Myelofibrosis and Myelodysplastic Syndrome

Myelofibrosis and myelodysplastic syndrome are two distinct yet serious disorders affecting the bone marrow and blood cells. Both conditions often result in low blood counts, necessitating treatments such as blood transfusions to replace deficient red blood cells or platelets. These disorders can lead to significant health complications, particularly in older individuals who are more frequently diagnosed with these conditions. Early detection and appropriate treatment are crucial in managing the symptoms and improving the quality of life for those affected by these bone marrow disorders.

Myelofibrosis and myelodysplastic syndrome, like low blood counts can be treated with blood transfusions, where red blood cells or platelets are replaced.  The Myelodysplastic Syndrome (MDS) is a term for a group of frequent malignant stem cell diseases, mainly encountered in older individuals. People with MDS have low numbers of red blood cells (anemia), and the cells may have a mutation in their DNA. Overall, MDS is relatively uncommon, with an incidence of between four to five people per a population of 100. However, in patients over the age of 60, this increases to around 20 to 50 incidences per one hundred.

The World Health Organization divides myelodysplastic syndromes into subtypes based on the kind of blood cells — red cells, white cells and platelets — involved. In about 1 in 3 patients, MDS can progress to a quickly growing cancer of bone marrow cells called acute myeloid leukemia.

Myelofibrosis (MF) is rare disorder in which abnormal blood cells and fibers build up in the bone marrow. Myelofibrosis is part of a group of diseases called myeloproliferative disorders / neoplasms (MPN), and are characterized for abnormal cells which sometimes harbor mutations in the JAK pathway. The symptoms associated with primary myelofibrosis differ and are associated to a build of abnormal blood cells and fibers in the bone marrow. Affected people may stay symptom-free for many years, and then develop the florid disease. Myelofibrosis can affect anyone; however, it is most frequently diagnosed in people older than 50.

Primary Myelofibrosis and Secondary Myelofibrosis

Primary myelofibrosis (also known as chronic idiopathic myelofibrosis) is myelofibrosis that has been diagnosed without any prior MPN’s, while secondary myelofibrosis is myelofibrosis that has developed after the patient has first been diagnosed with essential thrombocythemia (ET) or Polycythemia Vera (VR). This secondary myelofibrosis can also be known as post-polycythemia vera (PPV) or post-essential thrombocythemia (PET-MF).

When considering the difference between myelofibrosis and myelodysplastic syndrome, it is important to understand that while both conditions affect the bone marrow, their diagnostic criteria and progression vary. Myelodysplastic syndromes (MDS) are characterized by the bone marrow’s inability to produce enough healthy blood cells, leading to aplastic anemia and other blood disorders. In contrast, myelofibrosis symptoms often include an enlarged spleen, fatigue, and night sweats, caused by the excessive buildup of fibrous tissue in the bone marrow.

Myelodysplastic syndromes and myelofibrosis both impact blood cell production, but they differ in their underlying mechanisms and treatment approaches. MDS involves defective stem cells that result in ineffective hematopoiesis, whereas myelofibrosis involves the replacement of bone marrow with scar tissue. Understanding these distinctions is critical for developing targeted treatment strategies and managing patient outcomes effectively.

Myelofibrosis and Myelodysplastic Syndrome Symptoms

Symptoms of myelofibrosis can include fatigue, shortness of breath, belly discomfort, pain beneath the ribs, feeling full, muscle and bone pain, itching, and night sweats. Most patients with myelofibrosis have an enlarged spleen, and in some cases, an enlarged liver.

In primary myelofibrosis there are often low ranges of circulating red blood cells, a situation known as anemia. White blood cells and platelets are additionally misshapen and immature. Symptoms of anemia include fatigue, pallor, and shortness of breath.

Like Myelofibrosis, the symptoms for Myelodysplastic syndrome include fatigue, shortness of breath, skin pallor due to anemia and skin bruising due to low platelets.

What is myelofibrosis and myelodysplastic syndrome? Both are serious disorders of the bone marrow, but they differ in their pathophysiology and progression. Myelofibrosis is a type of myeloproliferative disorder, characterized by the excessive production of fibrous tissue in the bone marrow, which disrupts normal blood cell production. This can lead to symptoms like an enlarged spleen and severe anemia. On the other hand, myelodysplastic syndrome (MDS) involves defective stem cells that result in ineffective hematopoiesis and can progress to acute myeloid leukemia in some cases.

In some instances, patients with myelofibrosis may exhibit a leukemoid reaction, which is an extreme reaction to infection or other stressors, leading to a significantly elevated white blood cell count. Treatments for these conditions vary but may include medications like luspatercept, which helps manage anemia associated with MDS by promoting the maturation of red blood cells. 

Myelofibrosis Risk Factors

Advanced age is the main risk factor for myelofibrosis, most people diagnosed with it are over the age of 50. About 6% are under the age of 40. Other risk factors include exposure to radiation, chemicals, or other blood disorders such as essential thrombocythemia or polycythemia vera.

