Many persons with acute lymphocytic leukemia (ALL) have a good chance for remission with the current standard treatments. However, some persons have risk factors for not doing as well as others. In particular, an abnormal chromosome (called the Philadelphia chromosome) found in the leukemia cells of some individuals, indicates that the standard treatments may not be as successful as they are for those without the abnormal Philadelphia chromosome. Researchers in California now say that more intensive chemotherapy may improve the survival time for these persons with ALL.

Acute lymphocytic leukemia, also called acute lymphoblastic leukemia, is a cancer of the lymph system and bone marrow. The bone marrow (and circulating blood) contains early blood-forming cells, called stem cells, which grow and mature into the 3 blood cell types: white blood cells (protect the body from infection), red blood cells (carry oxygen to the tissues), and platelets (help the blood to clot). In the case of ALL, the early immature white blood cells, called lymphocytes, multiply rapidly and uncontrollably. These excess lymphocytes can cause swelling in the lymph tissues; can crowd out other important blood cells made by the marrow; and can spread to other parts of the body. Approximately 15 to 30% of adults with ALL have a genetic abnormality associated with their leukemia, called the Philadelphia chromosome, which consists of a switching or translocation of chromosomes 9 and 22. Because persons with the Philadelphia chromosome do not respond as well to the standard chemotherapies for ALL, more effective therapies are being developed.

Many treatment options are being studied for ALL, including new chemotherapy drugs, new ways to deliver chemotherapy (for example, directly to the brain and spine because leukemia can recur there), and new ways to use higher doses of chemotherapy in combination with stem cell transplantation or biologic therapies. Although the use of high-dose chemotherapy with a stem cell transplant carries certain risks, it may be a more effective option, particularly for those with ALL and the Philadelphia chromosome.

Higher doses of chemotherapy (high-dose chemotherapy) can kill more leukemia cells than standard doses of chemotherapy; however, they can also damage healthy cells, especially the young stem cells in the bone marrow. For this reason, a procedure called a stem cell transplantation may be used in combination with high-dose chemotherapy and/or radiation therapy to “rescue” the bone marrow and enhance the production of new blood cells. In the case of an allogeneic stem cell transplantation, stem cells are collected from the blood or bone marrow of a donor, are frozen, and then infused into the patient after he or she has undergone high-dose chemotherapy to kill the leukemia cells. This procedure replaces the patient’s own stem cells, which have been destroyed by the high-dose chemotherapy, thereby allowing more rapid recovery and production of the red blood cells, white blood cells, and platelets that the body needs. Although this procedure is more effective than standard-dose chemotherapy, it also carries more risks for treatment-related complications such as potentially life-threatening infections. It is hoped that with continued advances in supportive care for those undergoing a transplant, this procedure will come to be associated with fewer risks.

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Over a number of years, researchers at the City of Hope National Medical Center treated 23 persons with Philadelphia chromosome-positive ALL with high-dose etoposide chemotherapy and total-body radiation therapy. These persons then received allogeneic stem cell transplantation, using stem cells that were donated by a sibling. The results showed that 30% of these patients died of treatment-related complications. However, treatment outcomes appeared to be improved in persons who were treated after 1992. Overall, 65% of patients were alive and free of disease after 3 years. Of only those treated after 1992, 81% were alive and free of disease.

These findings suggest that recent improvements in supportive care, such as more effective prevention and treatment of infections, have resulted in better outcomes for persons with ALL undergoing stem cell transplantation. For persons with Philadelphia chromosome-positive ALL, high-dose chemotherapy with an allogeneic stem cell transplantation appears to be more effective than standard-dose chemotherapy. Individuals who have this type of cancer may wish to talk with their doctor about the risks and benefits of intensive chemotherapy with a stem cell transplant, or of participating in a clinical trial in which other new treatments are being studied. Sources of information on ongoing clinical trials that can be discussed with a doctor include a comprehensive, easy-to-use service provided by the National Cancer Institute (cancer.gov) and the Clinical Trials section and service offered by Cancer Consultants.com (www.411cancer.com). (Leukemia, Vol 13, No 12, pp 2053-2058, 1999)

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