How anemia could signal a rare blood cancer

Anemia is one of the most common and serious complications of myelofibrosis, a rare blood cancer where too many blood cells are produced in the bone marrow.

Iron deficiency symptoms can be severe or persistent fatigue, cold hands and feet, weakness, shortness of breath, a tingling or crawling feeling in the legs, or even tongue swelling or soreness. It’s a health concern that can be an emotional and physical drain on well-being.

But many don’t realize that there’s a connection between iron deficiency, formally known as anemia, and blood cancer.

This is especially concerning when anemia is prevalent among women of reproduction age at 21.3 per cent in Canada, according to the 2019 Canadian Health Measures Survey, the latest research available.

Anemia is one of the most common and serious complications of myelofibrosis, in particular, which is a rare blood cancer where too many blood cells are produced in the bone marrow. This causes scar tissue to build up in the marrow, leading to a decrease in normal red blood cells, white blood cells and the production of platelets. What can happen is the spleen and liver enlarge to compensate by taking on the role of making more blood cells. People with myelofibrosis – an estimated 1,400 to 2,177 Canadians are living with the disease – face poor overall survival, reduced quality of life and the need for frequent blood transfusions.

Dr. Vikas Gupta, a hematologist with United Health Network in Toronto and leading authority on anemia and blood cancer, says that he has focused his career on blood cancer because patients like those with myelofibrosis had nowhere to go until more recently. “We did not have any treatments available for these patients apart from the option of a bone marrow transplant, which was applicable to a very small proportion of patients.”

He says anemia-related symptoms are a huge problem for patients already under the duress of having an incurable blood cancer, and most patients with myelofibrosis will develop anemia as the disease progresses.

“Anemia is one of the major symptoms in patients with myelofibrosis at the time of diagnosis of myelofibrosis, present in about 1/3 of the patients. However, within the first year after diagnosis 75 to 80 per cent of patients will develop anemia, so it is an important part of the solution for treating the disease.”

Just because you’re not a female of reproductive age, doesn’t mean you’re not a risk. It is typically diagnosed in people between 50 and 80 years old but can occur at any age and often takes many years to develop. While Gupta says knowledge and therapy of myelofibrosis has progressed in the last 15 to 20 years, the cause isn’t fully understood.

What is known is that the disease develops from overactive signaling in the JAK, or Janus kinase, pathway that regulates blood cell production and inflammation. The over-activity has been linked to a number of genetic mutations.

In other words, cells mutate and can disrupt blood cell production, but there are few certainties.

“It takes a very long time for these mutations to turn into disease. If someone is found to have this mutation at a very low level, it’s not necessary that everybody will develop the disease, but there’s a high risk they will.”

How would you know if you had a problematic mutation?

You might experience symptoms like fatigue and weakness related to anemia, or symptoms related to an enlarged spleen where you have abdominal pain. You can also have fever, night sweats and weight loss. But here’s the thing: many times patients are completely asymptomatic, Gupta explains.

A blood test would show abnormalities, but imaging and a bone marrow examination would lead to a diagnosis – making those regular checkups with a doctor key to early diagnosis and better outcomes for patients.

His spleen was the size of a CFL football, she says, and he experienced fatigue and bone pain.

“There’s just a host of physiological symptoms that one goes through and they can be very debilitating, but probably fatigue is the biggest, not having energy because your red blood cells are not being born in your bone marrow to give you the oxygen you need. In the late stages he developed pulmonary hypertension, so he was oxygen dependent.”

And to manage his anemia, he became dependent on blood transfusions since 2010 with one transfusion a year at first. As his disease progressed, by 2017 and 2018, he was transfusion-dependent every 10 days. “He was more like an 80 year old,” Petruk says of his deteriorating final days.

Now medications are seeing significant improvements that can replace the need for blood transfusions in severely anemic patients. Gupta talks about the discovery of the JAK2 mutation in late 2004 that sparked growing interest in developing a group of drugs called JAK inhibitor therapy for inflammatory and hematological conditions. The first generation was approved by Health Canada in 2012. Now there are three JAK inhibitor drugs for Canadians with myelofibrosis, with Ojjaara (momelotinib) approved in November 2024 as a breakthrough for patients because it treats both the anemia and other symptoms of the cancer. Some patients with anemia couldn’t tolerate JAK inhibitors because it didn’t address their anemia – but now there’s another option for them, Gupta says. His team participated in clinical trials for Ojjaara, which is an oral medication taken once daily.

“For many patients, their anemia improves on Ojjaara. Since anemia is a prominent symptom in patients with myelofibrosis, that’s why availability of Ojjaara is so important. This drug addresses all sets of symptoms.”

For Petruk, she’s happy to see a drug approved that can improve quality of life for patients. Her husband may have survived longer had the medication come sooner. He was on one of the first JAK inhibitors in 2016.

“Unfortunately, when it became evident that that drug had stopped working for him, he couldn’t go on any clinical trials because there’s inclusion criteria in clinical trials. And he had developed hepatitis antibodies,” Petruk says. “So there was nothing else. He had a consult for a stem cell transplant and they found a match, but they only gave him 10 per cent success.”

Her advocacy work gives her a sense of purpose that has kept her going. “It keeps his legacy alive. I’m doing it because I couldn’t help him. But hopefully I can help others.”

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