Extended Follow-up of Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia

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Abstract
Children who survive acute lymphoblastic leukemia are at risk for leukemia-related or treatment-related complications, which can adversely affect survival and socioeconomic status. We determined the long-term survival and the rates of health insurance coverage, marriage, and employment among patients who had attained at least 10 years of event-free survival. A total of 856 eligible patients were treated between 1962 and 1992 in 13 consecutive clinical trials. Survival rates, the cumulative risk of a second neoplasm, and selected indicators of socioeconomic status were analyzed for the entire group and for patients who did or did not receive cranial or craniospinal radiation therapy during initial treatment. Fifty-six patients had major adverse events, including 8 deaths during remission, 4 relapses, and 44 second neoplasms (41 of them radiation-related); most of the second neoplasms were benign or of a low grade of malignant potential. The risk of a second neoplasm was significantly higher in the 597 patients who received radiation therapy (irradiated group) than in the 259 patients who did not receive radiation therapy (nonirradiated group) (P=0.04; estimated cumulative risk [±SE] at 20 years, 20.9±3.9 percent vs. 0.95±0.9 percent). The death rate for the irradiated group slightly exceeded the expected rate in the general U.S. population (standardized mortality ratio, 1.90; 95 percent confidence interval, 1.12 to 3.00), whereas that for the nonirradiated group did not differ from the population norm (standardized mortality ratio, 1.75; 95 percent confidence interval, 0.34 to 5.00). The rates of health insurance coverage, marriage, and employment in the nonirradiated group were similar to the age- and sex-adjusted national averages. Despite having health insurance rates similar to those in the general population, men and women in the irradiated group had higher-than-average unemployment rates (15.1 percent vs. 5.4 percent and 35.4 percent vs. 5.2 percent, respectively), and women in the irradiated group were less likely to be married (35.2 percent vs. 48.8 percent). Children with acute lymphoblastic leukemia who did not receive radiation therapy and who have attained 10 or more years of event-free survival can expect a normal long-term survival. Irradiation is associated with the development of second neoplasms, a slight excess in mortality, and an increased unemployment rate.