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A myelofibrosis diagnosis can be scary, especially since it¡¯s not a disease that many people have heard of. That¡¯s why having more information about the condition is so important and can help determine your best path forward.  

We sat down with , who specializes in myelofibrosis and related conditions, to answer common questions about this rare blood cancer. 

1. What is myelofibrosis?

Myelofibrosis is a subtype of a group of blood cancers called myeloproliferative neoplasms (MPNs). Patients with myelofibrosis have scar tissue, also called fibrosis, that forms in their bone marrow. This tissue causes normal production of blood cells ¡ª red blood cells, platelets and a type of white blood cell called granulocytes ¡ª to be disrupted.

In early stages of the disease, blood counts are often normal or even high. But as the disease progresses, low blood counts, especially low hemoglobin (anemia) and low platelets (thrombocytopenia), can increasingly become problems.

Myelofibrosis can occur as the primary disease, in which case it is called primary myelofibrosis. Or it can be due to progression from another type of myeloproliferative neoplasm, such as polycythemia vera, or PV, or essential thrombocythemia, or ET. When this happens, it is called secondary myelofibrosis.

2. Is myelofibrosis a type of leukemia?

Yes, myelofibrosis is considered a rare form of chronic leukemia. In some people, the disease can progress to acute myelogenous leukemia (AML).

3. What are the symptoms of myelofibrosis?

In the early stages of the disease, some people may not experience any symptoms. However, as the body¡¯s normal production of blood cells is disrupted, this leads to the four hallmarks of myelofibrosis. They are:

• an enlarged spleen
• anemia
• bone marrow fibrosis
• disease-associated symptoms (a catch-all term described below)

Clinical trials of myelofibrosis treatments usually use improvement of these hallmarks to determine success or failure of the drug or other intervention. 

The spleen enlarges because it starts trying to take over the production of blood cells from the fibrotic bone marrow. This can sometimes be painful, but some patients simply report a feeling of fullness when they eat. The liver can enlarge, too, as part of the same process.

Anemia, or a lack of red blood cells, occurs because the bone marrow can¡¯t produce enough of them and an enlarged spleen destroys them. Some drugs widely used to treat myelofibrosis, such as ruxolitinib, can cause or worsen anemia. This can lead to fatigue, dizziness, headaches and shortness of breath.  

Bone marrow fibrosis is more of a hallmark of the disease than a symptom ¡ª it refers to the scar tissue building up in the bone marrow. It is considered the defining feature of myelofibrosis. However, it can be minimal or even absent in the increasingly diagnosed, ¡°prodromal¡± condition called ¡°prefibrotic primary myelofibrosis.¡±

Finally, ¡°disease-associated symptoms¡± is the catch-all term for the other symptoms people with myelofibrosis experience, including:

• fatigue
• night sweats, fever
• frequent infections
• bone pain
• itching
• weight loss
• trouble concentrating
• the tendency to bruise easily

Although less common than in PV or ET, people with myelofibrosis can develop blood clots, too. 

4. What treatments are available for myelofibrosis?

This is a very exciting time because many new medications are being developed to treat myelofibrosis.

A key feature of the disease is an overactive JAK-STAT signaling pathway. Although more than half of patients with myelofibrosis have a mutation in the JAK2 gene, this signaling pathway is universally activated in this disease, regardless of ¡°driver¡± mutation. That¡¯s why JAK2 inhibitors are proving to be effective drugs for most people with myelofibrosis. The Food and Drug Administration (FDA) approved ruxolitinib, a JAK1/2 inhibitor, to treat myelofibrosis in November 2011, based partly on clinical trials led by my colleagues here at MD Anderson. It was the only medication that could treat myelofibrosis until 2019, when the FDA approved fedratinib, a JAK2 inhibitor. This was followed by pacritinib (a JAK2, ACVR1/ALK2 and IRAK1 inhibitor) in 2022 for patients with very low platelets (less than 50,000 per microliter), in whom ruxolitinib and fedratinib are not felt to be safe. In 2023, the FDA approved momelotinib, a potent ACVR1/ALK2 and JAK1/2 inhibitor, specifically for myelofibrosis patients with anemia. 

There also drugs being tested in clinical trials for patients who develop resistance to JAK inhibitors?or who have a suboptimal response. These include a selective nuclear export inhibitor, a HDM2 inhibitor, a telomerase inhibitor, a PIM1 kinase inhibitor and multiple BET inhibitors, among many others. 

There is also a new generation of JAK2 inhibitors that we hope will be more potent against or selective for the mutated JAK2 protein than those currently available. Researchers are also studying some novel immunotherapeutic approaches against mutated CALR, the second most common driver mutation after JAK2. Finally, several novel agents, such as an anti-hemojuvelin antibody and activin receptor ligand traps, are being tested to treat anemia caused by myelofibrosis.

5. Is myelofibrosis curable?

For those who are eligible, an allogeneic stem cell transplant can cure myelofibrosis. However, many people aren¡¯t good candidates for a stem cell transplant, and the procedure has considerable risks. So, some people may prefer to stay on medication that can control the disease for extended periods of time rather than undergoing a stem cell transplant. 

6. What is the life expectancy for someone with myelofibrosis?

There¡¯s no single answer about the life expectancy for a patient newly diagnosed with myelofibrosis. Some people may live for many years without the disease getting worse before eventually dying of something completely unrelated. However, there are several prognostic models available with online calculators that can give individual patients a rough idea of their life expectancy and help inform decisions about stem cell transplantation.

7. What¡¯s your advice for newly diagnosed myelofibrosis patients and their caregivers?

Learn as much as you can about the disease, and seek treatment from a hematologist with expertise in myelofibrosis. Here at MD Anderson, the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms is the largest single-institution research center for MPNs worldwide. My colleagues and I have conducted more than 100 clinical trials, and we have many more ongoing. We hope that these will help us improve the quality of life and the outcomes of patients worldwide.