Leukemia is a disease of the white blood cells. All types of blood cells are produced by the bone marrow (the spongy tissue inside the large bones of the body): red blood cells, which carry oxygen and other materials to all tissues of the body; platelets, which help make the blood clot; and white blood cells, which fight infection.

All of these cells arise from stem cells, which are blood cells at their very earliest stage of development. Stem cells can develop into different types of white cells, including lymphocytes and neutrophils.

In leukemia, the immature white cell loses its ability to mature and specialize (differentiate) its function. As a result, the marrow produces too many of one type of cell that replaces normal blood cells and results in bone marrow failure. These abnormal white cells flood the blood stream and lymph system, and may invade vital organs such as the brain, testes, ovaries, or skin.

The bone marrow is the factory for all new blood and immune cells. When it does not work correctly, cells that prevent bleeding and infection, or that carry nourishment and oxygen to vital organs and tissues, cannot do their jobs properly.

Leukemia can be acute, progressing quickly with many immature cancer cells, or chronic, progressing slowly with more mature-looking cancer cells.

The most common type of leukemia in children is acute lymphocytic leukemia (ALL). Other types of leukemia that occur less frequently in children are acute myeloid leukemia (AML), and chronic myeloid leukemia (CML).

Types of Childhood Leukemia

Acute Lymphocytic Leukemia (ALL)

Acute lymphocytic or lymphoblastic leukemia, known as ALL, is the most common childhood leukemia, accounting for 80 percent of all acute leukemias in children. ALL is most common in children between the ages of 3 and 7. It occurs when too many immature lymphocytic cells (lymphoblasts) are produced and multiply rapidly, crowding out normal blood cells and making the child susceptible to bleeding and infection. These cells can be found in the blood, the bone marrow, the lymph nodes, the spleen, and other organs.

There are two different types of lymphocytes: T cells and B cells. Often the leukemia arises in the immature lymphocytes. Less frequently, however, leukemia cells develop in T or B cells before becoming cancerous. This type of lymphocytic leukemia is referred to as T or B cell leukemia.

Risk Factors

Most cases of ALL seem to have no apparent cause. However, radiation, some toxins such as benzene, and some chemotherapy agents are thought to contribute to the start of leukemia. Abnormalities in chromosomes may also play a role in the development of acute lymphocytic leukemia.

Risk factors for ALL include Down syndrome, a sibling with leukemia, and exposure to radiation, chemicals, and drugs. The incident rate is six out of 100,000 children.

Cancer Symptoms

As the leukemia cells multiply in the bone marrow, the production of normal blood cells slows, so the child may become tired and lethargic, or short of breath due to anemia caused by a lack of oxygen carrying red blood cells. Bruises may develop, and bleeding may occur due to low numbers of clotting cells called platelets. Sometimes, a child may suffer from infections because of low numbers of normal white blood cells.

A child is likely to feel unwell in general and may complain of aches and pains in his or her arms, legs, or joints, and/or have swollen gums or glands. Other signs and symptoms may include nosebleeds, excessive bruising, pinpoint red spots on the skin (petechiae), fever, weight loss, and the sensation of an irregular heart rate (palpitations). Often symptoms can mimic those of a viral infection, but when they continue for more than a week or two, other causes should be investigated.

Diagnostic Tests

Blood tests are administered to determine if there are abnormal leukemia cells in the blood stream, and if the number of normal white blood cells, red blood cells and platelets is low. A sample of bone marrow is removed from the hip bone (biopsy) to confirm the presence of abnormal white blood cells (leukemia cells) in the bone marrow. A lumbar puncture (spinal tap) is done to remove a sample of spinal fluid to see whether it contains any leukemia cells. A chest X-ray will indicate any enlarged glands in the chest.

Other tests may be necessary, depending on the child’s symptoms.

Classification of ALL currently depends on a number of specific, sophisticated tests, such as immunophenotyping, karyotyping, and terminal deoxynucleotidyltransferase (TdT) activity. The combined results of these tests allow pinpoint molecular diagnosis, which helps guide the treatment decisions, and clarify the likely prognosis.

