Longitudinal Outcomes of Reproductive Function in Male Pediatric Hematopoietic Stem Cell Transplant Survivors

Allogeneic hematopoietic stem cell transplant (allo-HSCT) is a known contributor of gonadal toxicity in adolescent survivors, but long-term fertility outcomes in this population are underreported. The role of Inhibin B (Inh B) as a biomarker of spermatogenic activity in male allo-HSCT survivors is not well defined, underscoring an important gap in survivorship research. To characterize longitudinal reproductive outcomes using Inh B as a surrogate marker of spermatogenic activity and to determine the incidence of hypogonadism in male pediatric and young adult allo-HSCT survivors. We conducted a retrospective review of 123 male patients who underwent single allo-HSCT between January 2015-May 2024 and survived ≥1-year post-HSCT. Patients were <21y at transplant and reached age 11y during follow-up; those with Fanconi Anemia were excluded. Demographics were collected, including age at HSCT, primary pathology, alkylator exposure, and conditioning regimen. Inh B ≥ 50 pg/mL was indicative of increased likelihood for spermatogenic potential. Post-HSCT Inh B levels were analyzed in subgroups of 1-3y (early), 4-6y (middle), and 7-9y (late) post-HSCT. Semen analysis was analyzed when available as an additional correlative study. The median age at HSCT was 11.6y (IQR, 7.3-15.5y), with a median follow-up of 2y (1-10y) post-HSCT. Seventy-two patients (59%) had ≥1 Inh B value post-HSCT. Forty-six (37%) patients had an underlying hematologic malignancy and 82 patients (67%) received myeloablative conditioning regimen (Table 1). Five (4%) patients were diagnosed with hypogonadism post-HSCT. Median Inh B significantly increased from 56pg/ml at 1-3y to 111 pg/mL at 7-9y post HSCT ( p=0.003) (Figure 1). Inh B ≥ 50 pg/mL was not significantly associated with conditioning regimen, cyclophosphamide equivalent dosing (CED), or age at transplant (AAT) at any time point. Inh B levels <50 pg/ml were observed in patients with a diagnosis of malignancy at 4-6y post-HSCT (p=0.05), but this difference was not seen at 1-3 or 7-9y post-HSCT (p=NS). Among 7 patients (6%) with semen analysis, all had oligo/azoospermia and 5 (71%) had an Inh B <50 pg/mL within 1 yr of testing. The incidence of hypogonadism is reassuringly low in our cohort. Median Inh B values were noted to increase longitudinally, suggesting possible improving spermatogenic potential over time. However, a small number of patients with semen analysis all showed severely impaired spermatogenesis. Low Inh B was not associated with conditioning regimen, CED, AAT, but may be more common at middle time points after HSCT among patients with malignancy. Additional analysis is needed to evaluate the validity of Inh B as a surrogate marker of fertility compared to semen analysis.