title: Birth defects in offspring of adult survivors of childhood acute lymphoblastic leukemia. A Childrens Cancer Group/National Institutes of Health Report.
abstract: BACKGROUND
  It is not known if therapy for acute lymphoblastic leukemia (ALL) during childhood increases the risk of birth defects in the offspring of adult survivors. The Childrens Cancer Group (CCG), in collaboration with the National Institutes of Health (NIH), conducted a retrospective cohort study of adults successfully treated for childhood ALL to determine if their offspring had an increased incidence of birth defects compared with the offspring of their sibling controls.
  
  
  METHODS
  Study subjects were patients who had been enrolled on CCG ALL protocols, who were treated for ALL prior to age 20, who survived at least 2 years, and who were at least age 18. Survivors (N=593) and sibling controls (N=409) were interviewed by telephone.
  
  
  RESULTS
  The mean age of survivors was 22.6 years; the mean age of controls was 25.2 years. Among survivors, 93 (15.7%) had given birth to or fathered a total of 140 live-born offspring, (mean age, 3.4 years), and 122 (29.8%) sibling controls had given birth to or fathered a total of 228 live-born offspring (mean age, 5.9 years). There was no difference in the rate of birth defects between offspring of survivors and offspring of controls (3.6% [5 of 140] vs. 3.5% [8 of 228]; relative risk, 1.02; 95% confidence interval, 0.34, 3.05). No specific ALL therapy was associated with an increased rate of birth defects. Only female survivors reported offspring with birth defects (P=0.0735).
  
  
  CONCLUSIONS
  Adult survivors of childhood ALL in our study were not at greater risk for having offspring with birth defects compared with sibling controls. Although this is the largest group of ALL survivors studied to date, the number of offspring is still not large enough to detect small but significant differences in rare events such as birth defects. Studies following this cohort into later adulthood and studies of additional ALL survivors are necessary to adequately quantify the risks.
authors.affiliation: Department of Hematology/Oncology, Children's National Medical Center, Washington, DC, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Kenney
authors.forename: H S
authors.initials: HS
authors.lastname: Nicholson
authors.forename: C
authors.initials: C
authors.lastname: Brasseux
authors.forename: J L
authors.initials: JL
authors.lastname: Mills
authors.forename: L L
authors.initials: LL
authors.lastname: Robison
authors.forename: L K
authors.initials: LK
authors.lastname: Zeltzer
authors.forename: A T
authors.initials: AT
authors.lastname: Meadows
authors.forename: G H
authors.initials: GH
authors.lastname: Reaman
authors.forename: J
authors.initials: J
authors.lastname: Byrne
mesh_terms: D000328:Adult; D002648:Child; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D017741:Survivors