Difference between revisions of "Polycythemia vera medical therapy"

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__NOTOC__
 
__NOTOC__
 
{{Polycythemia vera}}
 
{{Polycythemia vera}}
{{CMG}} {{AE}} {{MJK}} {{shyam}}
+
{{CMG}} {{AE}} {{IO}} {{MJK}} {{shyam}}
 
==Overview==
 
==Overview==
 
The mainstay of therapy for polycythemia vera is [[phlebotomy]], [[aspirin]], [[hydroxyurea]] (alone or with [[phlebotomy]]), [[interferon-alpha]] and pegylated [[interferon-alpha]], [[chlorambucil]]. Some of these medications are targeted agents that work specifically in polycythemia vera, while others are non-specific therapies that can have numerous off-target adverse effects. Some of these treatments can modify the course of the disease, while others simply alleviate symptom burden.
 
The mainstay of therapy for polycythemia vera is [[phlebotomy]], [[aspirin]], [[hydroxyurea]] (alone or with [[phlebotomy]]), [[interferon-alpha]] and pegylated [[interferon-alpha]], [[chlorambucil]]. Some of these medications are targeted agents that work specifically in polycythemia vera, while others are non-specific therapies that can have numerous off-target adverse effects. Some of these treatments can modify the course of the disease, while others simply alleviate symptom burden.
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==Medical Therapy==
 
==Medical Therapy==
 
Medical therapy for polycythemia vera include:<ref name="pmid3704665">{{cite journal| author=Berk PD, Goldberg JD, Donovan PB, Fruchtman SM, Berlin NI, Wasserman LR| title=Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols. | journal=Semin Hematol | year= 1986 | volume= 23 | issue= 2 | pages= 132-43 | pmid=3704665 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3704665  }} </ref><ref name="pmid9209196">{{cite journal| author=Lamy T, Devillers A, Bernard M, Moisan A, Grulois I, Drenou B et al.| title=Inapparent polycythemia vera: an unrecognized diagnosis. | journal=Am J Med | year= 1997 | volume= 102 | issue= 1 | pages= 14-20 | pmid=9209196 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9209196  }} </ref><ref name="pmid3749925">{{cite journal| author=Kaplan ME, Mack K, Goldberg JD, Donovan PB, Berk PD, Wasserman LR| title=Long-term management of polycythemia vera with hydroxyurea: a progress report. | journal=Semin Hematol | year= 1986 | volume= 23 | issue= 3 | pages= 167-71 | pmid=3749925 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3749925  }} </ref><ref name="pmid10803930">{{cite journal| author=Lengfelder E, Berger U, Hehlmann R| title=Interferon alpha in the treatment of polycythemia vera. | journal=Ann Hematol | year= 2000 | volume= 79 | issue= 3 | pages= 103-9 | pmid=10803930 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10803930  }} </ref><ref name="pmid16804923">{{cite journal| author=Silver RT| title=Long-term effects of the treatment of polycythemia vera with recombinant interferon-alpha. | journal=Cancer | year= 2006 | volume= 107 | issue= 3 | pages= 451-8 | pmid=16804923 | doi=10.1002/cncr.22026 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16804923  }} </ref><ref name="pmid25069759">{{cite journal| author=Huang BT, Zeng QC, Zhao WH, Li BS, Chen RL| title=Interferon α-2b gains high sustained response therapy for advanced essential thrombocythemia and polycythemia vera with JAK2V617F positive mutation. | journal=Leuk Res | year= 2014 | volume= 38 | issue= 10 | pages= 1177-83 | pmid=25069759 | doi=10.1016/j.leukres.2014.06.019 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25069759  }} </ref><ref name="pmid19826111">{{cite journal| author=Quintás-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S et al.| title=Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. | journal=J Clin Oncol | year= 2009 | volume= 27 | issue= 32 | pages= 5418-24 | pmid=19826111 | doi=10.1200/JCO.2009.23.6075 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19826111  }} </ref><ref name="pmid23782935">{{cite journal| author=Quintás-Cardama A, Abdel-Wahab O, Manshouri T, Kilpivaara O, Cortes J, Roupie AL et al.| title=Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a. | journal=Blood | year= 2013 | volume= 122 | issue= 6 | pages= 893-901 | pmid=23782935 | doi=10.1182/blood-2012-07-442012 | pmc=PMC3739035 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23782935  }} </ref><ref name="pmid17264301">{{cite journal| author=Finazzi G, Barbui T| title=How I treat patients with polycythemia vera. | journal=Blood | year= 2007 | volume= 109 | issue= 12 | pages= 5104-11 | pmid=17264301 | doi=10.1182/blood-2006-12-038968 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17264301  }} </ref><ref name="pmid23633335">{{cite journal| author=Squizzato A, Romualdi E, Passamonti F, Middeldorp S| title=Antiplatelet drugs for polycythaemia vera and essential thrombocythaemia. | journal=Cochrane Database Syst Rev | year= 2013 | volume= 4 | issue=  | pages= CD006503 | pmid=23633335 | doi=10.1002/14651858.CD006503.pub3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23633335  }} </ref><ref name="pmid14711910">{{cite journal |vauthors=Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T |title=Efficacy and safety of low-dose aspirin in polycythemia vera |journal=N. Engl. J. Med. |volume=350 |issue=2 |pages=114–24 |date=January 2004 |pmid=14711910 |doi=10.1056/NEJMoa035572 |url=}}</ref><ref name="pmid27884974">{{cite journal| author=Vannucchi AM| title=From leeches to personalized medicine: evolving concepts in the management of polycythemia vera. | journal=Haematologica | year= 2017 | volume= 102 | issue= 1 | pages= 18-29 | pmid=27884974 | doi=10.3324/haematol.2015.129155 | pmc=5210229 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27884974  }} </ref>
 
