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Acute Lymphoblastic Leukemia (ALL)

What is Acute Lymphoblastic Leukemia?

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%.

What Causes Acute Lymphoblastic Leukemia?

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.

Graphic showing the blood forming process and how it results in blast cells. The graphic begins with a blood stem cell. To the left, it branches off into myeloid stem cell, which branches into platelets, red blood cells, myeloblast, and monoblast. The myeloblast changes into white blood cells (also called granulocytes) and the monoblast changes into a monocyte. The right branch of blood stem cell goes to lymphoid stem cell, which branches into lymphoblasts (which changes into white blood cells) and blast cells.

ALL affects white blood cells called lymphocytes. Patients with ALL have too many immature white blood cells (blasts) in their bone marrow. These cells don’t work normally. They crowd out normal white blood cells, red blood cells, and platelets.

What Are Signs and Symptoms of Acute Lymphoblastic Leukemia?

Acute leukemia means symptoms worsen quickly.

Children may become very sick and need medical attention right away.

In ALL, signs and symptoms may include:

  • Fatigue
  • Pain in the bones or joints
  • Fever
  • Frequent infections
  • Easy bruising and bleeding that is hard to stop
  • Tiny, flat, dark-red skin spots (petechiae)
  • Lumps in the neck, underarm, stomach or groin
  • Pain or fullness below the rib cage
  • Paleness
  • Loss of appetite
  • Shortness of breath
  • Enlarged liver
  • Enlarged spleen
Illustration of two histology slides side by side highlights the difference between normal bloody cells and blood cells in newly diagnosed ALL.

Children with leukemia usually have a high number of white blood cells in their blood.

How is Acute Lymphoblastic Leukemia Diagnosed?

Doctors may suspect leukemia after doing a physical exam, taking a medical history, and looking at the results of blood tests.

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.

If cancer is diagnosed, more tests will be run on the bone marrow to pinpoint the subtype of the cancer.

Tests After Cancer is Diagnosed

The care team will run tests to find out if it is in other parts of the body.

Lumbar Puncture

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.

Chest X-ray

A chest X-ray will be done to see if leukemia cells have formed a mass in the middle of the chest.

Other Imaging Tests and Laboratory Tests

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.

Fertility Counseling

Fertility counseling and/or preservation options should be presented to males and females, especially in adolescents.

Treatment of Acute Lymphoblastic Leukemia

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.

Risk group

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.

In some cases, treatment may also include targeted therapy, immunotherapy, and hematopoietic cell transplant (also called bone marrow transplant or stem cell transplant).

Risk groups are determined by:

  • Whether the cancer began in B-lymphocytes or T-lymphocytes — B-cell ALL is considered lower-risk than T-cell ALL.
  • Age — Children between the ages of 1 and 9 with B-cell ALL are generally considered low-or standard-risk. Children younger than 1 and 10 or older are considered high-risk patients. (This age cut-off may vary among treatment centers.)
  • White blood cell count at diagnosis — Children with a count of fewer than 50,000 are considered low-risk.
  • Certain changes in the chromosomes or genes
  • Number of chromosomes — Hyperdiploid cases (more than 50 chromosomes) are considered lower-risk while hypodiploid cases (children with less than 44 chromosomes) are considered higher-risk.
  • Response to treatment — Cases where leukemia cells drop dramatically during the first few weeks of therapy are considered low-risk.
  • Minimal Residual Disease — Many pediatric cancer centers use highly sensitive tests to measure for minimal residual disease (MRD.)
  • Whether leukemia cells are found in the cerebrospinal fluid (CSF) at the time of diagnosis — If cells have spread to the CSF, the case is treated with more intrathecal therapy.

Three phases of treatment

Treatment for ALL has 3 phases and takes about 2 to 3 years to complete.

Other therapies

In some cases, doctors may recommend additional treatment options.

Targeted therapy

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.

Targeted therapies drugs imatinib or dasatinib have been shown to be effective in treating Philadelphia chromosome-positive ALL and Philadelphia-like ALL.

Ruxolitinib may be used to treat a type of ALL called Philadelphia-like ALL.

Immunotherapy

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.

Hematopoietic cell transplant (also called bone marrow transplant or stem cell transplant)

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

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.)

What Are the Side Effects of Acute Lymphoblastic Leukemia Treatment?

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:

What is the Prognosis of Acute Lymphoblastic Leukemia?

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.

Late Effects of Acute Lymphoblastic Leukemia Treatment

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 Focus of Acute Lymphoblastic Leukemia Research

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