Cancer of the blood and bone marrow – Acute lymphocytic leukemia

Acute lymphocytic leukemia (ALL) is a type of cancer of the blood and bone marrow — the spongy tissue inside bones where blood cells are made.

It’s called acute leukemia because it progresses rapidly and affects immature blood cells, rather than mature ones. It’s called lymphocytic leukemia because it affects a group of white blood cells called lymphocytes, which normally fight infection. Acute lymphocytic leukemia is also known as acute lymphoblastic leukemia and acute childhood leukemia.

Normally, your bone marrow produces immature cells (stem cells) in a controlled way, and they mature and specialize into the various types of blood cells, as needed. In people with acute lymphocytic leukemia, this production process goes awry. Large numbers of immature, abnormal lymphocytes are produced and released into the bloodstream. These abnormal cells multiply rapidly and can crowd out healthy blood cells, leaving you vulnerable to infection and easy bleeding. Leukemic cells can also collect in certain areas of the body, including the central nervous system and spinal cord, which can cause serious problems.

Acute lymphocytic leukemia is the most common type of cancer in children; it also occurs in adults. It worsens quickly if not treated, but it usually responds well to treatment.

Symptoms

General signs and symptoms of the early stages of acute lymphocytic leukemia may mimic signs and symptoms of the flu or other common diseases. These include:

  • Fever
  • Weight loss
  • Loss of appetite
  • Weakness, fatigue or a general decrease in energy

More specific signs and symptoms of acute leukemia are caused by a lack of properly functioning blood cells, resulting from overcrowding by leukemia cells. A range of problems can occur, depending on the type of blood cell affected:

  • Red blood cells. These cells carry oxygen from your lungs to all parts of your body. A shortage of red blood cells (anemia) can cause shortness of breath, fatigue and pale skin.
  • White blood cells. These infection fighters help your body ward off germs. A shortage of white blood cells (leukopenia) or of a particular type of white blood cells called neutrophils (neutropenia) can result in frequent infections.
  • Blood platelets. These cells help prevent and control bleeding by prompting your blood to clot. A shortage of blood platelets (thrombocytopenia) can result in easy bleeding and bruising, including frequent or severe nosebleeds, bleeding from the gums, or tiny red marks caused by bleeding into the skin (petechiae).

Acute lymphocytic leukemia can produce painless lumps in the lymph nodes in your neck, underarm, stomach or groin. It can also bring about bone pain, joint pain or pain below your ribs on the left side from swelling of the spleen. If it spreads outside the blood to your central nervous system or other organs, it can cause headache, weakness, seizures, vomiting, dizziness and blurred vision.

A particular type of ALL called T-cell ALL often causes an organ in the chest near your heart known as the thymus to become swollen. An enlarged thymus can press on the windpipe, causing coughing and shortness of breath. Or it can press on a large vein that carries blood from your arms and head to your heart, causing swelling of the arms and head. This is a medical emergency, but it does respond to treatment.

Causes

The cause of acute leukemia is damage to the DNA of developing cells in the bone marrow. Under normal circumstances, your DNA is like a set of instructions for your cells, telling them how and when to grow and divide. Certain genes in your DNA called oncogenes promote cell division. Other genes, called tumor suppressor genes, slow down cell division and cause cells to die at the appropriate times.

Leukemia can occur when damage to DNA turns on oncogenes or turns off tumor suppressor genes. When this happens, blood cell production goes awry. The bone marrow produces immature cells that develop into leukemic white blood cells called lymphoblasts. These abnormal cells are unable to function properly, and they can build up and crowd out healthy cells.

The mutations that cause leukemia are usually acquired — rather than inherited — but researchers and doctors don’t understand exactly what causes these mutations. One type of mutation that can cause acute lymphocytic leukemia is called the Philadelphia chromosome. This mutation is often found in another type of leukemia, but it’s present in about one-quarter of acute lymphocytic leukemia cases. It’s caused by a translocation between chromosomes 9 and 22, which means that parts of chromosomes 9 and 22 swap places with each other.

Acute lymphocytic leukemia is the most common cancer in children and adolescents. It’s most common in early childhood, peaking between ages 2 and 5, and it affects more boys than girls. In the United States, it’s slightly more common among white children than black children. ALL also accounts for about 20 percent of adult leukemia.

