Background: The NIH non-myeloablative regimen has been successfully implemented for pediatric sickle cell disease (SCD) patients undergoing matched sibling donor (MSD) hematopoietic stem cell transplant (HSCT) in an effort to prevent late complications, including infertility and other endocrine sequelae. This retrospective cohort analysis evaluated the prevalence of endocrine complications in 17 pediatric SCD patients who underwent non-myeloablative MSD HSCT. Procedure: Medical records between June 2013 and June 2020 were reviewed. Data was extracted from baseline and 1,2,3, and 5-years post HSCT. Results: There were 12 females and 5 males. Follicle stimulating hormone (FSH) elevation post HSCT occurred in 42.8%; 4 females and 2 males. All females with elevated FSH had subsequent normalization of their values with time. FSH elevation in males did not resolve. Post HSCT secondary amenorrhea or oligomenorrhea was described in 4 females; however, improvement or resolution occurred in all. One female subject with normal gonadotrophin levels post HSCT had a successful pregnancy and live birth. Vitamin D deficiency (100% when measured), and obese or overweight body mass index post HSCT (41.2%) were also reported. Conclusions: A notable endocrine issue post HSCT described in this cohort is FSH elevation. The elevation was transient in females, and we identified one successful pregnancy, suggesting that non-myeloablative conditioning may convey favorable fertility outcomes compared to busulfan-based conditioning. Not all patients had baseline endocrine evaluations or consistent post HSCT endocrine testing. We recommend standardizing pre- and post HSCT endocrinology assessments for this population.

Background/Objectives. Despite advances in the treatment of sickle cell disease (SCD), cerebrovascular and cognitive consequences can be lifelong. Hematopoietic cell transplantation (HCT) is an established curative therapy and recent studies have demonstrated efficacy with reduced toxicity nonmyeloblative (NMA) regimens, but little is known about neuropsychological outcomes. The objective of this study was to describe neuropsychological, behavioral, and quality of life outcomes with medical correlates in children with SCD who received an NMA matched sibling donor (MSD) HCT. Design/Methods. This retrospective cohort analysis of nine patients with hemoglobin SS SCD underwent MSD HCT using the National Institutes of Health (NIH) NMA protocol. Results. Mean full scale intellectual functioning (FSIQ) was average pre-HCT (FSIQ=92.1, SD 9.0; n=8) and 2 years post-HCT (mean FSIQ=96.6; SD 11.1; N=9). Neuropsychological functioning was largely average across all cognitive domains. Moderate improvements were seen in processing speed and verbal memory (Cohen’s d=0.50-0.57) post-HCT, and declines occurred in measures of attention and fine motor speed and dexterity (Cohen’s d=0.70-0.81). Parents reported improved quality of life (Cohen’s d=0.91), less impact of SCD on their family, and less worry about their child’s future (Cohen’s d=1.44). Exploratory analysis showed relationships between pre-HCT hemoglobin (r=0.74, p<0.05) and creatinine (r=-0.75, p<0.01) with cognitive functioning, and a positive relationship between processing speed and time post-HCT (r=0.73). Conclusion. Neuropsychological functioning in a sample of children and adolescents treated identically with NMA MSD HCT remained stable or improved in most cognitive domains, and improvements in quality of life and family functioning were observed.