title: Safety considerations when treating myelofibrosis.
abstract: BACKGROUND
  Myelofibrosis (MF) is a clonal disorder leading to marrow fibrosis, cytopenias and extramedullary haematopoiesis.
  
  
  METHODS
  Generic management of MF with a specific focus on the efficacy and safety profile of the Janus Kinase (JAK)1/JAK 2 kinase inhibitor, ruxolitinib (Novartis Pharmaceuticals, Basel, Switzerland), will be discussed. This agent has manageable haematological side effects and possesses both beneficial and potentially detrimental immunosuppressive effects. Multiple JAK inhibitors are in various stages of development but some have been withdrawn due to unexpected toxicities such as the occurrence of Wernicke's encephalopathy (Fedratinib; Sanofi, Paris). Traditional therapies such as hydroxycarbamide, interferon, immunomodulatory drugs and androgens will also be discussed.
  
  
  CONCLUSIONS
  Therapeutic options in MF have expanded with the introduction of JAK inhibitors. Ruxolitinib benefits many patients with symptomatic MF. Other JAK inhibitors such as momelotinib may have the additional benefit of alleviating anaemia. Unfortunately, there is no current JAK inhibitor option for patients with severe thrombocytopenia as pacritinib was recently put on clinical hold due to adverse events. Careful consideration needs to be given towards optimal management of patients who lose their response/are resistant to JAK inhibitor therapies and those with a high risk mutational status but lower risk prognostic score.
authors.affiliation: a Department of Haematology , Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital , London , UK.
authors.forename: J M
authors.initials: JM
authors.lastname: O'Sullivan
authors.affiliation: b Department of Haematology , King's College Hospital NHS Foundation Trust , London , UK.
authors.forename: D P
authors.initials: DP
authors.lastname: McLornan
authors.affiliation: a Department of Haematology , Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital , London , UK.
authors.forename: C N
authors.initials: CN
authors.lastname: Harrison
mesh_terms: D001549:Benzamides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001952:Bridged-Ring Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors*; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C561234:11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene; D001549:Benzamides; D001952:Bridged-Ring Compounds; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C546012:N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; C540383:ruxolitinib; D053612:Janus Kinases
keywords: JAK inhibitors; myelofibrosis; ruxolitinib; safety