How I treat myelofibrosis

Blood. 2014 Oct 23;124(17):2635-42. doi: 10.1182/blood-2014-07-575373. Epub 2014 Sep 16.

Abstract

Myelofibrosis (MF) is a BCR-ABL1-negative myeloproliferative neoplasm characterized by clonal myeloproliferation, dysregulated kinase signaling, and release of abnormal cytokines. In recent years, important progress has been made in the knowledge of the molecular biology and the prognostic assessment of MF. Conventional treatment has limited impact on the patients' survival; it includes a wait-and-see approach for asymptomatic patients, erythropoiesis-stimulating agents, androgens, or immunomodulatory agents for anemia, cytoreductive drugs such as hydroxyurea for the splenomegaly and constitutional symptoms, and splenectomy or radiotherapy in selected patients. The discovery of the Janus kinase (JAK)2 mutation triggered the development of molecular targeted therapy of MF. The JAK inhibitors are effective in both JAK2-positive and JAK2-negative MF; one of them, ruxolitinib, is the current best available therapy for MF splenomegaly and constitutional symptoms. However, although ruxolitinib has changed the therapeutic scenario of MF, there is no clear indication of a disease-modifying effect. Allogeneic stem cell transplantation remains the only curative therapy of MF, but due to its associated morbidity and mortality, it is usually restricted to eligible high- and intermediate-2-risk MF patients. To improve current therapeutic results, the combination of JAK inhibitors with other agents is currently being tested, and newer drugs are being investigated.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Anemia / complications
  • Anemia / therapy*
  • Female
  • Humans
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Janus Kinases / antagonists & inhibitors*
  • Janus Kinases / genetics
  • Janus Kinases / metabolism
  • Male
  • Middle Aged
  • Mutation
  • Primary Myelofibrosis / complications
  • Primary Myelofibrosis / genetics
  • Primary Myelofibrosis / therapy*
  • Pyrazoles / therapeutic use
  • Pyrrolidines / therapeutic use
  • Splenomegaly / complications
  • Splenomegaly / surgery*
  • Stem Cell Transplantation / methods*
  • Sulfonamides / therapeutic use
  • Transplantation, Homologous

Substances

  • INCB018424
  • Pyrazoles
  • Pyrrolidines
  • Sulfonamides
  • Fedratinib
  • JAK2 protein, human
  • Janus Kinase 2
  • Janus Kinases