Pediatric Leukemia

Leukemia is the most common form of pediatric cancer. It affects approximately 3,250 children each year in the US, accounting for about 30% of childhood cancers. It can occur at any age, although it is most commonly seen in children between 2 and 6 years of age. The disease occurs slightly more frequently in males than in females, and is more commonly seen in Caucasian children than with African-American children, or children of other races.

Leukemia is cancer of the blood and develops in the bone marrow. The bone marrow is the soft, spongy center of the long bones that produces the three major blood cells: white blood cells to fight infection; red blood cells that carry oxygen; and platelets that help with blood clotting and stop bleeding.

When a child has leukemia, the bone marrow, for an unknown reason, begins to make white blood cells that do not mature correctly, but continue to reproduce themselves. Normal, healthy cells only reproduce when there is enough space for them to fit. The body can regulate the production of cells by sending signals when to stop. With leukemia, these cells do not respond to the signals to stop, and reproduce regardless of space available. These abnormal cells reproduce very quickly and do not function as healthy white blood cells to help fight infection.

A majority of childhood leukemias are acquired genetic diseases. This means that gene mutations and chromosome abnormalities in cells occur sporadically.

The immune system plays an important role in protecting the body from diseases, and possibly cancer. An alteration or defect in the immune system may increase the risk for developing leukemia. Factors such as exposure to certain viruses, environmental factors, chemical exposures and various infections have been associated with damage to the immune system. However, with the exception of specific genetic syndromes, little is known about the causes of childhood leukemia.

There are several main types of leukemia in children.

Acute lymphocytic leukemia (ALL)

Acute lymphocytic leukemia (ALL), also called lymphoblastic or lymphoid, accounts for approximately 75% of childhood leukemia.

In this form of the disease, the lymphocyte cell line is affected. The lymphocytes normally fight infection. With acute lymphocytic leukemia, the bone marrow makes too many of these lymphocytes and they do not mature correctly. The lymphocytes overproduce and crowd out other blood cells. Immature blood cells (blasts) do not work properly to fight infection. Acute leukemia can occur over a short period of days to weeks. Chromosome abnormalities (extra chromosomes and structural changes in the chromosome material) are present in the majority of the blast cells of ALL patients.

Acute myelogenous leukemia (AML)

Acute myelogenous leukemia (AML), also called granulocytic, myelocytic, myeloblastic or myeloid, accounts for approximately 19% of childhood leukemia.

Acute myelogenous leukemia is a cancer of the blood in which too many granulocytes, a type of white blood cell, are produced in the marrow. The granulocytes normally fight infection. With acute myelogenous leukemia, the bone marrow makes too many of these cells and they do not mature correctly. The granulocytes overproduce and crowd out other blood cells. Immature blood cells (blasts) do not work properly to fight infection. Acute leukemia can occur over a short period of days to weeks. Children with certain genetic syndromes, including Fanconi anemia, Bloom syndrome, Kostmann syndrome and Down syndrome, are at a higher risk of developing AML than other children.

Chronic myelogenous leukemia (CML)

Chronic myelogenous leukemia (CML) is uncommon in children. Chronic myelogenous leukemia is cancer of the blood in which too many granulocytes, a type of white blood cell, are produced in the marrow. The granulocytes normally fight infection. With this disease, the bone marrow makes too many of these cells and they do not mature correctly. The marrow continues to produce these abnormal cells which crowd out other healthy blood cells.

Chronic myelogenous leukemia can occur over a period of months or years. A specific chromosome rearrangement is found in patients with CML. Part of chromosome #9 breaks off and attaches itself to chromosome #22, so that there is an exchange of genetic material between these two chromosomes. This rearrangement changes the position and functions of certain genes, which results in uncontrolled cell growth. Other chromosome abnormalities can also be present.

The difference between lymphocytic and myelogenous is the stage of development on what is called the pluripotent stem cell. The pluripotent stem cell is the first stage of development of all of the blood cells (white blood cells, red blood cells and platelets). This stem cell goes through stages of development until it matures into a functioning cell. The type of leukemia is determined by which stage of development a cell is in when it becomes malignant or cancerous.

The stem cell matures into either the lymphoid or myeloid cells. The lymphoid cells mature into either B-lymphocytes or T-lymphocytes. If the leukemia is among these cells, it is called acute lymphocytic leukemia (ALL). If the leukemia is found even further along in this stage of development, it can be further classified as B-cell ALL or T-cell ALL. The more mature the cell, the more difficult it is to treat.

The myeloid cells develop into platelets, red blood cells and specialized white blood cells called neutrophils and macrophages. There are many classifications of AML. The type of leukemia is determined by the stage of development when the normal cells become leukemia cells.

Because leukemia is cancer of the blood-forming tissue called the bone marrow, the initial symptoms are often related to irregular bone marrow function. The bone marrow is responsible for storing and producing about 95% of the body's blood cells, including the red blood cells, white blood cells and platelets.

