eMedicine Specialties > Pediatrics: General Medicine > Hematology

Polycythemia: Treatment & Medication

Author: Sun Choo, MD, Pediatric Resident, University of California Los Angeles
Coauthor(s): Kristin Baird, MD, Staff Clinician, Pediatric Oncology Branch; Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA
Contributor Information and Disclosures

Updated: Nov 2, 2009

Treatment

Medical Care

  • Primary polycythemia: The goals of therapy are to maximize survival while minimizing the complications of therapy as well as of the disease itself.
    • Phlebotomy and myelosuppressive chemotherapy are the cornerstones of therapy and have produced a median survival time of 9-14 years after the beginning of treatment.
    • The goal of phlebotomy is to maintain normal red cell mass and blood volume, with a target hematocrit of less than 45% for men and less than 42% for women. The mean survival time of adult patients treated solely with phlebotomy is 13.9 years; however, a high risk of thromboembolic complications is observed.
    • In the past, the use of anticoagulants, including antiplatelet drugs such as aspirin and dipyridamole (Persantine), was associated with an increased risk of bleeding without an associated decrease in thrombotic events; therefore, anticoagulants have not previously been recommended. However, a large European study, results of which were published in the New England Journal of Medicine by Landolfi et al,24 showed a decrease in thrombotic events in those patients receiving low-dose aspirin therapy and recommended aspirin therapy for those patients for whom no contraindications were noted.
    • Hydroxyurea as a myelosuppressive agent is also widely used in high-risk patients with polycythemia vera (ie, >60 y, history of thrombosis) who require cytoreductive therapy, reducing the need for phlebotomy.25 However, similarly to those treated with chlorambucil, these patients also experience higher rates of malignancy.
    • Interferon alpha is effective in eliminating J AK2V617F expression and inducing hematologic remission. Its use is limited by side effects, cost, and route of administration. The pegylated form and low dose treatment has decreased the rate of discontinuation of the drug secondary to side effects. In a French study, patients with polycythemia vera treated with interferon alpha showed a high rate of hematologic and molecular response.26
    • In the past, patients have been treated with chlorambucil and busulfan. However, these patients exhibited the highest rates of secondary malignancy including acute leukemia, lymphocytic lymphomas, and skin and GI carcinomas. The rates of malignancy appear lower with busulfan than with the other alkylating agents. Currently, these agents are rarely used.
    • Patients treated with phosphorus-32 (32 P) tolerate treatment well and have prolonged periods of remission. However, these patients also exhibit increased rates of acute leukemias (10-15%). The mean survival time with32 P treatment is 10.9 years; therefore, phosphorous is rarely used.
    • Current recommendations for treatment of young patients primarily rely on phlebotomy because the thrombosis is far less likely to occur in children and the long-term risks of leukemia over a longer life span are increased.
  • Secondary polycythemia: Phlebotomy is used for symptomatic hyperviscosity. The goal is to treat the underlying cause of polycythemia.

Surgical Care

  • Surgery is not typically indicated. Occasionally, splenectomy is performed late in the course of the disease if massive splenomegaly causes adverse effects such as early satiety, anemia, or thrombocytopenia from sequestration.
  • Please note that these patients have a high risk of complications during surgical procedures.

Consultations

  • Consult a neurologist and neurosurgeon if evidence of a stroke is present.

Diet

  • Diet is unrestricted.

Activity

  • Contact sports and other activities should be limited for individuals in hypercoagulable and hypocoagulable states.

Medication

Current recommendations for treatment of young patients with polycythemia primarily rely on phlebotomy.

Antineoplastic agents

The following medications are not approved for pediatric polycythemia but are extrapolated from other pediatric treatment regimens, including leukemia and myelodysplastic syndrome.


Interferon alfa 2a and 2b (Roferon-A [alfa-2a], Intron A [alfa-2b])

A recombinant purified protein used IV for CML, hairy cell leukemia, and Kaposi sarcoma. Inhibits cellular growth and alters cell differentiation.

Adult

CML: 9 million U/d IM/SC; initiate with 3 million U/d, increase by 3 million U every third day; not to exceed 9 million U/d

Pediatric

2.5-5 million U/d IM/SC

Theophylline may increase toxicity; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in brain metastases, severe hepatic or renal insufficiencies, seizure disorders, multiple sclerosis, or compromised CNS; use has been associated with depression, suicidal ideation and suicide attempts, and GI hemorrhage


Chlorambucil (Leukeran)

Antineoplastic alkylating agent of nitrogen mustard type used for CLL, giant follicular lymphoma, Hodgkin lymphoma, and lymphosarcoma.

