Childhood acute lymphoblastic leukemia (ALL)

Signs and symptoms of ALL in children

Signs and symptoms are changes in the body that may indicate the presence of disease. A sign is a change that the doctor sees during an exam or in a laboratory test result. A symptom is a change that a patient can see and/or feel. 

It is common for a child with ALL to feel a loss of well-being because of the lack of normal, healthy blood cells. 

Symptoms of anemia (low red blood cell count) include: 

• Fatigue
• Shortness of breath during normal physical activities
• Dizziness
• Pale complexion 

Symptoms of neutropenia (low number of neutrophils, a type of white blood cell important in fighting infections) include: 

• Frequent infections
• Recurrent fevers 

Symptoms of thrombocytopenia (a low platelet count) include: 

• Bruising easily
• Prolonged bleeding from minor cuts
• The appearance of pinhead-sized red spots on the skin, called “petechiae”
• Frequent or severe nosebleeds
• Bleeding gums
• Heavier or more frequent menstrual periods (if your child has begun menstruating) 

Symptoms may also be related to leukemia cells collecting in other parts of the body. These symptoms may include: 

• Unexplained weight loss or loss of appetite
• Pain in bones and joints
• Swollen lymph nodes
• Enlarged spleen or liver
• Abdominal pain
• Wheezing, coughing, or painful breathing 

The symptoms of ALL may be similar to those of other blood disorders or medical conditions. Speak with your child’s doctor if your child has any of the above symptoms. 

Diagnosing ALL in children

View a 3D model of ALL’s impact on the body. Click the "Interact in 3D" button to begin. 

Diagnosing childhood ALL and identifying a child’s ALL subtype usually involves a series of tests. An accurate diagnosis of the ALL subtype is important because it helps the doctor estimate how the disease will progress and determine the appropriate treatment. 

In children, a diagnosis of ALL generally requires a finding that 25 percent or more of the cells in the bone marrow are leukemic blasts of lymphoid origin (lymphoblasts). 

Some of the tests used to diagnosis ALL may be repeated both during and after a child’s treatment to evaluate whether treatment is working. 

This infographic describes the steps doctors take to diagnose acute leukemia:  

Pre-treatment testing 

Before your child starts treatment, the doctor will perform tests to learn more about your child’s leukemia and overall health, and to find out if the leukemia has spread to other parts of the body. Doctors use this information for treatment planning. These tests will include blood tests and a lumbar puncture. The lumbar puncture is to check for leukemia cells in the fluid that flows around the brain and spinal cord, called the "cerebrospinal fluid." 

Blood and bone marrow tests  

Blood and bone marrow tests are used to diagnose ALL and the ALL subtype. Open each section below to learn more. 

Biomarker testing 

These laboratory tests check for changes in the proteins, genes, and chromosomes of the cancer cells. Each person's cancer has a unique pattern of biomarkers. Biomarker testing is used to help determine the subtype of ALL and plan treatment. Open each section below to learn more.

Childhood ALL subtypes

ALL subtypes are identified by certain features of the leukemia cells. Determining the ALL subtype is an important factor in treatment planning. The doctor will discuss with you which drug combinations are recommended based on your child’s ALL subtype.

Leukemia cells can be classified by the unique set of proteins found on their surface. These unique sets of proteins are known as “immunophenotypes.” Based on immunophenotyping of the leukemia cell, the World Health Organization (WHO) classifies ALL into two main subtypes.

• B-cell lymphoblastic leukemia/lymphoma: This subtype begins in immature cells that would normally develop into B-cell lymphocytes. B-cell ALL is the most common ALL subtype, accounting for approximately 80 percent of cases among children with ALL.
• T-cell lymphoblastic leukemia: This subtype of ALL originates in immature cells that would normally develop into T-cell lymphocytes. This subtype is less common than B-cell ALL and occurs more often in adults than in children. T-cell ALL accounts for approximately 15 percent to 20 percent of ALL cases in children.

Genetic changes

In addition to classifying ALL as either B-cell or T-cell, it can be further classified based on changes to certain chromosomes and genes. 

About 75 percent of childhood cases of ALL can be classified into subgroups based on chromosomal abnormalities and genetic mutations. Not all children who have ALL exhibit the same genetic changes. Some changes are more common than others, and some have a greater effect on the patient’s prognosis.

Philadelphia Chromosome-Positive ALL: About 2 percent to 4 percent of children with ALL have a subtype called Philadelphia chromosome-positive ALL (also known as “Ph+ ALL” or “Ph-positive ALL”). The leukemia cells of these patients have what is known as the “Philadelphia chromosome,” which is formed by a translocation between parts of chromosomes 9 and 22. This new, abnormal chromosome 22 is the Philadelphia chromosome. This chromosomal alteration creates a gene called BCR-ABL1, producing a protein called a tyrosine kinase, which causes the leukemia cells to grow and divide out of control.

