title: Imatinib mesylate causes growth deceleration in pediatric patients with chronic myelogenous leukemia.
abstract: BACKGROUND
  Imatinib mesylate, a tyrosine kinase inhibitor, is used in the treatment of chronic myelogeneous leukemia (CML). Given its ease of administration and manageable side effects in adults, imatinib mesylate was introduced as therapy for pediatric CML. Recently published case reports describe growth deceleration in children treated with imatinib. This study details the growth phenotype of seven pediatric patients maintained in remission on imatnib mesylate over an extended period of time.
  
  
  METHODS
  This study is a retrospective chart review of pediatric patients with CML at Oregon Health & Science University treated with imatinib. Height, weight, and body mass index (BMI) measurements were collected before and during treatment. Median standard deviation scores (SDS) were analyzed by Wilcoxon Rank-Sum test and Wilcoxon signed rank cohort analysis.
  
  
  RESULTS
  Individual patient analysis demonstrated five of seven subjects with a statistically significant decrease in height SDS pre versus during treatment. The whole group analysis showed a trend to significance for difference in median height SDS pre and during treatment (P = 0.078). Bone age was delayed in all four patients in whom bone ages were obtained. IGF-1, IGFBP-3, and thyroid levels during treatment were normal. Four patients experienced an improvement in height SDS during puberty. However, three patients approaching near final adult height failed to achieve genetic height potential determined by mid-parental target height.
  
  
  CONCLUSIONS
  Growth in children with CML appears to be adversely impacted by imatinib therapy. BMI and IGF-1/IGFBP-3 are maintained during treatment, suggesting a direct effect of imatinib on the growth plate.
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors.forename: Maynika V
authors.initials: MV
authors.lastname: Rastogi
authors.forename: Linda
authors.initials: L
authors.lastname: Stork
authors.forename: Brian
authors.initials: B
authors.lastname: Druker
authors.forename: Carolyn
authors.initials: C
authors.lastname: Blasdel
authors.forename: Thuan
authors.initials: T
authors.lastname: Nguyen
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Boston
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001549:Benzamides; D001827:Body Height / Q000187:drug effects*; D015992:Body Mass Index; D002648:Child; D005260:Female; D006130:Growth Disorders / Q000139:chemically induced*; D006801:Humans; D000068877:Imatinib Mesylate; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D013963:Thyroid Hormones / Q000097:blood; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D010879:Piperazines; D011743:Pyrimidines; D013963:Thyroid Hormones; D007334:Insulin-Like Growth Factor I; D000068877:Imatinib Mesylate