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Childhood Leukemia Survivors at Long-Term Risk of Second Cancer

Odds for a variety of tumors kept rising in 30-year study

TUESDAY, March 20, 2007 (HealthDay News) -- The longest such study of its kind has found that people who survive acute lymphoblastic leukemia (ALL) in childhood are at higher risk of developing a secondary cancer well into middle-age.

The risk for these tumors only increases over time, the 30-year study found.

"The most important message from this paper is that all patients who are treated for ALL in childhood need lifelong follow-up to ensure that they do not develop any complications," said lead researcher Dr. Nobuko Hijiya, an oncologist at St. Jude Children's Research Hospital, in Memphis, Tenn.

Her team published its findings in the March 21 issue of the Journal of the American Medical Association.

ALL remains the most common cancer affecting American children and adolescents, with doctors diagnosing about 4,000 new cases each year. Fortunately, recent advances mean the disease is now curable in more than 80 percent of cases.

"Just 30 years ago, children with ALL received more or less a death sentence when they were diagnosed," said Deborah Banker, vice president of research communications with the Leukemia and Lymphoma Society. "That's no longer true. I have in my job literally met 20 or more individuals who are long-term survivors with no negative sequelae. They have had their own children and lead happy lives."

However, "now that our research has afforded us high survival rates, we've become aware of the other consequences of those treatments," Banker said.

Smaller, shorter-duration studies had already hinted that therapies aimed at curing ALL might also raise long-term risk for secondary cancers.

In this study, Hijiya's team calculated the 30-year cumulative number of secondary cancers in almost 2,200 children treated at St. Jude for ALL between 1962 and 1998.

They found that rates of secondary cancer did not plateau but kept rising over time.

For example, of the 1,290 kids who achieved a complete remission of their ALL, about 4.2 percent developed a secondary cancer within 15 years, nearly 5.4 percent did so by the 20-year mark, and, by 30 years, almost 11 percent had been diagnosed with a new cancer.

Most of these malignancies were slow-growing, "low-grade" cancers, such as meningiomas (tumors near the brain and spinal cord) and basal cell carcinomas of the skin. These cancers are highly curable.

But a minority were more aggressive, higher-grade carcinomas. After excluding meningiomas and basal cell carcinomas, the 30-year risk of these more serious types of cancer rose 13.5-fold in childhood ALL survivors compared to the general population.

Hijiya said that while a person's genetics can boost their lifetime odds for cancer, the powerful ALL treatments these people received as children are probably the main cause of most of these secondary malignancies.

"Especially radiation and drugs called epipodophyllotoxins," Hijiya said. However, she added that the use of both of these interventions has been greatly curtailed over the past decade. That means that the long-term risk for children being treated for ALL today is likely to be much lower.

"At St. Jude and elsewhere in the U.S. or other countries, we have eliminated radiation and epipodophyllotoxins from initial therapy," Hijiya noted. Instead, doctors now favor less toxic treatments.

Radiation, especially, "has been significantly curtailed, because [doctors] recognized that there were intellectual deficits as well as organ trouble associated with that," Banker said. "They've been really backing off the dosing."

Instead, the leukemia society and other groups have been focusing in recent years on developing highly sophisticated, targeted new drugs that destroy the tumor cell without impacting on healthy cells. According to Banker, the advent of genetic testing is also helping physicians spot those patients who might benefit from a particular medication or be at especially high risk for side effects.

"The long-term goal is to have new treatments that won't cause these long-term effects," Banker said. "The new targeted drugs are hopefully not going to be broadly toxic."

Still, ALL survivors, including those treated for the disease in young adulthood, will probably have to be closely tracked all their lives, the experts said.

"The [secondary cancers] are typically slow-growing tumors," Hijiya noted. "Some of these patients who have these cancers years later may have already had them for years. So, that's the reason the patient should be monitored very closely. By finding them earlier, they might be even more curable."

More information

Find out more about ALL at the American Cancer Society.

SOURCES: Nobuko Hijiya, M.D., assistant professor, pediatrics, University of Tennessee, and assistant member, hematology-oncology, St. Jude Children's Research Hospital, Memphis; Deborah Banker, Ph.D., vice president, research communications, Leukemia and Lymphoma Society, White Plains, N.Y.; March 21, 2007, Journal of the American Medical Association
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