Growth in children after bone marrow transplantation

Growth velocity pattern and growth hormone (GH) secretion were evaluated in 18 prepubertal patients (13 males, 5 females), receiving an allogeneic (7 patients) or autologous (11 patients) bone marrow transplantation (BMT). Children were affected by oncological or hematological malignancies and the age range was between 2 and 11 years. Nine patients received a conditioning regimen consisting of chemotherapy and fractionated total body irradiation (TBI) (12 Gy in 6 fractions over 3 days), whereas 9 children also received previous prophylactic cranial irradiation during first-line chemotherapy. GH secretion in response to pharmacological stimuli (insulin, arginine and/or L Dopa) was evaluated when growth failure occurred. The 9 prepubertal patients who had received previous prophylactic cranial irradiation during first-line chemotherapy, showed a significant decrease in growth rate already 1 year after BMT and this reduced growth rate presented a progressive further decrease in the 2nd and 3rd year after BMT. On the contrary, in the 9 prepubertal children treated with TBI and chemotherapy alone, growth rate presented an impressive decrease only during the 3rd year. In the two groups of patients, pretransplantation growth rates were comparable, while, due to the earlier growth failure in children receiving TBI and previous prophylactic cranial irradiation, mean standard deviation score (SDS) significantly differed at 1 and 2 years following BMT. Such a difference disappeared at 3 years after BMT, because of the late decrease in growth rate in patients given TBI and chemotherapy alone. GH deficiency was demonstrated in 8 out of the 9 patients receiving TBI and previous prophylactic cranial irradiation 0.5-2 years after BMT and in 7 of the 9 children given TBI and chemotherapy alone 3-4.5 years following BMT. Seven children were treated with human recombinant GH (0.6 U/kg/week s.c.). A successful response to hormonal replacement therapy was observed over the first year of treatment in 5 children. Our data demonstrate that fractionated TBI has a deleterious effect on growth velocity and GH secretion. Prophylactic cranial irradiation during first-line chemotherapy results in an earlier occurrence of growth impairment. Children showing GH deficiency after BMT can respond to GH treatment with an increase in height velocity similar to that observed in patients with idiopathic GH deficiency.