Growth and growth hormone secretion after bone marrow transplantation.

Abstract

This study analyses the growth and the growth hormone secretion of children given various conditioning protocols before bone marrow transplantation (BMT). Twenty nine children (14 boys, 15 girls) given BMT were classified according to their conditioning protocol: total body irradiation (TBI) given as a single exposure of 10 Grays (Gy, group I, 11 cases), or 8 Gy (group II, four cases), 12 Gy given as six fractionated doses (Group HI, seven cases), or chemotherapy alone (group IV, seven cases). The arginine-insulin stimulated growth hormone peak, 2-7.5 years after BMT, was >10 WAg/l in all patients except four from group I (6.9-8.9 pg/l). A second growth hormone secretion evaluation was performed in 10 group I patients because of persistent low growth velocity despite a normal growth hormone peak. There were no significant changes in the mean (SEM) stimulated growth hormone peak (18-4 (2.2) v 20*1 (3.6) ig/l) at 3 (0.3) to 5-2 (0.6) years after BMT. The sleep growth hormone peaks and concentrations (n=6) were normal. The mean cumulative height changes (SD) during the three years after BMT were: -1-4 (0.2) in group I, -0.1 (0-4) in group l, -0.4 (0.2) in group HI, and 1 5 (0.5) in group IV; this was significant in groups I and IV. The final heights of two monozygotic twins (BMT donor and recipient) had differed by 17-5 cm, despite them both having normal growth hormone peaks and puberty. Eight patients, treated for congenital immune deficiency syndrome, were growth retarded at the time of BMT. Of these, only those conditioned by chemotherapy alone had significant catch up growth (2 (0.6) SD) while those conditioned by a single 8 Gy exposure did not (0(0-4) SD).It is concluded that the total radiation dose is critical for growth evolution, as is the fractionation schedule. For the TBI doses and the interval since BMT studied, there was no correlation between growth hormone peak and the height loss. The rapidity of decreased growth velocity after TBI and the comparison between the monozygotic twins suggest that radiation induced skeletal lesions are partly responsible for the decreased growth.

Growth hormone treatment impact on growth rate and final height of patients who received HSCT with TBI or/and cranial irradiation in childhood: a report from the French Leukaemia Long-Term Follow-Up Study (LEA)

“…In the entire cohort of 944 patients there were 257 patients who had had HSCT. Among these 188 had had TBI (14 had also had previous CI) and 12 had had only CI. Among no transplanted patients 121 had had CI.…”

“…The literature contains a number of studies about factors that adversely affect growth in children treated for AL (age at the time of AL treatment, irradiation dose and fraction size, and so on). 3,6,[9][10][11][12][13][14] By contrast, only a few studies have evaluated the impact of GH replacement therapy on growth rate and FH in these children. 1,2,7,[15][16][17] A better understanding of the factors influencing response to GH will allow the identification of patients who can benefit from appropriate hormonal replacement therapy.…”

Endocrine dysfunction and parameters of the metabolic syndrome after bone marrow transplantation during childhood and adolescence

“…1,2 High rates of skeletal complications, 3 growth disturbances, 4 and thyroid 5,6 and gonadal dysfunction 7 have been described in survivors, although data on the frequency of metabolic syndrome are still sparse. 8 The relative risk of these complications is likely to be influenced by the underlying disease, previous treatments, post-BMT treatments and age at BMT.…”

Final height in pediatric patients after hyperfractionated total body irradiation and stem cell transplantation

“…6 However, radiation-induced damage to the growth plates, particularly those of the spine, is another possible mechanism for growth failure after TBI. 5,8 When considering the different schedules of delivering radiotherapy, patients treated with standard fractionated TBI seem to achieve better final heights than those treated with single-dose TBI. 9 The specific effect on final height of hyperfractionated TBI (use of smaller doses administered 2-3 times daily), a treatment modality in use at our center since 1979, has so far not been reported.…”

“…3 Impaired linear growth and reduced final height have been shown to occur in individuals treated during childhood with single-dose and fractionated TBI. [3][4][5][6][7] Growth hormone (GH) deficiency, resulting from the exposure of the hypothalamus-pituitary region to irradiation may contribute to the height loss, especially in individuals who were treated with cranial radiotherapy before SCT. 6 However, radiation-induced damage to the growth plates, particularly those of the spine, is another possible mechanism for growth failure after TBI.…”