Acute lymphocytic leukemia (ALL) is a type of cancer that affects white blood cells. White blood cells help your body fight infection. Blood cells build up in your bone marrow. However, bone marrow leukemia produces abnormal white blood cells. These cells expel healthy blood cells, making it difficult for the blood to do its job. In acute lymphocytic leukemia (ALL) or acute lymphoblastic leukemia, there are too many lymphocytes or lymphoblasts (a type of white blood cells). ALL is the most common type of cancer to affect children.
Possible risk factors for ALL include being male, being white, having had previous chemotherapy treatment, being exposed to high levels of radiation, and being older than 70 years of age.
Symptoms of ALL include:
- Weakness or feeling tired
- Easy bleeding or bruising
- Bleeding under the skin
- Shortness of breath
- Weight loss or loss of appetite
- Pain in the bones or stomach
- Pain or a feeling of fullness below the ribs
- Painless lumps in the neck, armpits, stomach, or groin
To diagnose acute lymphocytic leukemia, a blood and bone marrow test is performed. Treatment includes chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Targeted therapy uses substances that attack cancer cells without damaging normal cells. Once the leukemia goes into remission, you will need additional treatment to ensure that the leukemia does not recur.
Overview of Adult Acute Lymphocytic Leukemia
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).
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 left untreated.
The bone consists of compact bone, spongy bone, and bone marrow. Compact bone forms the outer layer of bone. Spongy bones are located at the ends of the bones and contain red bone marrow. Bone marrow is usually found in the centre of most bones and has many blood vessels. There are two types of bone marrow: red and yellow. Red bone marrow contains blood stem cells that can turn into red blood cells, white blood cells, or platelets. Meanwhile, yellow bone marrow is mostly made of fat.
Leukemia can 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. Blood stem cells can become myeloid stem cells or lymphoid stem cells. Lymphoid stem cells become white blood cells.
Myeloid stem cells form one of three types of mature blood cells:
- Red blood cells that carry oxygen and other substances to all body tissues.
- Platelets that form blood clots to stop bleeding.
- Granulocytes (white blood cells) that fight infection and disease.
Lymphoid stem cells become lymphoblast cells and then one of three types of lymphocytes (white blood cells):
- B lymphocytes that make antibodies to help fight infection.
- T lymphocytes, which help the B lymphocytes form antibodies that help fight infection.
- Natural killer cells that attack cancer cells and viruses.
Blood stem cells go through several steps to become red blood cells, platelets, or white blood cells.
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, because 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 can lead to infection, anemia, and easy bleeding. Cancer can also spread to the central nervous system (brain and spinal cord).
Symptoms and Risk Factors of Adult Acute Lymphocytic Leukemia
Signs and Symptoms of Acute Lymphocytic Leukemia
The initial signs and symptoms of ALL may be like the flu or other common illnesses. Check with your doctor if you experience any of the following:
- Weakness or feeling tired.
- Fever or night sweats.
- Easy bruising or bleeding.
- Petechiae (flat spots under the skin caused by bleeding).
- Difficulty breathing
- Weight loss or loss of appetite.
- Pain in the bones or stomach.
- Pain or a feeling of fullness below the ribs.
- Painless lumps in the neck, armpits, stomach, or groin.
- Have multiple infections.
All of the above and other signs and symptoms may be caused by adult acute lymphoblastic leukemia or by other conditions.
Risk factors of Acute Lymphocytic Leukemia
Previous chemotherapy and exposure to radiation can increase the risk of developing ALL.
Risk factor refers to the increased risk of getting a disease. Having risk factors does not mean you will get cancer; not having risk factors does not mean you will not get cancer either. Talk to your doctor if you think you might be at risk. Possible risk factors of ALL include the following:
- Fair skin.
- Older than 70 years.
- Past treatment with chemotherapy or radiation therapy.
- Exposure to high levels of radiation in the environment (such as nuclear radiation).
- Certain genetic disorders, such as Down syndrome.
Diagnosis of Adult Lymphocytic Leukemia
The following tests and procedures can be used:
- Physical exam and medical history: An exam of the body to check for 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 previous illnesses and treatments will also be taken.
- Complete blood count (CBC) with differential: A procedure in which a blood sample 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 (a protein that carries oxygen) in red blood cells.
- The portion of the blood sample that is made up of red blood cells
Blood is drawn by inserting a needle into a vein and allowing blood to flow into the tube. The blood sample is sent to the laboratory and red blood cells, white blood cells, and platelets are counted. CBC is used to test, diagnose and monitor a variety of conditions.
