Chronic myeloid leukemia (CML) in children — clear answers for worried parents

Chronic Myeloid Leukaemia (CML) is a cancer of the blood-forming cells in the bone marrow. In CML, an abnormal myeloid stem cell acquires a specific genetic change — most often the Philadelphia chromosome — and begins to multiply slowly, gradually crowding out healthy blood cells. CML is quite rare in childhood. Most cases of CML occur in adults, and it accounts for only a small fraction of all childhood leukaemias. It is seen most often in older children and adolescents rather than in young children or infants. A child's CML is managed along the same broad principles as adult CML but by a paediatric oncology team, because growth, development, and long-term side effects need to be factored into every treatment decision.

CML usually develops slowly, and many children have few or no symptoms in the early phase of the disease. When symptoms do appear, the most common are: unusual tiredness or lack of energy that does not improve with rest; a feeling of fullness or discomfort on the left side of the abdomen, caused by an enlarged spleen; unexplained weight loss or loss of appetite; night sweats; and a low-grade fever. Some children are found to have CML when a routine blood count done for another reason shows an unexpectedly high white cell count. Because the symptoms are non-specific, a diagnosis is rarely made on symptoms alone — the key investigation is a full blood count followed by specialist blood and bone marrow testing. If your child has any of these signs persisting for more than two to three weeks, a GP evaluation with a full blood count is the right starting point.

The Philadelphia chromosome is a genetic change found in the leukaemia cells of most children and adults with CML. It forms when pieces of two chromosomes — chromosome 9 and chromosome 22 — swap places with each other. This swap creates an abnormal fusion gene (called BCR-ABL) that drives the production of a faulty protein. That protein tells the myeloid stem cells to divide uncontrollably. The Philadelphia chromosome matters for two reasons: it confirms the diagnosis of CML, and it is a very precise treatment target. Therapies designed to switch off the BCR-ABL protein have transformed the outlook for people with CML over the past two decades. Most children with CML who carry the Philadelphia chromosome respond well to these targeted treatments.

Diagnosis begins with a full blood count (CBC), which typically shows a markedly elevated white blood cell count with a characteristic pattern. A blood film examined under a microscope will show immature myeloid cells at various stages of development. These findings raise strong suspicion of CML, but confirmation requires two further tests. First, bone marrow aspiration and biopsy: a small sample of bone marrow is taken from the hip under sedation or general anaesthesia and examined for the proportion of blasts (immature cells) and for characteristic marrow changes. Second, genetic testing: the bone marrow or blood sample is tested for the Philadelphia chromosome using cytogenetics (chromosome analysis) and for the BCR-ABL fusion gene using a molecular test called PCR. The PCR test is also used throughout treatment to monitor how well the leukaemia is responding — called molecular response monitoring.

For most children with CML in the chronic phase (the most common presentation), treatment involves daily oral targeted therapy rather than the intensive intravenous chemotherapy used in ALL or AML. These medications work by switching off the abnormal BCR-ABL protein that drives the disease. Most children take the tablets every day and are monitored closely with regular blood counts and PCR tests to track how well the leukaemia cells are being suppressed. Many children can attend school and maintain a relatively normal daily routine during treatment. The duration of treatment, and the question of whether treatment can eventually be stopped, depends on the depth and duration of the molecular response — this is discussed in detail with the family as treatment progresses. Stem cell transplant is reserved for a minority of cases where the disease does not respond adequately to oral targeted therapy, or where the disease has progressed to an accelerated or blast phase. The CION paediatric oncology team reviews each child's case at a multidisciplinary tumour board before recommending any approach.

CML can exist in three phases that reflect how far the disease has progressed. The chronic phase is the earliest and most common phase at diagnosis. The bone marrow is producing too many myeloid cells, but they are relatively mature and still functional. Children in the chronic phase often have mild or no symptoms and respond well to oral targeted therapy. The accelerated phase is an intermediate stage in which the proportion of immature blast cells in the bone marrow or blood is rising. Symptoms tend to worsen, and the disease may be less responsive to standard treatment. The blast phase (also called blast crisis) is the most advanced stage, in which the bone marrow and blood contain a large proportion of immature blast cells — resembling acute leukaemia. Blast phase CML requires more intensive treatment. Most children with CML are diagnosed in the chronic phase; reaching blast phase is now uncommon when appropriate treatment is started promptly.