Adult

0.1-0.2 mg/kg/d PO; adjust dose according to blood count

Pediatric

Not established; limited data available

Live virus vaccines (eg, MMR) may result in severe or fatal infection when used in immunosuppressed patients

Documented hypersensitivity; previous resistance to medication

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in history of seizure disorders or current bone marrow suppression


Hydroxyurea (Hydrea)

Inhibitor of deoxynucleotide synthesis. PO antineoplastic agent used in CML, melanoma, ovarian carcinoma, and some head and neck carcinomas.

Adult

20-30 mg/kg/d PO

Pediatric

Administer as in adults

Coadministration with fluorouracil can increase neurotoxicity; live virus vaccines (eg, MMR) may result in severe or fatal infection when used in immunosuppressed patients

Documented hypersensitivity; severe pancytopenia (WBC <2.5 X 109/L, platelets <100 X 109/L, severe anemia)

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Closely monitor CBC counts, LFT findings, and renal function regularly throughout therapy


Busulfan (Myleran)

Potent cytotoxic drug that, at recommended dosage, causes profound myelosuppression. As alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Adult

4-8 mg/d PO; may administer up to 12 mg/d; maintenance dosing range is 1-4 mg/d to 2 mg/wk; discontinue regimen when WBC reaches 10,000-20,000 cells/mL; resume therapy when WBC reaches 50,000/mL

Pediatric

0.06-0.12 mg/kg/d or 1.8-4.6 mg/m2/d PO; titrate dose to maintain WBC >40,000/mL; reduce dose by 50% if WBC is 30,000-40,000/mL; discontinue if WBC <20,000/mL

CYP3A3/4 enzyme substrate; acetaminophen, cyclophosphamide, itraconazole, and thioguanine may increase toxicity; phenytoin may decrease levels

Documented hypersensitivity; severely depressed bone marrow function; breastfeeding women; failure to respond to previous treatment

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; may cause pulmonary fibrosis; if WBC count is high, hydration and allopurinol should be used to prevent hyperuricemia


Pipobroman (Vercyte, Vercite)

The mechanism of action is not fully understood; however, the drug is considered to be an alkylating agent. Pipobroman has been used with some success for treatment of polycythemia vera and chronic granulocytic leukemia. The product was discontinued by the manufacturer in the United States in 1996 but is available in Europe.

Adult

1 mg/kg/d PO initially for at least 30 d; if refractory, may increase to 1.5-3 mg/kg/d
Maintenance: 0.1-0.2 mg/kg/d PO; typically initiated when hematocrit has decrease by 50-55%

Pediatric

<15 years: Not established
>15 years: Administer as in adults

May decrease effect of live virus vaccines (eg, MMR) when administered within 3 mo of vaccination

Documented hypersensitivity; myelosuppression (severe thrombocytopenia)

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Monitor hematocrit or hemoglobin, platelet count, and differential leukocyte counts to evaluate the degree of leukopenia and thrombocytopenia; serum uric acid determinations should be monitored for possible occurrence of hyperuricemia; monitor for signs and symptoms of infection secondary to myelosuppression; hematuria, bruising, or bleeding may signal thrombocytopenia; caution with previous radiation or chemotherapy (potential additive toxicity); common adverse effects include leukopenia, thrombocytopenia, and anemia; acute leukemia risk increases with treatment duration and total cumulative dose

More on Polycythemia

Overview: Polycythemia
Differential Diagnoses & Workup: Polycythemia
Treatment & Medication: Polycythemia
Follow-up: Polycythemia
Multimedia: Polycythemia
References
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References

  1. [Guideline] Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. Aug 15 2007;110(4):1092-7. [Medline].

  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. Feb 15 2002;99(4):1144-9. [Medline].

  3. Adamson JW, Fialkow PJ, Murphy S, et al. Polycythemia vera: stem-cell and probable clonal origin of the disease. New England Journal of Medicine. 1976;295:913-916. [Medline].

  4. James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. Apr 28 2005;434(7037):1144-8. [Medline].

  5. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. Apr 28 2005;352(17):1779-90. [Medline]. [Full Text].

  6. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. Apr 2005;7(4):387-97. [Medline].

  7. Vainchenker W, Constabtinescu S. A Unique Activating Mutation in JAK2 (V617F) Is at the Origin of Polycythemia Vera and Allows a New Classification of Myeloproliferative Diseases. Hematology. 2005;195-200. [Medline]. [Full Text].

  8. Zhao R, Xing S, Li Z, et al. Identification of an acquired JAK2 mutation in polycythemia vera. J Biol Chem. Jun 17 2005;280(24):22788-92. [Medline].

