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Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow. It is the most common form of childhood cancer.
About 3,000 children and teens younger than 20 are diagnosed with ALL each year in the United States.
ALL most often occurs in children ages 2 to 5. It can also occur in older children and adolescents. It affects slightly more boys than girls.
ALL in infants is rare. About 90 cases of ALL in children younger than 1 are diagnosed each year in the United States.
The most common treatment for ALL is chemotherapy. Many advances have been made in ALL treatment. The overall cure rate for ALL in children is about 90%.
In leukemia, cancer cells grow rapidly in the bone marrow. These cancer cells are immature white blood cells called blasts. When this happens, healthy blood cells — white blood cells, red blood cells, and platelets — can’t do their jobs correctly.
ALL affects white blood cells called lymphocytes. These cells fight infection and help protect the body against disease.
There are two types of lymphocytes: B-lymphocytes and T-lymphocytes. ALL may arise from either type of lymphocyte, so cases of ALL are either known as B-cell or T-cell ALL. B-cell ALL is the most common.
Most cases of ALL have no known cause.
Certain inherited syndromes are linked to an increased risk of ALL.
Inherited syndromes associated with increased risk of ALL include:
Acute leukemia means symptoms worsen quickly.
Children may become very sick and need medical attention right away.
In ALL, signs and symptoms may include:
Bone marrow tests are required to confirm a leukemia diagnosis.
If leukemia is found, additional tests will be run to find out if ALL is in other parts of the body and to gather information about the subtype of ALL.
During the exam and history, the provider will:
A provider will draw blood to run tests. These tests include:
A bone marrow aspiration and biopsy will confirm a diagnosis of cancer. Patients usually have these procedures at the same time. Patients will either be sedated or have appropriate pain medication.
If cancer is diagnosed, more tests will be run on the bone marrow to pinpoint the subtype of the cancer.
Immunophenotyping is used to diagnose specific types of leukemia. It compares the cancer cells to normal cells of the immune system.
Immunohistochemistry and flow cytometry are the laboratory tests.
Immunohistochemistry is a test that uses antibodies to show specific proteins in a sample of tissue. The complexes of proteins and antibodies are stained brown or red and can be seen under a microscope.
In flow cytometry, cells are stained with a light-sensitive dye, placed in a fluid, and passed in a stream before a laser or other type of light. The test measures the number of cells, the percentage of live cells, and certain characteristics of cells, such as size, shape, and the presence of leukemia markers on the cell surface.
The doctor will recommend running laboratory tests to identify specific genes, proteins, and other factors involved in the leukemia.
This is important because cancer is caused by mistakes (mutations) in the cell’s genes. Identifying these mistakes helps diagnose the specific subtype of leukemia.
Using this information, doctors can choose treatment options tailored to the individual case.
Children whose leukemia shows mutations associated with a good outcome may receive less toxic treatments.
Doctors may prescribe more intensive treatments for patients with a leukemia with mutations associated with poorer outcomes.
Mutations may be identified for which a treatment targeted to that specific mutation are available.
ALL has several subtypes. In many cases, doctors can use the subtype of ALL to make treatment decisions based on the risk group of the leukemia. See treatment section for more information.
Subtypes of ALL (World Health Organization, 2016)
Natural killer (NK) cell lymphoblastic leukemia/lymphoma (provisional entity)
The care team will run tests to find out if it is in other parts of the body.
A lumbar puncture will show if leukemia has spread to the central nervous system. The test is also called an LP or spinal tap.
Patients may receive chemotherapy at the same time this is done. This is called prophylactic intrathecal chemotherapy. It is given to prevent ALL from spreading to the cerebrospinal fluid.
A chest X-ray will be done to see if leukemia cells have formed a mass in the middle of the chest.
Other imaging studies and laboratory tests may be performed if patients have certain signs and symptoms.
Female patients of childbearing age may have pregnancy testing.
Male patients may be examined by ultrasound to see if the provider suspects testicle involvement. This is rare in ALL. It happens in 1-2% of males.
Chemotherapy is the main treatment for childhood ALL. Treatment involves a combination of medicines. It takes 2 to 3 years to complete.
Treatment is generally given on an outpatient basis. But there may be times when the patient will need to be in the hospital.
Many cancer centers and hospitals in the United States treat ALL. The specific drugs, dosage, and schedule of delivery may vary somewhat. But the treatment principles are the same.
The treatment plan will depend on the results of the patient’s diagnostic tests.
Patients will have a surgical procedure to get a central venous access device. This device reduces the need for needle sticks. Patients can have blood drawn for laboratory tests and receive intravenous (IV) medicines, fluids, blood products, and nutrition through the device. After treatment has completed, it will be removed.
Patients may have to miss some school during treatment. But the treatment center, school, parents, and student can work together so the student can keep up with school as much as possible.
Doctors are increasingly able to tailor treatments to individual patients based on their risk group.
Risk group refers to the chance that the patient’s cancer either won’t respond to treatment (refractory), or it will return after an initial response to treatment (relapse). There are treatment options for relapsed or refractory ALL.
Risk groups have different names depending on the treatment center. In general, these risk groups are called low, standard, high, and very high.
The method of chemotherapy and types of medicine depend on the child’s risk group. For example, children and teens with high-risk leukemia generally receive more anticancer drugs and/or higher doses than children with low-risk ALL.
