Adult Acute Lymphoblastic Leukemia (ALL)

• Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell).
• Leukemia may affect red blood cells, white blood cells, and platelets.
• Previous chemotherapy and exposure to radiation may increase the risk of developing ALL.
• Signs and symptoms of adult ALL include fever, feeling tired, and easy bruising or bleeding.
• Tests that examine the blood and bone marrow are used to detect (find) and diagnose adult ALL.
• Certain factors affect prognosis (chance of recovery) and treatment options.

Adult acute lymphoblastic leukemia (ALL; also called acute lymphocytic leukemia) is a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated.

Leukemia may affect red blood cells, white blood cells, and platelets.

Normally, the bone marrow makes blood stem cells (immature cells) that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell.

A myeloid stem cell becomes one of three types of mature blood cells:

• Red blood cells that carry oxygen and other substances to all tissues of the body.
• Platelets that form blood clots to stop bleeding.
• Granulocytes (white blood cells) that fight infection and disease.

A lymphoid stem cell becomes a lymphoblast cell and then one of three types of lymphocytes (white blood cells):

• B lymphocytes that make antibodies to help fight infection.
• T lymphocytes that help B lymphocytes make the antibodies that help fight infection.
• Natural killer cells that attack cancer cells and viruses.

In ALL, too many stem cells become lymphoblasts, B lymphocytes, or T lymphocytes. These cells are also called leukemia cells. These leukemia cells are not able to fight infection very well. Also, as the number of leukemia cells increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This may cause infection, anemia, and easy bleeding. The cancer can also spread to the central nervous system (brain and spinal cord).

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Possible risk factors for ALL include the following:

• Being male
• Being white
• Being older than 70
• Past treatment with chemotherapy or radiation therapy
• Being exposed to high levels of radiation in the environment (such as nuclear radiation)
• Having certain genetic disorders, such as Down syndrome

Early signs and symptoms of ALL may be like the flu or other common diseases. Check with your doctor if you have any of the following:

• Weakness or feeling tired
• Fever or night sweats
• Easy bruising or bleeding
• Petechiae (flat, pinpoint spots under the skin, caused by bleeding)
• Shortness of breath
• Weight loss or loss of appetite
• Pain in the bones or stomach
• Pain or feeling of fullness below the ribs
• Painless lumps in the neck, underarm, stomach, or groin
• Having many infections

These and other signs and symptoms may be caused by adult acute lymphoblastic leukemia or by other conditions.

The following tests and procedures may be used:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as infection or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.
• Complete blood count (CBC) with differential: A procedure in which a sample of blood is drawn and checked for the following:
  • The number of red blood cells and platelets.
  • The number and type of white blood cells.
  • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
  • The portion of the blood sample made up of red blood cells.
• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.
• Peripheral blood smear: A procedure in which a sample of blood is checked for blast cells, the number and kinds of white blood cells, the number of platelets, and changes in the shape of blood cells.
• Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for abnormal cells.

The following tests may be done on the samples of blood or bone marrow tissue that are removed:

• Cytogenetic analysis: A laboratory test in which the cells in a sample of blood or bone marrow are looked at under a microscope to find out if there are certain changes in the chromosomes of lymphocytes. For example, in Philadelphia chromosome-positive ALL, part of one chromosome switches places with part of another chromosome. This is called the "Philadelphia chromosome."
• Immunophenotyping: A process used to identify cells, based on the types of antigens or markers on the surface of the cell. This process is used to diagnose the subtype of ALL by comparing the cancer cells to normal cells of the immune system. For example, a cytochemistry study may test the cells in a sample of tissue using chemicals (dyes) to look for certain changes in the sample. A chemical may cause a color change in one type of leukemia cell but not in another type of leukemia cell.

The prognosis (chance of recovery) and treatment options depend on the following:

• The age of the patient
• Whether the cancer has spread to the brain or spinal cord
• Whether there are certain changes in the genes, including the Philadelphia chromosome
• Whether the cancer has been treated before or has recurred (come back)

The extent or spread of cancer is usually described as stages. It is important to know whether the leukemia has spread outside the blood and bone marrow in order to plan treatment. The following tests and procedures may be used to determine if the leukemia has spread:

• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
• Lumbar puncture: A procedure used to collect a sample of cerebrospinal fluid (CSF) from the spinal column. This is done by placing a needle between two bones in the spine and into the CSF around the spinal cord and removing a sample of the fluid. The sample of CSF is checked under a microscope for signs that leukemia cells have spread to the brain and spinal cord. This procedure is also called an LP or spinal tap.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of the abdomen, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).

There is no standard staging system for adult ALL.

The disease is described as untreated, in remission, or recurrent.

Untreated adult ALL

The ALL is newly diagnosed and has not been treated except to relieve signs and symptoms such as fever, bleeding, or pain.

• The complete blood count is abnormal.
• More than 5% of the cells in the bone marrow are blasts (leukemia cells).
• There are signs and symptoms of leukemia.

Adult ALL in remission

The ALL has been treated.

