Pubertal development and final height after autologous bone marrow transplantation for acute lymphoblastic leukemia (original) (raw)
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International journal of pediatric endocrinology, 2013
Models assessing characteristics contributing to response to recombinant human growth hormone (rhGH) response rarely address growth extremes in both years 1 and 2 or examine how children track from year to year. Using National Cooperative Growth Study (NCGS) data, we determined characteristics contributing to responsiveness to rhGH and the pattern of change from years 1 to 2. Height velocity standard deviation score (HV SDS) for 2 years for prepubertal children with idiopathic GH deficiency (IGHD) (n = 1899) and idiopathic short stature (ISS) (n = 1186) treated with similar doses for two years were computed. Group 1 = HV SDS < -1; 2 = HV SDS -1 to +1; 3 = HV SDS > +1. For IGHD, mean age was 7.5 years and similar in all groups. Year 1 HV SDS was associated with greater body mass index (BMI) SDS, lower pre-treatment HV, baseline height SDS, greater target height SDS minus height SDS, and lower maximum stimulated GH (P <0.0001). Year 2, 172/271 (73%) in group 1 moved to either...
The Journal of Clinical Endocrinology & Metabolism, 2004
Lean body mass (LBM), fat mass (FM), and total bone mineral content are significantly reduced in adult GHD subjects who had received pediatric GH. To test the hypothesis that continued GH therapy after final height is necessary to attain adult body composition, we performed a prospective, multinational, randomized, controlled, 2-yr study in patients who completed pediatric GH treatment at final height. Patients were randomized to GH at 25.0 g/kg⅐d (pediatric dose; n ؍ 58) or 12.5 g/kg⅐d (adult dose; n ؍ 59) or no GH treatment (control; n ؍ 32). LBM and FM were measured by dual energy x-ray absorptiometry and were centrally evaluated. IGF-I, IGFbinding protein-3, and lipid concentrations were also measured centrally. During the 2 yr, GH-treated patients gained a significant amount of LBM compared with controls (P < 0.001), but the change with the higher pediatric dose (14.2 ؎ 11.7%) was not different from that seen with the lower adult dose (12.7 ؎ 9.4%; P ؍ 0.970). Similarly, the decrease in FM was significantly (P ؍ 0.029) influenced by treatment, but with no dose effect (adult dose, ؊7.1 ؎ 22.8%; pediatric dose, ؊6.0 ؎ 26.6%; P ؍ 0.950). When the GH treatment effect was analyzed by gender, males gained 15.6 ؎ 9.8% and 14.3 ؎ 11.7% LBM (P ؍ 0.711) and lost 12.4 ؎ 22.2% and 11.0 ؎ 27.1% FM (P ؍ 0.921) with the low and high doses, respectively. Females gained 8.3 ؎ 7.3% and 12.5 ؎ 12.8% LBM with the two doses (P ؍ 0.630), but increased their FM by 3.5 ؎ 16.2% with the lower dose and lost only 1.2 ؎ 23.2% FM with the higher dose (P ؍ 0.325). A similar pattern was seen in IGF-I SD score; the 2-yr GH dose response was significantly higher with the pediatric than with the adult dose in females (P ؍ 0.008), but not males (P ؍ 0.790). The divergent pattern of change in LBM and FM in males and females is consistent with normal developmental sexual dimorphism and indicates that GH-dependent progress to target body composition continues after the age at which GH treatment is usually terminated. Dose requirements may have to be adjusted by gender, with females requiring a higher dose than males. (J Clin Endocrinol Metab 89: [4857][4858][4859][4860][4861][4862] 2004)
Journal of Pediatric Endocrinology and Metabolism, 1995
Thirty-two short, slowly growing prepubertal children with normal GH levels (after Clonidine stimulation and overnight sampling) were treated with GH hormone for 2 consecutive years at a dose of 0.1 IU/kg/day s.c. Fifteen similar children were followed for 2 years without therapy (controls). Height velocity increased in our treated group from 3.8 ± 0.9 cm/yr to 7.3 ±1.3 cm/yr and 7.1 ± 0.9 cm/yr in the first and second years of therapy, with 85.7% and 87.5% of our patients growing >2 cm/yr above baseline. Height SDS changed from-2.4 ± 0.4 to-2.0 ± 0.7 in the first year and to-1.8 ± 0.5 during the second year of treatment, while bone ages increased at a slightly higher rate than chronological ages. An increase in the final height predictions of our patients during therapy was noted. Height velocity increment in the control group was not significant and height SDS of this group did not change. GH therapy in short, slowly growing non-GH deficient children seems to be effective and safe in the short term; however, its efficacy in increasing the final height of this group of patients is still undetermined.
