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-dose chemotherapy and/or radiation therapy with an allogeneic stem cell transplant (SCT). When a SCT is needed, it is usually given following chemotherapy with or without total-body radiation, to kill the leukemia. 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 advocated 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 blood, characterized by the presence of too many immature lymphocytes, or white blood cells. Not only can the excess 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 (carry oxygen to the tissues) and platelets (help with blood clotting), 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 chemotherapy and/or radiation therapy.
Chemotherapy drugs and radiation therapy are used to treat cancer. Higher doses of chemotherapy kill more cancer cells than lower doses of chemotherapy in certain types of cancer. When higher doses of chemotherapy kill more cancer than lower doses, doctors say there is a “dose response effect”. The delivery of higher doses of chemotherapy is referred to as “dose intensive or high-dose chemotherapy”. Unfortunately, the higher doses of chemotherapy used to destroy cancer cells also cause damage or side effects to normal cells. One of the body's normal cells that is most sensitive to destruction by high-dose chemotherapy and radiation is the bone marrow containing the blood producing stem cells.
Stem cells are early blood-forming cells that grow and mature in the bone marrow into the 3 main blood cell types: white blood cells, red blood cells, and platelets. Stem cells live predominantly in the bone marrow but can circulate in the blood. When high-dose chemotherapy is used to treat cancer, one of the major side effects is destruction of the stem cells living in the bone marrow. In order to administer high-dose chemotherapy with the goal of curing a cancer, stem cells must be collected for infusion before treatment with high-dose chemotherapy. The stem cells can then be infused to “rescue” bone marrow and hasten blood cell production.
A stem cell transplant involves the removal of the cells responsible for producing all blood cells. These “stem cells” live in the bone marrow and circulate in the blood in small quantities that have been damaged by chemotherapy or radiation therapy. High-dose chemotherapy or radiation destroys the blood producing stem cells along with the leukemia so collection of stem cells for reinfusion without high-dose chemotherapy or radiation is necessary. 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 directly from the patient.
Researchers at the International Bone Marrow Transplant Registry sought to determine whether the use of chemotherapy alone before an allogeneic SCT is as effective as the use of both 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 of chemotherapy consisting of 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 chemotherapy combined with 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 chemotherapy died from complications related to the SCT. Long-term complications were not reported.
The researchers concluded that children with ALL who received chemotherapy plus total-body radiation therapy had an increased survival time over those who received the combination chemotherapy without radiation therapy. (Journal of Clinical Oncology, Vol 18, No 2, pp 340-347, 2000)
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