• The complete blood count is normal.
• 5% or fewer of the cells in the bone marrow are blasts (leukemia cells).
• There are no signs or symptoms of leukemia other than in the bone marrow.

Recurrent adult acute lymphoblastic leukemia (ALL) is cancer that has recurred (come back) after going into remission. The ALL may come back in the blood, bone marrow, or other parts of the body.

Different types of treatment are available for patients with adult acute lymphoblastic leukemia (ALL). Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

The treatment of adult ALL usually has two phases.

The treatment of adult ALL is done in phases:

• Remission induction therapy: This is the first phase of treatment. The goal is to kill the leukemia cells in the blood and bone marrow. This puts the leukemia into remission.
• Post-remission therapy: This is the second phase of treatment. It begins once the leukemia is in remission. The goal of post-remission therapy is to kill any remaining leukemia cells that may not be active but could begin to regrow and cause a relapse. This phase is also called remission continuation therapy.

Treatment called central nervous system (CNS) sanctuary therapy is usually given during each phase of therapy. Because standard doses of chemotherapy may not reach leukemia cells in the CNS (brain and spinal cord), the cells are able to "find sanctuary" (hide) in the CNS. Systemic chemotherapy given in high doses, intrathecal chemotherapy, and radiation therapy to the brain are able to reach leukemia cells in the CNS. They are given to kill the leukemia cells and lessen the chance the leukemia will recur (come back). CNS sanctuary therapy is also called CNS prophylaxis.

Four types of standard treatment are used:

1. Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid (intrathecal chemotherapy), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Intrathecal chemotherapy may be used to treat adult ALL that has spread, or may spread, to the brain and spinal cord. When used to lessen the chance leukemia cells will spread to the brain and spinal cord, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis.

2. Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:

• External radiation therapy uses a machine outside the body to send radiation toward the cancer.
• Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

The way the radiation therapy is given depends on the type of cancer. External radiation therapy may be used to treat adult ALL that has spread, or may spread, to the brain and spinal cord. When used this way, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis. External radiation therapy may also be used as palliative therapy to relieve symptoms and improve quality of life.

3. Chemotherapy with stem cell transplant

Stem cell transplant is a method of giving chemotherapy and replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.

4. Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibody therapy and tyrosine kinase inhibitor therapy are types of targeted therapy used to treat adult ALL.

Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory, from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. Blinatumomab is a monoclonal antibody used with stem cell transplant to treat adult ALL.

Tyrosine kinase inhibitor therapy blocks the enzyme, tyrosine kinase, that causes stem cells to develop into more white blood cells (blasts) than the body needs. Imatinib mesylate (Gleevec), dasatinib, and nilotinib are tyrosine kinase inhibitors used to treat adult ALL.

Biologic therapy

Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Chimeric antigen receptor (CAR) T-cell therapy

CAR T-cell therapy is a type of immunotherapy that changes the patient's T cells (a type of immune system cell) so they will attack certain proteins on the surface of cancer cells. T cells are taken from the patient and special receptors are added to their surface in the laboratory. The changed cells are called chimeric antigen receptor (CAR) T cells. The CAR T cells are grown in the laboratory and given to the patient by infusion. The CAR T cells multiply in the patient's blood and attack cancer cells. CAR T-cell therapy is being studied in the treatment of adult ALL that has recurred (come back).

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country.

Side effects from cancer treatment that begin during or after treatment and continue for months or years are called late effects. Late effects of treatment for ALL may include the risk of second cancers (new types of cancer). Regular follow-up exams are very important for long-term survivors.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Untreated Adult Acute Lymphoblastic Leukemia

Standard treatment of adult acute lymphoblastic leukemia (ALL) during the remission induction phase includes the following:

• Combination chemotherapy.
• Tyrosine kinase inhibitor therapy with imatinib mesylate, in certain patients. Some of these patients will also have combination chemotherapy.
• Supportive care including antibiotics and red blood cell and platelet transfusions.
• CNS prophylaxis therapy including chemotherapy (intrathecal and/or systemic) with or without radiation therapy to the brain.

Adult Acute Lymphoblastic Leukemia in Remission

Standard treatment of adult ALL during the post-remission phase includes the following:

• Chemotherapy.
• Tyrosine kinase inhibitor therapy.
• Chemotherapy with stem cell transplant.
• CNS prophylaxis therapy including chemotherapy (intrathecal and/or systemic) with or without radiation therapy to the brain.

Recurrent Adult Acute Lymphoblastic Leukemia

Standard treatment of recurrent adult ALL may include the following:

• Combination chemotherapy and/or monoclonal antibody therapy with blinatumomab followed by stem cell transplant.
• Low-dose radiation therapy as palliative care to relieve symptoms and improve the quality of life.
• Tyrosine kinase inhibitor therapy with dasatinib for certain patients.

Some of the treatments being studied in clinical trials for recurrent adult ALL include the following:

• A clinical trial of stem cell transplant using the patient's stem cells.
• A clinical trial of biologic therapy.
• A clinical trial of chimeric antigen receptor (CAR) T-cell therapy.
• A clinical trial of new anticancer drugs.