title: Impact on survival and toxicity by duration of weight extremes during treatment for pediatric acute lymphoblastic leukemia: A report from the Children's Oncology Group.
abstract: OBJECTIVE
  Previous studies regarding the influence of weight on event-free survival (EFS) and treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL) considered only weight at diagnosis. Inasmuch as weight varies substantially over treatment, we hypothesized its impact on EFS is instead determined by cumulative time spent at an extreme weight during therapy and on TRT by weight at the time of toxicity.
  
  
  METHODS
  In a cohort of 2,008 children treated for high-risk ALL in Children's Oncology Group study CCG-1961, we determined the effect on EFS of cumulative time receiving therapy at an extreme weight (either obese or underweight) between end of induction and start of maintenance therapy. We also evaluated the association between weight category and incidence and patterns of TRT during 13,946 treatment courses.
  
  
  RESULTS
  Being obese or underweight at diagnosis and for ≥ 50% of the time between end of induction and start of maintenance therapy resulted in inferior EFS (hazard ratios, 1.43 and 2.30, respectively; global P < .001). Normalization of weight during that period resulted in mitigation of this risk comparable to never being obese or underweight. Obese or underweight status at start of each treatment course was significantly associated with specific patterns of TRT.
  
  
  CONCLUSIONS
  Influence of weight extremes on EFS and TRT is not set at diagnosis as previously reported but is moderated by subsequent weight status during intensive postinduction treatment phases. These observations suggest that weight is a potentially addressable risk factor to improve EFS and morbidity in pediatric ALL.
authors.affiliation: Etan Orgel, Jonathan Jaques Children's Cancer Center, Miller Children's Hospital, Long Beach; Etan Orgel, Paul S. Gaynon, and David R. Freyer, Keck School of Medicine, University of Southern California; Etan Orgel, Richard Sposto, Jemily Malvar, Paul S. Gaynon, and David R. Freyer, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles; Richard Sposto, University of Southern California, Los Angeles, CA; Nita L. Seibel, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; and Elena Ladas, Center for Comprehensive Wellness, Columbia University, New York, NY.
authors.forename: Etan
authors.initials: E
authors.lastname: Orgel
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
authors.forename: Jemily
authors.initials: J
authors.lastname: Malvar
authors.forename: Nita L
authors.initials: NL
authors.lastname: Seibel
authors.forename: Elena
authors.initials: E
authors.lastname: Ladas
authors.forename: Paul S
authors.initials: PS
authors.lastname: Gaynon
authors.forename: David R
authors.initials: DR
authors.lastname: Freyer
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D013851:Thinness / Q000150:complications* / Q000503:physiopathology; D013997:Time Factors; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D014750:Vincristine; D001215:Asparaginase; D011241:Prednisone; D003630:Daunorubicin