Philadelphia Chromosome-like (Ph-like) ALL: About 15 percent of children with ALL have a subtype of B-cell ALL called “Ph-like ALL.” This is a high-risk subtype of ALL in children that seems to peak in adolescents and young adults and is more likely to be seen in males and patients with Down syndrome. It is associated with an unfavorable prognosis. Ph-like ALL has genetic features similar to Ph+ ALL, but without the BCR-ABL1 fusion gene that defines Ph+ ALL. Instead, patients have a highly diverse range of genetic mutations that activate tyrosine kinase signaling. 

Prognostic factors 

Children with ALL are often categorized into one of three risk groups—standard risk, high risk, or very high risk—based on prognostic factors. This is called risk stratification. Typically, children with ALL in the low-risk group have a better prognosis and receive less intensive treatment than those in the two higher-risk groups. 

Prognostic factors for children with ALL include: 

• Age: ALL tends to be more aggressive in infants younger than 12 months old and children older than 10 years
• White blood cell count: Children with white blood cell counts of 50 x 109 L or greater at the time of diagnosis need stronger treatment
• Genetic factors: Certain changes in the chromosomes or genes can make the leukemia cells either easier or harder to treat. These changes help determine whether your child may benefit from treatment with more intensive therapies.
• Central nervous system involvement: Children with ALL who have leukemia cells in the central nervous system at diagnosis are at a higher risk of disease relapse
• Treatment response: Children who have a better response to the initial induction therapy have a lower risk of disease relapse. For children with T-cell ALL, risk stratification is primarily based on their early treatment response.

After diagnosis: Navigating your child's care 

Navigating your child’s blood cancer care isn’t always simple or straightforward—but we’re here to guide you through it. Whether your child is newly diagnosed or in remission, you’ll find the information, support, and resources you need to navigate every step of their blood cancer journey.

Visit Navigating care for children and teens

Treatment for children with ALL 

The main treatment for ALL is chemotherapy given in phases. Most treatment regimens take two to three years to complete. 

Not every child with ALL receives the same treatment. Your child’s doctor will tailor your child’s treatment based on their ALL subtype and other factors, such as age, health, and how the cancer responds to treatment. 

Your child’s treatment may also include:

Chemotherapy and other drug therapies 

There are multiple phases of chemotherapy treatment. Open each section below to learn more.

Targeted therapy  

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells. Not all cancers have the same targets. Each type of targeted therapy works a little bit differently, but they all interfere with the growth and survival of cancer cells.  

To find the most effective treatment, your child’s doctor may run tests to identify the genes, proteins, and other factors in your child’s cancer cells. This helps the doctor choose the most effective treatment based on the specific factors of the disease. Targeted therapy may be used alone or in combination with chemotherapy. Some types of targeted therapy include:  

Monoclonal antibodies 

Monoclonal antibodies are proteins that are made in a laboratory. They can bind to substances in the body, including cancer cells. Most are designed to attach to one specific substance. These drugs can be used alone to destroy cancer cells or to carry drugs, toxins, or radioactive substances directly to the cancer cells. These drugs include: 

• Blinatumomab (Blincyto®)
• Inotuzumab ozogamicin (Besponsa®) 

Chimeric antigen receptor (CAR) T-cell therapy 

CAR T-cell therapy is a type of immunotherapy in which a patient's T cells (a type of white blood cell) are changed in the laboratory so that they will attack cancer cells. 

While CAR T-cell therapy can be an effective treatment, it is also associated with a relatively high rate of serious complications. As a result, it can only be given at specialized centers that have expertise in delivering this type of treatment. 

Ph-positive ALL therapy

Tyrosine kinase inhibitors (TKIs) 

In addition to chemotherapy combinations, children with Philadelphia chromosome-positive (Ph+) ALL and Philadelphia chromosome-like (Ph-like) ALL are also given a tyrosine kinase inhibitor (TKI) medication. 

Tyrosine kinases are enzymes that are a part of many cell functions including cell signaling, growth, and division. These enzymes may become too active in patients with an ALL subtype called Philadelphia chromosome-positive ALL (Ph+ ALL). 

TKIs work to block these overactive enzymes and may stop cancer cells from growing. TKIs are pills taken by mouth. They are generally not used alone to treat ALL. Instead, they are added to a combination chemotherapy regimen. The following TKIs have been approved to treat Ph+ ALL in children: 

• Imatinib (Gleevec®)
• Dasatinib (Sprycel®) 

Some children with Ph-like ALL may be treated with a TKI called ruxolitinib (Jakafi®), usually in a clinical trial. 