Medical therapy for polycythemia vera include:<ref name="pmid3704665">{{cite journal| author=Berk PD, Goldberg JD, Donovan PB, Fruchtman SM, Berlin NI, Wasserman LR| title=Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols. | journal=Semin Hematol | year= 1986 | volume= 23 | issue= 2 | pages= 132-43 | pmid=3704665 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3704665  }} </ref><ref name="pmid9209196">{{cite journal| author=Lamy T, Devillers A, Bernard M, Moisan A, Grulois I, Drenou B et al.| title=Inapparent polycythemia vera: an unrecognized diagnosis. | journal=Am J Med | year= 1997 | volume= 102 | issue= 1 | pages= 14-20 | pmid=9209196 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9209196  }} </ref><ref name="pmid3749925">{{cite journal| author=Kaplan ME, Mack K, Goldberg JD, Donovan PB, Berk PD, Wasserman LR| title=Long-term management of polycythemia vera with hydroxyurea: a progress report. | journal=Semin Hematol | year= 1986 | volume= 23 | issue= 3 | pages= 167-71 | pmid=3749925 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3749925  }} </ref><ref name="pmid10803930">{{cite journal| author=Lengfelder E, Berger U, Hehlmann R| title=Interferon alpha in the treatment of polycythemia vera. | journal=Ann Hematol | year= 2000 | volume= 79 | issue= 3 | pages= 103-9 | pmid=10803930 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10803930  }} </ref><ref name="pmid16804923">{{cite journal| author=Silver RT| title=Long-term effects of the treatment of polycythemia vera with recombinant interferon-alpha. | journal=Cancer | year= 2006 | volume= 107 | issue= 3 | pages= 451-8 | pmid=16804923 | doi=10.1002/cncr.22026 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16804923  }} </ref><ref name="pmid25069759">{{cite journal| author=Huang BT, Zeng QC, Zhao WH, Li BS, Chen RL| title=Interferon α-2b gains high sustained response therapy for advanced essential thrombocythemia and polycythemia vera with JAK2V617F positive mutation. | journal=Leuk Res | year= 2014 | volume= 38 | issue= 10 | pages= 1177-83 | pmid=25069759 | doi=10.1016/j.leukres.2014.06.019 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25069759  }} </ref><ref name="pmid19826111">{{cite journal| author=Quintás-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S et al.| title=Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. | journal=J Clin Oncol | year= 2009 | volume= 27 | issue= 32 | pages= 5418-24 | pmid=19826111 | doi=10.1200/JCO.2009.23.6075 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19826111  }} </ref><ref name="pmid23782935">{{cite journal| author=Quintás-Cardama A, Abdel-Wahab O, Manshouri T, Kilpivaara O, Cortes J, Roupie AL et al.| title=Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a. | journal=Blood | year= 2013 | volume= 122 | issue= 6 | pages= 893-901 | pmid=23782935 | doi=10.1182/blood-2012-07-442012 | pmc=PMC3739035 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23782935  }} </ref><ref name="pmid17264301">{{cite journal| author=Finazzi G, Barbui T| title=How I treat patients with polycythemia vera. | journal=Blood | year= 2007 | volume= 109 | issue= 12 | pages= 5104-11 | pmid=17264301 | doi=10.1182/blood-2006-12-038968 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17264301  }} </ref><ref name="pmid23633335">{{cite journal| author=Squizzato A, Romualdi E, Passamonti F, Middeldorp S| title=Antiplatelet drugs for polycythaemia vera and essential thrombocythaemia. | journal=Cochrane Database Syst Rev | year= 2013 | volume= 4 | issue=  | pages= CD006503 | pmid=23633335 | doi=10.1002/14651858.CD006503.pub3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23633335  }} </ref><ref name="pmid14711910">{{cite journal |vauthors=Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T |title=Efficacy and safety of low-dose aspirin in polycythemia vera |journal=N. Engl. J. Med. |volume=350 |issue=2 |pages=114–24 |date=January 2004 |pmid=14711910 |doi=10.1056/NEJMoa035572 |url=}}</ref><ref name="pmid27884974">{{cite journal| author=Vannucchi AM| title=From leeches to personalized medicine: evolving concepts in the management of polycythemia vera. | journal=Haematologica | year= 2017 | volume= 102 | issue= 1 | pages= 18-29 | pmid=27884974 | doi=10.3324/haematol.2015.129155 | pmc=5210229 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27884974  }} </ref>
*'''[[Phlebotomy]]'''
 
