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 Hematopoietic stem cell transplantation can be curative for children with difficult to treat leukemia. The conditioning regimen utilised is known to influence outcomes. We report outcomes of the conditioning regimen used at the Alberta Children’s Hospital, consisting of busulfan (with pharmacokinetic target of 3750μmol*min/day +/-10%) for 4 days, higher dose (250 mg/m2) fludarabine and 400 centigray of total body irradiation. Procedure This retrospective study involved children receiving transplant for acute lymphoblastic leukemia (ALL). It compared children who fell within the target range for busulfan with those who were either not measured or were measured and fell outside this range. All other treatment factors were identical. Results Twenty-nine children (17 within target) were evaluated. All subjects engrafted neutrophils with a median (IQR) time of 14 days (8-30 days). The cumulative incidence of acute graft versus host disease was 44.8% (95% CI 35.6 – 54.0%), while chronic graft versus host disease was noted in 16.0% (95% CI 8.7% - 23.3%). At two years, the overall survival was 78.1% (95% CI 70.8% - 86.4%) and event free survival was 74.7% (95% CI 66.4% - 83.0%). Cumulative incidence of relapse was 11.3% (95% CI 5.1% - 17.5%). There were no statistically significant differences in between the group that received targeted busulfan compared with the untargeted group. Conclusion The current regimen used in children with ALL results in outcomes comparable to standard treatment with acceptable toxicities and significant reduction in radiation dose. Targeting Busulfan dose in this cohort did not result in improved outcomes.