients with p. vera.
- Hydroxyurea (alone or with phlebotomy).[12,13]
- Interferon-alpha [14,18,19] and pegylated interferon-alpha.[20,21]
- Rarely, chlorambucil or busulfan may be required, especially if interferon or hydroxyurea are not tolerated, as is often seen in patients older than 70 years.
- Low-dose aspirin (≤100 mg) daily, unless contraindicated by major bleeding or gastric intolerance.[8,16]
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with polycythemia vera. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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- Streiff MB, Smith B, Spivak JL: The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members' practice patterns. Blood 99 (4): 1144-9, 2002. [PUBMED Abstract]
- McMullin MF, Bareford D, Campbell P, et al.: Guidelines for the diagnosis, investigation and management of polycythaemia/erythrocytosis. Br J Haematol 130 (2): 174-95, 2005. [PUBMED Abstract]
- Campbell PJ, Green AR: The myeloproliferative disorders. N Engl J Med 355 (23): 2452-66, 2006. [PUBMED Abstract]
- Marchioli R, Finazzi G, Landolfi R, et al.: Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol 23 (10): 2224-32, 2005. [PUBMED Abstract]
- Elliott MA, Tefferi A: Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 128 (3): 275-90, 2005. [PUBMED Abstract]
- Chait Y, Condat B, Cazals-Hatem D, et al.: Relevance of the criteria commonly used to diagnose myeloproliferative disorder in patients with splanchnic vein thrombosis. Br J Haematol 129 (4): 553-60, 2005. [PUBMED Abstract]
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- Bonicelli G, Abdulkarim K, Mounier M, et al.: Leucocytosis and thrombosis at diagnosis are associated with poor survival in polycythaemia vera: a population-based study of 327 patients. Br J Haematol 160 (2): 251-4, 2013. [PUBMED Abstract]
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- Marchioli R, Finazzi G, Specchia G, et al.: Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 368 (1): 22-33, 2013. [PUBMED Abstract]
- Lamy T, Devillers A, Bernard M, et al.: Inapparent polycythemia vera: an unrecognized diagnosis. Am J Med 102 (1): 14-20, 1997. [PUBMED Abstract]
- Kaplan ME, Mack K, Goldberg JD, et al.: Long-term management of polycythemia vera with hydroxyurea: a progress report. Semin Hematol 23 (3): 167-71, 1986. [PUBMED Abstract]
- Lengfelder E, Berger U, Hehlmann R: Interferon alpha in the treatment of polycythemia vera. Ann Hematol 79 (3): 103-9, 2000. [PUBMED Abstract]
- Kiladjian JJ, Cassinat B, Chevret S, et al.: Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood 112 (8): 3065-72, 2008. [PUBMED Abstract]
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- Quintás-Cardama A, Kantarjian HM, Giles F, et al.: Pegylated interferon therapy for patients with Philadelphia chromosome-negative myeloproliferative disorders. Semin Thromb Hemost 32 (4 Pt 2): 409-16, 2006. [PUBMED Abstract]
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