ROLE OF BUSULFAN AND TOTAL-BODY IRRADIATION ON GROWTH OF PREPUBERTAL CHILDREN RECEIVING BONE-MARROW TRANSPLANTATION AND RESULTS OF TREATMENT WITH RECOMBINANT HUMAN GROWTH-HORMONE

Seventy-six prepubertal children receiving autologous or allogeneic bo ne marrow transplantation (BMT) were enrolled in a prospective study o n the impact of different pretransplant preparative regimens on growth . Patients were divided into three groups: group I, consisting of 37 c hildren who had received total body irradiation (TBI) and cytotoxic dr ugs as preparative regimen; group II, including 17 children receiving prophylactic cranial irradiation before being conditioned with TBI and cytotoxic drugs; and group III, composed of 22 patients transplanted after a busulfan (BU)-containing myeloablative therapy. All patients h ave a minimum followup of 2 years, whereas 48 and 34 patients have bee n studied until 3 and 4 years after transplant, respectively. Height a nd growth rate were expressed as standard deviation score (SDS). Growt h hormone IGH) secretion in response to pharmacologic stimuli was eval uated after documented growth failure. Patients with GH deficiency wer e treated with recombinant human GH, and response to therapy was evalu ated. The main impairment of growth rate in patients belonging to grou p II was observed in the first year after TBI (growth rate SDS changin g from -0.12 +/- 0.23 to -1.23 +/- 0.25, P < .005), with only a slight loss in the following years, whereas in group I children growth failu re occurred in the third year after TBI (-1.36 +/- 0.28 SDS in compari son to a pre-BMT SDS of 0.10 +/- 0.15, P < .005). Therefore, growth ve locity between these two groups differed significantly in the first 2 years (P < .01) but subsequently equalized. On the contrary, all BU-tr eated children but 2 grew normally. GH deficiency was shown in the vas t majority of children with growth impairment. Twenty-three children t reated with recombinant human GH are evaluable; a successful response was observed in all but 1, with the mean growth rate increasing from - 2.29 +/- 0.27 before treatment to 0.86 +/- 0.38 and to 1.66 +/- 0.56 S DS at 1 and 2 years after treatment, respectively (P < .001). In concl usion, growth rate impairment was common in patients receiving TBI, wi th the speed of onset of both decreased growth velocity and GH deficie ncy depending mainly on the total dose of radiation. On the contrary, patients receiving BU did not experience significant problems in terms of growth velocity. The timely start of appropriate hormonal replacem ent therapy may ameliorate the final growth of children undergoing BMT . (C) 1995 by The American Society of Hematology.