The findings, which appear in the August 14 issue of the New England Journal of Medicine, result from a long-term follow-up study of a large number of childhood ALL survivors.
The study found that survivors who did not receive brain radiation as part of their treatment have survival, employment and marital rates comparable to those of the general population. However, people who had received brain radiation as part of their treatment for childhood ALL had a slight increase in death rate due to the development of second cancer, and higher unemployment rates than the general population. In addition, females had lower marital rates, according to Ching-Hon Pui, M.D., director of the Leukemia/Lymphoma division at St. Jude. Pui, the American Cancer Society – F. M. Kirby Clinical Research Professor at St. Jude, is lead author of the study.
"The good news is that ALL patients who did not receive radiation therapy and achieved 10 years or more of survival after treatment without a significant problem can look forward to a normal extended survival," Pui said. "Patients who had received radiation need long-term monitoring for early diagnosis and treatment of second tumors. Fortunately, most of the second tumors are low grade in malignancy and can be cured readily."
The study defines the term "cure" for ALL patients as 10 or more years of complete cancer remission. "We and others previously observed the occurrence of relapse in patients who have been free of leukemia for five years after treatment and thus could not define cure with certainty," said Melissa Hudson, M.D., director of the After Completion of Therapy program at St. Jude and a senior author of the report. This new standard could be used to measure the effectiveness of all current and future ALL treatments, according to Hudson.
The study included 856 patients treated between 1962 and 1992. Among these patients, 56 had major adverse events, including eight deaths in remission (not due to cancer recurrence), four relapses of the cancer and 44 second tumors (ones that occur after successful treatment for ALL). A total of 41 of the tumors were related to radiation therapy, and most were benign (non-cancerous) growths or cancers that were not aggressive. The risk for developing a second tumor was significantly higher in the 597 irradiated patients, compared with the 259 non-irradiated patients.
Second tumors continue to develop in patients who had received radiation to the head or head and spinal region even 20 years after their initial treatment of childhood ALL, according to Pui. This finding was new because survivors of other studies were followed for an average of only 4.6 to 7.6 years.
Most of these late-onset tumors in the St. Jude survey, however, were either benign or were relatively easily treatable, for example, thyroid cancer and basal cell carcinoma (a common form of skin cancer). Thus, the rate of death for the patients who developed second tumors was relatively low (12 deaths among 44 patients).This contrasts with the high mortality rate among patients with early-onset second tumors (ones that developed within 10 years of the diagnosis of ALL) in other studies.
"That reflects the more aggressive nature of the earlier-onset tumors," Hudson said.
The higher unemployment rates for patients who had received radiation treatment for ALL, and lower marital rates among irradiated females occurred despite the relatively low radiation doses used. The effect on women may reflect hormonal problems caused by radiation--which interferes with growth and body development--as well as cognitive problems that interfere with social and emotional development.
"This study reflects our unique capability and commitment to follow our survivors indefinitely through our After Completion of Therapy program and Cancer Registry here at St. Jude," said William Evans, Pharm.D., scientific director of St. Jude and a co-author of the study. "This study provided us important information to further refine therapy for our current and future patients."
With a cure rate of 80 percent in childhood ALL now achieved at St. Jude, attention is increasingly focused on the quality of life of survivors.
"One of the modifications that we made to our current treatment protocols is to use intensive chemotherapy instead of radiation to control leukemia in the central nervous system," Pui said. "This approach appears promising among more than 100 patients treated thus far. Elimination of radiation-related complications can help us to push the cure rate toward 90 percent and to improve the quality of life of our survivors."
Other authors of the report include Cheng Cheng, Ph.D.; Wing Leung, M.D., Ph.D.; Shesh N. Rai, Ph.D.; Gaston K. Rivera, M.D.; John T. Sandlund, M.D.; Raul C. Ribeiro, M.D., Mary V. Relling, Pharm.D., and Larry E. Kun, M.D.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tennessee, St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit http://www.stjude.org.
Journal
New England Journal of Medicine