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Background: Health-related quality of life (HRQoL) was assessed in a cohort of long-term childhood acute lymphoblastic leukemia (ALL) survivors., Procedure: Rand-36-Item health Survey (RAND-36) was used to assess subjective HRQoL in 74 survivors of ALL an average of 20 years after the diagnosis. Cranial irradiation had been administered to 46 of the survivors, while 28 survivors had solely been treated with chemotherapy. The control group consisted of 146 healthy young adults selected from local population registry. Survivors were examined by a physician and late effects were graded using the Common Terminology Criteria for Adverse Events (CTCAEv3)., Results: ALL survivors achieved significantly higher scores than the controls on three of the eight HRQoL subscales; role limitations due to emotional problems (P = 0.030), mental health (P = 0.030) and vitality (P = 0.004). In comparison to controls, survivors with a follow-up of more than 20 years had significantly higher scores on vitality (P = 0.006) and mental health (P = 0.011). Survivors with severe (grade 3 and 4) late effects scored significantly better than controls on vitality (P = 0.043) and mental health (P = 0.040). Patients who had been treated for an ALL relapse and had received the most intensive chemo- and radiotherapy had significantly higher scores on mental health (P = 0.004) and vitality (P = 0.004) than the controls., Conclusions: Long-term survivors of childhood ALL reported equal or better HRQoL in RAND-36. Higher HRQoL scores were associated with more severe late effects and intensive therapy. Our findings support the idea of response bias., ((c) 2010 Wiley-Liss, Inc.)