Chemotherapy Plus Radiation Therapy Improves Survival over Chemotherapy Alone

Chemotherapy + Radiation Therapy Improves Survival over Chemotherapy Alone for Children Undergoing Stem Cell Transplant

Children who have acute lymphoblastic leukemia (ALL) who have or are likely to have a relapse after initial therapy often undergo further treatment with high doses of chemotherapy and/or radiation therapy with an allogeneic stem cell transplantation (SCT). When a SCT is needed, it is usually given following high doses chemotherapy, often with total-body radiation, to kill the leukemia cells. However, because radiation therapy in children can sometimes cause serious side effects, including problems with the child’s growth and with second cancers, some researchers have studied the use of chemotherapy alone (without radiation therapy) before a SCT. A recent evaluation by the International Bone Marrow Transplant suggests that chemotherapy alone may not be as effective for these children as chemotherapy and radiation therapy together.

Childhood acute lymphoblastic leukemia, also called acute lymphocytic leukemia, is the most common cancer occurring in children. ALL 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. Not only can this excess of lymphocytes cause swelling in the lymph tissues, but they can also crowd out other important blood cells made by the marrow, such as red blood cells and platelets, preventing these cells from doing their jobs properly.

Many treatment options are being studied for childhood 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 SCT with high doses of chemotherapy and/or radiation therapy. Higher doses of chemotherapy (called dose-intensive or 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.

A stem cell transplantation is a procedure that allows the stem cells that are destroyed by high-dose chemotherapy to be replaced with healthy stem 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 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.

Researchers at the International Bone Marrow Transplant Registry sought to determine whether the use of high-dose chemotherapy alone before an allogeneic SCT is as effective as the use of both high-dose chemotherapy and radiation therapy. They compared the outcomes of 627 children with ALL who underwent an allogeneic SCT after being treated with either A) a chemotherapy drug called cyclophosphamide plus total-body radiation therapy or B) a combination chemotherapy with cyclophosphamide and busulfan, without radiation therapy. These children had various stages of cancer, but most were in their second remission. The results showed that 3-year survival rates were 55% for those who received radiation therapy, compared with 40% who received the combination chemotherapy. The risk of relapse (recurrence, or return of the cancer) was similar in the 2 groups; however, more children who were treated with the busulfan died from complications related to the SCT. Long-term complications were not reported.

The researchers concluded that children with ALL who received high-dose chemotherapy plus total-body radiation therapy had an increased survival time over those who received the combination chemotherapy without radiation therapy. Future studies are needed to develop more effective chemotherapies to be given before SCT for children with ALL. Parents of children who have ALL may wish to talk with their doctor about the risks and benefits of the high-dose chemotherapy plus radiation therapy with SCT regimen, or of participating in a clinical trial in which other new treatments are being studied. Other sources of information on ongoing clinical trials include a comprehensive, easy-to-use service provided by the National Cancer Institute (cancer.gov) and the Clinical Trials section and service offered by CancerConsultants.com (www.411cancer.com). (Journal of Clinical Oncology, Vol 18, No 2, pp 340-347, 2000)

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