  9. Tefferi A. JAK2 mutations in polycythemia vera--molecular mechanisms and clinical applications. N Engl J Med. Feb 1 2007;356(5):444-5. [Medline].

  10. Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. Feb 1 2007;356(5):459-68. [Medline].

  11. Cario H, Pahl HL, Schwarz K, et al. Familial polycythemia vera with Budd-Chiari syndrome in childhood. Br J Haematol. Oct 2003;123(2):346-52. [Medline].

  12. Teofili L, Foa R, Giona F, Larocca LM. Childhood polycythemia vera and essential thrombocythemia: does their pathogenesis overlap with that of adult patients?. Haematologica. Feb 2008;93(2):169-72. [Medline].

  13. Teofili L, Giona F, Martini M, et al. Markers of myeloproliferative diseases in childhood polycythemia vera and essential thrombocythemia. J Clin Oncol. Mar 20 2007;25(9):1048-53. [Medline].

  14. Rives S, Pahl HL, Florensa L, Bellosillo B, Neusuess A, Estella J. Molecular genetic analyses in familial and sporadic congenital primary erythrocytosis. Haematologica. May 2007;92(5):674-7. [Medline].

  15. Rumi E, Passamonti F, Della Porta MG, et al. Familial chronic myeloproliferative disorders: clinical phenotype and evidence of disease anticipation. J Clin Oncol. Dec 10 2007;25(35):5630-5. [Medline].

  16. Cario H. Childhood polycythemias/erythrocytoses: classification, diagnosis, clinical presentation, and treatment. Ann Hematol. Mar 2005;84(3):137-45. [Medline].

  17. Greer JP, Foerster J, Rodgers GM, et al. Erthrocytosis. In: Pine JW, Jacobs AE,. Wintrobe's Clinical Hematology. Twelfth. Lippincott, Williams and Wlkins; 2009.

  18. Sarkar S, Rosenkrantz TS. Neonatal polycythemia and hyperviscosity. Semin Fetal Neonatal Med. Aug 2008;13(4):248-55. [Medline].

  19. Ma X, Vanasse G, Cartmel B, Wang Y, Selinger HA. Prevalence of polycythemia vera and essential thrombocythemia. Am J Hematol. May 2008;83(5):359-62. [Medline].

  20. Johansson P. Epidemiology of the myeloproliferative disorders polycythemia vera and essential thrombocythemia. Semin Thromb Hemost. Apr 2006;32(3):171-3. [Medline].

  21. Cario H, Schwarz K, Herter JM, Komrska V, McMullin MF, Minkov M. Clinical and molecular characterisation of a prospectively collected cohort of children and adolescents with polycythemia vera. Br J Haematol. Aug 2008;142(4):622-6. [Medline].

  22. Smith CA, Fan G. The saga of JAK2 mutations and translocations in hematologic disorders: pathogenesis, diagnostic and therapeutic prospects, and revised World Health Organization diagnostic criteria for myeloproliferative neoplasms. Hum Pathol. Jun 2008;39(6):795-810. [Medline].

  23. McMullin MF, Bareford D, Campbell P, et al. Guidelines for the diagnosis, investigation and management of polycythaemia/erythrocytosis. Br J Haematol. Jul 2005;130(2):174-95. [Medline].

  24. Landolfi R, Marchioloi R, Kutti J, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. New England Journal of Medicine. 2004;350:114-124. [Medline]. [Full Text].

  25. Zhan H, Spivak JL. The diagnosis and management of polycythemia vera, essential thrombocythemia, and primary myelofibrosis in the JAK2 V617F era. Clin Adv Hematol Oncol. May 2009;7(5):334-42. [Medline].

  26. 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. Oct 15 2008;112(8):3065-72. [Medline].

  27. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. Mar 19-25 2005;365(9464):1054-61. [Medline].

  28. Ebert BL, Bunn HF. Regulation of the erythropoietin gene. Blood. Sep 15 1999;94(6):1864-77. [Medline]. [Full Text].

  29. Gomella TL, Cunningham MD, Eyal FG, eds. Neonatal polycythemia. In: Neonatology: Management, Procedures, On-call Problems, Diseases and Drugs. 3rd ed. Norwalk, CT: Appleton & Lange; 1994.

  30. Goyal RK, Longmore GD. Abnormalities of cytokine receptor signalling contributing to diseases of red blood cell production. Ann Med. Jun 1999;31(3):208-16. [Medline].

