Hematopoietic stem cell transplantation (HSCT) in children with sickle cell disease (SCD) was associated with normalization of cerebral hemodynamic parameters after transplant, including whole-brain cerebral blood flow (CBF) and oxygen extraction fraction (OEF), according to study results published in the journal Blood.
“In this cohort of children with severe SCD, we demonstrate that CBF and OEF normalize after a successful HSCT,” the investigators wrote in their report. The investigators had tested a hypothesis that children with SCD who undergo HSCT will experience a normalization of cerebral hemodynamics, relative to baseline prior to transplant.
To assess this hypothesis, the investigators used magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) to measure both whole-brain CBF and OEF. These MRI/MRA-based analyses occurred at 1 to 3 months before HSCT and at 12 to 24 months after HSCT. Also, CBF and OEF measures in these patients with SCD who underwent HSCT were compared with results from 2 control groups. The control groups included participants without SCD and participants with SCD who were recipients of chronic red blood cell transfusion therapy (CRTT), in whom measurements were obtained before and after scheduled transfusions.
There were 10 children with SCD who underwent HSCT and were evaluated in this study. Among these children, overt strokes had previously occurred in 3 patients, and 5 had a history of silent cerebral infarctions. Matched sibling donors were involved in HSCT for 7 participants, while 3 participants underwent HSCT with 8/8 matched unrelated donors. Myeloid engraftment by 2 months after HSCT reached levels ranging from 62% to 100%.
Among participants with SCD undergoing HSCT, the median pretransplant CBF value, of 93.5 mL/100 g/min, was elevated compared with that of the non-SCD control group (69.8 mL/100 g/min; P =.023). The median pretransplant OEF was 36.8% in those undergoing HSCT, which was also elevated compared with that of the non-SCD control group (30.9%; P =.010).
In participants with SCD, in the period of 1 to 2 years after HSCT, both CBF and OEF median values had significantly decreased. The median CBF at this time was 72.7 mL/100 g/min (P =.004), and the median OEF was 27.0% (P =.002). The values were similar to those of the non-SCD control group.
Compared with posttransfusion CBF and OEF values for children with SCD receiving CRTT, children who had undergone HSCT had showed greater decreases. The median change in CBF for children after HSCT was -19.4 mL/100 g/min, compared with -0.9 mL/100 g/min in children after CRTT transfusion (P =.024). The median change in OEF after HSCT was -8.1%, compared with -3.3% for children after CRTT transfusion (P =.001).
“In conclusion, we demonstrate that cerebral hemodynamic and metabolic stress are relieved by successful HSCT in children with SCD, and CBF and OEF normalize after HSCT,” the investigators concluded in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Hulbert ML, Fields ME, Guilliams KP, et al. Normalization of cerebral hemodynamics after hematopoietic stem cell transplant in children with sickle cell disease. Blood. 2023;141(4):335-344. doi:10.1182/blood.2022016618.