Recent advances in the diagnosis and management of primary myelofibrosis

Abstract

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) in which dysregulation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways is the major pathogenic mechanism. Most patients with PMF carry a driver mutation in the JAK2, MPL (myeloproliferative leukemia), or CALR (calreticulin) genes. Mutations in epigenetic regulators and RNA splicing genes may also occur, and play critical roles in PMF disease progression. Based on revised World Health Organization diagnostic criteria for MPNs, both screening for driver mutations and bone marrow biopsy are required for a specific diagnosis. Clinical trials of JAK2 inhibitors for PMF have revealed significant efficacy for improving splenomegaly and constitutional symptoms. However, the currently available drug therapies for PMF do not improve survival. Although allogeneic stem cell transplantation is potentially curative, it is associated with substantial treatment-related morbidity and mortality. PMF is a heterogeneous disorder and decisions regarding treatments are often complicated, necessitating the use of prognostic models to determine the management of treatments for individual patients. This review focuses on the clinical aspects and outcomes of a cohort of Japanese patients with PMF, including discussion of recent advances in the management of PMF.

Keywords: Long-term outcome; Prognostic score; Primary myelofibrosis.

Figure 1.

Survival curves of 780 patients with primary myelofibrosis in a Japanese registry diagnosed between 1999 and 2015. Adapted from Takenaka et al., with permission from Springer Nature [28]. OSR, open surgical repair; CI, confidence interval.

Figure 2.

Survival curves of 780 patients with primary myelofibrosis in a Japanese registry, stratified by prognostic scoring system risk groups at diagnosis. (A) International Prognostic Scoring System (IPSS), (B) Dynamic IPSS (DIPSS), (C) Dynamic IPSS plus additional prognostic factors (DIPSS plus). Adapted from Takenaka et al., with permission from Springer Nature [28].

Figure 3.

Treatment algorithm for primary myelofibrosis. DIPSS plus, Dynamic International Prognostic Scoring System plus additional prognostic factors; epo, erythropoietin; alloSCT, allogeneic stem cell transplant; JAK2, Janus kinase 2.