Myelofibrosis: blood factory under siege

Dr Romana Jassat unpacks myelofibrosis, a rare blood cancer, including its causes, symptoms, and treatment options.

Myelofibrosis, a rare type of blood cancer, belongs to a group of blood disorders known as myeloproliferative neoplasms (MPNs).   

It’s a complex disease with considerable variation in presentation, ranging from slowly progressive disease that remains stable for years to more aggressive forms that significantly affect quality of life and survival.

It affects the bone marrow, the soft, spongy tissue inside the bones where blood cells are produced. The bone marrow can be thought of as the body’s blood factory. In myelofibrosis, this factory gradually becomes replaced by scar-like tissue, making it increasingly difficult to produce healthy blood cells.

There are two main forms: primary and secondary. Primary myelofibrosis develops  on its own without a preceding blood disorder. Secondary myelofibrosis develops as a complication of other MPNs, most commonly essential thrombocythemia or polycythaemia vera. Regardless of how it starts, the result is progressive bone marrow scarring and impaired blood cell production.

Impaired blood production

The three major blood cell lines produced in the bone marrow are red blood cells, white blood cells, and platelets, all playing an essential role in the body. 

When red blood cell production declines, you develop anaemia, which commonly causes fatigue. You may become dependent on blood transfusions. A reduction in platelet production may result in easy bruising and bleeding, while low white blood cell counts increase the risk of serious infections and hospitalisations.

The body attempts to compensate for failing bone marrow by producing blood cells elsewhere. The spleen (organ situated on the left side of the abdomen) often takes over this role. This process, known as extramedullary haematopoiesis, causes the spleen to enlarge and may lead to abdominal discomfort and a feeling of fullness after minimal food intake.

What causes myelofibrosis?

Most cases of myelofibrosis are associated with acquired genetic mutations that develop during a person’s lifetime. The three most common are the JAK2, CALR, and MPL mutations. These mutations aren’t inherited from parents and can’t currently be prevented. They lead to abnormal signalling within blood-forming stem cells, causing excessive stimulation of the bone marrow and inflammation. Over time, this contributes to the development of fibrosis, or scarring, within the bone marrow.

How is myelofibrosis diagnosed?

Diagnosis requires a combination of blood tests, molecular testing, and a bone marrow biopsy. Many patients ask whether a bone marrow biopsy is truly necessary. The biopsy provides crucial information about bone marrow structure, the degree of fibrosis, and the overall disease burden. It remains one of the most important investigations for confirming the diagnosis and assessing prognosis.

How is myelofibrosis treated?

Treatment is highly individualised and depends on factors such as age, symptoms, blood counts, and genetic profile. 

Supportive care remains an important part of management and includes blood transfusions and medications to stimulate red blood cell production. 

One of the most significant advances in recent years has been the development of targeted therapies known as JAK inhibitors. These medications can reduce spleen size, improve symptoms, such as fatigue, and significantly enhance quality of life for many patients.

Can myelofibrosis be cured?

At present, the only potentially curative treatment is an allogeneic stem cell transplant, where diseased bone marrow is replaced with healthy donor stem cells. 

Stem cell transplantation carries significant risk, and it’s generally reserved for selected patients with higher-risk disease who are fit enough to undergo the procedure.

Closing thought

The treatment landscape for myelofibrosis continues to evolve at a rapid pace. Newer therapies aim not only to control symptoms but also to target the underlying disease process itself.

While myelofibrosis remains a challenging condition, the outlook for patients has improved dramatically over the past decade. Advances in molecular testing, risk assessment, and targeted therapy are transformative. Increasingly, patients are no longer defined by the scars of the disease, but by the promise of modern medicine and the hope it continues to bring.

Dr Romana Jassat is a specialist physician and clinical haematologist who completed her training at the University of the Witwatersrand. She practices at Alberts Cellular Therapy (ACT), Pretoria East, and consults weekly at the ABJ Oncology practice in Vereeniging.

Header image by Freepik