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==Medical Therapy== | ==Medical Therapy== | ||
Medical therapy for polycythemia vera include:<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_5</ref><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> | Medical therapy for polycythemia vera include:<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_5</ref><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> | ||
*'''[[Phlebotomy]]''': Phlebotomy is a therapeutic cytoreductive procedure that involves withdrawal of blood from a patient's body with the goal of reducing [[red blood cell]] mass and hemoglobin. The goal hematocrit is less than 45%. In practice, this goal is not commonly achieved, and most clinicians target a goal of 50%.<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> Patients with a hematocrit higher than 45% have a 4-fold increased risk for thrombosis.<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> In some cases, a hematocrit goal of 42% can be targeted, such as in female patients.<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 alone can be used for low-risk patients, defined as those under age 60 with no thrombosis history. | *'''[[Phlebotomy]]''': [[Phlebotomy]] is a therapeutic cytoreductive procedure that involves withdrawal of blood from a patient's body with the goal of reducing [[red blood cell]] mass and hemoglobin. The goal hematocrit is less than 45%. In practice, this goal is not commonly achieved, and most clinicians target a goal of 50%.<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> Patients with a hematocrit higher than 45% have a 4-fold increased risk for thrombosis.<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> In some cases, a hematocrit goal of 42% can be targeted, such as in female patients.<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 alone can be used for low-risk patients, defined as those under age 60 with no [[thrombosis]] history. | ||
**''Adverse effects'': Phlebotomy can cause iron deficiency and pain at the insertion site. Iron deficiency can result in fatigue. | **''Adverse effects'': [[Phlebotomy]] can cause iron deficiency and pain at the insertion site. Iron deficiency can result in fatigue. | ||
*'''[[Aspirin]]''': Aspirin is an irreversible inhibitor of cyclo-oxygenase (prostaglandin endoperoxide synthase) and thus inhibits for the formation of the prothrombotic molecule thromboxane A2. Low-dose aspirin of 81mg has been shown to help prevent thrombosis in patients with polycythemia vera. | *'''[[Aspirin]]''': Aspirin is an irreversible inhibitor of cyclo-oxygenase (prostaglandin endoperoxide synthase) and thus inhibits for the formation of the prothrombotic molecule [[thromboxane A2]]. Low-dose aspirin of 81mg has been shown to help prevent thrombosis in patients with polycythemia vera. | ||
**''Adverse effects'': Aspirin can cause increased bleeding risk and possibly hemorrhage. | **''Adverse effects'': Aspirin can cause increased bleeding risk and possibly hemorrhage. | ||
*'''[[Hydroxyurea]]''': Hydroxyurea is a cytoreductive agent that inhibits ribonucleotide reductase, which is essential is nucleic acid metabolism. By inhibiting ribonucleotide reductase in hematopoietic cells, hydroxyurea results in decreased stem cell proliferation and decreased [[red blood cell]] mass. Hydroxyurea should be given to patients who are considered high-risk, such as those above age 60 and/or with thrombosis history. | *'''[[Hydroxyurea]]''': Hydroxyurea is a cytoreductive agent that inhibits ribonucleotide reductase, which is essential is nucleic acid metabolism. By inhibiting ribonucleotide reductase in hematopoietic cells, hydroxyurea results in decreased stem cell proliferation and decreased [[red blood cell]] mass. Hydroxyurea should be given to patients who are considered high-risk, such as those above age 60 and/or with thrombosis history. | ||
**''Adverse effects'': Hydroxyurea can cause cytopenias, skin ulcers, and secondary malignancies. | **''Adverse effects'': Hydroxyurea can cause [[cytopenias]], skin ulcers, and secondary [[malignancies]]. | ||
*'''[[Ruxolitinib]]''': This is a JAK2 inhibitor that is used in cases of polycythemia that are refractory to [[interferon]] therapy. This medication has been shown to produce excellent hematologic and spleen responses, with response rates of approximately 90%. The use of ruxolitiib can reduce the need for phlebotomy. Ruxolitinib also results in improved symptom burden as measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), which a validated tool for the assessment of disease burden from a subjective standpoint.<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> Patients receiving ruxolitinib report improvement in spleen symptoms, inflammation, and microvascular abnormalities. | *'''[[Ruxolitinib]]''': This is a JAK2 inhibitor that is used in cases of polycythemia that are refractory to [[interferon]] therapy. This medication has been shown to produce excellent hematologic and spleen responses, with response rates of approximately 90%. The use of ruxolitiib can reduce the need for phlebotomy. Ruxolitinib also results in improved symptom burden as measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), which a validated tool for the assessment of disease burden from a subjective standpoint.<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> Patients receiving ruxolitinib report improvement in spleen symptoms, inflammation, and microvascular abnormalities. | ||
