SUN-200 - Longitudinal Outcomes of Fertility Potential in Male Pediatric Hematopoietic Stem Cell Transplant Survivors

Objective:
Hematopoietic stem cell transplant (HSCT) contributes to gonadal toxicity in childhood survivors, but long-term fertility outcomes are understudied. We aimed to describe the longitudinal fertility potential in males after HSCT.

Methods:
We performed a retrospective study of males with allogeneic HSCT from 2015 to 2024. Subjects were < 21yo at time of HSCT, reached ≥11yo during the study, and survived >1y post-HSCT. Patients with Fanconi anemia were excluded. Inhibin B (Inh B) was used as a marker of Sertoli cell activity, and values < 50 pg/mL were hypothesized to correlate with lower Sertoli cell function and potentially decreased fertility. Data was aggregated to compare Inh B at early (1-3y), middle (4-6y) and late (7-9y) timepoints post-HSCT in subgroups by chi-squared analysis. When available, semen analysis was compared to Inh B.

Results:
A total of 123 patients had median follow-up of 2y post-HSCT (range 1–10y). Median age at HSCT was 11.6y (IQR 7.3–15.5y). Forty-six patients (37%) had malignancy, and 82 (67%) had myeloablative conditioning (MAC). Five patients (4%) were diagnosed with hypogonadism.
Seventy-two patients (59%) had ≥1 Inh B measurement post-HSCT. Median Inh B increased from 56 pg/mL at 1–3y post-HSCT to 111 pg/mL at 7–9y (p=0.003). Inh B < 50 pg/mL was not associated with age at HSCT, conditioning regimen, or cyclophosphamide equivalent dosing (CED) at any timepoint. Patients with malignancy had lower Inh B levels at 4–6y post-HSCT (p=0.05), which was not observed at 1–3y or 7–9y (p=NS).

Semen analysis was available for 9 subjects. Two were evaluated post-HSCT: one had azoospermia with low InhB 6y post-HSCT, and one had azoospermia with normal InhB 1y post-HSCT. Four had semen analysis before HSCT but after prior chemotherapy; all showed azoospermia or oligospermia. Three of the 4 (75%) had low InhB levels ≥2y post-HSCT.

Conclusion:
Median Inh B levels increased over time, consistent with increasing Sertoli cell activity in male HSCT survivors. The incidence of hypogonadism was low. Conditioning regimen, CED, and age at HSCT were not associated with low Inh B levels, though transient suppression may occur in malignancy. A small number of patients uniformly showed impaired spermatogenesis following chemotherapy either prior to or with HSCT. While most of these subjects demonstrated low InhB when tracked post-HSCT, further study is needed to validate InhB data with semen analysis in pediatric HSCT survivors.

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