Chronic Leukemia Treatment Strategies

Chronic leukemia treatment methods center on controlling the symptoms and slowing the progression of the disease. With the exception of the stem cell transplant for CML, curative therapies do not yet exist. Chronic leukemia treatment options depend on the type of cancer: CLL and CML respond to different therapies.

An allogeneic stem cell transplant is the only curative treatment for CML, although the chances of a true cure are slim. Stem cells are immature cells that develop into the different types of blood cells. "Allogeneic" means that the stem cells used in the transplant come from a donor, as opposed to "autologous," in which stem cells are harvested from the patient's own bone marrow.

Treatment begins with intensive chemotherapy, radiotherapy or a combination of the two. Both treatments suppress the bone marrow, killing both the leukemic cells and healthy stem cells. Following initial treatment, donor stem cells are injected intravenously, then they migrate to the bone marrow and mature into healthy white blood cells, red blood cells and platelets.

With a suitable donor, transplantation is effective, producing long-term survival in eighty percent of cases. Siblings are the best donors, with a twin being the best possible donor. If siblings and family members are not available, donor matching may produce a suitable match. Transplant success rates are far from perfect, however, and in twenty percent of cases CML returns within five years of the transplant.

Interferon-alpha and hydroxyurea are two of the most common chemotherapy drugs used to treat CML. Hydroxyurea lowers white blood cell levels in both the blood and bone marrow. Side effects include gastrointestinal problems, skin rashes and mouth ulcers.

Interferon-alpha controls white blood cell and platelet counts in eighty percent of patients. The drug has been shown to reduce the amount of abnormal Philadelphia chromosome-positive cells in the bloodstream by as much as forty percent. This reduction in Philadelphia chromosome-positive cells reflects a slowing progression of CML, and an improved long-term survival rate. Interferon-alpha is often combined with other chemotherapy drugs. Side effects include flu-like symptoms, nausea and weight loss.

Gleevec, also known as STI571, is a promising new chronic myelogenous leukemia treatment. Gleevec is a tyrosine-kinase inhibitor, which blocks the function of the bcr-abl protein. The bcr-abl protein is an abnormal fusion protein expressed by the Philadelphia chromosome and contributes to the rapid reproduction of white blood cells.

In clinical trials, Gleevec slowed the rate of CML progression and patients had fewer leukemic cells in the blood and bone marrow than people taking interferon-alpha and cytarabine. Further testing is required to see whether Gleevec improves long-term survival rates.

Side effects of Gleevec include nausea and vomiting, fluid retention, muscle cramps, fatigue, headaches and skin rashes.

Chronic lymphocytic leukemia treatment concentrates on symptom relief. As long as symptoms are absent, treatment is avoided because the treatment itself may worsen the disease. Once symptoms appear, chemotherapy and corticosteroids are the most-used options, although radiotherapy may occasionally be used.

For many years, chlorambucil was a mainstay of CLL chemotherapy. In recent years, the drug has been largely replaced by fludarabine and cladribine. Cladribine is most often used to treat hairy cell leukemia, a form of CLL that is very drug-resistant.

Clinical trials have shown that fludarabine produces more remissions than chlorambucil, and that the remissions last longer. However, fludarabine does not improve survival rates and has some side effects, including severe infections and low blood counts.

Monoclonal antibodies are a promising area of cancer research. The antibodies are designed to bind to cancer cells, targeting them for destruction by the immune system. Two types of monoclonal antibodies are used to treat CLL. Alemtuzumab (also known as Campath-1H) binds to the cell surface marker CD 52, which is present on both normal and cancerous lymphocytes. Alemtuzumab may be used if fludarabine proves ineffective.

Rituximab binds to CD 20, a protein found on some types of CLL cells. Clinical trials are investigating its effectiveness when combined with chemotherapy. Some evidence indicates that monoclonal antibodies may make cancerous cells more sensitive to the effects of chemotherapy drugs.

Leukemia treatment may produce a number of complications as blood cell counts fluctuate. Blood transfusions may be required to replenish red blood cells or platelets.

 

Hypogammaglobulinemia, or the lack of infection-fighting antibodies, may require supplementation with gamma globulin transfusions.

White blood cells are necessary to combat infection, but they may not function correctly due to chronic leukemia. In addition, chemotherapy and radiotherapy often suppress the immune system. Patients must be monitored carefully for infections and fevers, and they are often treated with broad-based antibiotics.

Resources

Beers, M. H., & Berkow, R. (ed). Leukemia. The Merck Manual of Diagnosis and Therapy, 17th Edition. Merck Research Laboratories, NJ, 1999.

Food and Drug Administration (FDA). (2002). Gleevec approved for first line treatment of chronic myeloid leukemia (CML). FDA News.

Leukemia and Lymphoma Society. (updated 2002). Blood and marrow stem cell transplantation.

Leukemia and Lymphoma Society. (updated 2004). Leukemia.

Leukemia and Lymphoma Society. (updated 2002). New approaches to treatment.

National Cancer Institute. (updated 2005). Chronic myelogenous leukemia (PDQ) treatment.

National Cancer Institute. (2000). Fludarabine prolongs leukemia remission.

O'Dwyer, M., Mauro, M. & Druker, B. (2002). Recent advancements in the treatment of chronic myelogenous leukemia. Annual Review of Medicine, 53, 369-381.