There does not appear to be a gender bias in myelofibrosis, and men and women are equally at risk of developing the condition. Most cases of MF occur as a result of a genetic mutation in the bone marrow.

When myelofibrosis occurs on its own, it is called major myelofibrosis. If it occurs as a result of a separate disease, it is known as secondary myelofibrosis (for example, scar tissue in the bone marrow as a complication of an autoimmune disease).

Understanding the difference between myelodysplastic syndrome and myelofibrosis is crucial for accurate diagnosis and treatment. While both conditions affect the bone marrow and blood cell production, they have distinct characteristics and genetic markers. Myelodysplastic syndrome (MDS) primarily involves defective stem cells leading to ineffective hematopoiesis, whereas myelofibrosis is marked by the excessive buildup of fibrous tissue in the bone marrow. The differential diagnosis between these conditions often involves bone marrow biopsy, genetic testing, and evaluating patient history.

In presentations (often abbreviated as PPT) and discussions about these conditions, it’s important to highlight key genetic mutations such as CALR (calreticulin), which is commonly found in myelofibrosis patients. Primary myelofibrosis, also known as chronic idiopathic myelofibrosis, occurs without any prior hematologic disorder, whereas secondary myelofibrosis develops as a progression from other conditions like essential thrombocythemia or polycythemia vera. Proper understanding and differentiation between these syndromes are essential for developing effective treatment strategies and improving patient outcomes.

Myelofibrosis Causes

Primary myelofibrosis is a chronic disorder that affects the bone marrow’s ability to produce blood cells. The condition is often associated with genetic mutations, particularly in the JAK2, CALR, and MPL genes. Myelofibrosis treatment typically involves managing symptoms and may include medications, blood transfusions, or even stem cell transplants in severe cases. Recent advancements in targeted therapies have shown promise in improving patient outcomes by specifically addressing these genetic mutations.

• Recent research shows that about 50-60% of people with MF have a mutation in a protein called JAK2, a protein that regulates blood cell production.
• 30% of patients have a mutation in a gene called calreticulin called CALR, 5-10% of patients have mutations in the platelet hormone receptor called MPL.
• Patients with MF have other mutations in many genes, but these are also seen in blood diseases. Current research focuses on whether different mutation patterns may be important for the outcome or prognosis of the disease, as well as for response to treatment.
• Patients with MF are not born with these mutations, but get them throughout their lives. It is important to note that MF is rarely inherited and is not passed from parent to child, but some families seem to develop the disease more easily than others.

Myeloproliferative Neoplasms and Leukemia

Myeloproliferative neoplasms are a group of disorders resulting from poorly formed or dysfunctional blood cells. These neoplasms are considered to be cancer, due to the abnormal function of cells. Leukemia, a blood cancer which results in a higher level of white blood cells can be considered a myeloproliferative neoplasm. A few types of leukemia include:

• Chronic neutrophilic leukemia: a rare type of leukemia where neutrophils are overproduced (a type of white blood cell)
• Chronic eosinophilic leukemia: a form of leukemia where too many eosinphils (a type of white blood cell) are found in the bone marrow, blood and other tissues
• Chronic myelogenous leukemia: an uncommon type of leukemia that occurs in the bone marrow, causing an overproduction of white blood cells.

Myelofibrosis and Myelodysplastic Syndrome Treatments

Myelofibrosis symptoms and myelodysplastic syndrome low blood counts can be treated with blood transfusions, where red blood cells or platelets are replaced. Active treatment with drugs called hypomethylating agents are used in MDS. Studies have shown that lenalidomide is extremely efficient in treating peripheral blood and bone marrow abnormalities in certain people with MDS (a condition called MDS with 5q minus). Another treatment for Myelofibrosis and Myelodysplastic Syndrome is a bone marrow transplant.

The use of JAK inhibitors, leading to regulatory approval of ruxolitinib, represented a major therapeutic advance in myelofibrosis (MF). Some individuals with major myelofibrosis have been treated with allogeneic stem cell transplantation. In allogeneic stem cell transplantation, stem cells are donated from another particular person, often from a closely matched family member. There are current studies analyzing the best treatments after MF progresses on Ruxolitinib. Massive Bio uses artificial intelligence and patient support to match to novel treatments and clinical trials, including for myelodysplastic syndrome and myelofibrosis treatments.

Your Guide To Managing a Myelofibrosis Diagnosis

We know that a myelofibrosis diagnosis can be difficult, and parsing through all the treatment options can be overwhelming. If you’ve recently been diagnosed or relapsed with myelofibrosis, you might be wondering what the right next step is. We don’t want you to go through this alone, so we’ve created an actionable guide with 7 steps you can take to navigate a myelofibrosis diagnosis. Fill out the form below to get your guide today.