- Blood chemistry study: A procedure in which a blood sample is examined to measure the amount of certain substances released into the blood by organs and tissues in the body. An unusual amount of a substance (higher or lower than normal) may be a sign of disease.
- Peripheral blood smear: A procedure in which a blood sample is checked for blast cells, white blood cell count and type, platelet count, and changes in blood cell shape.
- Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hip or sternum. The bone marrow, blood, and bone are viewed under a microscope to look for abnormal cells.
After a small area of skin is numbed, a bone marrow needle is inserted into the patient’s hip bone. The samples of blood, bone, and bone marrow are removed to be viewed under a microscope
The following tests can be performed on a sample of blood or bone marrow tissue that is removed:
- Cytogenetic analysis: A laboratory test in which cells in a sample of blood or bone marrow sample are viewed under a microscope for specific changes in lymphocyte chromosomes. For example, on the Philadelphia-ALL chromosome positive, part of one chromosome switches places with part of another chromosome. This is called the “Philadelphia chromosome.”
A piece of chromosome 9 and a piece of chromosome 22 break off and switch places. The bcr-abl gene is formed on chromosome 22 where the chromosome 9 pieces attach. The altered chromosome 22 is called the Philadelphia chromosome.
- Immunophenotyping: A process used to identify cells, based on the type of antigen or markers on the cells’ surface. This process is used to diagnose subtypes of ALL by comparing cancer cells with normal cells of the immune system. For example, cytochemical research can test cells in a tissue sample using chemicals (dyes) to look for certain changes in the sample. A chemical can cause a discoloration in one type of leukemia cell but not in another type of leukemia cell
Stages of Adult Acute Lymphoblastic Leukemia
The extent or spread of cancer is usually described as staging. It is important to know whether the leukemia has spread beyond the blood and bone marrow to plan treatment. The following tests and procedures can be used to determine whether leukemia has spread:
- Chest x-ray: X-ray of the organs and bones inside the chest. X-rays are a type of energy beam that can penetrate the body and onto film, creating images 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 fluid. The CSF sample is examined 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
The patient lies in a curled position on a table. After a small area in the lower back is numbed, a spinal needle (long and thin needle) is inserted into the lower part of the spine to remove cerebrospinal fluid (CSF, shown in blue). The fluid may be sent to a laboratory for testing.
- CT scan (CAT scan): A procedure that makes a series of detailed images of the abdomen, taken from multiple angles. The images are created by a computer connected to an x-ray machine. A dye may be injected into a vein or swallowed to help an organ or tissue appear more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
- MRI (magnetic resonance imaging): A procedure that uses magnets, radio waves, and a computer to create a series of detailed images 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 being untreated, in remission, or recurrent.
Untreated adult ALL
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 blast cells (leukemia cells).
- There are signs and symptoms of leukemia.
Adult ALL in remission
ALL has been treated.
- The complete blood count is normal
- 5% or less of the cells in the bone marrow are blast cells (leukemia cells).
- There are no signs or symptoms of leukemia other than the bone marrow.
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent adult acute lymphoblastic leukemia (ALL) is cancer that has recurred (came back) after going into remission. ALL can return in the blood, bone marrow, or other parts of the body.
Treatment for Adult Acute Lymphocytic Leukemia
Different types of treatments are available to treat adult acute lymphoblastic leukemia (ALL). Some are standard treatments (currently used treatment), and some are being tested in clinical trials. A clinical trial is research intended to help improve current treatments or obtain information on new treatments for cancer patients. When clinical trials show that the new treatment is better than standard treatment, the new treatment can become standard treatment. Certain clinical trials are only open to patients who have not started treatment.
Treatment of adult ALL usually has two phases
Treatment of adult ALL is carried out in stages:
- Remission induction therapy: This is the first phase of treatment. The goal is to kill 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 starts after the leukemia is in remission. The goal of post-remission therapy is to kill any remaining leukemia cells that may be inactive but can start to grow back 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. Since standard chemotherapy doses cannot reach the leukemia cells in the CNS (brain and spinal cord), they can “find hiding places” in the CNS. Systemic chemotherapy given in high doses, intrathecal chemotherapy, and radiation therapy to the brain can reach leukemia cells in the CNS. It is given to kill leukemia cells and lower the chance the leukemia will recur (come back). CNS sanctuary therapy is also referred to as CNS prophylaxis.