Possible risk factors include:

  • Cancer therapy. Children and adults who’ve had certain types of chemotherapy and radiation therapy or treatment for other kinds of cancer may have a small, but greater, risk of developing acute lymphocytic leukemia than does the general population.
  • Exposure to radiation. People exposed to very high levels of radiation, such as survivors of an atomic bomb blast or a nuclear reactor accident, have an increased risk of developing acute lymphocytic leukemia. This includes children who were exposed to significant radiation during the first months of prenatal development.
  • Genetic disorders. Certain genetic disorders, such as Down syndrome, are associated with some increased risk of acute lymphocytic leukemia.
  • Having a brother or sister with ALL. People who have a sibling or twin with ALL are slightly more likely to develop ALL.

However, most people with acute lymphocytic leukemia have no known risk factors.

Diagnosis

If you or your child has signs or symptoms of leukemia, blood and bone marrow tests are in order. These tests can determine if you or your child has leukemia, and if so, what kind. There are four main types of leukemia and many subtypes. You or your child may undergo the following diagnostic tests:

  • Blood tests. Most people with acute leukemia have too many white blood cells, not enough red blood cells and not enough platelets. The presence of blast cells — immature cells usually found in the bone marrow but not circulating in the blood — is another indicator of acute leukemia.
  • Bone marrow test. A blood test can suggest leukemia, but it usually takes a bone marrow test to confirm the diagnosis. In this test, a doctor or nurse uses a needle to remove a sample of bone marrow to look for leukemia cells. The sample is taken from the hipbone (posterior iliac crest).If your doctor suspects leukemia, you may be referred to a doctor who specializes in cancer (oncologist) or a doctor who specializes in blood and blood-forming tissues (hematologist) for this procedure. If your doctor suspects that your child has leukemia, you may be referred to a pediatric cancer center with pediatric doctors who specialize in cancer and blood.

A doctor who specializes in diagnosing cancer and other tissue abnormalities typically examines any blood and bone samples under a microscope. He or she can classify blood cells into specific types based on their size, shape and other features. This specialist can also look for certain changes in the chromosomes in the lymphocytes and find out whether the leukemia cells began from the B lymphocytes or T lymphocytes. This information helps your doctor craft a treatment plan.

If you or your child has acute lymphocytic leukemia, your doctor will want to find out if the cancer has spread to the brain and spinal cord or other parts of the body. A chest X-ray, ultrasound, spinal tap or additional blood tests can provide that information.

For most kinds of cancer, the next step is determining the stage of the cancer. But acute lymphocytic leukemia has no standard staging system. In adults, acute lymphocytic leukemia is simply classified as untreated, in remission or recurrent. For children with ALL, risk groups are used instead of stages. A child with ALL is placed in a standard, high-risk or very high-risk group based on:

  • Age. Infants and children older than 10 are generally placed in a high-risk category.
  • White blood cell count. The higher the white blood cell count at the time of diagnosis, the higher the risk group.
  • Immunophenotype. In ALL, the immunophenotype refers to whether the cancer began in the B lymphocytes (B-cell ALL) or the T lymphocytes (T-cell ALL). About 85 percent of cases are B cell, and about 15 percent are T cell. In general, children with B-cell ALL do better than those with T-cell ALL, so children with B-cell ALL are usually in a lower risk group while those with T-cell ALL are in a higher risk group.
  • Cytogenetics. This refers to any changes in the chromosomes in the lymphocytes. The presence of certain kinds of hard-to-treat mutations also places children in a higher risk group.

Knowing the risk group is important because it helps determine a treatment plan.

Treatment

Children with acute lymphocytic leukemia (ALL) who undergo treatment have about an 80 percent cure rate. Newer treatments may soon boost the child cure rate to as high as 90 percent. Adults have around a 40 percent cure rate.

In general, treatment for acute lymphocytic leukemia falls into three phases:

  • Induction therapy. The purpose of the first phase of treatment is to kill most of the leukemia cells in the blood and bone marrow.
  • Consolidation therapy. Also called post-remission therapy, this phase of treatment is aimed at destroying the leukemia cells remaining in the brain or spinal cord. Extra spinal taps and radiation therapy are considered crucial during this phase to decrease the risk of relapse.
  • Maintenance therapy. The third phase of treatment prevents leukemia cells from regrowing. The treatments used in this stage are often given at much lower doses.

