title: Pubertal development and fertility in survivors of childhood acute myeloid leukemia treated with chemotherapy only: a NOPHO-AML study.
abstract: BACKGROUND
  More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings.
  
  
  METHODS
  We included 137 children treated for AML according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)-AML-84, -88, and -93 trials, who were alive by June 2007. Patients with relapse or treated with HSCT were excluded. AML survivors participated in a physical and biochemical examination (n = 102) and completed a questionnaire (n = 101). One of their siblings completed an identical questionnaire (n = 84).
  
  
  RESULTS
  At a median follow-up of 11 years (range 5-25) after diagnosis of AML the survivors (median age 16 years, range 5-36) were either prepubertal or had entered puberty normally. Serum levels of FSH, LH, testosterone, estradiol, sex hormone binding globulin (SHBG), inhibin A and B, and testicular volumes were within normal ranges. Anti-Müllerian hormone (AMH) levels were decreased in 5 of 40 postpubertal females. Mean reported age at menarche was 13.1 (range 11-17) years. Among survivors 15 years of age or older 31% of females reported pregnancies and 9% of males reported pregnancies in their partners, rates comparable with the frequency reported by their siblings.
  
  
  CONCLUSIONS
  Most AML survivors treated with chemotherapy had normal pubertal development and fertility, however, AMH levels were decreased in 13% of postpubertal females. Longer follow-up is necessary to evaluate possible risk of premature ovarian failure.
authors.affiliation: Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Molgaard-Hansen
authors.forename: Anne-Sofie
authors.initials: AS
authors.lastname: Skou
authors.forename: Anders
authors.initials: A
authors.lastname: Juul
authors.forename: Heidi
authors.initials: H
authors.lastname: Glosli
authors.forename: Kirsi
authors.initials: K
authors.lastname: Jahnukainen
authors.forename: Marianne
authors.initials: M
authors.lastname: Jarfelt
authors.forename: Guðmundur K
authors.initials: GK
authors.lastname: Jónmundsson
authors.forename: Johan
authors.initials: J
authors.lastname: Malmros
authors.forename: Karsten
authors.initials: K
authors.lastname: Nysom
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
mesh_terms: D000293:Adolescent; D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000453:epidemiology; D011627:Puberty / Q000187:drug effects*; D011795:Surveys and Questionnaires; D017741:Survivors / Q000706:statistics & numerical data*; D055815:Young Adult
chemical_list: D054304:Anti-Mullerian Hormone; D005640:Follicle Stimulating Hormone
keywords: acute myeloid leukemia; children; fertility; late effects; premature ovarian failure; puberty