For example, the cells of some leukemias contain chromosomal abnormalities. Those with the Philadelphia chromosome, or with the t(4;11) translocation, have a poorer prognosis, and intensive treatment, including an early bone marrow transplant, might be recommended. Other genes can indicate a very favorable prognosis.

Treatment

Chemotherapy (oral and/or intravenous treatment with anticancer drugs) is the main treatment for ALL and has several phases:

• Induction: This phase lasts for approximately four weeks, and typically requires the child to stay in the hospital. A bone marrow test is taken at the end of the induction treatment to see if the leukemia is in remission, meaning there is no evidence of leukemia.
• Intensification therapy: Even if bone marrow tests do not show leukemia cells, indicating the patient is in remission, it is possible that some cells have survived. Additional chemotherapy drugs are given to destroy any of these remaining leukemia cells that may have survived the induction phase of treatment. These are usually given in three blocks of intensive treatment.
• Central Nervous System (CNS) treatment: ALL sometimes develops in the brain and spinal cord. Doctors try to prevent this by injecting a drug, usually methotrexate, directly into the spinal fluid. Occasionally, radiation therapy (targeted X-rays to destroy tumors) to the brain is also necessary.
• Maintenance or consolidation therapy: This phase of chemotherapy treatment lasts for up to 2 1/2 years from diagnosis and involves taking daily tablets at home and having intermittent, intravenous chemotherapy (treatment with anticancer drugs). During maintenance treatment most children will be able to take part in their normal daily activities.
• Bone marrow/stem cell transplantation (BMT): Since leukemia is a disease caused by abnormal bone marrow function, bone marrow or stem cell transplantation (BMT) can potentially cure the disease when chemotherapy fails. In this treatment, the diseased bone marrow is destroyed using high doses of chemotherapy (anticancer drugs) and radiation. Healthy donor (allogeneic) stem cells or bone marrow, or self-donated (autologous) stem cells or bone marrow, purged of any leukemia cells, are given to the patient intravenously and travel to the bone to repopulate the bone marrow. This treatment is only indicated in cases where the ALL is likely to recur following standard chemotherapy, or for children whose leukemia has come back following standard treatment.

During treatment, some patients may require the transfusion of blood products to treat anemia and/or bleeding.

Acute Myeloid Leukemia (AML)

Acute myeloid leukemia, known as AML, occurs when too many neutrophils develop from immature cells of the myeloid line. As the production of these abnormal cells increases, production of normal cells decline. AML is less common in children than ALL.

Risk Factors

In general, the causes of AML are unknown. Children with Down syndrome have an increased risk of developing AML during the first three years of life.

Cancer Symptoms

As the leukemia cells multiply in the bone marrow, the production of normal blood cells slows, so the child may become tired and lethargic, or short of breath due to anemia caused by a lack of oxygen carrying red blood cells. Bruises may develop, and bleeding may occur due to low numbers of clotting cells called platelets. Sometimes, the child may suffer from infections because of low numbers of normal white blood cells. A child is likely to feel unwell in general, experience fever or chills, and may complain of aches and pains in his or her arms, legs, or joints.

Diagnostic Tests

Blood tests are administered to determine if there are abnormal leukemia cells in the blood stream and if the number of normal white blood cells, red blood cells, and platelets is low. A sample of bone marrow is removed from the hip bone (biopsy) to confirm the presence of abnormal white blood cells (leukemia cells) in the bone marrow. A lumbar puncture (spinal tap) is done to remove a sample of spinal fluid to see whether it contains any leukemia cells. A chest X-ray will indicate if there are any enlarged glands in the chest.

