Myelofibrosis

Disease information

Overview
Causes
and Symptoms
Treatment

Overview

Myelofibrosis, also known as MF, is a rare bone marrow disorder. It's part of the family of diseases called myeloproliferative neoplasms. In MF, the marrow cells grow and reproduce abnormally, leading to the production of various substances such as cytokines and growth factors. These substances can cause fibrosis, or scarring, in the bone marrow. This can lead to a host of complications such as an enlarged spleen, also known as splenomegaly. Sometimes, the body tries to compensate for the abnormal marrow by producing blood cells in other organs like the spleen or liver, a process called extramedullary hematopoiesis. Another characteristic of MF is the presence of unusual red blood cells in the bloodstream, a condition known as leukoerythroblastosis. While MF is a rare disorder, affecting approximately 0.15 out of every 100,000 people each year, it's important to know that there are treatment options available.

Causes and Symptoms

Myelofibrosis is a condition with causes that remain somewhat of a mystery. In about 60% of cases, we find mutations in what's called the JAK2 gene. In another 20-35% of cases, mutations occur in the CALR gene, and in 5-8% of instances, the MPL gene is affected. These genetic changes are believed to instigate fibrosis, or scarring, in the bone marrow. However, these mutations are not inherited from parents but are acquired at some point in one's life. The precise reason for these mutations remains unknown. Interestingly, there are patients with myelofibrosis who do not carry these genetic mutations, and their prognosis tends to be less favorable.

Most people with myelofibrosis do not exhibit symptoms at the time of diagnosis. In many cases, the condition is detected because of unusual results on a blood test done during a routine health check-up. As the disease progresses and begins to disrupt the normal production of blood cells, individuals may start to experience various signs and symptoms.

Abdominal pain, bloating, loss of appetite, and weight loss due to an enlarged spleen.
Hepatomegaly, excessive night sweats, skin itching, fever
Frequent infections due to a lack of white blood cells.
Bone or joint pain.

▲ Abdominal pain and bloating due to an enlarged spleen, etc

Treatment

The treatment strategy for myelofibrosis should indeed be determined by considering the patient's prognosis (risk group), as well as the type and severity of symptoms. Given that myelofibrosis often carries a poorer prognosis compared to other proliferative disorders of the bone marrow, it's crucial to classify risk groups using prognostic scoring systems. These include the International Prognostic Scoring System (IPSS), Dynamic International Prognostic Scoring System (DIPSS), DIPSS-plus, and Mutation-enhanced International Prognostic Scoring System (MIPSS). In deciding on the most appropriate treatment, the patient's age, overall health status, and any existing comorbidities must be taken into account. At present, the only treatment that is known to potentially provide a cure is allogeneic hematopoietic stem cell transplantation. However, this is a complex procedure with significant risks, and it's not suitable for everyone. There are also a variety of drug treatments currently under clinical investigation, aimed at improving symptoms and quality of life for patients with myelofibrosis. These treatments may not provide a cure, but they can potentially make a significant difference in managing the disease and its symptoms.

Alleviate anemia, splenomegaly, and systemic symptoms. Medications such as hydroxyurea, ruxolitinib (Jakafi), and fedratinib (Inrebic) are used.
Allogeneic hematopoietic stem cell transplantation
Clinical study