Higher Alkylating Agent Exposure Associated With Impaired Spermatogenesis in Adult Survivors of Childhood Cancer
In a study in the St. Jude Lifetime Cohort Study population reported in The Lancet Oncology, Green et al found that increasing alkylating agent exposure was associated with impaired spermatogenesis in adult male survivors of childhood cancer who did not undergo radiation therapy as part of their treatment. Impaired spermatogenesis was, however, unlikely at a cumulative cyclophosphamide equivalent dose of < 4,000 mg/m2.
Study Details
The study included semen analysis in 214 survivors of childhood cancer with a median age of 7.7 years at diagnosis and 29.0 years at assessment who had received alkylating agent chemotherapy but no radiation therapy for childhood cancer. Alkylating agent exposure was estimated using cyclophosphamide equivalent dose. Azoospermia was defined as no sperm detected, oligospermia as concentrations of > 0 to < 15 million sperm/mL, and normospermia as concentrations ≥ 15 million/mL.
Association With Exposure
Azoospermia was found in 53 patients (25%), oligospermia in 59 (28%), and normospermia in 102 (48%). Of 35 patients receiving cyclophosphamide equivalent dose < 4,000 mg/m2, 31 (89%) were normospermic. Cyclophosphamide equivalent dose was negatively correlated with sperm concentration, with a correlation coefficient of −0.37 (P < .0001). Mean cyclophosphamide equivalent dose was 10,830 (±7,274) mg/m2 in patients with azoospermia, 8,480 (±4,264) mg/m2 in those with oligospermia, and 6,626 (±3,576) mg/m2 in those with normospermia.
On multivariate analysis, each 1,000 mg/m2 increase in cyclophosphamide equivalent dose was associated with an odds ratio (OR) of 1.22 for azoospermia (P < .0001) and 1.14 for oligospermia (P = .006). Neither age at diagnosis nor age at assessment was a significant predictor of azoospermia or oligospermia.
The investigators concluded: “Impaired spermatogenesis was unlikely when the [cyclophosphamide equivalent dose] was less than 4000 mg/m2. Although sperm concentration decreases with increasing [cyclophosphamide equivalent dose], there was substantial overlap of [cyclophosphamide equivalent dose] associated with normospermia, oligospermia, and azoospermia. These data can inform pretreatment patient counselling and use of fertility preservation services.”
Daniel M. Green, MD, of St. Jude Children’s Research Hospital, is the corresponding author for The Lancet Oncology article.
The study was funded by the National Cancer Institute and American Lebanese Syrian Associated Charities. The authors declared no competing interests.
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