Growth Hormone Deficiency after Chemotherapy for Acute Lymphoblastic Leukemia in Children Who Have Not Received Cranial Radiation.

Chemotherapy-related growth failure is a significant problem in children with acute lymphoblastic leukemia (ALL). Growth impairment after cranial radiation (CR) is likely to result in diminished adult height, but growth impairment following chemotherapy without CR is usually followed by catch-up growth and normal final height. We report two ALL survivors treated with chemotherapy without CR who required growth hormone (GH) replacement due to absence of catch-up growth. A 15 year old boy and a 12 year old girl, off therapy for 9 and 6 years, respectively, developed growth failure. Peak GH responses to stimulation using arginine and clonidine were inadequate, 3.4 ng/ml and 0.1–3.0 ng/ml, respectively (normal >10 ng/ml). Additional studies included bone age, magnetic resonance imaging of the hypothalamic-pituitary area, insulin-like growth factor (IGF-1), insulin-like growth factor-binding protein (IGF-BP3), and thyroid function tests. Other causes of growth failure were ruled out; the children had received neither CR nor radiation of the long bones, were not subjected to transplantation, and showed no evidence of premature puberty or hypothyroidism. Chemotherapy included methotrexate, 6 mercaptopurine, vincristine, adriamycin, cyclophosphamide, l-asparaginase, dexamethasone, cytarabine, 6 thioguanine, and intrathecal methotrexate. Both children responded to GH replacement therapy. Of 235 ALL survivors treated at our single institution since 1997 with chemotherapy without CR, the 2 we report here were diagnosed with GH deficiency resulting in growth deceleration, generally thought to be primarily a complication of CR. Children treated for ALL should be carefully monitored for growth failure.