Pubertal development and fertility in survivors of childhood acute myeloid leukemia treated with chemotherapy only: a NOPHO-AML study

Pediatr Blood Cancer. 2013 Dec;60(12):1988-95. doi: 10.1002/pbc.24715. Epub 2013 Aug 23.

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.

Procedure: 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.

Keywords: acute myeloid leukemia; children; fertility; late effects; premature ovarian failure; puberty.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Mullerian Hormone / blood
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Child
  • Child, Preschool
  • Female
  • Fertility / drug effects*
  • Follicle Stimulating Hormone / blood
  • Follow-Up Studies
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Male
  • Primary Ovarian Insufficiency / chemically induced
  • Primary Ovarian Insufficiency / epidemiology
  • Puberty / drug effects*
  • Surveys and Questionnaires
  • Survivors / statistics & numerical data*
  • Young Adult

Substances

  • Anti-Mullerian Hormone
  • Follicle Stimulating Hormone