Abstract 173 Poster Session III, Monday, 5/3 (poster 125)

We have administered rhGH 0.3 mg/kg/wk SQ to seven cardiac transplant patients with severe growth failure. The average age of the patients at transplant was 6.4yrs (range 14mos to 13 yrs). Three patients had a 2nd transplant due to rejection at 4.8, 5.2 and 8yrs, respectively, after their first, all before study entry. All were on a triple immunosuppression regimen with cyclosporine, azathioprine and prednisone. The mean growth velocity (GV) prior to rhGH therapy was 3.0cm/yr ±1.9(range 0.2 to 5.1). Peak GH levels ranged from 1.7 to 14.2ng/ml after standard double stimulation; four of the six were considered to be GH deficient. At the start of therapy, the average height standard deviation score (HtSDS) was -4.3 (-2.8 to -6.4). Bone ages were retarded an average 4.9yrs behind chronologic age (range 3.3 to 5.9yrs). The patients have been treated for 6 mos to 2.5yrs. Two patients treated over 2yrs grew 10.7 and 11.6cm respectively the first yr and 13.4 and 11.4cm the second year. Their HtSDS's improved from -4.0 to -2.8 and -6.4 to -3.2. One patient has grown 9.2 cm in one year. Three patients treated for 6mos have increased their GV from 0.2 to 8.9, 2.1 to 9.7 and 5.1 to 16.4cm/yr, respectively. The patient with the lowest GH response to stimulation also received a renal allograft for chronic renal failure, but did not grow despite 16mos on rhGH. Overall, the mean GV post-rhGH was significantly higher than pre-treatment at 8.6cm/yr ± 3.1(p< 0.05). Adverse effects possibly related to rhGH included two rejection episodes: a grade 1B rejection following a rapid increase in height that responded to adjustment of immunosuppression; and a hemodynamically significant rejection in a different patient attributed to non-compliance with the medical regimen. Persistent tachycardia with a normal biopsy was seen in one patient after 9mos of therapy; it resolved after stopping rhGH. No other patients had clinical or pathologic evidence of rejection. A patient with pre-existing scoliosis required surgical repair after 20mos on rhGH. There were no serious infections. Three patients had had a prior history of tumor - osteogenic sarcoma, non-Hodgkin's lymphoma and post-transplant lymphoproliferative disorder- but to date there has been no evidence of recurrence. Except for the patient with worsening renal function, all laboratory parameters remained stable on rhGH, including fasting blood sugar and glycosylated hemoglobin. In conclusion, there has thus far been one serious rejection episode; other sequelae were related to rapid growth: worsening scoliosis, and the need for dosage changes. Careful cardiac monitoring should be performed. This preliminary data indicates that improved GV can be achieved using rhGH in children growing poorly after heart transplantation.

This research is supported in part by a grant from The Genentech Foundation.