For information about the drugs listed on this page, visit our cancer drug listing or learn more about chemotherapy treatment for children with ALL. 

Stem cell transplantation 

The goal of stem cell transplantation is to cure the patient’s cancer by destroying the cancer cells in the bone marrow with high doses of chemotherapy and then replacing them with new, healthy blood-forming stem cells. The healthy blood stem cells will grow and multiply, forming new bone marrow and blood cells. There are two main types of stem cell transplantation. They are: 

• Allogeneic: patients receive stem cells from a matched or a partially mismatched related donor or an unrelated donor
• Autologous: patients receive their own stem cells 

Stem cell transplantation is not used as the first or primary treatment for children with ALL. It may be used as a treatment for high-risk ALL patients, or for patients who do not respond to other treatments.

Allogeneic stem cell transplantation 

Allogeneic stem cell transplantation involves transferring stem cells from a healthy person (the donor) to the patient. This is the most common type of stem cell transplantation used to treat ALL. 

In preparation for the transplant, patients are given strong doses of chemotherapy, with or without radiation therapy, to kill the remaining leukemic cells in their bodies. This also kills cells in the bone marrow, including healthy blood-forming cells. 

After, patients receive infusions of the donor stem cells. The donated stem cells restore the bone marrow’s ability to form new blood cells. This creates a new immune system for the patient that helps the body fight infections and other diseases. 

Donor stem cells come from an HLA-matched: 

• Family member (often a sibling)
• Unrelated donor
• Umbilical cord blood unit

Autologous Stem Cell Transplantation 

Autologous stem cell transplantation is not commonly used to treat patients with ALL, but it may be a treatment option for ALL patients who are participating in a clinical trial.

Clinical trials  

When it comes to finding the right treatment for your child's cancer, a clinical trial may be an option. Your child will have access to new or improved therapies under study and not yet on the market. Discuss with your child's doctor the possibility of participating in a clinical trial, where treatment is administered in a safe, closely monitored environment. 

Learn more about clinical trials. 

Get free clinical trial support! Visit our Clinical Trial Support Center (CTSC).

Connect with registered nurses with expertise in blood cancers who can personally assist you or your caregiver through each step of the clinical trial process. 

Side effects of ALL treatment 

Most ALL treatment side effects are temporary and subside once the body adjusts to therapy or after the therapy is completed. If side effects become severe, children may need to be hospitalized. 

Talk with your child’s doctor about potential side effects. Drugs and other therapies can prevent or manage many side effects. 

Common side effects and complications 

• Low blood cell counts: ALL and its treatment can cause a decrease in normal blood cell production
• Infection: During treatment, low white blood cell counts increase the risk of infection and may make it more difficult for your child’s body to fight infection. Your child’s healthcare team may give them antibiotics to prevent infections. If your child shows signs of infection, contact their healthcare team immediately.
• Tumor lysis syndrome (TLS): Children with ALL may be at risk for developing a condition called TLS. This condition occurs when a large number of cancer cells die within a short period of time, releasing their contents into the blood. TLS can be severe during the early phases of treatment, especially for children who have very high white blood cell counts before induction therapy. Uric acid is one of the chemicals released by dying cancer cells. Very high levels of uric acid and other chemicals can cause severe damage to the kidneys and heart. If untreated, TLS can lead to heart arrhythmias, seizures, loss of muscle control, acute kidney failure, and even death. Children with ALL are constantly monitored for the development of TLS and are given drugs, such as allopurinol (Zyloprim®) or rasburicase (Elitek®), to prevent or lessen the effects of this condition.
• Pain: Bone pain may occur in children with ALL at the time of diagnosis, or during a relapse, due to the infiltration of leukemia cells in the bone marrow. Pain medications and physical therapy are very effective approaches for patients with pain from leukemia or leukemia treatment.
• Graft-versus-host disease (GVHD): A serious risk of allogeneic stem cell transplantation is graft-versus-host disease (GVHD), which develops if the donor's immune cells attack the patient’s normal tissue. GVHD's effects can range from minor to life threatening.
• Corticosteroid use side effects: This may include high blood sugar and corticosteroid-induced diabetes and stomach ulcers

Other common side effects

• Hair loss
• Rashes
• Itchy skin
• Mouth sores
• Diarrhea
• Nausea and vomiting
• Headaches
• Loss of appetite
• Fatigue 

There are drugs and other supportive therapies to either prevent or manage many of these side effects. 

Learn more about blood cancer treatment side effects and how to manage them. 

Fertility 

Some cancer treatments can affect your child’s fertility (the ability to have children in the future). Before your child begins treatment, it is important to talk with the doctor about whether the treatment could affect your child’s fertility. You may also want to speak with a fertility specialist. A fertility specialist is a doctor who diagnoses and treats problems related to infertility. The fertility specialist can talk to you about possible options for preserving your child’s fertility.  

