title: Polycythemia vera: current pharmacotherapy and future directions.
abstract: BACKGROUND
  In the past, management of polycythemia vera (PV) was built upon a cornerstone of control over erythrocytosis, through therapeutic phlebotomy, as well as the use of low-dose aspirin. Historically, selected patients were managed with additional cytoreductive therapies to decrease the risk of vascular events, with the recognition that these therapies likely did not impede progression.
  
  
  METHODS
  Recent clinical trials have demonstrated, in a randomized fashion, that optimal control of the hematocrit to target levels < 45% are important for decreasing the risk of vascular events. We are identifying that our historical set of cytoreductive agents, such as hydroxyurea, may be replaced in the future. The first candidate is pegylated interferon alpha-2a, which is demonstrating the ability to control vascular events and control extended hematopoiesis, while potentially having impact on fibrotic progression and Janus kinase 2 (JAK2) V1617F mutant allele burden. Ruxolitinib, as well as other JAK2 inhibitors in development, are demonstrating that this class of agents is making a very meaningful impact on the risk of vascular events in PV, controlling expanded hematopoiesis, as well as helping with symptomatic burden.
  
  
  CONCLUSIONS
  Future goals include attaining a better understanding of the specific roles of JAK inhibitor therapy and whether their use in combination with standard therapies offers greater efficacy than single agents alone.
authors.affiliation: Mayo Clinic, Department of Internal Medicine, Scottsdale, AZ, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hensley
authors.forename: Holly
authors.initials: H
authors.lastname: Geyer
authors.forename: Ruben
authors.initials: R
authors.lastname: Mesa
mesh_terms: D000477:Alkylating Agents / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D006400:Hematocrit; D006401:Hematologic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles; D011087:Polycythemia Vera / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines; D011994:Recombinant Proteins / Q000627:therapeutic use; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000477:Alkylating Agents; D006401:Hematologic Agents; D016898:Interferon-alpha; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C540383:ruxolitinib; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C100416:peginterferon alfa-2a; D001241:Aspirin; D006918:Hydroxyurea