When leukemia occurs, the abnormal white blood cells (blasts) begin to reproduce very rapidly and begin crowding out and competing for nutrients and space with the other healthy cells. The following are the most common symptoms of leukemia. However, each child may experience symptoms differently. Symptoms may include:

• Anemia is present when red blood cells are unable to be produced because of the crowding in the marrow. With anemia, the child may appear tired, pale, and may breathe faster to compensate for the decrease in oxygen carrying capacity. The number of red blood cells on a blood count (and the hemoglobin) will be below normal.
• Bleeding and/or bruising can occur when platelets are unable to be produced because of the crowding in the marrow. Petechiae are tiny red dots often seen on the skin of a child with low number of platelets. Petechiae are very small blood vessels that have leaked or bled. The number of platelets on a blood count will be below normal. Thrombocytopenia is the term used for a decreased number of platelets.
• Recurrent infections. Although there may be an unusually high number of white blood cells on a blood count of a child with leukemia, these white blood cells are immature and do not fight infection. The child may have had repetitive viral or bacterial infections over the past few weeks. The child with leukemia often shows symptoms of an infection such as fever, runny nose and cough.
• Bone and joint pain can happen when the bone marrow is overcrowded and “full.”
• Abdominal distress happens when leukemia cells collect in the kidney, liver and spleen, causing enlargement of these organs. Abdominal pain may cause a child to have loss of appetite and weight loss.
• Swollen lymph nodes under the arms, in the groin, chest, and in the neck happen when leukemia cells collect in the nodes, causing swelling. Lymph nodes are responsible for filtering the blood.
• Difficulty breathing (dyspnea). With T-cell ALL, these leukemia cells tend to clump together around the thymus. This mass of cells present in the middle of the chest can cause pain and difficulty breathing (dyspnea) Wheezing, coughing and/or painful breathing requires immediate medical attention.

With acute leukemia (ALL or AML), these symptoms may occur suddenly in a matter of days or weeks. With chronic leukemia (CML), these symptoms may develop slowly over months to years.

It is important to understand that the symptoms of leukemia may resemble other blood disorders or medical problems. These are common symptoms of the disease, but do not include all possible symptoms. Children may experience symptoms differently. Always consult your child's physician for a diagnosis.

Children’s National's leukemia team, which consists of doctors, nurses, researchers, social workers, a psychologist, an art therapist, a child life specialist, a nutritionist, and a chaplain, work collaboratively to provide the best care for patients during clinic visits.

Each patient is seen by a doctor or nurse practitioner. During each visit, staff will review:

• Any symptoms or side effects the patient has experienced.
• Exact doses of medicines taken.
• Medications needing refills.
• Next stage of chemotherapy, if the child is about to begin a new phase.

All medications should be brought to each visit.

The patient cannot receive scheduled chemotherapy until checked by a doctor or nurse, and in some cases, must have lab results before the process can begin.

There are various stages in the treatment of leukemia, including the following:

• Induction is a combination of chemotherapy and/or radiation and medications given to stop the process of abnormal cells being made in the bone marrow. Remission is the goal in this stage of treatment. Remission means the leukemia cells are no longer being made. This phase may last approximately one month and can be repeated if the goal is not achieved.
• Intensification is continued treatment even though leukemia cells may not be visible. The leukemia cells may not be visible in a blood test or bone marrow examination, but it is possible that the cells are still present in the body.
• Maintenance is the stage that maintains leukemia-free bone marrow by continuing less intense chemotherapy for a longer duration. This phase can last months to several years. Regular visits to your child's physician are required in order to determine response to treatment, detect any recurrent disease, and manage any side effects of the treatment.
• Relapse may occur even with aggressive therapy. Relapse is when the bone marrow begins making abnormal cells again. Relapse can occur during any of the stages of treatment, or may occur months or years after treatment has ended.

In addition to a complete medical history and physical examination, diagnostic procedures for leukemia may include:

• Bone marrow aspiration and/or biopsy is a procedure that involves taking a small amount of bone marrow fluid (aspiration) and/or solid bone marrow tissue (called a core biopsy), usually from the hip bones, to be examined for the number, size, and maturity of blood cells and/or abnormal cells.
• Complete blood count (CBC) measures the size, number and maturity of different blood cells in a specific volume of blood.
• Additional blood tests may include blood chemistries, evaluation of liver and kidney functions, and genetic studies.
• X-ray is a diagnostic test that uses invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film.
• Computer-assisted tomography scan (CT or CAT scan) is a diagnostic imaging procedure that uses a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general x-rays.
• Magnetic resonance imaging (MRI) is a diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body.
• Ultrasound (sonography) uses high-frequency sound waves and a computer to view internal organs as they function, and to assess blood flow through various vessels.
• Lymph node biopsy
• Spinal tap/lumbar puncture. A special needle is placed into the lower back, into the spinal canal in the area below the spinal cord. The pressure in the spinal canal and brain can then be measured. A small amount of cerebral spinal fluid (CSF) can be removed and sent for testing to determine if there is an infection or other problems. CSF is the fluid that bathes your child's brain and spinal cord.

Specific treatment for leukemia is determined by the physician based on the:

• Child's age, overall health and medical history.
• Type, location and size of the tumor.
• Extent of the disease.
• Child's tolerance for specific medications, procedures or therapies.
• Expectations for the course of the disease.
• The patient and family’s opinion or preference.

Treatment usually begins by addressing the presenting symptoms such as anemia, bleeding and/or infection. In addition, treatment for leukemia may include (alone or in combination) the following:

• Chemotherapy.
• Intrathecal medications/chemotherapy inserted through a needle into the spinal cord into the area called the subarachnoid space.
• Radiation therapy.
• Blood and marrow transplantation.
• Biological therapy.
• Supportive care for pain, fever, infection and nausea/vomiting.
• Blood transfusions of red blood cells and platelets.
• Continuous follow-up care to determine response to treatment, detect recurrent disease, and manage late effects of treatment.

Prognosis greatly depends on:

• The extent of the disease.
• The disease’s response to treatment.
• Genetics.
• The child’s age and overall health.
• The child's tolerance of specific medications, procedures or therapies.
• New developments in treatment.

As with any cancer, prognosis and long-term survival can vary greatly from child to child. Prompt medical attention and aggressive therapy are important for the best prognosis. Continuous follow-up care is essential for the child diagnosed with leukemia.

Side effects of radiation and chemotherapy, as well as second malignancies, can occur in survivors of leukemia. New methods are continually being discovered to improve treatment and to decrease side effects of the treatment for the disease.