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Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for late effects of cancer therapy. Five-year ALL survivors (< 21 years at diagnosis; n = 5760 eligible, 4151 participants), diagnosed from 1970 to 1986 were compared with the general population and a sibling cohort (n = 3899). Cumulative mortality of 5760 5-year survivors was 13% at 25 years from diagnosis. Recurrent ALL (n = 483) and second neoplasms (SNs; n = 89) were the major causes of death. Among 185 survivors, 199 SNs occurred, 53% in the CNS. Survivors reported more multiple chronic medical conditions (CMCs; odds ratio [OR], 2.8; 95% CI, 2.4-3.2) and severe or life-threatening CMCs (OR, 3.6; 95% CI, 3.0-4.5) than siblings. Cumulative incidence of severe CMCs, including death, 25 years from diagnosis was 21.3% (95% CI, 18.2-24.4; 23.3% [95% CI, 19.4-27.2] and 13.4% [95% CI, 8.4-18.4] for irradiated and nonirradiated survivors, respectively). Survivors reported more adverse general and mental health, functional impairment, and activity limitations compared with siblings (P < .001). Rates of marriage, college graduation, employment, and health insurance were all lower compared with sibling controls (P < .001). Long-term survivors of childhood ALL exhibit excess mortality and morbidity. Survivors who received radiation therapy as part of their treatment or had a leukemia relapse are at greatest risk for adverse outcomes.

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 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. Rates (percentage), Age Standardized to Siblings Sibling Non-relapse Relapse p-value Relapse vs. Non * p for rows 1 & 2 HS grad 97 93 97 College grad 52 41 41 .78* Never married 21 34 46 .10 Ever employed 100 98 97 .07 Health Insurance 90 86 88 .86

Survival rates for childhood AML continue to improve. Limited data exist on the comprehensive assessment of late medical and social effects experienced by these aggressively treated individuals. This analysis includes 272 5-yr survivors of AML participating in the CCSS diagnosed ≤ age 21, between 1970–1986. AML survivors who received a blood or marrow transplant are excluded from the current analysis. Comparisons among treatment groups and to a sibling control group are age and gender adjusted. Survivors (55% female) were on average 7 yrs old at dx and 28 yrs at follow-up, 56% received chemotherapy only, 34% chemotherapy/RT. Average follow-up was 22.6 yrs (16.1–33.5). Among these 5-yr survivors, overall survival was 97% (95% CI, 94–98%) at 10 yrs and 94% (95% CI, 92–97%) at 20 yrs. Six individuals reported 8 recurrences a mean of 11.1 yrs (5.6–16.6) from diagnosis, 2 died from relapse, 1 from congestive heart failure (CHF), and 1 from a myocardial infarction (MI). All cause standardized mortality ratio was 4.7 (95% CI 2.8–7.5). Cumulative incidence of recurrent AML at 10 and 20 years was 1.8% (95% CI 0.2–3.4%) and 3.7% (95% CI 1.4–5.9%), respectively. Eight survivors reported 10 subsequent malignant neoplasms (SMN) (5 breast cancers, 3 CNS tumors, 1 ovarian tumor, 1 salivary gland tumor) a mean of 18.7 yrs (9.2–26.4) from diagnosis, 3 with a history of RT exposure. SMN cumulative incidence at 20 yrs was 1.6% (95% CI 0.02–3.3%) with a standardized incidence ratio of 3.2 (95% CI 1.4–6.0). Six cardiac events (5 CHF and 1 MI) occurred a mean of 16.4 yrs (12.8–18.4) from diagnosis, 20-yr cumulative incidence 2.4% (95% CI 0.5–4.4%). Among those aged 25 yrs or more, marriage rates were similar among AML survivors and the general U.S. population (59%), but lower compared to siblings (69%) (p