Modifications of Growth Velocity and the Insulin-Like Growth Factor System in Children with Acute Lymphoblastic Leukemia: A Longitudinal Study1
B. Argüelles,
V. Barrios,
J. Pozo,
M. T. Muñoz and
J. Argente
Universidad Autónoma, Department of Pediatrics, Division of
Pediatric Endocrinology, Laboratory of Research, Hospital Universitario
Niño Jesús, 28009 Madrid, Spain
Address all correspondence and requests for reprints to: Jesús Argente, M.D., Ph.D., Division of Pediatric Endocrinology, Laboratory of Research, Hospital Niño Jesús, Avenida. Menéndez Pelayo 65, 28009 Madrid, Spain. E-mail:
argentefen{at}teleline.es
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
growthis regulated by the GH-insulin-like growth factor (IGF) system,
whichmay 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 prepubertalchildren 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
diseaseand therapy on this system and its relationship with growthin
these patients. Intensive chemotherapy compromised growth,with a
catch-up period beginning when maintenance therapy beganand increased
growth after stopping therapy. Weight increased6 months after
chemotherapy withdrawal, whereas the body massindex was increased both
at 6 months after diagnosis and 6 monthsafter therapy suppression.
Serum IGF-I, IGF-II, IGFBP-3, andtotal and free ALS levels were
significantly decreased at diagnosis.Normalization of IGF-II and
IGFBP-3 occurred 6 months afterdiagnosis, and normalization of IGF-I
and total and free ALSoccurred 1 yr after terminating therapy. IGFBP-1
and IGFBP-2levels were significantly increased at diagnosis and
decreasedafter stopping therapy. Free IGF-I was elevated throughout
thestudy. IGF and IGFBP-3 levels showed a close relationship togrowth
velocity at the end of chemotherapy, with this correlationremaining
until at least 1 yr after therapy withdrawal. In conclusion,intensive
chemotherapy compromises linear growth in prepubertalALL patients, and
this phenomenon is associated with alterationsin the IGF system.
However, when therapy is reduced or stopped,catch-up growth occurs,
but various parameters of the GH-IGFaxis remain impaired. This
suggests the need for a longer periodof follow-up to assess the
long-term risks of therapy and diseaseon this system.
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