Treatment

Chemotherapy (oral and/or intravenous treatment with anticancer drugs) is the main treatment for AML and has several phases:

• Induction: This phase lasts for approximately six weeks, and typically requires the child to stay in the hospital. A bone marrow test is taken at the end of the induction treatment to see if the leukemia is in remission, meaning there is no evidence of leukemia.
• Intensification therapy: Even if bone marrow tests do not show leukemia cells, indicating the patient is in remission, it is possible that some cells have survived. Additional chemotherapy drugs are given to destroy any of these remaining leukemia cells that may have survived the induction phase of treatment.
• Central Nervous System (CNS) treatment: AML sometimes develops in the brain and spinal cord. Doctors try to prevent this by injecting drugs directly into the spinal fluid. Occasionally, radiation therapy (targeted X-rays to destroy tumors) to the brain is also necessary.
• Bone marrow/stem cell transplantation (BMT): Since leukemia is a disease cause by abnormal bone marrow function, bone marrow or stem cell transplantation (BMT) can potentially cure the disease when chemotherapy fails. In this treatment, the diseased bone marrow is destroyed, using high doses of chemotherapy (anticancer drugs). Healthy donor (allogeneic) stem cells or bone marrow, or self-donated (autologous) stem cells or bone marrow, purged of any leukemia cells, are given to the patient intravenously and travel to the bone to repopulate the bone marrow.

During treatment, some patients may require the transfusion of blood products to treat anemia and/or bleeding.

Research

Our researchers have identified a genetic mutation, called FLT3, that is unique to AML. AML patients who have the mutation may benefit from drug therapy with a type of drug known as a tyrosine kinase inhibitor. This type of drug can block cell signaling proteins from telling AML cells to grow. Inhibiting the gene’s ability to communicate with cells can slow the growth, and promote the death of AML cells.

Chronic Myeloid Leukemia (CML)

Chronic myeloid leukemia (CML) occurs when too many neutrophils develop from immature cells of the white blood cell myeloid line.

The disease occurs in both middle-aged adults and children, and is associated with a chromosomal abnormality called the Philadelphia chromosome. CML is characterized by a chronic phase that can last for months, or years. The disease may have few or no symptoms during the chronic phase. Eventually, however, patients progress from the chronic phase to a more dangerous “accelerated phase,” during which time the leukemia cells grow more quickly.

Risk Factors

Known risk factors for developing CML are exposure to ionizing radiation and benzene.

Cancer Symptoms

Acceleration of the disease may cause symptoms including: fever, without infection; bone pain; pressure under the ribs, caused by an enlarged spleen; fatigue; night sweats; bleeding; bruising; and red pinpoint marks on the skin (petechiae). Within five years from diagnosis with CML, most patients will progress to a “blast crisis,” wherein there is a very high count of immature white blood leukemia cells.

Diagnostic Tests

A blood test is administered to determine if there are increased numbers of white blood cells and what type. A bone marrow biopsy is taken, in which a sample of bone marrow is removed from the hip bone to confirm the abnormal white cell production. A test for the presence of the Philadelphia chromosome is performed.

Treatment

Treatment is aimed at reducing the growth of the leukemia cells in the bone marrow and may bring about a remission (when no leukemia can be found) with good control of the symptoms of the disease.

The chronic phase can be controlled with chemotherapy, oral and/or intravenous treatment with anticancer drugs, which can often be given on an outpatient basis.

A bone marrow or stem cell transplant is often recommended to treat CML. Since leukemia is a disease cause by abnormal bone marrow function, bone marrow or stem cell transplantation can potentially cure the disease. In this treatment, the diseased bone marrow is destroyed, using high doses of chemotherapy (treatment with anticancer drugs). Healthy donor (allogeneic) stem cells or bone marrow, or self-donated (autologous) stem cells or bone marrow, purged of any leukemia cells, are given to the patient intravenously and travel to the bone to repopulate the bone marrow.

Research

The FDA recently approved a new drug for CML called imatineb (Gleevec), which has been shown to be particularly effective in adult patients whose disease has not responded to standard treatment or bone marrow transplant (BMT). This drug works directly on the leukemic cells to slow their growth.