Bone marrow fibrosis is scarring of the marrow. Excess reticulin and collagen fibers replace the spongy tissue where blood cells are made, so the marrow produces fewer red cells, white cells and platelets. It is most often caused by myelofibrosis and related myeloproliferative neoplasms, but it can also follow other blood cancers, infections, autoimmune disease and some metabolic bone conditions. It is diagnosed with a bone marrow biopsy, and treatment is aimed at the underlying cause.
As a specialist in haematology, I find patients are often alarmed by the word “fibrosis” on a biopsy report. The finding varies enormously in significance, from mild reactive change to a defining feature of a serious disease. This guide explains the difference.
What Is Bone Marrow Fibrosis?
Healthy marrow is a soft, cellular tissue supported by a fine scaffold of reticulin fibers. For a refresher on its normal structure, see this overview of bone marrow composition and function. In fibrosis, that scaffold thickens and multiplies. In advanced cases it is joined by dense collagen, and sometimes by new bone formation, a change called osteosclerosis.
As the scarring spreads, blood-forming cells have less room to work. The body compensates by making blood cells in other organs, mainly the spleen and liver. This is called extramedullary hematopoiesis, and it explains why an enlarged spleen is such a common feature. More on how marrow structure supports blood production is in our article on bone marrow tissue and its clinical implications.
What Causes Bone Marrow Fibrosis?
The fibers are made by normal marrow fibroblasts. The trigger is usually an abnormal population of cells, especially megakaryocytes (the platelet-producing cells), that release fibrogenic cytokines. The best known are transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF). PDGF also has wider roles in blood vessels and tissue repair, covered in our piece on PDGF in vascular biology and disease.
Primary causes
Primary myelofibrosis is a myeloproliferative neoplasm, a chronic blood cancer arising from a mutated stem cell. Most patients carry a driver mutation in JAK2, CALR or MPL, and all three switch on the same growth-signaling pathway. Myelofibrosis can also develop years after polycythemia vera or essential thrombocythemia, when it is called post-PV or post-ET myelofibrosis.
Secondary causes
Fibrosis can also appear alongside many other hematologic disorders and non-blood conditions:
- Other blood cancers, including chronic myeloid leukemia, hairy cell leukemia, acute megakaryoblastic leukemia, myelodysplastic syndromes, lymphoma and myeloma
- Cancers that have spread to the marrow, such as breast or prostate cancer
- Infections, notably tuberculosis
- Autoimmune disease, such as systemic lupus erythematosus (autoimmune myelofibrosis)
- Hyperparathyroidism, renal bone disease and severe vitamin D deficiency
- Radiation or certain toxic exposures
Grading Marrow Fibrosis
Pathologists grade fibrosis on a silver (reticulin) stain using the WHO system, which runs from MF-0 to MF-3. The grade helps with diagnosis and follow-up.
| Grade | What the pathologist sees | Typical meaning |
|---|---|---|
| MF-0 | Scattered linear reticulin, no intersections | Normal marrow |
| MF-1 | Loose network of reticulin with many intersections | Mild; may be reactive or early disease |
| MF-2 | Diffuse, dense reticulin with focal collagen or osteosclerosis | Overt fibrosis |
| MF-3 | Diffuse, dense reticulin with coarse collagen bundles, often osteosclerosis | Advanced fibrosis |
Signs and Symptoms
Early fibrosis may cause no symptoms and be found only through abnormal blood counts. As it progresses, patients may notice:
- Fatigue and breathlessness from anemia
- Fullness or discomfort under the left ribs, or feeling full quickly, from an enlarged spleen
- Night sweats, fevers, itching and weight loss, known as constitutional symptoms
- Bone or joint pain
- Easy bruising or bleeding from low platelets, or conversely blood clots, since myeloproliferative neoplasms carry a raised risk of clotting disorders
How Bone Marrow Fibrosis Is Diagnosed
A complete blood count may show anemia with low or high white cell and platelet counts. The blood film is often characteristic. It shows teardrop-shaped red cells (dacrocytes) and immature red and white cells in the circulation, a pattern called a leukoerythroblastic picture.
An attempted marrow aspirate frequently yields little or nothing, a “dry tap”, because the scarred marrow cannot be drawn up. The key test is therefore a trephine biopsy, a small core of bone and marrow examined with reticulin and collagen stains. Molecular tests for JAK2, CALR and MPL mutations and cytogenetics help confirm a myeloproliferative neoplasm and estimate prognosis. Imaging can measure spleen size.
Treatment and Management
Treatment depends on the cause. Secondary fibrosis often improves when the underlying condition, such as an infection, autoimmune disease or vitamin D deficiency, is treated.
For myelofibrosis, options include:
- JAK inhibitors, such as ruxolitinib, fedratinib, pacritinib and momelotinib, to shrink the spleen and ease symptoms
- Allogeneic stem cell transplantation, currently the only treatment with curative potential, considered for fitter patients with higher-risk disease
- Anemia management with transfusions, erythropoiesis-stimulating agents or other agents
- Monitoring alone for low-risk patients without symptoms
- Clinical trials of newer agents for suitable patients
Supportive care matters as much as disease-directed treatment. Patients who need regular transfusions are monitored for iron overload. Those with low white cell counts are advised on infection prevention, and anyone with a myeloproliferative neoplasm has their clotting risk assessed, since thrombosis is a recognized complication. In my practice, I also pay close attention to fatigue, nutrition and bone health, because these shape day-to-day quality of life.
Key Takeaways
- Bone marrow fibrosis is scarring that crowds out blood-forming tissue.
- Primary myelofibrosis is the classic cause, but many other conditions can produce fibrosis.
- Diagnosis rests on a trephine biopsy graded MF-0 to MF-3, supported by blood film and mutation testing.
- Treatment targets the underlying cause; JAK inhibitors control symptoms and transplant can be curative.
For related topics, visit the bone marrow guide.
Frequently Asked Questions
Is bone marrow fibrosis the same as myelofibrosis?
Not exactly. Bone marrow fibrosis is the tissue finding, while myelofibrosis is a specific blood cancer in which fibrosis is a defining feature. Fibrosis can also occur in many other conditions.
Can bone marrow fibrosis be reversed?
Secondary fibrosis often regresses once its cause is treated. In myelofibrosis, successful stem cell transplantation can reverse the scarring over time, while JAK inhibitors mainly control symptoms and spleen size.
Why was my bone marrow aspirate a “dry tap”?
Scarred marrow holds its cells tightly in a fibrous mesh, so liquid marrow cannot be drawn into the needle. A dry tap is a strong clue to fibrosis or heavy infiltration, and a trephine core biopsy is needed to see what is happening.
Is bone marrow fibrosis life-threatening?
It depends on the cause and grade. Mild reactive fibrosis may be of little consequence, whereas advanced myelofibrosis is a serious chronic disease. Your hematologist will use prognostic scoring systems to guide treatment.
How often will my blood counts be checked?
That depends on the cause, the grade of fibrosis and your treatment. People starting a JAK inhibitor are usually checked frequently at first, because these drugs can lower blood counts. Stable patients on monitoring alone are typically seen less often, with repeat biopsies only if the picture changes.
