Chronic Myeloid Leukemia (CML)

Chronic myeloid leukemia (CML) is rare in children — about 2–3% of childhood leukemias — and is most often found in older children and teenagers.

What is CML?

CML is caused by an acquired exchange between chromosomes 9 and 22 (the Philadelphia chromosome) that creates the BCR-ABL1 gene. This gene makes the marrow produce too many white blood cells. It is not inherited.

Signs and symptoms

• Tiredness and pale skin
• A swollen tummy or pain on the left side from a large spleen
• Fever, night sweats and weight loss
• Bruising or bleeding
• Sometimes no symptoms — CML is found on a blood test

Phases

• Chronic phase — most children are diagnosed here
• Accelerated phase — the disease is becoming more active
• Blast phase — behaves like acute leukemia

Children are different from adults

CML in children is often more active at diagnosis, and long-term treatment can affect growth. Care is therefore planned by a pediatric team experienced in CML, with attention to growth, bones and puberty.

The diagnosis is confirmed by finding the Philadelphia chromosome or the BCR-ABL1 gene, and the phase of CML is defined at the start.

Blood tests

A complete blood count usually shows a very high white cell count; a smear shows cells at all stages of maturity.

Bone marrow tests

Aspiration and biopsy (under sedation) define the phase and allow chromosome testing.

FISH (fluorescence in situ hybridization)

Shows the BCR-ABL1 fusion in the cells.

PCR testing

Measures the amount of BCR-ABL1 in the blood. It is repeated regularly to monitor the response to treatment.

Flow cytometry

Used if blast phase is suspected, to identify the type of blasts.

Imaging

Ultrasound to measure the spleen and liver.

Most children with chronic-phase CML are treated with a daily targeted tablet and have an excellent long-term outlook.

Targeted therapy

Tyrosine kinase inhibitors (TKIs) — imatinib, dasatinib or nilotinib — block BCR-ABL1. Doses are adjusted for body size, and growth is checked regularly.

Chemotherapy

Hydroxyurea may be used for a short time to bring down very high counts. Intensive chemotherapy is used for blast phase.

Bone marrow / stem cell transplant

Transplant is considered for advanced-phase CML or when CML does not respond to TKIs.

Monitoring

Regular PCR tests, growth and bone-health checks, and support to help children and teenagers take their medicine every day.

Our pediatric hematologists provide long-term CML care for children and teenagers.