Dr. Aaron Gerds, a hematologist-oncologist at Cleveland Clinic, explains why myelofibrosis is often misunderstood, who is most at risk, and how treatment has evolved into a more personalized, targeted approach.
For those unfamiliar with myelofibrosis, how would you explain what this disease is and who is most at risk?
First and foremost, it’s an important point that often gets brushed aside: A lot of clinicians call myelofibrosis a blood disease or blood disorder. But I want to be clear that it is a blood cancer, and being a blood cancer means it is a type of chronic leukemia. Patients can live a long time and not even know they have it. It’s very different from acute leukemia. There are mutations that occur in people’s bone marrow and cause uncontrolled growth of cells, and by definition, that’s cancer. It’s been recognized by the World Health Organization and other entities as a cancer for quite some time now, but there’s still this idea out there that it’s “just a blood disease.” I don’t think that does the disease — or the patients — any justice.
Myelofibrosis is a unique type of chronic blood cancer. One of the central pathologic features is scar tissue in the bone marrow — “myelo” means bone marrow; “fibrosis” means scar tissue.
Clinically, patients are often symptomatic. They may have cytokine-mediated symptoms — e.g., night sweats, fevers, itchy skin — all driven by inflammatory substances released by the myelofibrosis cells. These are the same substances that make you feel like you have the flu. So, some patients feel like they have a low-grade flu all the time.
Another hallmark is an enlarged spleen. The spleen is an organ on the left side of your body and is part of your immune system. It can become very large, partially due to those cytokines and sometimes because bone marrow cells migrate there and grow.
Lastly, abnormal blood counts are common. That’s often what alerts primary care doctors. Patients may be anemic (low red blood cells), thrombocytopenic (low platelets), or have leukocytosis (high white blood cell counts). They’re referred to a hematologist, and that leads to a diagnosis.
Is there any particular group of people who are at higher risk?
At the center of myelofibrosis are mutations that drive a pathway inside cells called the JAK-STAT pathway. About 95% of patients have a mutation in one of three genes — JAK2, CALR, or MPL — and ultimately, each mutation activates the same pathway.
What’s important is that mutations in blood-forming cells can happen in the general population. Studies looking at thousands of people across age groups found that as we age, we acquire low-level mutations in blood cells. This is called age-related clonal hematopoiesis. In people in their 20s, mutations are rare. But by the time people reach their 80s, roughly 1 in 4 or 1 in 5 will have a detectable mutation. These individuals do not have blood cancer; they have normal blood counts, but these mutations carry about a 1% per year risk of turning into a blood cancer.
So, part of this is simply aging. Cells divide constantly, and massive amounts of genetic information must be copied perfectly each time. Errors happen. We’re also exposed to environmental factors and radiation; it’s genomic wear and tear over time.
There are some known risk factors. High benzene exposure — commonly found in cigarette smoke — increases risk. Certain occupational exposures and environmental contamination cases have also been linked. Ionizing radiation is another factor, such as radiation treatment for prior cancers. But for the vast majority of patients, this is part of aging and accumulated genetic changes over a lifetime.
What are the treatment options currently available, and how has care evolved over time?
Whenever we talk about treating myelofibrosis, we usually begin with the one therapy that has demonstrated curative potential: stem cell transplant. This is a procedure where a patient’s diseased bone marrow is replaced with healthy donor stem cells. In effect, we are giving the patient a new immune system, one that can recognize the cancer cells as abnormal and eliminate them.
A transplant is not appropriate for every patient. It is an intensive therapy with meaningful risks, particularly in the early months following the procedure. Because of that, it’s typically reserved for patients with higher-risk disease who are otherwise healthy enough to tolerate it. The decision involves balancing short-term risk against long-term potential benefit. For some patients, it can dramatically alter the trajectory of the disease. For others, careful medical management may be the better path. These are nuanced, highly individualized conversations.
For patients who are not candidates for transplant — which is the majority — treatment is guided by what the disease is doing in that specific individual. Myelofibrosis can behave very differently from person to person. Some patients have minimal symptoms and stable blood counts for years. In those cases, careful observation is often appropriate. Observation does not mean doing nothing; it means monitoring closely, tracking changes in blood counts, symptoms, and spleen size, and intervening at the right moment.
When treatment is needed, it is usually because the patient is experiencing significant symptoms, enlargement of the spleen, or worsening blood counts. One major advance over the past decade has been the development of targeted therapies that interfere with the abnormal signaling pathways driving the disease. These medications do not eliminate the cancer entirely, but they can significantly shrink the spleen and improve symptoms such as fatigue, night sweats, itching, and fevers. For many patients, these therapies meaningfully improve quality of life and have been shown to extend survival.
Another important area of treatment focuses on managing anemia, which is extremely common in myelofibrosis. Low red blood cell counts can cause fatigue, shortness of breath, and weakness. Some therapies are designed specifically to stimulate red blood cell production, while others help the bone marrow produce blood cells more effectively. In certain cases, medications may be combined to both control symptoms and improve anemia at the same time.
For patients with low platelet counts or other specific blood count abnormalities, treatment strategies may be adjusted accordingly. One of the complexities of myelofibrosis is that therapies must be tailored not only to the disease itself but also to how the disease is affecting the individual patient’s blood counts and overall health.
Over time, care for myelofibrosis has shifted significantly. Years ago, treatment options were limited, and the focus was largely supportive. Today, we have targeted therapies that address the underlying biology of the disease, more refined approaches to symptom control, and a deeper understanding of risk stratification, meaning we can better predict how aggressive the disease is likely to be in a given patient.
Rather than applying a single standard treatment to all patients, we now evaluate risk level, symptom burden, spleen size, genetic mutations, and overall health to determine the best course of action. For some, that means watchful monitoring. For others, it means targeted therapy. For a select group, it may mean pursuing a potentially curative transplant.
Ultimately, treatment in myelofibrosis is about balancing quality of life, disease control, and long-term planning. It is not a one-size-fits-all disease, and the management strategy reflects that complexity.
