Hematology

Myelofibrosis

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Myelofibrosis
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Fernando Martínez Sáez
Medically reviewed by our Medical staff

Last update: 10-07-2025

How else can it be called?

  • Agnogenic myeloid metaplasia

  • Idiopathic myelofibrosis

  • Chronic myelosclerosis

  • Myelofibrosis with myeloid metaplasia

  • ICD-10: D47.4

  • ICD-11: 2A20.2

What is myelofibrosis?

Myelofibrosis is a type of blood cancer (myeloproliferative neoplasm) in which healthy bone marrow tissue is gradually replaced by fibrous (scar) tissue.

This condition arises from genetic mutations that trigger abnormal growth in hematopoietic stem cells, leading to the accumulation of scar tissue in the bone marrow. Bone marrow—the soft, spongy tissue inside large bones—normally produces blood cells, including red blood cells, white blood cells, and platelets.

In myelofibrosis, blood stem cells proliferate uncontrollably, generating immature blood cells and excessive fibrous scar tissue. As this scar tissue builds up in the bone marrow, it disrupts normal blood cell production.

Consequently, the marrow produces poor-quality blood cells, forcing the body to compensate by shifting some blood cell production to other organs, such as the spleen and liver (a process called extramedullary hematopoiesis). This leads to spleen enlargement (splenomegaly) and liver enlargement (hepatomegaly). However, extramedullary hematopoiesis is inefficient, ultimately resulting in anemia.

As a consequence, the blood produced by the bone marrow is of poor quality and to compensate for this problem, the production of blood cells also begins to take place in other parts of the body such as the spleen or liver (extramedullary hematopoiesis) causing the enlargement of the spleen (splenomegaly) and of the liver (hepatomegaly). Extramedullary hematopoiesis is not effective enough and anemia ends up appearing.

What is its incidence?

The annual incidence of myelofibrosis is estimated to be between 0.4 and 1.4 cases per 100,000 people.

Most patients are over 50 years old, with an average age at diagnosis of 65. However, myelofibrosis can occur at any age.

The disease affects adult men and women equally, though there is a slight male predominance. In contrast, among pediatric patients, it is more common in girls (2:1 ratio).

What are the causes?

The cause of primary (idiopathic) myelofibrosis remains unknown. In contrast, secondary myelofibrosis may develop as a consequence of other blood disorders, including leukemia, lymphoma, or myelodysplastic syndromes.

Risk factors associated with myelofibrosis include:

  • Exposure to petrochemicals (e.g., benzene, toluene)
  • Contact with radioactive thorium dioxide
  • High-dose radiation exposure

Additionally, studies suggest a potential link between myelofibrosis and autoimmune diseases, such as lupus or scleroderma.

From a genetic perspective, most patients carry mutations in one of three key genes:

  • JAK2 (50% of cases)
  • CALR (20–35% of cases)
  • MPL (5–10% of cases)

What symptoms may occur?

Symptoms of myelofibrosis typically develop gradually over time. Approximately one-third of patients experience no symptoms (asymptomatic).

The condition is often first suspected when a routine medical examination reveals an enlarged spleen (splenomegaly) or an enlarged liver (hepatomegaly).

Possible symptoms include:

  • Fatigue
  • Weight loss
  • Pale skin
  • Fever
  • Night sweats
  • Weakness
  • Palpitations
  • Shortness of breath (dyspnea)
  • Itching (pruritus)
  • Early satiety (feeling full after small meals)
  • Abdominal pain or discomfort
  • Pain in the upper left part of the body below the ribs
  • Unexpected bleeding
  • Bone pain, especially in legs
  • Frequent infections

How is it diagnosed?

Diagnosing myelofibrosis can be challenging because its symptoms resemble those of other diseases (mainly leukemias).

During examination, the doctor may check for an enlarged spleen or liver.

Blood tests are performed to detect anemia, leukocytosis, or thrombocytopenia.

A bone marrow biopsy is essential for diagnosis, though advanced fibrosis may make it difficult to obtain a sample.

Imaging tests like X-rays and MRI may also be used.

How is it treated?

The only potentially curative treatment is allogeneic hematopoietic stem cell transplantation, which is reserved for selected candidates.

Generally, treatment focuses on symptom management and quality of life improvement. Many asymptomatic patients require no treatment.

Palliative medications for myelofibrosis include:

  • Androgens (male hormones): Used to treat anemia, though they may cause masculinizing effects in women (e.g., facial/body hair growth)
  • Glucocorticoids: Effective for anemia and may improve pediatric cases
  • Iron, folic acid and vitamin B12: Can help reduce anemia
  • Hydroxyurea: Reduces spleen/liver enlargement, symptoms, anemia, and sometimes marrow fibrosis
  • Interferon alpha: Decreases spleen size, alleviates bone pain, and may increase platelets
  • JAK inhibitors (ruxolitinib, fedratinib, momelotinib, pacritinib): Reduce spleen size and control constitutional symptoms

Additional options for specific cases:

  • Splenectomy (spleen removal)
  • Radiation therapy
  • Blood transfusions

What is the prognosis?

Myelofibrosis is a progressive disease that typically requires ongoing therapy for management. In approximately 20% of cases, it may transform into acute myeloid leukemia (AML).

Spontaneous remission occurs rarely.

The average survival rate for patients diagnosed with myelofibrosis is six years.

Medically reviewed by our Medical staff on 10-07-2025

Bibliography

  • Harrison’s Hematology and oncology. Dan L. Longo. Third edition. 2017. Pag 161 ISBN: ISBN: 978-1-25-983582-7
  • Myelofibrosis (MF). Leukemia & Lymphoma Society. 2017. Available on: https://www.lls.org
  • The Gale Encyclopedia of medicine. Second Edition. Jacqueline L. Longe. Vol 3. pag 2281 ISBN 0-7876-5492-2

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