Pharmacologic management of myelofibrosis

J Oncol Pharm Pract. 2017 Dec;23(8):591-601. doi: 10.1177/1078155216670229. Epub 2016 Sep 26.

Abstract

Myelofibrosis is a BCR-ABL-negative myeloproliferative neoplasm characterized by abnormal hematopoiesis. Alterations to the Janus kinase-signal transducer and activator of transcription pathway result in dysregulation of gene transcription and cell proliferation. Patients with symptomatic myelofibrosis present with a variety of signs and symptoms including, but not limited to myelosuppression, marked splenomegaly, abdominal discomfort, fatigue, and blood transfusion-dependence. Traditional myelosuppressive therapies including hydroxyurea, azacitidine, and cladribine aim to reduce constitutional symptoms and control the burden of disease. Immunomodulators can potentially reverse anemia associated with myelofibrosis, but are poorly tolerated by most patients. The novel Janus kinase 2 (JAK2) inhibitor, ruxolitinib, has demonstrated marked improvements to constitutional symptoms and splenomegaly. While survival benefit has not yet been demonstrated, continued research into pharmacologic management of myelofibrosis offers the promise of altering the course of disease progression.

Keywords: Myelofibrosis; myeloproliferative neoplasm; ruxolitinib.

Publication types

  • Review

MeSH terms

  • Anemia / diagnosis
  • Anemia / drug therapy
  • Disease Management*
  • Humans
  • Janus Kinase 2 / antagonists & inhibitors*
  • Nitriles
  • Primary Myelofibrosis / diagnosis
  • Primary Myelofibrosis / drug therapy*
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*
  • Pyrimidines
  • Splenomegaly / diagnosis
  • Splenomegaly / drug therapy

Substances

  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • JAK2 protein, human
  • Janus Kinase 2