:*The goal [[hematocrit]] is less than 45%. Because this goal may not be achieved in practice, a goal of 50% is targeted by most clinicians. 
 
:*In a normal sized adult, a standard one unit [[phlebotomy]] (500ml) should reduce the [[hematocrit]] by 3 percentage points.
 
:*In low risk patients (patients under 60 years with no history of [[thrombosis]]), [[phlebotomy]] alone can be used.
 
:*Some common adverse effects are [[iron deficiency]] and pain at the insertion site.
 
 
 
*'''[[Aspirin]]'''
 
*'''[[Aspirin]]'''
 
**It is an irreversible inhibitor of cyclo-oxygenase (prostaglandin endoperoxide synthase) and so inhibits the formation of [[thromboxane A2]] (a prothrombotic molecule).
 
**It is an irreversible inhibitor of cyclo-oxygenase (prostaglandin endoperoxide synthase) and so inhibits the formation of [[thromboxane A2]] (a prothrombotic molecule).
Line 36: Line 30:
 
**Can be used with intolerance to [[Interferon-alpha|interferon]] or [[hydroxyurea]]. They are no longer included in the current standard of care for polycythemia vera.
 
**Can be used with intolerance to [[Interferon-alpha|interferon]] or [[hydroxyurea]]. They are no longer included in the current standard of care for polycythemia vera.
 
**They can lead to secondary [[myelodysplastic syndrome]] and secondary [[Leukemia|leukemias]], which typically occur 5-7 years after exposure to these medications.
 
**They can lead to secondary [[myelodysplastic syndrome]] and secondary [[Leukemia|leukemias]], which typically occur 5-7 years after exposure to these medications.
 +
 +
*'''[[Phlebotomy]]'''
 +
:*The goal [[hematocrit]] is less than 45%. Because this goal may not be achieved in practice, a goal of 50% is targeted by most clinicians. 
 +
:*In a normal sized adult, a standard one unit [[phlebotomy]] (500ml) should reduce the [[hematocrit]] by 3 percentage points.
 +
:*In low risk patients (patients under 60 years with no history of [[thrombosis]]), [[phlebotomy]] alone can be used.
 +
:*Some common adverse effects are [[iron deficiency]] and pain at the insertion site.
  
 
==References==
 
==References==

Latest revision as of 03:21, 14 September 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ifeoma Odukwe M.D. [2] Mohamad Alkateb, MBBCh [3] Shyam Patel [4]

Overview

The mainstay of therapy for polycythemia vera is phlebotomy, aspirin, hydroxyurea (alone or with phlebotomy), interferon-alpha and pegylated interferon-alpha, chlorambucil. Some of these medications are targeted agents that work specifically in polycythemia vera, while others are non-specific therapies that can have numerous off-target adverse effects. Some of these treatments can modify the course of the disease, while others simply alleviate symptom burden.

