Primary myelofibrosis: 2021 update on diagnosis, risk‐stratification and management

Abstract

Disease Overview: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutations. Additional disease features include bone marrow reticulin/collagen fibrosis, aberrant inflammatory cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival. Diagnosis: Bone marrow morphology is the primary basis for diagnosis. Presence of JAK2, CALR, or MPL mutation, expected in around 90% of the patients, is supportive but not essential for diagnosis; these mutations are also prevalent in the closely related MPNs, namely polycythemia vera (PV) and essential thrombocythemia (ET). The 2016 World Health Organization classification system distinguishes "prefibrotic" from "overtly fibrotic" PMF; the former might mimic ET in its presentation. Furthermore, approximately 15% of patients with ET or PV might progress into a PMF-like phenotype (post-ET/PV MF) during their clinical course. Adverse Mutations: SRSF2, ASXL1, and U2AF1-Q157 mutations predict inferior survival in PMF, independent of each other and other risk factors. RAS/CBL mutations predicted resistance to ruxolitinib therapy. Adverse Karyotype: Very high risk abnormalities include −7, inv (3), i(17q), +21, +19, 12p-, and 11q-. Risk Stratification: Two new prognostic systems for PMF have recently been introduced: GIPSS (genetically-inspired prognostic scoring system) and MIPSS70+ version 2.0 (MIPSSv2; mutation-and karyotype-enhanced international prognostic scoring system). GIPSS is based exclusively on mutations and karyotype. MIPSSv2 includes, in addition, clinical risk factors. GIPSS features four and MIPSSv2 five risk categories. Risk-adapted Therapy: Observation alone is advised for MIPSSv2 "low" and "very low" risk disease (estimated 10-year survival 56%-92%); allogeneic hematopoietic stem cell transplant (AHSCT) is the preferred treatment for "very high" and "high" risk disease (estimated 10-year survival 0%-13%); treatment-requiring patients with intermediate-risk disease (estimated 10-year survival 30%) are best served by participating in clinical trials. In non-transplant candidates, conventional treatment for anemia includes androgens, prednisone, thalidomide, and danazol; for symptomatic

Impact of the rs1024611 Polymorphism of CCL2 on the Pathophysiology and Outcome of Primary Myelofibrosis

“…Myelofibrosis (MF) is the most aggressive Philadelphia-chromosome negative myeloproliferative neoplasm (MPN), typified by abnormal proliferation and differentiation of hematopoietic progenitors, variable degree of bone marrow fibrosis and cytopenias, elevated circulating CD34 + cells, splenomegaly and risk of blast transformation (BT) [ 1 , 2 ]. MF represents the paradigm of onco-inflammatory disorders: chronic inflammation, fueled by the malignant hematopoietic clone itself, contributes to systemic manifestations and elicits clonal evolution, in a self-perpetrating vicious cycle [ 3 , 4 , 5 ].…”

Myelofibrozis hastalarında Ruxolitinib kullanımı: tek merkez deneyimi ve JAK-2 allel yükü ile Ruxolitinib yanıtı arasındaki ilişki

“…However, an additional treatment may be required for leukocytosis and thrombocytosis. In a recent study, it has been shown that ruxolitinib can be used alone or in combination for MF treatment [27]. Platelet level was increased (>1.500.000/ mm 3 ) in one of our patients after ruxolitinib treatment.…”

Tobacco use in the Myeloproliferative neoplasms: symptom burden, patient opinions, and care

“…With the development of questionnaires specific to MPN symptoms, it has become evident that MPN patients often suffer from a severe symptom burden leading to both affected functionality and reduced quality of life [ 17 , 23 , 24 ]. Targeted treatment with the JAK1/2-inhibitor, ruxolitinib, reduces splenomegaly and constitutional symptoms significantly for some MF and PV patients, but the majority of MPN patients do not benefit from ruxolitinib treatment and discontinuation rates are high due to treatment-related anemia and thrombocytopenia [ 25 , 26 ]. Hence, the need for interventions alleviating symptom burden is still urgent.…”