Risk groups are determined by:
Minimal residual disease (MRD) is a term used when there are so few leukemia cells in the bone marrow that they cannot be found using a microscope.
Highly sensitive tests such as flow cytometry, polymerase chain reaction (PCR), and next generation sequencing can detect 1 leukemia cell in 10,000-1,000,000 normal cells in the bone marrow.
Children who have positive MRD (more than 1 cell in 10,000) after induction therapy are at the greatest risk of relapsing. The timing of MRD measurement varies depending on the center.
The goal of this phase is to use a combination of chemotherapies to destroy leukemia cells in the blood and bone marrow and bring the disease into remission. This phase is intense and may require hospital stays.
Central nervous system (CNS) sanctuary therapy may be given to destroy leukemia cells in the spinal fluid.
Doctors will look at how leukemia responds to induction therapy to determine how to proceed with therapy.
The goal of this more intensive phase involves a different combination of drugs to destroy any remaining cells that could cause leukemia to relapse. It may require hospital stays.
Patients who have Philadelphia chromosome-positive ALL may receive imatinib during this phase.
If the leukemia stays in remission after the first 2 phases, maintenance therapy can begin. Its goal is to use a combination of chemotherapy drugs to destroy any leukemia cell that might remain after the first induction and consolidation phases.
Patients will likely have weekly chemotherapy and blood tests with periods of high-dose chemotherapy known as reinduction.
The first 9 months of treatment of ALL is usually the most intensive. Often patients can return to school after the first 9 months.
The patient will return for follow-up visits once every 4 months.
These visits may include:
Follow-up visits may change to once every 6 months.
Follow-up visits may change to once a year.
Treatment for ALL has 3 phases and takes about 2 to 3 years to complete.
The goal of induction therapy is to kill leukemia cells in the blood and bone marrow and bring the disease into remission.
This phase usually lasts 4-6 weeks. It is the most intensive phase of treatment.
Central nervous system (CNS) sanctuary therapy (also called CNS prophylaxis) will also be given during this time to kill leukemia cells that remain in the spinal fluid. These drugs are injected into the fluid-filled space between the thin layers of tissue that cover the spinal cord (intrathecally).
Patients will have a bone marrow aspirate/ biopsy during this phase to find out how the leukemia is responding to therapy.
The goal of consolidation/ intensification therapy is to destroy any remaining cells that could begin to grow and cause the leukemia to relapse. This phase usually lasts 8-16 weeks.
It may involve 6-8 cycles of chemotherapy over a period of up to 8 months.
The goal of maintenance therapy is to destroy any cancer cells that might have survived the first 2 phases. Maintenance may last 2 to 3 years.
Maintenance regimens may involve daily doses of 6-mercaptopurine (6-MP), weekly methotrexate, and periodic doses of vincristine and corticosteroids.
In some cases, doctors may recommend additional treatment options.
Targeted therapy uses medicines that seek out and attack cancer cells without harming surrounding normal cells. This type of therapy is only possible if the cancer has detectable gene markers that respond to available targeted drugs.
Ruxolitinib may be used to treat a type of ALL called Philadelphia-like ALL.
Immunotherapy is a type of cancer treatment that uses the immune system to fight cancer. In general, immunotherapies work by helping the immune system find cancer cells. It can then attack cancer cells and/or increase the immune system’s ability to respond to cancer.
Immunotherapy may include monoclonal antibody drugs such as blinatumomab, inotuzumab ozogamicin, and rituximab. The chimeric antigen receptor (CAR) T cell, such as tisagenlecleucel, may also be a possible treatment.
A hematopoietic cell transplant (also called bone marrow transplant or stem cell transplant) may be recommended for children who are at high risk for relapse or whose ALL is resistant to treatment. Patients must be medically able and have a suitable donor.
Doctors sometimes look at how well induction chemotherapy worked to decide whether a transplant is needed.
Radiation is rarely used in ALL treatment. It may be given in cases where ALL has spread to the brain, spinal cord, or testicles. A 2019 study showed that radiation to the central nervous system for ALL may be omitted.
Radiation may also be given to prepare patients to receive a hematopoietic cell transplant (commonly known as bone marrow transplant or stem cell transplant.)
Side effects are hard to predict. They depend on the medicine and how a person reacts to it. Different people can have different reactions to the same medicine.
Side effects can happen during any phase of ALL treatment. The first weeks of treatment (induction phase) are the most intense and the most likely to produce serious side effects. There are treatments for these side effects.
Side effects may include:
About 98% of children with ALL go into remission within weeks after starting treatment.
More than 90% of children with ALL can be cured. Patients are considered cured after about 5 years in remission.
Survival rates for ALL patients in low-risk groups can be more than 95%.
If patients have a form of ALL that does not respond to treatment (refractory) or comes back after treatment (relapsed), the medical team will discuss treatment options.
Some ALL patients may have late effects. A late effect is a health problem that occurs months or years after treatment has ended.
Cancer patients should continue to be followed by their treatment center care team and/or a primary care provider in the community after cancer treatment. Late effects can often be treated or, in some cases, prevented.
Different treatments may have different late effects. Not all patients will have late effects. Patients who had the exact same treatment may experience different late effects.
Current research focuses on developing more effective treatments for children whose cancer doesn’t respond to the original therapy.
Researchers are also focused on developing treatments that don’t cause as many side effects during therapy and late effects in cancer survivors.
Reviewed: February 2020