Children with acute lymphocytic leukemia typically receive treatment to kill leukemia cells hiding in the central nervous system during each phase of therapy. This is called central nervous system sanctuary therapy, central nervous system preventive therapy or intrathecal chemotherapy. In this type of chemotherapy, anti-cancer drugs are injected directly into the fluid that covers the spinal cord. This kills cancer cells that can’t be reached by chemotherapy drugs given by mouth or through an intravenous line.

The three phases of treatment typically take two and a half to three and a half years. Therapies used in the three phases may include:

  • Chemotherapy. Chemotherapy is the major form of remission induction therapy for children and adults with acute lymphocytic leukemia. It usually lasts about four weeks, sometimes longer.If you or your child has ALL, you or your child will probably stay in the hospital during the induction cycle because the chemotherapy destroys many normal blood cells in the process of killing leukemia cells. This can cause anemia, infection and bleeding. Children with standard-risk ALL usually receive three drugs for the first month of treatment — vincristine, L-asparaginase, and a corticosteroid such as prednisone or dexamethasone. Children in the high-risk group may also receive an anthracycline drug such as daunorubicin. Adults with ALL receive a similar combination that usually includes vincristine, a corticosteroid and an anthracycline drug.Some of these same medications are also used in the consolidation and maintenance phases. However, the later phases usually rely on less intensive regimens that don’t require staying in the hospital. If you or your child experiences side effects from chemotherapy, be sure to discuss them with your doctor because medications that may ease some of the consequences of chemotherapy, such as nausea and vomiting, are available.
  • Other drug therapy. The drug imatinib mesylate (Gleevec) has been developed specifically to attack cells that have the Philadelphia chromosome. Doctors have been successful in using this medication to treat people with chronic myelogenous leukemia (CML), which is almost always linked to the presence of the Philadelphia chromosome. So far, the drug hasn’t proved as effective in treating people with ALL who have the Philadelphia chromosome, but research continues. The drug is currently being tested in combination with chemotherapy and some reports suggest this combination may be more effective than Gleevec alone.In 2006, the Food and Drug Administration (FDA) gave accelerated approval to the drug dasatinib (Sprycel) for treatment of people with CML and with ALL who have the Philadelphia chromosome. Initial studies showed that dasatinib reduced the number of leukemia cells found in the blood and bone marrow. However, more study of this new treatment is needed to determine what it can do, whether it can prolong the lives of people with these leukemias and what side effects it may cause.Another drug under investigation in ALL is rituximab (Rituxan), a monoclonal antibody. This medication targets a molecule called CD20, which is found in some lymphomas and some adult cases of ALL. Rituximab is currently used in lymphoma treatment and early research in ALL has been positive, but more studies need to be done.

    Additionally, other new drugs are being developed and some are currently in clinical trials.

  • Radiation therapy. If the cancer cells have spread to the central nervous system, your doctor may recommend radiation therapy. This therapy uses high-energy radiation beams to kill cancer cells.
  • Bone marrow transplant. This is another option for consolidation therapy for patients at high risk of relapse or for treating relapse when it occurs. This procedure allows someone with leukemia to re-establish healthy stem cells, by replacing his or her leukemic bone marrow with leukemia-free marrow.If you choose this treatment, you or your child will receive high doses of chemotherapy or radiation therapy to destroy any leukemia-producing bone marrow. This marrow is then replaced by bone marrow from a compatible donor (allogeneic transplant). In some cases, people are able to use their own bone marrow for transplantation (autologous transplant). This may be possible if you or your child goes into remission and then harvests healthy bone marrow for a future transplant.
  • Stem cell transplant. Stem cell transplant is also used for consolidation therapy. It’s similar to bone marrow transplant except the stem cells are collected from circulating blood (peripheral blood), rather than the bone marrow, thanks to a medication that causes larger numbers of stem cells to be released from the bone marrow.As with bone marrow transplant, the cells used for transplant can be your own healthy cells, or they can be collected from a compatible donor. This procedure is used more frequently than bone marrow transplant because of shortened recovery times and possible decreased risk of infection. Researchers are also using stem cell transplants using stem cells collected from umbilical cord blood.
  • Clinical trials. Some adults and children with leukemia choose to enroll in clinical trials to try out experimental treatments or new combinations of known therapies. You can discuss clinical trials with your doctor to see if one might be an option for you. Also, the American Cancer Society and National Cancer Institute offer information on available clinical trials. The American Cancer Society can be reached at 800-ACS-2345, or 800-227-2345, and the National Cancer Institute’s number is 800-4-CANCER, or 800-422-6237.