ArticlesCumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study
Introduction
The treatment of children and adolescents with cancer has become increasingly successful, with about 80% of patients surviving 5 years or more after diagnosis.1 Irradiation of the testes or treatment with certain classes of chemotherapeutic agents, especially alkylating agents, might impair fertility,2, 3 a risk that increases with cumulative doses of alkylating agents, as estimated by the cyclophosphamide equivalent dose (CED).4 Published work about the relation between cumulative alkylating agent exposure and semen variables in adult survivors of childhood cancer is scarce, and often confounded by radiation exposure to the testes or hypothalamic–pituitary axis. We undertook the present study to investigate the independent role of alkylating agent exposure to test the hypothesis that increased exposure would be associated with decreased sperm concentration in a cohort of adult male survivors of childhood cancer who were not exposed to radiation therapy for their childhood cancer.
Section snippets
Study design and participants
Our analysis used data available as of April 30, 2013, for male participants in the St Jude Lifetime Cohort Study (SJLIFE) diagnosed and treated for cancer between 1970 and 2002. The continuing SJLIFE5, 6 study includes patients 0–28 years of age at diagnosis who meet the following criteria: diagnosis of childhood malignancy treated at St Jude Children's Research Hospital; survival for 10 years or more from diagnosis; and a present age 18 years or older. SJLIFE participants undergo risk-based
Results
Of 2400 males eligible for the SJLIFE study as of April 30, 2013, 1851 were excluded from the present analysis because of a history of any radiation treatment, no alkylating agent exposure, vasectomy, or present use of androgens. No patient underwent bilteral orchiectomy. Of the 549 men eligible for the semen analysis project, 226 (41%) participated in a SJLIFE on-campus assessment and agreed to semen analysis. 12 were unable to produce a semen specimen, resulting in 214 assessable participants
Discussion
Alkylating agents interfere with spermatogenesis, but there are few data for the effect of host and treatment factors on this risk in survivors of childhood cancer. Using the SJLIFE study, which includes a large cohort of well-characterised, unirradiated male survivors of childhood cancer, we show a correlation between increasing CED and the prevalence of azoospermia (panel). Although impaired spermatogenesis was less likely when the CED was less than 4000 mg/m2, we did not identify a
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