Bone Marrow Transplantation, 2012
The literature contains a substantial amount of information about factors that adversely influence the linear growth in up to 85% of patients undergoing haematopoietic SCT (HSCT) with TBI and/or cranial irradiation (CI) for acute leukaemia (AL). By contrast, only a few studies have evaluated the impact of growth hormone (GH) therapy on growth rate and final height (FH) in these children. We evaluated growth rates during the preand post-transplant periods to FH in a group of 25 children treated with HSCT (n ¼ 22), TBI (n ¼ 21) or/and CI (n ¼ 8) for AL and receiving GH therapy. At the start of GH treatment, the median height Z-score was À2.19 (À3.95 to 0.02), significantly lower than at AL diagnosis (Po0.001). Overall height gain from start of GH treatment to FH was 0.59Z (À2.72 to 2.93) with a median height Z-score at FH of À1.35 (À5.35 to 0.27). This overall height gain effect was greater in girls than in boys (P ¼ 0.04). The number of children with heights in the reference population range was greater after than before GH therapy (P ¼ 0.07). At FH the GVHD and GH treatments lasting o2 years were associated with shorter FH (P ¼ 0.02 and 0.05). We found a measurable beneficial effect of GH treatment on growth up to FH.
European Journal of Endocrinology, 2000
Objective: To investigate which pretreatment variables most significantly affect long-term growth response to GH therapy in children with apparently idiopathic GH deficiency (GHD) treated from a similar and very young age (less than 2 years), for the same period (7 years) and with the same therapeutic protocol. Design and methods: Twelve children with either isolated GHD or multiple pituitary hormone deficiency were treated with biosynthetic human GH (0.7 IU/kg per week) and were examined every 6 months. Height measurements were performed by Harpenden stadiometers. Bone age was evaluated every 12 months. Results: The onset of therapy was followed in all patients by an important height gain, which attained its zenith during the first year of treatment and became progressively less evident during the next 4 years. Cumulative height gain was 3.0 Ϯ 1.7 SDS. Thanks to the therapy, at the end of the 7-year treatment period, average height in the entire series was not significantly far from mean target height (TH) (¹0.7 Ϯ 1.3 vs ¹0.3 Ϯ 0.4 SDS) and average predicted height (PH) (¹0.2 Ϯ 1.4 SDS) was very close to TH. A stepwise regression analysis showed that both catch-up growth under therapy and PH at the end of the 7-year treatment period were positively influenced by birth weight (BW). Conclusions: a) Our 7-year prospective study on GHD infants treated with GH from less than 2 years of age confirmed the importance of early diagnosis and treatment of GHD in childhood. b) The influence of BW on growth response to GH therapy in GHD children persists over time, at least when treatment is begun from less than 2 years of age.
The Journal of Clinical Endocrinology & Metabolism, 2005
In children, GH secretion and sensitivity to GH are influenced by developmental changes. It is not clear whether the response to GH in very young children with GH deficiency (GHD) is the same as that in older, prepubertal children. A cohort of 265 children (180 males and 85 females) with idiopathic GHD from KIGS (Pfizer International Growth Database), with treatment started at less than 3 yr of age (mean age, 1.9 yr; group I) was compared with a cohort of 509 children (331 males and 178 females; group II) with treatment started at 7-8 yr of age (mean age, 7.5 yr). The following differences (P < 0.01) were found (given in mean values) between groups I and II at the start of GH treatment: 9% vs. 5% breech delivery, 38% vs. 14% multiple pituitary hormone deficiency, 4.2 vs. 5.9 ng/ml maximum GH in response to tests, ؊0.1 vs. ؊0.8 midparental height (MPH) SD score (SDS), ؊3.1 vs. ؊2.5 height SDS, 0.83 vs. 0.66 IU/kg⅐wk GH dose. After the first year of GH, the results were: 13.3 vs. 8.6 cm/yr height velocity, and 1.7 vs. 0.6 maximum change in height SDS. Using the previously developed growth prediction models for prepubertal children with idiopathic GHD more than 2 yr of age, our analysis revealed differences in the indexes of responsiveness in prediction models (Studentized residuals SDS, 0.7 vs.؊0.3) and strikingly higher responsiveness to treatment among the young cohort, but with large scatter. Thus, new prediction models of height velocity (centimeters per year) were derived by means of mul-