  31. Grier HE, Civin CI. Polycythemia vera. In: Orkin, SH, Oski FA eds. Nathan and Oski's Hematology of Infancy and Childhood. Vol 2. 5th ed. Philadelphia, PA: WB Saunders Co; 1998:1307-8.

  32. Hoffman R. Polycythemia. Hematology: Basic Principles and Practice. 3rd ed. 2000;Chapter 61:1130-1151.

  33. Jaffe ES, Harris NL, Stein H, Vardiman JW. World Health Organization Classification of Tumours of Hematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001:1-351.

  34. Johansson PL, Safai-Kutti S, Kutti J. An elevated venous haemoglobin concentration cannot be used as a surrogate marker for absolute erythrocytosis: a study of patients with polycythaemia vera and apparent polycythaemia. Br J Haematol. Jun 2005;129(5):701-5. [Medline].

  35. Jones AV, Silver RT, Waghorn K, et al. Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha. Blood. Apr 15 2006;107(8):3339-41. [Medline].

  36. Kralovics R, Prchal JT. Congenital and inherited polycythemia. Curr Opin Pediatr. Feb 2000;12(1):29-34. [Medline].

  37. Kwaan HC, Wang J. Hyperviscosity in polycythemia vera and other red cell abnormalities. Semin Thromb Hemost. Oct 2003;29(5):451-8. [Medline].

  38. Lee GR, Paraskevas F, Foerster John, eds. Polycythemia vera. In: Wintrobe's Clinical Hematology. 10th ed. Baltimore, MD: Williams & Wilkins; 1999:2380-5.

  39. Nelson WE, Behrman RE, Kliegman R, eds. Polycythemia vera. In: Nelson's Textbook of Pediatrics. 15th ed. Philadelphia, Pa: WB Saunders; 1996.

  40. Pappas A, Delaney-Black V. Differential diagnosis and management of polycythemia. Pediatric Clinics of North America. 2004;51:1063-86. [Medline].

  41. Passamonti F, Malabarba L, Orlandi E, et al. Polycythemia vera in young patients: a study on the long-term risk of thrombosis, myelofibrosis and leukemia. Haematologica. Jan 2003;88(1):13-8. [Medline].

  42. Passamonti F, Rumi E, Pungolino E, et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. Am J Med. Nov 15 2004;117(10):755-61. [Medline].

  43. Pizzo PA, Poplack DG, eds. Myleoproliferative disorders. In: Principles and Practice of Pediatric Oncology. 4th ed. 2002:627.

  44. Prchal JF, Prchal JT. Molecular basis for polycythemia. Curr Opin Hematol. Mar 1999;6(2):100-9. [Medline].

  45. Quintas-Cardama A, Kantarjian H, Manshouri T, et al. Pegylated Interferon Alfa-2a Yields High Rates of Hematologic and Molecular Response in Patients With Advanced Essential Thrombocythemia and Polycythemia Vera. J Clin Oncol. Oct 13 2009;[Medline].

  46. Rosenkrantz TS. Polycythemia and hyperviscosity in the newborn. Seminars in Thrombosis and Hemostasis. 2003;29:515-527. [Medline].

  47. Spivak JL. Polycythemia vera: myths, mechanisms, and management. Blood. Dec 15 2002;100(13):4272-90. [Medline]. [Full Text].

  48. Spivak JL, Silver RT. The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternative proposal. Blood. Jul 15 2008;112(2):231-9. [Medline].

  49. Tefferi A. Essential thrombocythemia, polycythemia vera, and myelofibrosis: current management and the prospect of targeted therapy. Am J Hematol. Jun 2008;83(6):491-7. [Medline].

  50. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. Jan 2008;22(1):14-22. [Medline].

  51. Walters MC, Abelson HT. Interpretation of the complete blood count. Pediatr Clin North Am. Jun 1996;43(3):599-622. [Medline].

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Further Reading

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Keywords

polycythemia vera, PV, polycythemia rubra vera, erythrocytosis, absolute erythrocytosis, relative erythrocytosis, familial erythrocytosis, primary familial and congenital polycythemia, PFCP, primary familial polycythemia, treatment, diagnosis

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Contributor Information and Disclosures

Author

Sun Choo, MD, Pediatric Resident, University of California Los Angeles
Disclosure: Nothing to disclose.

Coauthor(s)

Kristin Baird, MD, Staff Clinician, Pediatric Oncology Branch
Disclosure: Nothing to disclose.

Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA
Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Scott MacGilvray, MD, Clinical Associate Professor of Pediatrics, East Carolina University School of Medicine
Scott MacGilvray, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association
Disclosure: MedImmune Speakers Bureau Honoraria Speaking and teaching

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

James L Harper, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center
James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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