Twenty Year Follow up of Survivors of Childhood Acute Lymphoid Leukemia: A Report from the Childhood Cancer Survivor Study (CCSS).

Background: Survival for ALL has improved substantially: current five-year survival rates are approximately 80% yet survivors continue to experience late medical and social effects.

Objective: To report rates of mortality and second neoplasm (SN) and selected social outcomes from a large cohort of childhood ALL survivors.

Methods: Five year survivors of ALL (n=4151) diagnosed < age 21, from 1970–1986 were compared to population rates or a sibling control group (n=3899) for mortality, SN, education, marriage, health insurance and employment.

Results: Survivors and siblings were 53% and 48% male; median ages were 26 and 31yrs respectively. Survivors had a mean age of 6 yrs (range 0–20) at diagnosis and had a mean follow-up of 22 yrs (range 16–34). Sixty two percent received chemotherapy (CT) + radiation therapy (RT), 5.2% underwent marrow transplant with CT +/− RT, while 27% received CT only. Among 5yr survivors, 417 deaths occurred; cumulative mortality was 12% at 25 yrs. Recurrent ALL accounted for 67% of deaths, while 13% (n=55) died of SN. Standardized mortality rate (95% confidence intervals) for malignant SNs was 14.0 (10.7–17.9). Survival at 25 yrs was 94% for patients who never reported relapse and 59% for patients who reported a relapse (p<0. 001). For patients treated between 1970–1974, 1975–1979 and 1980–1986, 15-yr survival from cohort entry improved from 85% to 90% to 92%, (p< 0. 001). Improvement was seen both in non-relapsed (94%, 95% and 97% respectively, p= 0.015) and relapsed survivors (41%, 62% and 70% respectively, p< 0. 001) for the same era. 199 SNs (excluding non-melanoma skin cancer) occurred among 185 survivors; 52% occurred in the CNS. 89% of all SNs occurred in RT patients. Cumulative incidence at 25 yrs was 9% and the standardized incidence rate was 5.6 (95% CI 4.8–6.4). Age standardizing to siblings aged 25–49, rates for high school completion among survivors and siblings were 93% and 97%, respectively, with college graduation rates of 41% and 52% (p< 0.001, for education overall). 35% of survivors never married, compared to 21% siblings (p<0.001), 97% of survivors reported ever working vs. 100% of siblings (p<0.001), rate of health insurance was lower for survivors (86%) vs. siblings (90%), p<0.001. Comparison of rates for selected social outcomes among survivors who did or did not experience a recurrence are reported in Table-1.

Conclusion: In the largest long-term follow-up study of its kind, the CCSS cohort demonstrated a significant improvement in survival over time among 5-yr survivors of ALL with and without history of relapse. Death after cohort entry was due most commonly to ALL, although SNs contributed substantially. HS graduation rates for survivors were comparable to the sibling cohort, but the rates were significantly lower for college graduation and for marraige. Although lower than siblings, majority of survivors reported being employed and having health insurance. There was no significant difference between the survivors of relapsed and non-relapsed ALL, with respect to their socioeconomic outcomes.