Longitudinal Ovarian Reserve in Female Adolescents/Young Adults With Lymphoma: A Report From Children's Oncology Group Study ALTE11C1

ABSTRACT Background Children's Oncology Group (COG) study ALTE11C1 prospectively evaluated ovarian reserve in female adolescents/young adults (AYAs) with lymphoma from diagnosis to 1 year post‐end of treatment (EOT). Healthy peers provided normative comparisons. Procedure From 2013 to 2018, female participants ≥6 months post‐menarche with newly diagnosed lymphoma were enrolled at COG institutions, along with healthy peers. All completed study entry questionnaires and menstrual cycle‐independent blood draws for anti‐Müllerian hormone (AMH), follicle‐stimulating hormone (FSH), and estradiol; lymphoma participants had four additional draws during and after treatment. Associations between biomarkers, disease and treatment characteristics were evaluated. Logistic regression and recursive partitioning analyses identified predictors of diminished ovarian reserve (DOR: AMH <1 ng/mL) at 1 year post‐EOT. Results Analyses included 168 participants and 125 healthy peers. Participants had lower AMH than healthy peers at study entry (2.1 vs. 4.1 ng/mL; p < 0.01) and 1 year post‐EOT (1.7 vs. 4.1 ng/mL; p < 0.01). AMH declined during treatment, with partial recovery post‐EOT to below study entry levels ( p < 0.01). Those with advanced stage Hodgkin lymphoma and/or B symptoms had the lowest AMH. By 1 year post‐EOT, 34% had DOR; study entry AMH less than 1 ng/mL ( p = 0.003) and higher alkylator exposure ( p = 0.01) were independent predictors. Most participants with study entry AMH less than 1 ng/mL (76%) or CED ≥6.6 g/m 2 (75%) demonstrated DOR at 1 year post‐EOT. No participant had acute ovarian failure at 1 year post‐EOT. Conclusions Lymphoma and its treatments affect ovarian reserve in female AYA patients. Low AMH at diagnosis and high alkylator exposure predict post‐therapy DOR and can guide fertility preservation counseling.