Related Experiment Videos
Modifications of growth velocity and the insulin-like growth factor system in children with acute lymphoblastic
B Argüelles1, V Barrios, J Pozo
1Universidad Autónoma, Department of Pediatrics, Hospital Universitario Niño Jesús, Madrid, Spain.
Insights
Intensive chemotherapy for acute lymphoblastic leukemia (ALL) impairs growth in children by altering the growth hormone-insulin-like growth factor (GH-IGF) system. While catch-up growth occurs after treatment cessation, long-term effects on the GH-IGF axis require further monitoring.
Area of Science:
- Pediatric Endocrinology
- Pediatric Oncology
- Growth Hormone Therapy
Background:
- Impaired growth in children with acute lymphoblastic leukemia (ALL) is multifactorial, stemming from the disease, infections, malnutrition, and treatment side effects.
- The growth hormone-insulin-like growth factor (GH-IGF) system is crucial for growth regulation and can be affected by catabolic states common in ALL patients.
Purpose of the Study:
- To investigate the impact of ALL and its intensive chemotherapy on the GH-IGF system in prepubertal children.
- To correlate alterations in the GH-IGF axis with growth patterns during and after treatment.
Main Methods:
- Serum levels of IGF-I, free IGF-I, IGF-II, IGF-binding proteins (IGFBP-1 to -3), and acid-labile subunit (ALS) were measured in 26 prepubertal children with ALL at diagnosis and at multiple time points up to 36 months post-treatment.
- Growth velocity, weight, and body mass index were monitored throughout the study period.
Main Results:
- Intensive chemotherapy significantly reduced linear growth and altered GH-IGF system parameters, including decreased IGF-I, IGF-II, IGFBP-3, and ALS levels at diagnosis.
- While IGF-II and IGFBP-3 normalized within 6 months post-diagnosis, IGF-I and ALS normalization occurred 1 year after therapy cessation.
- Catch-up growth was observed after reducing or stopping therapy, but free IGF-I remained elevated, and correlations between IGF/IGFBP-3 and growth velocity persisted post-treatment.
Conclusions:
- Intensive chemotherapy for ALL negatively impacts linear growth and the GH-IGF axis in prepubertal children.
- Despite catch-up growth following treatment reduction or cessation, persistent alterations in the GH-IGF system suggest potential long-term risks.
- Extended follow-up is necessary to fully assess the long-term consequences of ALL and its treatment on the GH-IGF axis and overall growth.
Abstract:
The basis of impaired growth in children with acute lymphoblastic leukemia (ALL) is multifactorial, including the disease itself, infections, undernutrition, and adverse effects of therapy. Because growth is regulated by the GH-insulin-like growth factor (IGF) system, which may be altered in catabolic states, we studied serum IGF-I, free IGF-I, IGF-II, the IGF-binding proteins (IGFBP-1 to -3), and total and free acid-labile subunit (ALS) levels in 26 prepubertal children with ALL at diagnosis (n = 26) and 6 (n = 21), 12 (n = 21), 18 (n = 21), 24 (n = 20), 30 (n = 16), and 36 months (n = 16) after beginning treatment to investigate the effects of disease and therapy on this system and its relationship with growth in these patients. Intensive chemotherapy compromised growth, with a catch-up period beginning when maintenance therapy began and increased growth after stopping therapy. Weight increased 6 months after chemotherapy withdrawal, whereas the body mass index was increased both at 6 months after diagnosis and 6 months after therapy suppression. Serum IGF-I, IGF-II, IGFBP-3, and total and free ALS levels were significantly decreased at diagnosis. Normalization of IGF-II and IGFBP-3 occurred 6 months after diagnosis, and normalization of IGF-I and total and free ALS occurred 1 yr after terminating therapy. IGFBP-1 and IGFBP-2 levels were significantly increased at diagnosis and decreased after stopping therapy. Free IGF-I was elevated throughout the study. IGF and IGFBP-3 levels showed a close relationship to growth velocity at the end of chemotherapy, with this correlation remaining until at least 1 yr after therapy withdrawal. In conclusion, intensive chemotherapy compromises linear growth in prepubertal ALL patients, and this phenomenon is associated with alterations in the IGF system. However, when therapy is reduced or stopped, catch-up growth occurs, but various parameters of the GH-IGF axis remain impaired. This suggests the need for a longer period of follow-up to assess the long-term risks of therapy and disease on this system.