**''Adverse effects'': Ruxolitinib can cause non-melanoma skin cancers, weight gain, reactivation of herpes zoster, and cytopenias. Active skin surveillance is required given the skin cancer risk. | **''Adverse effects'': Ruxolitinib can cause non-melanoma skin cancers, weight gain, reactivation of [[herpes zoster]], and [[cytopenias]]. Active skin surveillance is required given the skin cancer risk. | ||
*'''[[Interferon-alpha]]''': This medication results in reduction in [[red blood cell]] mass. The mechanism of action is not exactly known, but it is thought to induce apoptosis, modulate the immune system, and exert a direct inhibitory effect on hematopoietic cells.<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> Interferon-alpha can be given to patients who are considered high-risk, such as those above age 60 and/or with thrombosis history.<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> | *'''[[Interferon-alpha]]''': This medication results in reduction in [[red blood cell]] mass. The mechanism of action is not exactly known, but it is thought to induce [[apoptosis]], modulate the immune system, and exert a direct inhibitory effect on hematopoietic cells.<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> Interferon-alpha can be given to patients who are considered high-risk, such as those above age 60 and/or with [[thrombosis]] history.<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> | ||
**''Adverse effects'': Interferon-alpha can cause infusion reaction and cytopenias. Pegylated interferon-alpha is one formulation of this medication and has less toxicity than conventional interferon. However, this agent is not commonly used in the current era given the adverse effect profile, which leads to inability to tolerate this medication. Within 1 year of starting interferon, 20% of patients will discontinue this due to adverse effects. Approximately 15-20% of patients become resistant to interferon and require alternative therapy.<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> | **''Adverse effects'': Interferon-alpha can cause infusion reaction and [[cytopenias]]. Pegylated interferon-alpha is one formulation of this medication and has less toxicity than conventional interferon. However, this agent is not commonly used in the current era given the adverse effect profile, which leads to inability to tolerate this medication. Within 1 year of starting interferon, 20% of patients will discontinue this due to adverse effects. Approximately 15-20% of patients become resistant to interferon and require alternative therapy.<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> | ||
*'''[[Chlorambucil]]''' or '''[[busulfan]]''': These are alkylating agents that inhibit the proliferation of the malignant clone responsible for elevated [[red blood cell]] mass. These medications can be used if interferon or hydroxyurea are not tolerated. However, these medications are no longer included in the current standard of care for polycythemia vera. | *'''[[Chlorambucil]]''' or '''[[busulfan]]''': These are alkylating agents that inhibit the proliferation of the malignant clone responsible for elevated [[red blood cell]] mass. These medications can be used if interferon or hydroxyurea are not tolerated. However, these medications are no longer included in the current standard of care for polycythemia vera. | ||
**''Adverse effects'': [[Chlorambucil]] and [[busulfan]] can cause secondary myelodysplastic syndrome and secondary leukemias, which typically occur 5-7 years after exposure to these alkylating agents. | **''Adverse effects'': [[Chlorambucil]] and [[busulfan]] can cause secondary myelodysplastic syndrome and secondary leukemias, which typically occur 5-7 years after exposure to these alkylating agents. | ||
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{{Hematology}} | {{Hematology}} | ||
{{Hematological malignancy histology}} | {{Hematological malignancy histology}} | ||
[[Category:Disease]] | [[Category:Disease]] | ||
Revision as of 15:27, 17 August 2018
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Polycythemia vera Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Polycythemia vera medical therapy On the Web |
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American Roentgen Ray Society Images of Polycythemia vera medical therapy |
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Risk calculators and risk factors for Polycythemia vera medical therapy |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2] Shyam Patel [3]
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]
- Phlebotomy: Phlebotomy is a therapeutic cytoreductive procedure that involves withdrawal of blood from a patient's body with the goal of reducing red blood cell mass and hemoglobin. The goal hematocrit is less than 45%. In practice, this goal is not commonly achieved, and most clinicians target a goal of 50%.[12] Patients with a hematocrit higher than 45% have a 4-fold increased risk for thrombosis.[12] In some cases, a hematocrit goal of 42% can be targeted, such as in female patients.[12] Phlebotomy alone can be used for low-risk patients, defined as those under age 60 with no thrombosis history.
