CML: Pathology and Molecular Results

CML is sometimes found on a routine blood test before any symptoms appear. A complete blood count checks your red cells, white cells, and platelets. In CML, the white blood cell count is often very high. A bone marrow aspiration and biopsy, where a needle removes a small marrow sample from the hip bone, confirms the diagnosis and checks how far the disease has progressed.

Most people with CML have a specific genetic change called the Philadelphia chromosome. It happens when two chromosomes, 9 and 22, swap pieces. This creates a new, abnormal gene called BCR::ABL1. That gene tells cells to make a protein that pushes white blood cells to grow out of control. Three tests can find this change: cytogenetic analysis, which looks at chromosomes directly; FISH, which uses glowing DNA probes; and PCR, which measures how much BCR::ABL1 genetic material is in your blood. The American Cancer Society calls PCR a very sensitive test. Your team may use it again during treatment to track your response.

CML is classified by the percentage of immature cells, called blasts, in the blood or marrow.

• Chronic phase: fewer than 10% blasts. This is the most common phase at diagnosis, and it usually responds well to standard treatments.
• Accelerated phase: 10% to 19% blasts.
• Blast phase, also called blast crisis: 20% or more.

Blast phase tends to grow quickly, acting a lot like an acute leukemia. These figures come from the National Cancer Institute’s “Chronic Myeloid Leukemia (CML).”

Chronic-phase CML is treated with pills called tyrosine kinase inhibitors, or TKIs. These block the abnormal protein made by BCR::ABL1. NCI lists asciminib, imatinib, dasatinib, nilotinib, and bosutinib. Your team picks a starting drug based on your phase, other health conditions, and side-effect risks. For blast-phase CML, treatment may combine a TKI with a stem cell transplant or, in some cases, palliative chemotherapy to control symptoms.

After you start a TKI, your team may repeat PCR testing to check how much BCR::ABL1 is still in your blood or marrow. The American Cancer Society says the level should go down over time if treatment is working. Your team decides how often to test and what each result means for you.

Bariatric surgery can lower how much of an oral TKI your body absorbs, which can reduce how well it works. If you have had this surgery or are considering it, tell your care team so your drug and dose can be reviewed.

• What phase is my CML in, and what does that mean for urgency?
• What is my current BCR::ABL1 level, and what is the target at each check?
• Which TKI are we starting with, and why this one for me?
• What side effects should prompt a call before my next appointment?
• If my level stops falling, what happens next?

Between PCR checks, a few changes are worth reporting rather than saving for the next appointment. Symptoms that build quickly can be a sign the disease is moving out of chronic phase.

• Call 911 or go to an emergency department if bleeding does not stop, or you become short of breath at rest, or you have sudden severe pain in the left upper abdomen. Do not drive yourself.
• Call your care team right away, day or night, if you have a fever of 100.4 F (38 C) or higher, or a fever comes with shaking chills and feeling suddenly unwell. With few working white cells, an infection can escalate within hours, so this counts as a medical emergency. If you cannot reach them quickly, go to an emergency department.
• Call your care team the same day if you have drenching night sweats, or bruising and bleeding that are new for you.
• Call your care team within a day or two if fullness or pain below the ribs on the left side is growing, or you are losing weight without trying.
• Call your care team within a day or two if a side effect of your TKI is stopping you taking it as prescribed. Ask about a dose review rather than skipping doses on your own.

• National Cancer Institute — Chronic Myeloid Leukemia Treatment (PDQ).