Leukemia

Description
Leukemia, or cancer of the blood, is characterized by the production of abnormal white blood cells in bone marrow, the soft interior region of most bones. There are several types of leukemia, categorized according to the type of white blood cells most affected by cancer and the aggressiveness of the disease. Leukemia cells are able to multiply quickly and outlive normal blood cells.

Bone marrow is the home of blood stem cells that give rise to platelets (responsible for helping blood to clot), red blood cells (responsible for transporting oxygen to regions of the body), and white blood cells (responsible for fighting infection in body). Leukemia cells overwhelm and interfere with healthy blood cells, compromising blood cell function and transporting quickly through the bloodstream.

Symptoms of Disease
While symptoms of patients with leukemia may vary, most individuals experience low levels of normal blood cells, due to overcrowding by leukemia cells. Low platelet, red blood, and white blood cell counts can cause the following symptoms:

• Fatigue or shortness of breath - due to low red blood cell count
• Bruising - due to low platelets
• Loss of appetite
• Frequent infections with fever - due to low white blood cell count
• Nose bleeds or other excessive bleeding - due to low platelets

Leukemia forms in several different types of white blood cells (lymphocytes, granulocytes and monocytes), which are responsible for fighting infection. Leukemia limits an affected cell from maturing, and as a result, can partially impair or completely disrupt cell function. Leukemia is classified according to the type of cell affected by cancer and the level of dysfunction caused by cancer.

Most Common Types of Leukemia

• Acute myelogenous leukemia (AML): overproduction of immature myeloid (granulocytes and monocytes) white blood cells
• Chronic myelogenous leukemia (CML): abnormal accumulation of myeloid white blood cells
• Acute lymphocytic leukemia (ALL): overproduction of immature lymphocytes
• Chronic lymphocytic leukemia (CLL): abnormal accumulation of lymphocytes

Acute leukemia progresses much more quickly than the chronic disease. In acute leukemia, genetic mutations in the blood-forming cells result in an excess of immature, useless blood cells in the bone marrow and blood, essentially crowding out the production of healthy marrow cells. As a result, the marrow cannot produce enough red blood cells, many types of white blood cells and blood-clotting platelets, leaving individuals anemic and susceptible to infection and bleeding. In chronic leukemia, more mature, working cells are made. While chronic leukemia cells are more functional than acute leukemia cells, over time, they will also overcrowd and interfere with the function of healthy cells.

How common is Leukemia?

• In 2008, researchers estimate that approximately 44,270 cases of leukemia will be diagnosed among adults and children in the United States
  • Leukemia is the most common form of cancer in children
• CLL is the most commonly diagnosed leukemia in adults
  • Researchers estimate that 15,110 adults will be diagnosed with CLL this year
  • 4,390 people will die from CLL this year
• ALL is the most common leukemia in children
  • Researchers estimate that 3,040 of 4,220 new cases of ALL this year will be in children; 87 percent of children with ALL will survive at least five years after being diagnosed with cancer

Thanks to medical and technological advances, the survival rates of leukemia patients have dramatically improved over the last several decades. Overall, children tend to respond better to leukemia treatments; however, chemotherapy and radiation can have long-term effects on patients' health.

Diagnosis
To identify leukemia, a patient will need to undergo blood and bone marrow cell tests that provide information about total blood counts and any genetic abnormalities reflected in blood and bone marrow. These genetic abnormalities can include chromosomal translocation (the exchange of DNA between different chromosomes) or the possession of extra chromosomes. Imaging tests are used to identify the damage caused by leukemia and to identify if the cancer has spread to other regions of the body (metastasized).

Based upon the number, type and characteristics of abnormal cells found in blood and bone marrow tests, leukemia will be diagnosed. The type of leukemia will influence the treatment a patient will receive.

Treatment Options
Surgery
Because leukemia rapidly spreads throughout the body and does not form tumors, surgery has a limited role in treating leukemia. However, the spleen may be removed if it is enlarged.

Chemotherapy
Chemotherapy, the use of drugs to destroy cancer cells, is the major treatment of leukemia. Anti-cancer drugs can be taken by vein, muscle, cerebrospinal fluid (CSF) or mouth.

