From the Guidelines
Primary myelofibrosis is a rare bone marrow cancer where abnormal blood stem cells produce excessive scar tissue in the bone marrow, disrupting normal blood cell production, and its treatment depends on symptom severity and risk stratification, with ruxolitinib (Jakafi) being the primary medication for symptomatic patients, as recommended by recent guidelines 1.
Diagnosis and Risk Stratification
The diagnosis of primary myelofibrosis (PMF) requires meeting all 3 major criteria and 2 minor criteria, as proposed by the revised WHO criteria 1. The major criteria include the presence of megakaryocyte proliferation and atypia, not meeting WHO criteria for other myeloid neoplasms, and demonstration of JAK2 or other clonal markers. The minor criteria include leukoerythroblastosis, increased serum lactate dehydrogenase level, anemia, and palpable splenomegaly.
Treatment Options
Treatment options for PMF include watchful waiting with regular monitoring for low-risk asymptomatic patients, and ruxolitinib (Jakafi) for symptomatic patients, typically started at 15-20mg twice daily, which helps reduce spleen size and improve symptoms by inhibiting JAK1/JAK2 signaling 1. Other medications include fedratinib (Inrebic), hydroxyurea for cytoreduction, and danazol or erythropoiesis-stimulating agents for anemia.
Allogeneic Stem Cell Transplantation
Allogeneic stem cell transplantation remains the only potentially curative option but carries significant risks and is generally reserved for younger patients with high-risk disease, with a median survival time expected to be less than 5 years, as recommended by the European LeukemiaNet 1.
Ongoing Management
Regular blood counts, spleen size monitoring, and assessment for disease progression or transformation to acute leukemia are essential parts of ongoing management, with the goal of improving morbidity, mortality, and quality of life for patients with PMF. Some key points to consider in the management of PMF include:
- Risk stratification using the International Prognostic Scoring System (IPSS) for newly diagnosed patients and dynamic IPSS for patients being seen during their disease course, with the addition of cytogenetics evaluation and transfusion status 1.
- Treatment of anemia with erythropoiesis-stimulating agents, which produce improvements in 23%–60% of patients, and consideration of other options such as danazol or corticosteroids 1.
- Management of splenomegaly with hydroxyurea or other cytoreductive agents, and consideration of splenectomy in selected cases with symptomatic portal hypertension, drug-refractory painful splenomegaly, or frequent RBC transfusions 1.
From the Research
Definition and Characteristics of Primary Myelofibrosis
- Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation, often accompanied by JAK2, CALR, or MPL mutations 2.
- The 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 2.
- Bone marrow morphology is the primary basis for diagnosis, with the presence of JAK2, CALR, or MPL mutation being supportive but not essential for diagnosis 2, 3.
Diagnosis and Risk Stratification
- The 2016 World Health Organization classification system distinguishes "prefibrotic" from "overtly fibrotic" PMF, with the former potentially mimicking essential thrombocythemia (ET) in its presentation 2, 3.
- Two new prognostic systems for PMF have been introduced: GIPSS (genetically-inspired prognostic scoring system) and MIPSS70+ version 2.0 (mutation- and karyotype-enhanced international prognostic scoring system) 2, 3.
- GIPSS is based exclusively on mutations and karyotype, while MIPSS70+ version 2.0 includes both genetic and clinical risk factors 2, 3.
Treatment Options
- Observation alone is advised for MIPSS70+ version 2.0 "low" and "very low" risk disease, while allogeneic hematopoietic stem cell transplant is the preferred treatment for "very high" and "high" risk disease 2, 3.
- Conventional treatment for anemia includes androgens, prednisone, thalidomide, and danazol, while ruxolitinib is used for symptomatic splenomegaly and constitutional symptoms 2, 3.
- Erythropoiesis-stimulating agents (ESAs) have been shown to be safe and effective in managing anemia in myelofibrosis patients treated with ruxolitinib 4.
- New agents, such as luspatercept and KER-050, are being investigated for the treatment of anemia in myelofibrosis 5.