Myelofibrosis is a reactive and reversible process common to many malignant and benign bone marrow disorders. It can present de novo as primary myelofibrosis (PMF), or as secondary (reactive) myelofibrosis if caused by another disorder, drug treatment, or toxic agent.
PMF (the focus of this topic) is a chronic progressive myeloproliferative neoplasm (MPN). Median survival is approximately 6 years, which is much shorter than other MPNs (e.g., polycythemia vera, essential thrombocythemia). However, survival outcomes vary, ranging from <1 year to >30 years.
Bone marrow fibrosis, extramedullary hematopoiesis, leukoerythroblastosis, and splenomegaly are hallmarks of PMF.
Observation is appropriate for patients with asymptomatic, low-risk disease without hyperuricemia or a remedial cause for anemia.
Treatment with Janus kinase inhibitors and hematopoietic stem cell transplant (along with supportive care) should be considered for patients with symptomatic and/or high-risk disease. Hematopoietic stem cell transplant is the only treatment option with a potential for cure.
Death is usually due to bone marrow failure (hemorrhage, anemia, or infection), transformation to acute leukemia, portal or pulmonary hypertension, heart failure, cachexia, or severe myeloid metaplasia with organ damage.
Myelofibrosis is a reactive and reversible process common to many malignant and benign bone marrow disorders. It is characterized by bone marrow fibrosis with increased reticulin deposits and in some cases increased collagen deposits. Depending on the underlying cause, patients may have abnormalities in blood production and associated extramedullary hematopoiesis.
Myelofibrosis can present de novo as primary myelofibrosis (PMF), a chronic progressive myeloproliferative neoplasm (MPN) with its origin in a multipotent hematopoietic progenitor cell. The etiology of PMF is unknown, but it is commonly associated with somatic driver mutations in the Janus kinase 2 (JAK2), calreticulin (CALR), or myeloproliferative leukemia virus oncogene (MPL) genes. A specific clonal marker has not been identified.
Fibrosis in the bone marrow due to another disorder, drug treatment, or toxic agent is called secondary or reactive myelofibrosis.
History and exam
Key diagnostic factors
- history of radiation exposure
- history of industrial solvents exposure
- symptoms of anemia (fatigue, weakness, dyspnea, palpitations)
- constitutional symptoms (weight loss, night sweats, low-grade fever, cachexia, fatigue, and pruritus)
- splenomegaly ± hepatomegaly
- features of extramedullary hematopoiesis
Other diagnostic factors
- features of portal hypertension
- joint and bone pain
- hearing loss
- radiation exposure
- industrial solvents exposure
- age ≥65 years
- cytogenetic abnormalities
1st investigations to order
- CBC with differential
- peripheral blood smear
- bone marrow aspiration
- bone marrow biopsy
Investigations to consider
- genetic mutation analysis (including JAK2 V617F, calreticulin [CALR], MPL)
- fluorescence in situ hybridization (FISH) or breakpoint cluster region-abelson polymerase chain reaction (PCR)
- bone marrow cytogenetic analysis
- ultrasound of suspected site
- technetium 99 scan
- CT of suspected site
- MRI of suspected site
- serum uric acid
- antinuclear antibodies
- rheumatoid factor titer
- complement levels
- Coombs test
lower risk: asymptomatic
lower risk: symptomatic
higher risk: ages <50 years and suitable for stem cell transplant
higher risk: ages ≥50 years and suitable for stem cell transplant
higher risk: not suitable for stem cell transplant
- Polycythemia vera
- Essential thrombocythemia
- Chronic myeloid leukemia
- NCCN clinical practice guidelines in oncology: myeloproliferative neoplasms
- NCCN clinical practice guidelines in oncology: hematopoietic cell transplantation (HCT)
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