Growth and growth hormone secretion after treatment for acute lymphoblastic leukemia in childhood: 18-gy versus 24-gy cranial irradiation

Purpose: Cranial irradiation (CI) given during the first phase of treatment of childhood acute lymphoblastic leukemia (ALL) has been associated with significant long-term morbidity. As a result, the dose of radiotherapy has been reduced from 24 to 18 Gy to reduce the severity of these late effects. To compare the effects of 24 and 18 Gy CI on growth, puberty, and growth hormone (GH) secretion, a cohort of survivors of childhood ALL were studied. Patients and Methods:of a total of 48 children, 28 (14 boys, 14 girls) had received 24 Gy and 20 (eight boys, 12 girls) had received 18 Gy. Similar chemotherapy regimens had been used in both groups, and age at diagnosis (5.2 ± 2.7 vs. 5.1 ± 2.8 years, 18 Gy vs. 24 Gy) and mean height at diagnosis [standard deviation score (SDS) 0.17 ± 0.17 vs. 0.05 ± 0.17, 18 Gy vs. 24 Gy] were comparable. Results:Growth rates in both groups did not differ for the first 5 years after diagnosis. After this time, however, a significant height decrease was observed in children who had received 24 Gy but not in children who had received 18 Gy (at 8 years the change in SDS from diagnosis was −0.32 ± 0.14 vs. −0.73 ± 0.16, 18 Gy vs. 24 Gy, p < 0.05). Menarche occurred earlier in the girls in the 24-Gy group (at 12.9 ± 0.3 vs. 11.7 ± 0.4 years of age, 18 Gy vs. 24 Gy, p < 0.02). Overnight GH concentrations (12-h sampling every 20 min) were reduced in both groups compared with healthy age-matched control children but were even lower in the 24-Gy group (12.7 ± 0.7 mU/L vs. 7.9 ± 0.6 vs. 6.1 ± 0.5 [6.4 ± 0.4 ng/ml vs. 3.9–0.3 vs. 3.1 ± 0.3]; control vs. 18 Gy and 24 Gy, p < 0.001; 18 Gy vs. 24 Gy, p < 0.025). Conclusions:Although both doses of CI impair GH secretion, 24 Gy has a greater impact on growth in the long term. This effect may be exaggerated by the induction of early puberty in some children.