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Researchers Find Less Toxic Treatment Safe for Children With Cancer

More Study Needed, but Treatment May Reduce the Chances of Later Infertility, Stunted Growth and Secondary Cancers

New York, NY (Mar 19, 2004)

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 NewYork-Presbyterian Hospital/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 youngstersvulnerable to potentially life-threatening infections and dangerously low white-and red-blood cell counts before the new immune system begins functioning a processthat can take weeks or months. And in the long run, the high-dosechemotherapy or radiation may damage fertility, stunt growth and increase the risk of asecond, unrelated cancer later in life.

Physicians would like to find a way to avoid the toxicity of thistreatment,known as myeloablation, said Dr. Mitchell S. Cairo, professor ofpediatrics,medicine and pathology at Columbia University College of Physicians andSurgeonsand chief of the Division of Pediatric Hematology and Blood and MarrowTransplantationat the Children's Hospital of New York-Presbyterian/Columbia. Someof thesechildren may die of infections in the first few weeks after transplant,and ifthey do survive and the transplant is a success, they can have problemsfurtherdown the road.

Leaving the immune system somewhat intact may help preventinfections,particularly in those children who have a relatively low number of stemcellsavailable for transplant, said Dr. 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 astemcell transplant from cells collected from umbilical cord blood, it cantake longerfor the new immune system to begin functioning.

In the new study, Dr. Cairo and colleagues tried a variety of less toxictreatment regimens on a group of 21 children, teens and young adults, all underthe age of 21. The patients had cancers or blood disorders of the immunesystem.

We used what we call reduced intensity regimens thatusedchemotherapy drugs, and in one case radiation, to weaken the patient's ownimmunesystem, said Dr. Cairo. This has been tried in adults withsome success,but there is little data on this in children.

The children were then given transplants of stem cells collected fromthe umbilical cord blood of unrelated donors or stem cells from the bone marrow orblood of relatives. The children were also treated with medication to preventgraft-versus-host disease (GVHD), a potentially dangerous condition that occurs when thetransplanted 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 thestudy achieved at least a 50 percent donor chimerism, meaning their immunesystem contained a mixture of the patient's and the donor's cells. This is asign that the graft is taking. In about 24 percent of cases, thegraft failed to take.

These numbers are similar to those seen in adults undergoing areducedintensity regimen, said Dr. Cairo. However, the results shouldbeinterpreted with caution.

The study included children with a wide variety of ailments, fromleukemia and Hodgkin's disease to an inherited blood disorder calledbeta-thalassemia. The study participants had a variety of regimens using differentcombinations of drugs.

Larger studies are needed to look at how these results will varydependingon a child's diagnosis and drug treatment, said Dr. Cairo. Andalong-term follow-up is needed to determine their risk of GVHD and sideeffectsof treatment, such as growth stunting, secondary cancers andinfertility.

The study was funded in part by grants from the Pediatric CancerResearch Foundation, Swim Across America Foundation, Triple C Foundation and theNational Cancer Institute.2453084pubjvb9001&&13:49-11- 5-2004kebloom11:51- 8-18-200403_19_04

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