Approximately 75% to 80% of children having acute lymphocytic leukemia can likely be cured with the currently available standard treatments. However, some children have certain characteristics, or risk factors, that may make them less likely to respond as well to these therapies. Researchers now report that the most effective treatment for those who have such risk factors—a high white blood cell count and/or a genetic abnormality called the Philadelphia chromosome—may be high-dose chemotherapy with an allogeneic stem cell transplantation using a related stem cell donor.

Acute lymphocytic leukemia (ALL), 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. Many children with this disease can achieve remission (absence of all signs and symptoms of cancer) with the currently available standard therapies (standard-dose chemotherapy and/or radiation therapy).

However, some children with ALL also have characteristics, or risk factors, that make them less likely to respond as well to these therapies. One of these risk factors is an exceptionally high white blood cell count at diagnosis. A second and very important risk factor is a genetic abnormality that is associated with ALL and is characterized by the switching, or translocation, of the chromosomes 9 and 22 (called the Philadelphia chromosome). Because Philadelphia chromosome-positive ALL does not respond as well to the standard therapies, researchers continue to develop new, more promising treatment strategies and to investigate which treatments prove most effective for children with this type of disease.

One treatment option for Philadelphia chromosome-positive ALL that has been studied recently is the use of higher than standard doses of chemotherapy. High-dose chemotherapy can kill more leukemia cells than standard-dose chemotherapy; however, it can also damage more healthy cells, especially the young stem cells in the bone marrow. For this reason, a procedure called a stem cell transplantation is sometimes used in combination with high-dose chemotherapy and/or radiation therapy to “rescue” the bone marrow and enhance the production of new blood cells. The stem cells may be donated by 1 of 3 sources: an allogeneic transplant uses stem cells donated by someone who may or may not be a relative of the patient; a syngeneic transplant uses stem cells donated by an identical twin of the patient; and an autologous transplant uses stem cells collected directly from the patient, before receiving the high-dose chemotherapy. In the case of an allogeneic stem cell transplantation, stem cells are collected from the blood or bone marrow of the donor, are frozen, and then infused into the patient after he or she has undergone the high-dose therapy. This procedure replaces the patient’s own stem cells, which have been destroyed by the high-dose therapy, thereby allowing more rapid recovery and production of the red blood cells, white blood cells, and platelets that the body needs.

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Although this treatment strategy is considered more effective than standard-dose chemotherapy, it also carries a higher risk for treatment-related complications such as potentially life-threatening infections. Recently, researchers from several treatment centers in Europe and the United States combined their results of treatment received by children with ALL with the Philadelphia chromosome. The researchers analyzed the treatment outcomes of 326 children and young adults who received high-dose chemotherapy, with or without a stem cell transplantation, from 1986 to 1996. All the children had ALL with the Philadelphia chromosome, and some also had very high white blood cell counts. According to the number of white blood cells, the analysis showed that children who had a white blood cell count of less than 50,000 and were younger than 10 years old had a 5-year survival rate of 50%; those with a white blood cell count of more than 100,000 had a 5-year survival rate of about 20%. According to the treatment type, the most effective approach was high-dose chemotherapy combined with an allogeneic stem cell transplant using a related donor. Approximately 70% of children were cured with the allogeneic stem cell transplant with a related donor, compared with only 30% with an unrelated donor. This approach was more successful than high-dose therapy without a stem cell transplant or high-dose therapy with other types of stem cell transplant. Furthermore, there was an improvement in survival over time, with overall survival rates being 32% between 1986 and 1988 and 43% between 1995 and 1996.

These findings suggest that 1) high-dose chemotherapy with an allogeneic stem cell transplant using a related donor is more effective than other high-dose chemotherapy strategies in prolonging initial complete remissions in children with Philadelphia chromosome-positive ALL, and 2) ongoing scientific advances in the use of high-dose chemotherapy, stem cell transplant, and supportive therapy are resulting in improved outcomes for patients over time. Parents who have children with Philadelphia chromosome-positive ALL may wish to talk with their doctor about the risks and benefits of undergoing an allogeneic stem cell transplant (with a related donor) or of participating in a clinical trial in which other promising new treatments are being studied. Two 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). (New England Journal of Medicine, Vol 342, No 14, pp 998-1006, 2000)

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