Children who receive chemotherapy and survive acute lymphocytic leukemia (ALL) have a 200-fold increase in genetic damage that may increase their risk for new cancers or other diseases in adulthood, according to an article in the July 1st issue of Cancer Research.

"The treatments that are used to help children defeat this disease are keeping a very large percentage of them alive," said Barry A Finette, MD, PhD. "Pediatricians are continually monitoring these children as they live beyond 5, 10, and more recently, 15 years after their ALL is in remission. We now need to be proactive about studying any long-term genetic ramifications that these children may face due to the treatment therapy they endured during their bout with cancer."

Finette noted that children who are cured of ALL after chemotherapy have 5 to 20 times' greater risk of developing new cancers, as well as other complications. Subsequent illnesses may be associated with increased changes in the patient's genes resulting from their treatments during ALL therapy.

The American research team examined the frequencies of alterations found within a marker gene (HPRT reporter gene) in the T-cells of ALL patients at four intervals between diagnosis and completion of treatment. The HPRT reporter gene is a non-essential gene involved with DNA metabolism that is located on the X chromosome. It is often analyzed in the study of mutational events in humans.

At the time of diagnosis, the blood of patients contained an average of 1.4 cells with HPRT mutations out of every million T-cells. By the time the patients completed the second phase of treatment, an average of 52 T-cells per million cells contained HPRT mutations. By the final stage of treatment, an average of 93 of every million T-cells had mutations in HPRT. After treatment was completed, an average of 271 of every million T-cells contained HPRT mutations, more than a 200-fold increase.

The study included 45 children with acute lymphocytic leukemia who averaged 5.5 years of age at time of diagnosis. The number of HPRT mutations found in the patients at the time of diagnosis did not differ from healthy children of the same age, the researchers reported.

"These therapies have the potential to cause genetic damage to many different cell populations in their rapidly growing bodies," Finette said. "Because they have larger numbers of replicating cell populations during their growth and development stages than adults have, they are more susceptible than adults to genetically toxic effects of the chemotherapies."

Since the 1960s, the five-year survival rate for children with the disease has increased to almost 80 percent. Patient remission and long-term survival is credited to the development of national standardized chemotherapeutic treatment protocols. More than 70 percent of patients less than 20 years of age and 85 percent of patients less than 15 years old participate in standardized chemotherapy treatment regimes.

"Because of the effectiveness of the treatment employed today, we are able to give many more children a chance for a long life without cancer," Finette said. "Our studies are aimed at enabling us to better understand further challenges that we may face in keeping these patients healthy as they get 10, 15 or more years out from overcoming ALL."