Four types of standard treatment are used:
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. The chemotherapy is either taken by mouth or injected into a vein or muscle, and the drugs enter the bloodstream and reach cancer cells throughout the body (systemic chemotherapy). Chemotherapy can also be placed directly into the cerebrospinal fluid (intrathecal chemotherapy), organs, or body cavities (e.g. the stomach), or affect cancer cells in the areas concerned (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug. The way chemotherapy is given depends on the type and stage of cancer being treated.
Intrathecal chemotherapy may be used to treat adult ALL that has spread to the brain and spinal cord. When used to reduce the chance of leukemia cells to spread to the brain and spinal cord, this is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis.
Anticancer drugs are injected into the intrathecal space — the space that stores cerebrospinal fluid (CSF). There are two different ways to do this. First is to inject the drugs into the Ommaya reservoir (a dome-shaped container that is placed under the scalp during surgery; it holds the drugs as they flow through a small tube into the brain). The second way is to inject the drugs directly into the CSF in the lower part of the spinal column, after a small area on the lower back is numbed.
Radiation therapy is a cancer treatment that uses high-energy X-rays or other types of radiation to kill cancer cells or prevent them from growing. There are two types of radiation therapy:
- External radiation therapy uses a machine outside the body to send radiation towards the cancer.
- Internal radiation therapy uses radioactive substances placed in needles, beads, cables, or catheters that are placed directly into or near the cancer.
The way radiation therapy is given depends on the type of cancer. External radiation therapy may be used to treat adult ALL that has spread to the brain and spinal cord. When used to achieve this goal, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis. External radiation therapy can also be used as palliative therapy to relieve symptoms and improve quality of life.
Chemotherapy with stem cell transplant
Stem cell transplant is a method of giving chemotherapy and replacing blood-forming cells. Stem cells (immature blood cells) are removed from the patient or donor’s blood or bone marrow and are frozen and stored. After the patient completes chemotherapy, the stored stem cells are thawed and given back to the patient through an IV. These reinfused stem cells grow into (and restore) the body’s blood cells.
(Step 1): Blood is taken from a vein in the donor arm. The patient or other people may be the donor. The blood flows through a machine that removes the stem cells. Then the blood is returned to the donor through a vein in the other arm.
(Step 2): The patient receives chemotherapy to kill blood-forming cells. The patient may receive radiation therapy.
(Step 3): The patient receives stem cells through a catheter placed into a vein in the chest.
Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without damaging 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 in cancer cells or normal substances that can help cancer cells grow. The antibodies attach to these substances and kill the cancer cells, block their growth, or prevent them from spreading. Monoclonal antibodies are given by infusion. These antibodies may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. Blinatumomab and inotuzumab ozogamicin are monoclonal antibodies used with stem cell transplant to treat adult ALL.
Tyrosine kinase inhibitor therapy blocks an enzyme, tyrosine kinase, which causes stem cells to develop into more white blood cells (blasts) than the body’s needs. Imatinib Mesylate (Gleevec), dasatinib, and nilotinib are tyrosine kinase inhibitors used to treat adult ALL.
Stage-Based Treatment for Adult Acute Lymphocytic Leukemia
Untreated Adult Acute Lymphoblastic Leukemia
Standard treatment for acute lymphoblastic leukemia (ALL) in adults in the remission induction phase includes the following:
- Combination chemotherapy.
- Tyrosine kinase inhibitor therapy with imatinib mesylate, in selected patients. Some of these patients will also undergo combination chemotherapy.
- Additional treatment includes antibiotics and red blood cell & platelet transfusions.
- CNS prophylactic therapy includes chemotherapy (intrathecal and / or systemic) with or without radiation therapy to the brain.
Adult Acute Lymphoblastic Leukemia in Remission
Standard treatment of adult ALL in the post-remission phase includes the following:
- Tyrosine kinase inhibitor therapy.
- Chemotherapy with stem cell transplant.
- CNS prophylactic therapy includes chemotherapy (intrathecal and / or systemic) with or without radiation therapy to the brain.
Recurrent Adult Acute Lymphoblastic Leukemia
Standard treatment for recurring adult ALL may include the following:
- Combination chemotherapy followed by stem cell transplantation.
- Monoclonal antibody therapy (blinatumomab or inotuzumab ozogamicin) followed by stem cell transplantation.
- Low-dose radiation therapy as palliative care to relieve symptoms and improve quality of life.
- Tyrosine kinase inhibitor therapy with dasatinib for selected patients.
Some of the treatments being studied in clinical trials for recurrent adult ALL include the following:
- Stem cell transplant clinical trial using the patient’s stem cells.
- Biological therapy clinical trials.
- Clinical trials of chimeric antigen receptor (RAK) T cell therapy
- Clinical trials of new anticancer drug