Learn more about these and other long-term and late effects of blood cancer treatment on your child. 

School 

During treatment, there will be times when your child may be unable to attend school in person. However, there are resources to help your child continue to receive an education so that they will not fall behind.  

Once your child is in remission, they will likely be going back to school. This reentry to the classroom can be daunting for a child of any age. Educate family members, friends, school personnel, and healthcare providers about your child's possible long-term and late effects of treatment. Work with your child's teachers and medical providers to develop a program tailored to their needs that features baseline testing, special accommodations, and long-term planning. 

Find information, support, and resources for schooling during your child’s blood cancer treatment. 

Treatment outcomes 

The following are possible treatment outcomes for childhood ALL:

Refractory and relapsed childhood ALL  

Most children with ALL are cured with standard chemotherapy treatments. About 15 percent of young patients have ALL that returns after remission. This is referred to as a “relapse” of the disease (or “relapsed ALL”). Some children are unable to achieve a remission because their cancer does not respond to treatment. In these cases, the disease is referred to as “refractory” (or “refractory ALL”). 

Relapsed/refractory disease is very serious and can be more difficult to treat, but there are treatment options available. Treatment for relapsed or refractory ALL is usually more intensive than the treatment used following initial diagnosis. It is important to understand all your child’s treatment options. 

Before treatment, genetic testing of the leukemia cells is recommended for patients with relapsed or refractory disease. The mutational pattern of the leukemia cells may be different from when the disease was first diagnosed, and this can affect treatment decisions. 

For patients with Ph+ ALL, new mutations in the BCR-ABL1 gene may occur over time. Some mutations can lead to resistance to certain TKIs. Before a patient starts treatment, BCR-ABL1 mutation testing should be done to look for new mutations that may cause certain TKIs to stop working.

Treatment options for relapsed and refractory ALL  

Treatments for relapsed/ refractory ALL may include: 

• A clinical trial
• New or different chemotherapy drugs or new combinations of chemotherapy drugs
• For patients with Ph+ All, chemotherapy with a different TKI than the one used during initial therapy
• Blinatumomab (Blincyto®) for patients with B-cell ALL
• Inotuzumab ozogamicin (Besponsa®) for patients with B-cell ALL
• Nelarabine for patients with T-cell ALL
• Bortezomib for patients with T-cell ALL
• Allogeneic stem cell transplantation for patients with an available donor
• CAR T-cell therapy for patients with B-cell ALL
• Revumenib (Revuforj®) 

For information about the drugs listed on this page, visit our cancer drug listing. 

Long-term and late treatment effects in children with ALL  

While treatments for ALL have led to increased survival rates, some may cause significant long-term or late effects. Long-term effects of cancer treatment are medical problems that last for months or years after treatment ends. Late effects are medical problems that do not appear until years, or even possibly decades, after treatment ends. 

The long-term and late effects of childhood ALL treatment can include: 

• Increased risk for secondary cancer
• Heart damage
• Bone damage
• Cognitive effects, which can affect a child’s ability to learn and think 

Ask your child’s healthcare team the following questions: 

• What long-term and late effects are my child at risk for based on their treatment plan, age, sex, and overall health?
• What screenings will my child need to undergo for these effects? How frequently will they need to be screened?
• Will a healthcare provider coordinate these screenings? If so, which one?  

Read Beyond Treatment, from our Caring for Kids and Adolescents with Blood Cancer workbook for more information on survivorship and life after treatment.  

Follow-up care 

All children treated for ALL need to receive follow-up care. Follow-up care involves regular medical checkups after your child has finished treatment. These checkups may include blood work, as well as other tests, to check for a possible relapse of the cancer. These visits are also a time for doctors to test for other physical or emotional problems that may develop months or years after treatment. Even if your child is feeling entirely well, it is very important to keep the follow-up appointments. 

Coordination between your child's pediatrician and oncologist is important for the best care possible. Some treatment centers offer comprehensive follow-up care clinics for childhood cancer survivors.  

Each patient has a different follow-up care schedule. How often your child has follow-up visits is based on your child’s cancer type, overall health, and the treatments they received. For children with ALL, the National Comprehensive Cancer Network (NCCN) recommends the following tests during the first 3 years after treatment ends: 

Survivorship care plan 

Generally, “survivorship” refers to the health and well-being of a person after cancer treatment. Your child’s oncologist will help create a survivorship care plan for your child to guide follow-up care. Share the survivorship care plan with any healthcare providers your child sees. Learn more about survivorship care plans.

Our Survivorship Workbook allows you to collect all the important information you and your child needs throughout diagnosis, treatment, follow-up care, and long-term management of a blood cancer.