Gonadal Status and Sexual Function at Long-Term Follow-up after Allogeneic Stem Cell Transplantation in Adult Patients with Sickle Cell Disease.

Abstract

Objectives: Patients with adult sickle cell disease and severe sequelae are treated with nonmyeloablative allogeneic hematopoietic stem cell transplant. So far, data on gonadal effects are lacking for older cured patients. We assessed the gonadal reserve and sexual function of patients cured of sickle cell disease with transplant and with anti-T-lymphocyte globulin and posttransplant cyclophosphamide-containing regimen within the context of the Baskent Organ Damage Mitigation and Medical Care Development Program.

Materials and methods: All adult patients (≥18 years) with sickle cell disease who underwent peripheral stem cell transplant from September 2013 to July 2019 and were graft-versus-host disease free for 2 years and not immunosuppressed were invited to participate in this prospective observational study. Of 61 eligible patients, 43 participants (~10% from international registries) were included (median age at transplant was 29 years; range, 18-45 years). Gonadal status, risk of gonadal damage posttransplant, conception, and sexual function posttransplant were evaluated.

Results: Allogeneic hematopoietic stem cell transplant was associated with increased risk of secondary amenorrhea (odds ratio of 93; 95% CI, 4.94-17.50; P = .002) and ovarian insufficiency (odds ratio of 37.8; 95% CI, 2.03 to -700.94; P = .014) but not with female sexual dysfunction. Secondary ovarian insufficiency developed in all women posttransplant. Transplant was associated with significant risk of azoospermia (odds ratio of 4.35; 95% CI, 1.02-18.45; P = .017). Moderate-to-severe erectile dysfunction developed in 2 men (10%). Among female participants, 1 had spontaneous conception that ended in miscarriage and 1 had term delivery after in vitro fertilization. Among male participants, 1 had a child by in vitro fertilization and 1 experienced spontaneous conception.

Conclusions: Although spontaneous conception was shown in our patient group, gonadal damage was evident at >2 years posttransplant. This risk was associated with age in female patients. Better fertility preservation measures should be incorporated into medical care development programs.