Modifications of growth velocity and the insulin-like growth factor system in children with acute lymphoblastic leukemia: a longitudinal study

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.