• Although chemotherapy techniques wipe out cancer cells, many normal, rapidly dividing healthy cells are also killed by these treatments. The death of healthy cells causes undesirable side effects for cancer patients such as hair loss, mouth sores, nausea, reduced resistance to infection, bruising and more.
• To lessen the harmful side effects caused by chemotherapy, researchers are working to develop ways to tailor anti-cancer drugs that specifically target cancer cells and interfere with the chemical processes that promote cancer growth.

The goal of chemotherapy is to destroy leukemia cells and help to return blood counts to normal. There are a variety of anticancer drugs used either alone or in combination to treat leukemia.

Common chemotherapy drugs for the treatment of each type of leukemia are used:

• ALL
  • Prednisone
  • Vincristine (Oncovin®)
  • Cyclophosphamide (Cytoxan)
  • L-asparaginase (Elspar®)
  • Daunorubicin (Cerubidine®)
  • Methotrexate (Trexall)
• AML
  • Daunorubicin (Cerubidine®)
  • Cytarabine (Cytosaur ®)
  • Idarubicin (Zavedos®)
  • Etoposide (Etopophos®, Vepesid®)
  • Mitoxantrone (Novantrone)
• CML
  • Hydroxyurea (Hydrea®)
  • Busulfan (Myleran®)
• CLL
  • Fludarabine (Fludara®)
  • Chlorambucil (Leukeran®)
  • Cyclophosphamide (Cytoxan)

Additional drugs used in combination with chemotherapy:

• Imatinib mesylate (Gleevec®)
  • Only effective in leukemias that contain a specific chromosomal translocation (BCR-ABL), which is primarily CML
  • Disrupts leukemia cell activity, promoting cell death
  • Reduces some of the side effects seen in chemotherapy treatments because it targets specific traits seen only in leukemia cells and avoids healthy cells
• Dasatinib
  • Performs similar function as imatinib mesylate; often prescribed to patients who have become resistant to it
    
• Monoclonal antibodies: proteins specifically designed to attach to and promote death of leukemia cells

In addition to chemotherapy drugs, patients may also take medications to reduce side effects of chemotherapy, antibiotics to protect against infection, and blood transfusions to help replenish low blood counts. 

Radiation
Radiation therapy fights cancer by damaging cancer cells with a powerful blast of energy. While researchers direct radiation at cancer cells, they cannot be fully isolated and radiation often kills normal, healthy cells of the body.

Radiation therapy is most commonly used to target high percentages of leukemia cells gathered in specific regions of the body, such as the brain or cerebrospinal fluid. Some leukemia patients receive whole body radiation to help destroy leukemia cells, but this is only in preparation for bone marrow or blood stem cell transplant.

Bone Marrow or Blood Stem Cell Transplant
Many leukemia patients suffer from the side effects of losing healthy cells in addition to leukemia cells from chemotherapy and radiation. To help a patient to withstand high doses of chemotherapy and radiation, healthy stem cells and bone marrow can be transplanted to a leukemia patient. A stem cell and/or bone marrow treatment will help the patient to generate new, healthy blood cells.

Bone marrow and stem cell transplants are still very new and expensive.

New Scientific Developments
As researchers continue to better understand the molecular events leading to leukemia, they continue to work towards specific drugs that will halt the disease's progression. The development of new drugs and combinations of drugs that target particular proteins found in leukemia cells continues to be a major area of research and discovery.

Researchers also continue to work to improve other leukemia treatments. In June 2007, scientists reported a drug already proven safe in humans may be able to help increase the number of blood-producing stem cells, which may help to improve the effectiveness of stem cell transplants.

Because more children are surviving childhood leukemia than ever before, new research focuses on the long-term effects of cancer therapy on adult survivors of childhood leukemia. Studies have shown that adult survivors of childhood ALL are at a higher risk for obesity, developing cardiovascular disease, osteoporosis and more. In order to protect adult survivors of childhood leukemia from disease in the future, special medical attention needs to be focused on how children are treated and followed. Promoting healthy lifestyles in adult survivors could help minimize complications.

Related AACR Press Releases
Adult Survivors of Childhood Leukemia Exercise Less, Worsening Already High Risk for Obesity and Illness
July 23, 2007

Resources
American Cancer Society. Cancer Facts & Figures. Atlanta, American Cancer Society, 2008
1-800-ACS-2345
www.cancer.org

National Cancer Institute
1-800-4-CANCER
www.cancer.gov

The Leukemia & Lymphoma Society
(800) 955-4572
www.leukemia-lymphoma.org

Last reviewed: June 23, 2008