GROWTH IN CHILDREN AFTER BONE-MARROW TRANSPLANTATION

Growth velocity pattern and growth hormone (GH) secretion were evaluat ed in 18 prepubertal patients (13 males, 5 females), receiving an allo geneic (7 patients) or autologous (11 patients) bone marrow transplant ation (BMT). Children were affected by oncological or hematological ma lignancies and the age range was between 2 and 11 years. Nine patients received a conditioning regimen consisting of chemotherapy and fracti onated total body irradiation (TBI) (12 Gy in 6 fractions over 3 days) , whereas 9 children also received previous prophylactic cranial irrad iation during first-line chemotherapy. GH secretion in response to pha rmacological stimuli (insulin, arginine and/or L Dopa) was evaluated w hen growth failure occurred. The 9 prepubertal patients who had receiv ed previous prophylactic cranial irradiation during first-line chemoth erapy, showed a significant decrease in growth rate already 1 year aft er BMT and this reduced growth rate presented a progressive further de crease in the 2nd and 3rd year after BMT. On the contrary, in the 9 pr epubertal children treated with TBI and chemotherapy alone, growth rat e presented an impressive decrease only during the 3rd year. In the tw o groups of patients, pretransplantation growth rates were comparable, while, due to the earlier growth failure in children receiving TBI an d previous prophylactic cranial irradiation, mean standard deviation s core (SDS) significantly differed at 1 and 2 years following BMT. Such a difference disappeared at 3 years after BMT, because of the late de crease 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 an d 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 the rapy was observed over the first year of treatment in 5 children. Our data demonstrate that fractionated TBI has a deleterious effect on gro wth velocity and GH secretion. Prophylactic cranial irradiation during first-line chemotherapy results in an earlier occurrence of growth im pairment. Children showing GH deficiency after BMT can respond to GH t reatment with an increase in height velocity similar to that observed in patients with idiopathic GH deficiency.