Disease Overview
Treatment Overview
Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Persistent elevation of the hematocrit (>52% in men and >48% in women) should prompt investigation of polycythemia vera (p. vera).[1] In p. vera, formal staging is not done. Tests that are used to diagnose p. vera include:[2,3]

• Red blood cell volume (>36 mL/kg in men and >32 mL/kg in women).
• Oxygen saturation with arterial blood gas (>92%).
• Serum erythropoietin levels (very low or absent).
• JAK2 mutation in the presence of a high hematocrit (>52% in men and >48% in women).

Other confirmatory tests include:[2]

• Splenomegaly.
• Thrombocytosis (>400,000 platelets/mm³).
• Leukocytosis (>12,000/mm³).
• Leukocyte alkaline phosphatase (>100 units in the absence of fever or infection).

Erythroid progenitor cell assays are available at some academic centers.[2]

There is no staging system for this disease.

Patients older than 65 years have an increased risk of cardiovascular and thrombotic events and transformation to acute myelogenous leukemia or chronic idiopathic myelofibrosis.[4]

Therapy for p. vera includes intermittent, chronic phlebotomy to maintain the hematocrit below 45% in men.[5] The target level for women may need to be lower (e.g., hematocrit <40%), but there are no empiric data to confirm this recommendation.[6] 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), and possibly muscle weakness. In addition, progressive splenomegaly or pruritus not controllable by antihistamines may persist despite control of the hematocrit by phlebotomy. If phlebotomy becomes impractical, hydroxyurea or interferon-alpha can be added to control the disease.

The Polycythemia Vera Study Group randomized 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).[7] 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.[7][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.[7]

Interferon-alpha therapy resulted in avoidance of phlebotomy in 50% of patients, with 80% of patients experiencing marked reduction of splenomegaly, in a pooled analysis of 16 different trials.[8][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.[2,9] In a randomized study of 518 patients with no clear indication or contraindication for aspirin, those receiving 100 mg of aspirin versus placebo had reduction of the combined endpoint of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (relative risk = 0.41; 95% confidence interval, 0.18–0.91, P = .03).[10][Level of evidence: 1iA]

Guidelines based on anecdotal reports have been developed for the management of pregnant patients with p. vera.[1]

Treatment options:

1. Phlebotomy.[5]



2. Hydroxyurea (alone or with phlebotomy).[6,7]



3. Interferon-alpha.[8]



4. 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.[2]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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.

References

1. 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]
   
   
2. 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]
   
   
3. Campbell PJ, Green AR: The myeloproliferative disorders. N Engl J Med 355 (23): 2452-66, 2006.  [PUBMED Abstract]
   
   
4. 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]
   
   
5. Berk PD, Goldberg JD, Donovan PB, et al.: Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols. Semin Hematol 23 (2): 132-43, 1986.  [PUBMED Abstract]
   
   
6. Lamy T, Devillers A, Bernard M, et al.: Inapparent polycythemia vera: an unrecognized diagnosis. Am J Med 102 (1): 14-20, 1997.  [PUBMED Abstract]
   
   
7. 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]
   
   
8. Lengfelder E, Berger U, Hehlmann R: Interferon alpha in the treatment of polycythemia vera. Ann Hematol 79 (3): 103-9, 2000.  [PUBMED Abstract]
   
   
9. Kiladjian JJ, Cassinat B, Turlure P, et al.: High molecular response rate of polycythemia vera patients treated with pegylated interferon alpha-2a. Blood 108 (6): 2037-40, 2006.  [PUBMED Abstract]
   
   
10. Landolfi R, Marchioli R, Kutti J, et al.: Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 350 (2): 114-24, 2004.  [PUBMED Abstract]
    
    

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