Sickle cell disease is a potentially debilitating hemoglobinopathy associated with early mortality. The only established curative therapy is hematopoietic cell transplantation (HCT) with a matched sibling donor. The National Institutes of Health nonmyeloablative regimen of alemtuzumab/300 cGy total body irradiation and prolonged sirolimus exposure for graft-versus-host disease (GVHD) prophylaxis was administered to 16 children and adolescents. Infused products were unmanipulated granulocyte colony stimulating factor mobilized peripheral blood stem cells. All patients achieved mixed donor-recipient engraftment with no cases of secondary graft failure to date. Two patients have donor myeloid chimerism in the range of 30% to 40%. No sickling crises post-HCT have been observed. Event-free and overall survival rates are 100% with median follow-up of 19.5 months. No cases of GVHD have been observed. Sirolimus weaning was possible in all but one eligible patient to date. Ongoing followup and a larger prospective clinical trial are required to determine the long-term safety and efficacy of this regimen in children.

Background Sickle cell disease (SCD) is associated with renal complications starting as early as infancy. Allogeneic hematopoietic stem cell transplant (HSCT) treatments using newer nonmyeloablative (NMA) conditioning regimens show promising results in treating SCD in the pediatric population, but renal outcome parameters after transplantation have not been described. Aim To describe baseline renal parameters as well as short‐ and long‐term renal outcomes in pediatric patients with SCD who underwent NMA‐HSCT. Methods A retrospective chart review of pediatric patients who received NMA‐HSCT in Alberta, Canada. Short‐term renal outcomes evaluated were: (1) acute kidney injury (AKI), (2) fluid overload (FO), and (3) hypertension. Long‐term outcomes evaluated were: (1) estimated glomerular filtration rate (eGFR) development and at last follow‐up with hyperfiltration defined as eGFR ≥ 150 mL/min/1.73 m2, (2) proteinuria, and (3) hypertension. Results The mean follow‐up time was 128.6 weeks (standard deviations, 69.3). No posttransplant AKI events or FO were observed. eGFR remained > 90 mL/min/1.73 m2 at last follow‐up in all patients, whereas hyperfiltration was present in eight (44.4%) and four (22.2%) patients pre‐ and post‐HSCT, respectively, which are significantly different (P < 0.0001). Consequently, median GFR was significantly higher pre‐HSCT compared with 24 months HSCT (P < 0.009). Long‐term hypertension post‐HSCT was present in six patients (33.3%). Conclusion This study describes stable kidney function in children with SCD after NMA‐HSCT without evidence of AKI or FO episodes. Rates of hyperfiltration decreased post‐HSCT, which signifies that NMA‐HSCT could potentially preserve long‐term renal function in this population at risk of progressive chronic kidney disease. Further prospective studies are needed to confirm these novel findings.

Background: Pulmonary complications are common in sickle cell disease (SCD). The use of standard myeloablative conditioning regimens may increase the risk of lung injury. We report serial pulmonary function testing (PFT) outcomes in children with SCD who underwent a matched-sibling donor hematopoietic cell transplantation (HCT) using nonmyeloablative (NMA) protocol.Methods: This is a retrospective chart review describing pulmonary outcomes in pediatric patients post HCT. The conditioning regimen consisted of alemtuzumab and a single fraction of 300 cGy of total body irradiation (TBI), and sirolimus for graftversus-host disease (GVHD) prophylaxis. Serial PFT testing was performed pre and post HCT. The evaluated pulmonary measures included: forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1 ), FEV 1 /FVC, and forced expiratory flow (FEF 25-75 ).Results: Twelve subjects were included in the analysis. All had HbSS genotype, and five of the 12 patients had one or more episodes of acute chest syndrome prior to HCT. Serial PFT measures were completed per patient. No patient was diagnosed with chronic GVHD of any organ post HCT. The baseline median FVC, FEV 1 , FEV 1 /FVC, and FEF 25-75 were within the normal range and remained relatively unchanged post HCT.A linear mixed effects model, adjusting for gender and time from HCT, suggested no significant relationship between HCT and PFT parameters, including FVC, FEV 1 , and FEV 1 /FVC. Interestingly, the FEF 25-75 results exhibited a shift in the means post HCT (pre-HCT 86.2% predicted and post-HCT 93.05% predicted, p-value = .018). Conclusion:Our study suggests that HCT in children with SCD may prevent the anticipated decline in pulmonary function over time.

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Neuropsychological and quality-of-life outcomes in a cohort of children with sickle cell disease undergoing matched sibling donor hematopoietic cell transplant.

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.

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