Myelofibrosis: clinicopathologic features, prognosis, and management

Clin Adv Hematol Oncol. 2018 Feb;16(2):121-131.

Abstract

Myelofibrosis is one of the BCR-ABL-negative clonal disorders that collectively are known as myeloproliferative neoplasms (MPNs). It is caused by the proliferation of clonal hematopoietic stem cells, which over time leads to characteristic clinical features. The disease presentation is heterogeneous, however, with 30% of patients initially asymptomatic. This variation in clinical phenotype warrants careful risk stratification to guide appropriate management, and prognostic risk scores are continually being refined. Considerable advancements have been made in the understanding of MPN pathogenesis, in particular recognition of the driver mutations JAK2 V617F, CALR, and MPL, which has led to the development of ruxolitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2 that has transformed therapy for myelofibrosis. Although ruxolitinib decreases symptoms and is associated with a survival advantage, it has no clear disease-altering activity, and allogeneic hematopoietic stem cell transplant remains the sole curative option for myelofibrosis. Ongoing studies are evaluating newer JAK inhibitors, combinations of ruxolitinib with other targeted drugs, and targeted therapies that do not inhibit JAK. This review provides further detail regarding the clinical features, pathogenesis, risk stratification, and current management of myelofibrosis, including older and newer targeted treatments.

Publication types

  • Review

MeSH terms

  • Biomarkers
  • Biopsy
  • Cell Transformation, Neoplastic
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / methods
  • Disease Management
  • Disease Progression
  • Humans
  • Primary Myelofibrosis / diagnosis*
  • Primary Myelofibrosis / etiology
  • Primary Myelofibrosis / mortality
  • Primary Myelofibrosis / therapy*
  • Prognosis
  • Treatment Outcome

Substances

  • Biomarkers