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Growth and growth hormone secretion after bone marrow transplantation
R Brauner1, M Fontoura, J M Zucker
1Hôpital et Faculté Necker Enfants Malades, Paris, France.
Insights
Total body irradiation (TBI) conditioning before bone marrow transplantation (BMT) significantly impacts children's growth, with radiation dose and fractionation being critical factors. Growth hormone levels did not correlate with height loss post-TBI, suggesting radiation-induced skeletal damage plays a role.
Area of Science:
- Pediatric Endocrinology
- Hematology/Oncology
- Radiation Oncology
Background:
- Bone marrow transplantation (BMT) requires conditioning protocols that can affect long-term growth in children.
- Understanding the impact of different conditioning regimens on growth and growth hormone secretion is crucial for pediatric BMT survivors.
Purpose of the Study:
- To analyze the growth and growth hormone secretion in children following various conditioning protocols prior to BMT.
- To investigate the relationship between conditioning methods, growth hormone levels, and final height outcomes.
Main Methods:
- Twenty-nine children undergoing BMT were categorized into four groups based on conditioning: single-dose total body irradiation (TBI) at 10 Gy or 8 Gy, fractionated TBI (12 Gy), or chemotherapy alone.
- Growth hormone secretion was assessed via arginine-insulin stimulation tests and sleep studies at 2-7.5 years post-BMT.
- Height changes and final heights were compared across groups and correlated with conditioning protocols.
Main Results:
- Children conditioned with single-dose TBI (10 Gy) showed significant height loss (-1.4 cm) compared to those receiving chemotherapy alone (+1.5 cm).
- Growth hormone peaks were generally normal (>10 µg/l) in most patients, with no significant correlation found between growth hormone levels and height deficits.
- Monozygotic twins exhibited a significant height difference (17.5 cm) despite similar hormonal profiles, and chemotherapy-conditioned patients with congenital immune deficiency showed catch-up growth, unlike those receiving single-dose TBI.
Conclusions:
- The total radiation dose and fractionation schedule of TBI are critical determinants of growth outcomes after BMT.
- Radiation-induced skeletal lesions, rather than impaired growth hormone secretion, appear to be a primary cause of growth retardation post-TBI.
- Chemotherapy-alone conditioning may be associated with better growth recovery, particularly in growth-retarded children.
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 III, seven cases), or chemotherapy alone (group IV, seven cases). The arginine-insulin stimulated growth hormone peak, 2-7.5 years after BMT, was > 10 micrograms/l in all patients except four from group I (6.9-8.9 micrograms/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) micrograms/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 II, -0.4 (0.2) in group III, 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 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.