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Less Toxic Cancer Treatment Safe for Children, Say Columbia Researchers

Children undergoing a stem cell transplant to treat leukemia, blood disorders or other types of cancer can safely undergo a less toxic treatment regimen than one that is traditionally used, report researchers from Children's Hospital of New York-Presbyterian/Columbia University Medical Center in the journal Bone Marrow Transplantation.

Typically, such patients have their immune system destroyed with high doses of chemotherapy or radiation before the transplant procedure. This allows the transplanted stem cells to "take" and start producing a new, healthy immune system.

However, the destruction of the immune system leaves youngsters vulnerable to potentially life-threatening infections and dangerously low white- and red-blood cell counts before the new immune system begins functioning -- a process that can take weeks or months. And in the long run, the high-dose chemotherapy or radiation may damage fertility, stunt growth and increase the risk of a second, unrelated cancer later in life.

"Physicians would like to find a way to avoid the toxicity of this treatment, known as myeloablation," said Mitchell S. Cairo, professor of pediatrics, medicine and pathology at Columbia University College of Physicians and Surgeons and chief of the Division of Pediatric Hematology and Blood and Marrow Transplantation at the Children's Hospital of New York-Presbyterian/Columbia. "Some of these children may die of infections in the first few weeks after transplant, and if they do survive and the transplant is a success, they can have problems further down the road."

"Leaving the immune system somewhat intact may help prevent infections, particularly in those children who have a relatively low number of stem cells available for transplant," said Cairo, who is also the director of the Leukemia, Lymphoma and Myeloma Program at the Herbert Irving Comprehensive Cancer Center. "For example, in children receiving a stem cell transplant from cells collected from umbilical cord blood, it can take longer for the new immune system to begin functioning."

In the new study, Cairo and colleagues tried a variety of less toxic treatment regimens on a group of 21 children, teens and young adults, all younger than 21. The patients had cancers or blood disorders of the immune system.

"We used what we call 'reduced intensity' regimens that used chemotherapy drugs, and in one case radiation, to weaken the patient's own immune system," Cairo said. "This has been tried in adults with some success, but there is little data on this in children."

The children were then given transplants of stem cells collected from the umbilical cord blood of unrelated donors or stem cells from the bone marrow or blood of relatives. The children were also treated with medication to prevent graft-versus-host disease (GVHD), a potentially dangerous condition that occurs when the transplanted cells attack the patient's tissue. GVHD can cause a blistering rash, enlarged liver and intestinal problems such as diarrhea.

The researchers found that 85 percent or more of the children in the study achieved at least a 50 percent donor chimerism, meaning that their immune system contained a mixture of the patient's and the donor's cells. This is a sign that the graft is "taking." In about 24 percent of cases, the graft failed to take.

"These numbers are similar to those seen in adults undergoing a reduced intensity regimen," Cairo said. "However, the results should be interpreted with caution."

The study included children with a wide variety of ailments, from leukemia and Hodgkin's disease to an inherited blood disorder called beta-thalassemia. The study participants had a variety of regimens using different combinations of drugs.

"Larger studies are needed to look at how these results will vary depending on a child's diagnosis and drug treatment," Cairo said. "And a long-term follow-up is needed to determine their risk of GVHD and side effects of treatment, such as growth stunting, secondary cancers and infertility."

The study was funded in part by grants from the Pediatric Cancer Research Foundation, Swim Across America Foundation, Triple "C" Foundation and the National Cancer Institute.

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Published: Mar 25, 2004
Last modified: Jan 10, 2005

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