Medical Therapy

Medical therapy for polycythemia vera include:[1][2][3][4][5][6][7][8][9][10][11][12]

  • Ruxolitinib
    • This is a JAK2 inhibitor that is used in cases of polycythemia that are refractory to interferon therapy. It has been shown to produce splendid hematologic and spleen responses of about 90%. The recommended dose is 20mg PO twice daily. The need for phlebotomy can be reduced with ruxolitinib
    • When measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), which a validated tool for the assessment of disease burden from a subjective standpoint, ruxolitinib was shown to improve the symptoms in polycythemia vera patients. Patients receiving this medication report improvement in spleen symptoms, inflammation, and microvascular abnormalities.
    • Some side effects include non-melanoma skin cancers, weight gain, reactivation of herpes zoster, and cytopenias. Due to the risk of developing skin cancer, active surveillance of the skin is required.
  • Interferon-alpha
    • This medication results in a reduction in red blood cell mass. The mechanism of action is not exactly known, but it is thought to induce apoptosis, regulate the immune system, and has a direct inhibitory effect on hematopoetic cells. Those patients considered as high risk can be given this medication, such as those above age 60 and/or with thrombosis history.
    • It can cause infusion reaction and cytopenias. Pegylated interferon-alpha, which is a formulation of the medication is less toxic than the conventional interferon. Interferon alpha is not routinely used in this current era due to its intolerable adverse effect profile. About 20% of patients will discontinue this medication within one year of starting due to the side effects. Approximately 15-20% of patients become resistant to interferon and require alternative therapy.
  • The goal hematocrit is less than 45%. Because this goal may not be achieved in practice, a goal of 50% is targeted by most clinicians.
  • In a normal sized adult, a standard one unit phlebotomy (500ml) should reduce the hematocrit by 3 percentage points.
  • In low risk patients (patients under 60 years with no history of thrombosis), phlebotomy alone can be used.
  • Some common adverse effects are iron deficiency and pain at the insertion site.

References

  1. Berk PD, Goldberg JD, Donovan PB, Fruchtman SM, Berlin NI, Wasserman LR (1986). "Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols". Semin Hematol. 23 (2): 132–43. PMID 3704665.
  2. Lamy T, Devillers A, Bernard M, Moisan A, Grulois I, Drenou B; et al. (1997). "Inapparent polycythemia vera: an unrecognized diagnosis". Am J Med. 102 (1): 14–20. PMID 9209196.
  3. Kaplan ME, Mack K, Goldberg JD, Donovan PB, Berk PD, Wasserman LR (1986). "Long-term management of polycythemia vera with hydroxyurea: a progress report". Semin Hematol. 23 (3): 167–71. PMID 3749925.
  4. Lengfelder E, Berger U, Hehlmann R (2000). "Interferon alpha in the treatment of polycythemia vera". Ann Hematol. 79 (3): 103–9. PMID 10803930.
  5. Silver RT (2006). "Long-term effects of the treatment of polycythemia vera with recombinant interferon-alpha". Cancer. 107 (3): 451–8. doi:10.1002/cncr.22026. PMID 16804923.
  6. Huang BT, Zeng QC, Zhao WH, Li BS, Chen RL (2014). "Interferon α-2b gains high sustained response therapy for advanced essential thrombocythemia and polycythemia vera with JAK2V617F positive mutation". Leuk Res. 38 (10): 1177–83. doi:10.1016/j.leukres.2014.06.019. PMID 25069759.
  7. Quintás-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S; et al. (2009). "Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera". J Clin Oncol. 27 (32): 5418–24. doi:10.1200/JCO.2009.23.6075. PMID 19826111.
  8. Quintás-Cardama A, Abdel-Wahab O, Manshouri T, Kilpivaara O, Cortes J, Roupie AL; et al. (2013). "Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a". Blood. 122 (6): 893–901. doi:10.1182/blood-2012-07-442012. PMC 3739035. PMID 23782935.
  9. Finazzi G, Barbui T (2007). "How I treat patients with polycythemia vera". Blood. 109 (12): 5104–11. doi:10.1182/blood-2006-12-038968. PMID 17264301.
  10. Squizzato A, Romualdi E, Passamonti F, Middeldorp S (2013). "Antiplatelet drugs for polycythaemia vera and essential thrombocythaemia". Cochrane Database Syst Rev. 4: CD006503. doi:10.1002/14651858.CD006503.pub3. PMID 23633335.
  11. Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T (January 2004). "Efficacy and safety of low-dose aspirin in polycythemia vera". N. Engl. J. Med. 350 (2): 114–24. doi:10.1056/NEJMoa035572. PMID 14711910.
  12. Vannucchi AM (2017). "From leeches to personalized medicine: evolving concepts in the management of polycythemia vera". Haematologica. 102 (1): 18–29. doi:10.3324/haematol.2015.129155. PMC 5210229. PMID 27884974.

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