Chronic Myeloid Leukemia (CML)?
- Chronic Myeloid Leukemia (CML) is a type of cancer of the white blood cells.
- In CML, blast cells (or immature white blood cells) form and uncontrollably multiply and divide and can impair the body’s ability to make normal healthy blood cells.
- Although CML usually grows fairly slowly, it can also turn into a faster-growing acute leukemia.
- CML is not strongly associated with environmental factors or family history. Often, patients are diagnosed after a routine blood test suggests something may be wrong, and they are referred to a specialist.
As the disease progresses, CML cells crowd out healthy cells and eventually build up and spill over into the blood. CML cells can also land in other areas of the body, among them the spleen, intestinal tract, kidneys and lungs. Although CML usually grows fairly slowly, it can also turn into a faster-growing acute leukemia. When this happens, CML may become more difficult to treat.
Read MoreWho gets CML?
"That's a very interesting question," Dr. Frances Arena, Medical Director at NYU Langone Arena Oncology and Integration, tells SurvivorNet. "Our only known reason for getting CML is exposure to radiation such as the event at Chernobyl. We know high dose radiation exposure may lead to CML but that people generally do not get CML from low dose exposures such as sunlight or X-Rays. Outside of radiation exposure, we know it's primarily a disease of older people and that means people in their sixth and seventh decade."However, this is not always the case.
"I have a patient with CML in her 30s," Dr. Arena adds. "Also, men are slightly more likely to get the disease, although in my practice on Long Island, New York, it's about equal between men and women."
According to the American Cancer Society:
- There will be about 8,860 new diagnoses of CML in the United States in 2022 (an estimated 5,120 men and 3,740 women)
- It is estimated that approximately 1,220 people will die of the disease (an estimated 670 men and 550 women) however while that number is always changing it is likely that the majority of patients may have had long time from diagnosis to end of life.
Dr. Yang reiterates that risk factors for CML are not clear like they are with some other forms of cancer. "We don't know exactly why some people get CML," says Dr. Yang. "It's not a cancer that's strongly associated with environmental exposures and it's not thought to be hereditary."
How are you screened for CML?
"Way back when I was chief resident and later on, as the assistant chairman of medicine at Memorial Sloan Kettering in NYC, when we saw a patient with CML, they were usually very ill," Dr. Arena recalls. The reason? "We didn't pick up the disease as quickly as we now do. These days, every person who comes in for a routine physical or for some type of checkup gets a blood count."
"I can't tell you how many times a week someone is referred to me because their white blood cell count is elevated."
When a blood test is suspicious, further screening is advised, which would include a Complete Blood Count (CBC). In fact most patients with a high white count do not have CML.
Complete Blood Count (CBC)
Before symptoms develop, as Dr. Arena said, most people who have CML find out by having a routine blood test called a CBC or complete blood count. A CBC sees how many different kinds of cells are in your blood: red blood cells, white blood cells, and platelets (which are pieces of very large cells in the bone marrow called megakaryocytes). People with CML often have low numbers of red blood cells or blood platelets. If your blood test results show a high number of white blood cells it's an indication that you might have CML.
From there, other screening tests will be recommended by your healthcare provider. This may include bone marrow samples or genetic tests.
Bone Marrow Samples
Since leukemia begins in the bone marrow, checking to see if the patient has CML with a marrow sample is a crucial step. People with CML often have bone marrow that is hypercellular meaning it has more blood-forming cells than a normal sample would contain. These two tests are usually done at the same time:
- Bone marrow aspiration For this procedure, a doctor or nurse makes a small incision in your skin while you're lying on your side or on your stomach. A hollow needle is inserted into the bone and into the bone marrow, usually collected from the top ridge of the hipbone. Using a syringe attached to the needle, a sample of the liquid portion of the bone marrow is withdrawn. The aspiration only takes a few minutes, but during this time you may feel a sharp pain or stinging.
- Bone marrow biopsy This procedure is most often done immediately following the bone marrow aspiration. A slightly bigger needle is pushed down into the bone and a small piece of both bone and marrow is removed. When the procedures are completed, a light amount of pressure will be placed on the area to help prevent bleeding.
