Longitudinal Description of Gonadal Function in Sickle-cell Patients Treated With Hematopoietic Stem Cell Transplant Using Alkylator-based Conditioning Regimens

Objectives: This study describes the hormone profiles for gonadal late effects after alkylator-based hematopoietic stem cell transplant (HSCT) regimens used for sickle-cell disease (SCD). Methods: This is a retrospective chart review of subjects followed in the post-HSCT clinic for sickle-cell disease. Patient demographics, pubertal development, characteristics of pre-HSCT disease severity, treatment before HSCT, conditioning regimens, presence of graft versus host disease and follicle-stimulating hormone, anti-Müllerian hormone (AMH), luteinizing hormone and testosterone were abstracted from the medical record. Results: Forty subjects (24 female individuals) with SCD were 9 (±4.3) years old at HSCT and 7.9 years (±5.6) from HSCT. At the time of transplant, 8% of female individuals and no male individuals were pubertal and 58% of female individuals and 38% of male individuals had been treated with hydroxyurea. Post-HSCT, all of the female individuals had diminished ovarian reserve on the basis of low AMH values and 10 of the pubertal female individuals (71%) had premature ovarian insufficiency defined as follicle-stimulating hormone >40 mIU/mL ×2. There was no ovarian recovery and AMH remained very low or undetectable up to 13 years post-HSCT. In male individuals, luteinizing hormone and testosterone levels were normal for age. Conclusions: Post-HSCT for SCD, all female individuals had diminished ovarian reserve and most female individuals had POI, whereas male individuals had normal testosterone hormone production.