- Adverse effects: Phlebotomy can cause iron deficiency and pain at the insertion site. Iron deficiency can result in fatigue.
- Aspirin: Aspirin is an irreversible inhibitor of cyclo-oxygenase (prostaglandin endoperoxide synthase) and thus inhibits for the formation of the prothrombotic molecule thromboxane A2. Low-dose aspirin of 81mg has been shown to help prevent thrombosis in patients with polycythemia vera.
- Adverse effects: Aspirin can cause increased bleeding risk and possibly hemorrhage.
- Hydroxyurea: Hydroxyurea is a cytoreductive agent that inhibits ribonucleotide reductase, which is essential is nucleic acid metabolism. By inhibiting ribonucleotide reductase in hematopoietic cells, hydroxyurea results in decreased stem cell proliferation and decreased red blood cell mass. Hydroxyurea should be given to patients who are considered high-risk, such as those above age 60 and/or with thrombosis history.
- Adverse effects: Hydroxyurea can cause cytopenias, skin ulcers, and secondary malignancies.
- Ruxolitinib: This is a JAK2 inhibitor that is used in cases of polycythemia that are refractory to interferon therapy. This medication has been shown to produce excellent hematologic and spleen responses, with response rates of approximately 90%. The use of ruxolitiib can reduce the need for phlebotomy. Ruxolitinib also results in improved symptom burden as measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), which a validated tool for the assessment of disease burden from a subjective standpoint.[12] Patients receiving ruxolitinib report improvement in spleen symptoms, inflammation, and microvascular abnormalities.
- Adverse effects: Ruxolitinib can cause non-melanoma skin cancers, weight gain, reactivation of herpes zoster, and cytopenias. Active skin surveillance is required given the skin cancer risk.
- Interferon-alpha: This medication results in reduction in red blood cell mass. The mechanism of action is not exactly known, but it is thought to induce apoptosis, modulate the immune system, and exert a direct inhibitory effect on hematopoietic cells.[12] Interferon-alpha can be given to patients who are considered high-risk, such as those above age 60 and/or with thrombosis history.[12]
- Adverse effects: Interferon-alpha can cause infusion reaction and cytopenias. Pegylated interferon-alpha is one formulation of this medication and has less toxicity than conventional interferon. However, this agent is not commonly used in the current era given the adverse effect profile, which leads to inability to tolerate this medication. Within 1 year of starting interferon, 20% of patients will discontinue this due to adverse effects. Approximately 15-20% of patients become resistant to interferon and require alternative therapy.[12]
- Chlorambucil or busulfan: These are alkylating agents that inhibit the proliferation of the malignant clone responsible for elevated red blood cell mass. These medications can be used if interferon or hydroxyurea are not tolerated. However, these medications are no longer included in the current standard of care for polycythemia vera.
- Adverse effects: Chlorambucil and busulfan can cause secondary myelodysplastic syndrome and secondary leukemias, which typically occur 5-7 years after exposure to these alkylating agents.
References
- ↑ National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_5
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Lengfelder E, Berger U, Hehlmann R (2000). "Interferon alpha in the treatment of polycythemia vera". Ann Hematol. 79 (3): 103–9. PMID 10803930.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 12.0 12.1 12.2 12.3 12.4 12.5 12.6 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.