Genetic Tests
Gene testing to look for the BCR-ABL gene or for the Philadelphia chromosome is recommended. Genetic testing for both the BCR-ABL gene and the Philadelphia chromosome is done by analyzing blood samples.
- Testing for the Philadelphia chromosome Normal cells have 23 pairs of chromosomes and each is a certain size. But it is common for the cells in CML patients to have an abnormal chromosome called the Philadelphia (Ph) chromosome. Screening for the Ph chromosome helps the doctor to diagnose CML. That said, sometimes the Ph chromosome can't be seen but other tests can identify chromosome changes, as well as finding the BCR-ABL gene.
- Conventional Cytogenetics It's often recommended to have sample of chromosome (pieces of DNA) examined under a microscope to look for any changes. Since chromosomes can be seen most clearly when they are in the process of dividing, a sample of your either your bone marrow or blood is grown in a laboratory to get the cells to begin to divide. The drawback to this test is that it takes time (usually around 30 days) and doesn't always work.
- Fluorescent in situ hybridization (FISH) Using fluorescent dyes that only attach to specific genes or parts of chromosomes, this test looks for specific pieces of the BCR-ABL gene. It can be done using regular blood or bone marrow samples without needing to grow the cells in a lab. The results are faster than conventional cytogenetics.
- Polymerase chain reaction (PCR) This test is designed to not only find the BCR-ABLE gene in CML cells but it also measures how much is there. Using blood or bone marrow samples, the test is so sensitive that is able to detect small amounts of BCR-ABL, even when cytogenetic testing doesn't find the Philadelphia chromosome in bone marrow cells.
Is there a way to prevent getting CML?
No. Although there are some kinds of cancer that can be more likely prevented by making lifestyle changes and avoiding certain risk factors, there's no known way to prevent CML. However, a 2019 study found that a stress-responsive protein plays an important role in the recurrence of this type of leukemia.
What are the treatment options?
Targeted therapies, which go after specific proteins that control how cancer cells grow, divide, and spread, (as opposed to chemotherapy which may also kill healthy cells) have become a mainstay in treating CML.
"CML to me, has been the poster child for targeted medicines," Dr. Arena says. "Back in the day, we only had medicines like hydroxyurea, which was a blatant type of oral chemotherapy, that could keep the blood counts down but could have severe side effects. Also, the old chemotherapies didn't go after the molecular signature of the disease the BCR-ABL gene the way new targeted treatments do.
Dr. Arena points out that for the first time we have medicines that go ahead and really attack where this disease lives and what causes it. "So, it's not a chemotherapy," he says.
"These days there are plenty of treatment options available for patients and physicians. Patients with CML are treated with a class of drugs called tyrosine kinase inhibitors (TKIs)," explains Dr. Yang. "These targeted oral medications (pills) are specifically designed to kill the leukemia cells."
Several TKIs are currently approved for the treatment of newly diagnosed CML. These drugs work by blocking the protein made by the BCR-ABL gene. They include:
- Imatinib (Gleevec) Imatinib was the first targeted therapy approved by the U.S Food and Drug Administration (FDA) for CML in 2001
- Dasatinib (Sprycel)
- Nilotinib (Tasigna)
- Bosutinib (Bosulif)
- Ponatinib (Iclusig)
- Asciminib is a new therapeutic option in chronic-phase CML with treatment failure
"Most of my patients are not getting sick from the CM: medications,” says Dr. Arena. "There can be some side effects, such as fluid retention, but as we look at our different generations of medication, we find that even some of these kinds of side effects have become less and less."
The future of CML treatment
"The biggest advance in CML in the past five years is not a treatment per se, but a lack of treatment," explains Dr. Yang. "We had previously thought all patients with CML needed to stay in treatment for the rest of their lives. We now know that a portion of patients with CML who have responded well to treatment and who have achieved a deep remission can potentially stop their treatment and stay in remission long-term. Unfortunately, this situation does not apply to all patients and should only be done under the careful supervision of their treating physician."
Dr. Arena adds: "I can say to some of my patients: 'Let' stop the medicine! Let's stop the medicine!' And in greater than 50% of patients, their CML will not recur."
Researchers are currently investigating new strategies that may allow more patients to discontinue their treatment.
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