Chronic Myelogenous Leukemia (CML)

Chronic myelogenous (myeloid) leukemia (CML) is a cancer of the blood-forming cells in the bone marrow. It usually develops slowly, and with modern targeted tablets most people live a near-normal life span.

What is CML?

CML is caused by an exchange of genetic material between chromosomes 9 and 22. This creates the Philadelphia chromosome and an abnormal gene, BCR-ABL1, which drives the marrow to make too many white blood cells. The change is acquired during life — it is not inherited and cannot be passed to children.

Risk factors

• Usually no cause is found
• High-dose radiation exposure
• CML is more common in middle-aged and older adults and slightly more common in men

Symptoms of CML

• Tiredness and weakness
• Fullness or pain under the left ribs, or feeling full after small meals, from an enlarged spleen
• Night sweats, fever and weight loss
• Easy bruising or bleeding
• Many people have no symptoms and CML is found on a routine blood test

Phases of CML

• Chronic phase — most people are diagnosed here; blasts are below 10% and the disease responds very well to treatment.
• Accelerated phase — rising blasts, new chromosome changes or worsening counts show the disease is becoming more active.
• Blast phase (blast crisis) — the disease behaves like an acute leukemia and needs urgent, intensive treatment.

The diagnosis of CML rests on finding the Philadelphia chromosome or the BCR-ABL1 gene. Tests also identify the phase of the disease and set a baseline for monitoring.

Complete blood count (CBC) with differential

Typically shows a high white cell count with cells at all stages of maturity, often with raised basophils and platelets.

Peripheral blood smear

Examining the blood under a microscope shows the pattern of white cells and the proportion of blasts.

Bone marrow aspiration and biopsy

Confirms the phase of CML and allows full chromosome analysis.

Genetic tests

• Cytogenetic testing — shows the Philadelphia chromosome and any additional changes.
• FISH — detects the BCR-ABL1 fusion in blood or marrow cells.
• Quantitative PCR — measures the amount of BCR-ABL1 transcript; repeated every few months to track response on the International Scale.
• Mutation analysis — if response is not as expected, to choose the next drug.

Imaging

Ultrasound, CT or MRI may be used to measure the spleen or check for other problems.

Targeted tablets have made CML one of the most successfully controlled cancers. The goal is a deep molecular response, and in some patients treatment can later be stopped safely under close monitoring.

Factors that affect treatment and prognosis

• The phase of CML at diagnosis
• Risk scores (Sokal, ELTS) based on age, spleen size, blasts and platelets
• How quickly BCR-ABL1 levels fall on treatment
• Other health conditions and possible drug side effects

Targeted therapy (tyrosine kinase inhibitors)

Imatinib, dasatinib, nilotinib, bosutinib, ponatinib and asciminib block the BCR-ABL1 protein. The choice depends on risk, other illnesses and any resistance mutations.

Chemotherapy

Hydroxyurea may be used briefly to lower very high counts while tests are completed. Intensive chemotherapy is used in blast phase.

Bone marrow transplant

An allogeneic stem cell transplant is reserved for patients whose CML does not respond to several TKIs, or who present in, or progress to, advanced phase.

Treatment by phase

• Chronic phase — a daily TKI with regular PCR monitoring.
• Accelerated phase — a more potent TKI; transplant is considered if the response is not optimal.
• Blast phase — TKI combined with chemotherapy, followed by transplant when possible.

Follow-up care

Blood PCR tests every three months at first, then less often, along with checks for side effects, heart and metabolic health. Taking the tablets every day is the most important part of success.

Our hematologists provide long-term CML care with regular molecular monitoring.