Acute Lymphoblastic Leukemia (ALL)

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, most often diagnosed between the ages of 2 and 5. It is a cancer of immature lymphocytes (lymphoblasts) in the bone marrow.

Today around 90% of children with ALL are cured. Treatment takes about two to three years, most of it as an outpatient, and children usually return to school and normal activities during maintenance therapy.

Causes and risk factors

Childhood ALL is not caused by anything the child or parents did, and it is not contagious. Factors that slightly increase the risk include:

• Down syndrome and some other genetic syndromes
• Inherited immune deficiencies
• High-dose radiation exposure
• Having a sibling, especially an identical twin, with leukemia

Signs and symptoms

• Pale skin, tiredness and lack of energy
• Fever and frequent infections
• Bruising, red pin-point spots, nosebleeds
• Bone or joint pain, limping
• Swollen lymph nodes, a swollen tummy
• Loss of appetite and weight loss
• Breathing difficulty from a chest mass (in T-cell ALL) — an emergency

Types of childhood ALL

• B-cell ALL — about 85% of cases
• T-cell ALL — more common in older children and boys
• Genetic subtypes, such as hyperdiploid ALL or ETV6-RUNX1 ALL, which have an excellent outlook, and higher-risk subtypes such as KMT2A-rearranged or Philadelphia chromosome-positive ALL

Tests confirm ALL, identify its subtype and genetic features, and place the child in a risk group that sets the intensity of treatment.

Complete blood count (CBC) and peripheral blood smear

Low red cells and platelets, an abnormal white cell count and blasts in the blood suggest leukemia.

Bone marrow aspiration and biopsy

Performed under sedation to confirm the diagnosis.

Cytochemistry

Stains help distinguish ALL from AML.

Flow cytometry and immunohistochemistry

Show whether the leukemia is B-cell or T-cell and provide a "fingerprint" for later MRD testing.

Chromosome tests

Count the chromosomes and look for translocations that affect the risk group.

Fluorescent in situ hybridization (FISH)

Detects specific changes such as BCR-ABL1, ETV6-RUNX1 and KMT2A rearrangements.

Lumbar puncture

Checks for leukemia in the spinal fluid; the first dose of chemotherapy into the fluid is given at the same time.

Imaging tests

A chest X-ray looks for a mass in the chest before sedation; other scans are done as needed.

Treatment is risk-adapted: children with lower-risk ALL receive less intensive therapy to reduce side effects, while higher-risk ALL is treated more intensively.

Factors that affect treatment

• Age and white cell count at diagnosis
• B-cell or T-cell type, and genetic changes
• Leukemia in the spinal fluid or testes
• Measurable residual disease (MRD) at the end of induction — the most important factor

Risk groups

Children are grouped as standard (low), intermediate or high risk. Groups can change according to the MRD result.

Treatment phases

1. Induction (4–5 weeks) — achieves remission in more than 95% of children.
2. Consolidation (intensification) — further treatment, including protection of the brain and spinal cord.
3. Delayed intensification — a repeat of intensive therapy that reduces the chance of relapse.
4. Maintenance — daily tablets with monthly check-ups for about two years.

Treatment options

• Chemotherapy — the backbone of treatment
• Targeted therapy — tyrosine kinase inhibitors for Philadelphia chromosome-positive ALL
• Immunotherapy — blinatumomab and inotuzumab for higher-risk or relapsed B-ALL
• Radiation therapy — rarely needed, for leukemia in the brain or testes
• Bone marrow transplant — for very high-risk or relapsed ALL
• CAR T-cell therapy — for B-ALL that relapses or does not respond

Follow-up care

After treatment children are followed for many years for relapse and for late effects on growth, the heart, learning and fertility.

Our pediatric hemato-oncology team cares for children with ALL from diagnosis to long-term follow-up.