Related Experiment Video
Updated: Aug 13, 2025
Database-guided Flow-cytometry for Evaluation of Bone Marrow Myeloid Cell Maturation
Published on: November 3, 2018
Primary myelofibrosis: 2023 update on diagnosis, risk-stratification, and management
1Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
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 features include bone marrow reticulin/collagen fibrosis, aberrant inflammatory cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, risk of leukemic progression, and shortened survival.
Diagnosis:
Bone marrow examination with cytogenetic and mutation studies provides integrated diagnostic information; presence of JAK2, CALR or MPL mutation is expected but not required.
New Classification System:
The International Consensus Classification distinguishes "prefibrotic" from "overtly fibrotic" PMF; the former might mimic essential thrombocythemia (ET) in its presentation. Approximately 15% of patients with ET or polycythemia vera (PV) might progress into post-ET/PV MF.
Mutations:
SRSF2, ASXL1, and U2AF1-Q157 mutations predict inferior survival in PMF; RAS/CBL mutations predict resistance to ruxolitinib therapy. Type 1/like CALR mutation is associated with superior survival.
Karyotype:
Very high-risk abnormalities include -7, inv (3), i(17q), +21, +19, 12p- and 11q-. Favorable risk abnormalities include normal karyotype or isolated +9, 13q-, 20q-, 1q abnormalities and loss of Y chromosome.
Risk Stratification:
Contemporary prognostic systems include 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.
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 of choice for "very high" and "high" risk disease (estimated 10-year survival 0-13%), as well as in carefully selected patients with intermediate-risk disease (estimated 10-year survival 30%). Drug therapy in MF is currently palliative and targets anemia, splenomegaly, and constitutional symptoms. JAK2 INHIBITORS: Ruxolitinib, fedratinib, and pacritinib are FDA approved and respectfully utilized in patients failing treatment with hydroxyurea, ruxolitinib, or with platelet count <50 × 10 (9)/L. Momelotinib is another JAK2 inhibitor that is poised for approval sometime in 2023 and has shown erythropoietic benefits, in addition to affecting spleen and symptom responses.
Other Treatment Modalities:
Splenectomy is considered for drug-refractory splenomegaly and involved field radiotherapy for non-hepatosplenic EMH and extremity bone pain.
New Directions:
New agents, alone or in combination with ruxolitinib, are currently under clinical trial investigation (ClinicalTrials.gov) and preliminary results were presented at the 2022 ASH annual meeting and highlighted in the current review.
Insights
Primary myelofibrosis (PMF) is a bone marrow cancer with fibrosis, often driven by mutations like JAK2. Risk stratification guides treatment, from observation to stem cell transplant, with new drugs emerging.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by clonal stem cell proliferation, bone marrow fibrosis, and constitutional symptoms.
- Key features include JAK2, CALR, or MPL mutations, anemia, hepatosplenomegaly, and extramedullary hematopoiesis (EMH).
Approach:
- Diagnosis integrates bone marrow examination with cytogenetic and mutation studies.
- The International Consensus Classification differentiates prefibrotic and overtly fibrotic PMF.
- Contemporary prognostic systems like GIPSS and MIPSSv2 incorporate mutations, karyotype, and clinical factors for risk stratification.
Key Points:
- Specific mutations (SRSF2, ASXL1, U2AF1-Q157) and karyotype abnormalities predict survival and treatment response.
- Risk-adapted therapy ranges from observation for low-risk disease to allogeneic hematopoietic stem cell transplant (AHSCT) for high-risk disease.
- JAK2 inhibitors (ruxolitinib, fedratinib, pacritinib, momelotinib) and other modalities like splenectomy are used for symptom management.
Conclusions:
- Treatment strategies are tailored based on risk stratification, balancing observation, AHSCT, and pharmacotherapy.
- Ongoing research focuses on novel agents and combinations to improve outcomes for PMF patients.
Related Concept Videos
01:26Mitral Stenosis III: Medical Management
01:22Myocarditis IV: Nursing Management
01:14Myocarditis III: Medical Management
01:21Rheumatic Heart Disease III: Medical Management
01:09Introduction to Fibroblasts
01:26Atherosclerosis III: Management