Background Previous studies of health‐related quality of life (QoL) in childhood cancer survivors have hardly focused on factors associated with poor QoL. The aims of our study were: (1) to assess QoL in long‐term survivors (LTSs) of childhood acute lymphoblastic leukemia (ALL) and lymphomas compared to age‐matched controls from the general population (NORMs). (2) To investigate factors associated with poor QoL in LTSs. Procedure This population‐based cross‐sectional study enrolled 285 LTSs of ALL and lymphomas diagnosed between 1970 and 2002 at age <18 years. The LTSs completed an extensive mailed questionnaire including the Short Form 36 (SF‐36) as QoL‐measure. NORMs consisted of five age‐matched controls for each LTS (N = 1,425). Poor QoL was defined as SF‐36 physical or mental component summary score <40. Results The median age of LTSs' at survey was 30 years (range: 18–54), median follow‐up time 21 years (range: 7–39). Compared to NORMs, LTSs scored significantly lower on 7 of 8 SF‐36 subscales. Among LTSs 32% reported poor QoL versus 19% among NORMs (P < 0.001). Among LTSs, psychosocial, lifestyle‐ and health‐related variables, but not type of malignancy, treatment factors or socio‐demographic factors were clinically significantly associated with poor QoL in bivariate regression analyses. In multivariate analysis, levels of fatigue, anxiety and depression, as well as obesity and insomnia remained significantly associated with poor QoL. Conclusion Significantly more LTSs than age‐matched NORMs experienced poor QoL. Clinically significant associations with fatigue, anxiety, depression, obesity and insomnia were observed, which may be amenable for interventions, and thereby improvement of QoL in LTSs. Pediatr Blood Cancer 2013; 60: 849–855. © 2013 Wiley Periodicals, Inc.

Structural MRI of long-term survivors of childhood ALL demonstrated smaller volumes of multiple brain structures compared with healthy controls. Because of possible selection biases, these results must be interpreted with caution. Future studies are required to clarify the significance of these findings and the neurobiologic mechanisms involved.

Very long-term survivors of childhood ALL treated exclusively with chemotherapy showed no impairment in general intellectual ability, but significantly poorer performance in several neurocognitive domains than comparison peers. However, no associations emerged between neurocognitive impairment and treatment burden.