Acute Lymphoblastic Leukemia (ALL)

What acute lymphoblastic leukemia is

Bone marrow, the soft tissue inside bones, makes red blood cells, platelets and white blood cells. In ALL, a genetic change in a developing lymphocyte (a type of white cell) causes it to multiply out of control without maturing. These leukemic blasts:

• fill the bone marrow, so fewer normal blood cells are made
• spill into the blood
• can spread to the lymph nodes, spleen, liver, brain and spinal fluid, and testicles

"Acute" means it develops and progresses over days to weeks, so treatment starts promptly. ALL is classified as B-cell ALL (about 85 percent) or T-cell ALL.

Symptoms

Most symptoms come from the lack of normal blood cells:

Other symptoms:

• bone and joint pain, which can make a child limp or refuse to walk
• swollen lymph nodes in the neck, armpits or groin
• a swollen belly from an enlarged liver or spleen
• loss of appetite and weight loss
• night sweats
• headache, vomiting or vision changes if the brain or spinal fluid is involved
• breathlessness or cough from a mass in the chest, more common in T-cell ALL

Symptoms usually develop over a few weeks. Many of them are also common in everyday childhood illnesses; it is the combination, especially pallor, bruising and fever together, that raises concern.

Causes and risk factors

In most people no cause is found. ALL is not inherited in the usual sense and is not contagious. Factors that raise the risk include:

• Age: most common between 2 and 5 years
• Down syndrome and some other genetic conditions (Li-Fraumeni syndrome, ataxia telangiectasia)
• An identical twin with ALL
• High-dose radiation exposure and some previous chemotherapy
• Being male and of Hispanic ethnicity in the US

Diagnosis

1. Complete blood count and blood smear: often shows anemia, low platelets and abnormal white cell counts, with blasts visible under the microscope.
2. Bone marrow aspirate and biopsy: a sample from the hip bone confirms leukemia (usually 20 percent or more blasts) and allows detailed testing.
3. Flow cytometry: identifies whether the cells are B-cell or T-cell ALL.
4. Genetic tests: look for chromosome changes such as the Philadelphia chromosome (BCR-ABL1), which guide treatment and predict outcome.
5. Lumbar puncture: checks the spinal fluid for leukemia cells.
6. Chest X-ray, blood chemistry and heart tests before treatment.

Doctors then assign a risk group (standard, high or very high) based on age, white cell count, genetic features and, most importantly, how quickly the leukemia responds to treatment, measured by minimal residual disease (MRD) testing.

Treatment

Treatment is given at specialist centers, often within clinical trials, and lasts about 2 to 3 years.

Phases of chemotherapy

Targeted and immune treatments

• Tyrosine kinase inhibitors (such as imatinib, dasatinib or ponatinib) for Philadelphia chromosome-positive ALL
• Blinatumomab: an antibody that directs the immune system's T cells to B-cell leukemia cells
• Inotuzumab ozogamicin: an antibody linked to a cancer drug
• CAR T-cell therapy: the patient's own T cells are engineered to attack the leukemia, used for relapsed or resistant B-cell ALL

Stem cell transplant

An allogeneic (donor) stem cell transplant is used for very high-risk ALL, slow responders, and many adults or people who relapse.

Supportive care

• blood and platelet transfusions
• antibiotics, antifungals and preventive treatment for infections
• medicines to prevent tumor lysis syndrome at the start of treatment
• nutrition support, anti-nausea medicines and psychological support

Side effects and complications

Short-term side effects of treatment include infections during low white cell counts, nausea, hair loss, mouth sores, nerve problems and high blood sugar from steroids. Long-term effects in childhood survivors can include effects on growth, learning, heart, bone health and fertility, and a small risk of second cancers. Survivors are followed in long-term clinics.

Outlook

• Children: about 90 percent are cured with current treatment. Children aged 1 to 9 with low white counts and favorable genetics do best.
• Adults: long-term survival is about 30 to 45 percent, higher in younger adults treated with pediatric-style regimens, and improving with targeted drugs and immunotherapy.
• Relapse: most relapses happen during or within a few years of finishing treatment. Newer immune treatments have improved outcomes after relapse.

Frequently asked questions

What are the first signs of acute lymphoblastic leukemia?

Early signs include unusual tiredness, pale skin, easy bruising or tiny red spots on the skin, nosebleeds, repeated fevers or infections, bone or joint pain, and swollen glands. In children, limping or refusing to walk because of bone pain can be an early sign.

Is acute lymphoblastic leukemia curable?

Yes, in many people. About 90 percent of children with ALL are cured with modern treatment. In adults, cure rates are lower, roughly 30 to 45 percent, but they are rising with targeted therapies, immunotherapy and stem cell transplant.

What is the difference between ALL and AML?

Both are acute leukemias of the bone marrow. ALL comes from immature lymphocytes and is most common in children. Acute myeloid leukemia (AML) comes from immature myeloid cells and is more common in older adults. They are treated with different drug regimens.

How long is treatment for ALL?

Treatment usually lasts about 2 to 3 years. The most intensive phases, including induction and consolidation, take about 6 to 9 months, followed by about 2 years of lower-intensity maintenance treatment, mainly tablets taken at home.

Can adults get acute lymphoblastic leukemia?

Yes. Although ALL is most common in young children, about 4 in 10 cases occur in adults, with risk rising again after 50. Adults more often have high-risk genetic features such as the Philadelphia chromosome, which is now treated with targeted drugs.