Results from the longest follow-up study ever done of childhood acute lymphoblastic leukemia (ALL) survivors show the importance of long-term monitoring of former patients to identify complications they are at risk for developing later in life and to modify current treatments to reduce those risks, according to investigators at St. Jude Children's Research Hospital. ALL is the most common cancer in children and adolescents--with about 3,000 new cases diagnosed yearly in the United States.
The St. Jude study showed that adults who had received treatment for ALL during childhood are at increased risk for developing a secondary neoplasm during the next 30 years. Secondary neoplasms are new tumors that develop after successful treatment of an initial cancer.
The finding is important because the cure rate of children treated for ALL has increased dramatically since the 1960s, approaching 90 percent today at St. Jude. Therefore, it is important to monitor survivors during their entire lives to identify the long-term complications they might experience even decades after the end of their treatment, the researchers said.
Previous studies found a relatively low incidence of secondary neoplasm during the first 10 to 15 years after treatment for ALL. Those studies suggested that the incidence of these new tumors might not be significant 20 years after therapy. "On the contrary, our longer study shows that after 20 years the incidence continues to increase," said Nobuko Hijiya, M.D., assistant member in the St. Jude Oncology department. Hijiya is the first and corresponding author of the "JAMA" article.
The St. Jude study found that most of these late-onset secondary neoplasms are low-grade, or slow-growing, tumors that are curable--specifically, meningiomas (tumors arising from the membranes covering the brain) and basal cell carcinomas (skin cancer). However, a substantial number were more aggressive tumors such as soft tissue sarcomas (e.g., cancers of the muscle or blood vessels), and carcinomas (cancers that start in the linings of organs).
"Even though they are low-grade tumors and are considered curable, they may cause significant health issues," Hijiya said. For instance, meningiomas cause neurological problems and basal cell carcinomas may recur multiple times. "So it's very important that clinicians are aware of this new finding."
"Our study of long-term survivors of ALL shows that medical care should not end when the survivor goes home," said Ching-Hon Pui, M.D., chair of the St. Jude Oncology department and American Cancer Society FM Kirby Clinical Research Professor. "We are working not only to increase survival rates for ALL, but also to improve the quality of life of the survivors. For example, by omitting the use of radiation in the treatment of our current patients, we expect a lower rate of second cancer in the future." Pui is a co-author of the paper.
The St. Jude study, based on a review of the medical records of 2,169 children treated for ALL at the hospital from 1962 to 1998, showed that 123 developed a secondary neoplasm as their first event--major medical problem--following successful treatment of their cancer. Among this group of former patients, about one in 25 survivors (4.17 percent) are estimated to develop secondary neoplasms by 15 years, one in 20 survivors (5.37 percent) by 20 years and one in 10 survivors (10.85 percent) by 30 years.
The secondary neoplasms that developed after remission during this time included myeloid (bone marrow cell) cancers, lymphomas (white blood cell cancers in lymph nodes), basal cell carcinomas, other types of carcinomas, sarcomas (cancer of supportive tissue, such as bone and cartilage), meningiomas and other tumors.
"The results of our study underscore the need for ongoing, comprehensive follow-up of ALL survivors far into adulthood," said Melissa Hudson, M.D., director of the Cancer Survivorship Division and co-leader of the Cancer Prevention and Control Program at St. Jude. "The study provides an unprecedented look at the long-term effects of ALL and its treatment. This knowledge is critical to guide the development of safer and effective therapy for future children with ALL and health screening recommendations for long-term survivors." Hudson is a co-author of the paper.
Other authors of this paper include Shelly Lensing, Margie Zacher, Mihaela Onciu, Fred Behm, Bassem Razzouk, Raul Ribeiro, Jeffrey Rubnitz, John Sandlund, Gaston Rivera, William Evans and Mary Relling.
This work was supported in part by the National Institutes of Health and ALSAC.
A report on this work appears in the March 21 issue of the "Journal of the American Medical Association" ("JAMA").
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