Cerebral irradiation causes blunted pubertal growth in girls treated for acute leukemia

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Abstract
The improved treatment of childhood leukemia is a major achievement. The late effects of the treatment need further investigation. Growth inhibition has been demonstrated in earlier studies. Growth and the timing of puberty were studied in 179 girls who had been treated for acute lymphoblastic leukemia (ALL) in Denmark, Finland, Norway, and Sweden. The patients were divided into two groups according to mode of CNS prophylaxis: with or without cerebral irradiation. Longitudinal analysis of 103 patients showed no difference in prepubertal growth in irradiated and nonirradiated girls. Growth during puberty was normal in girls without irradiation and below normal in irradiated girls. There was no difference in growth between girls after 24 Gy or 20 Gy of cerebral irradiation. Irradiated girls had a final height which was one SD less than expected before puberty and menarche occurred one year earlier than in the nonirradiated girls. Prophylactic cerebral irradiation is the most important factor for subnormal growth after treatment for ALL. There is no short-term influence on growth but the effects of irradiation become apparent several years after therapy when girls enter puberty somewhat early and have a subnormal pubertal growth. Growth and growth hormone (GH) levels should be evaluated several years after CNS irradiation, and treatment with GH and/or luteinizing hormone releasing hormone (LHRH) analogues may be considered.