Normalization of cerebral hemodynamics following hematopoietic stem cell transplant in children with sickle cell disease.

Children with sickle cell disease (SCD) demonstrate cerebral hemodynamic stress and are at high risk of strokes. We hypothesized that curative hematopoietic stem cell transplant (HSCT) normalizes cerebral hemodynamics in children with SCD compared to pre-transplant baseline. Whole-brain cerebral blood flow (CBF) and oxygen extraction fraction (OEF) were measured by MRI 1-3 months before and 12-24 months after HSCT in ten children with SCD: three with prior overt strokes, five with prior silent strokes, and one with abnormal transcranial Doppler ultrasound velocities. HSCT recipients' CBF and OEF were compared to non-SCD controls and SCD participants receiving chronic red blood cell transfusion therapy (CRTT) before and after a scheduled transfusion. Seven participants received matched sibling donor HSCT; three received 8/8 matched unrelated donor HSCT. All received reduced-intensity preparation and maintained engraftment, free of hemolytic anemia and SCD symptoms. Pre-transplant, CBF (93.5 ml/100g/min) and OEF (36.8%) were elevated compared with non-SCD controls, declining significantly 1-2 years following HSCT (CBF 72.7 ml/100g/min, p=0.004; OEF 27.0%, p=0.002), with post-HSCT CBF and OEF similar to non-SCD control subjects. Furthermore, HSCT recipients demonstrated greater reduction in CBF (-19.4 ml/100g/min) and OEF (-8.1%) after HSCT than children with SCD receiving CRTT after a scheduled transfusion (CBF -0.9 ml/100g/min, p=0.024; OEF -3.3%, p=0.001). HSCT normalizes whole-brain hemodynamics following curative HSCT in children with SCD. This restoration of cerebral oxygen reserve may explain stroke protection following HSCT in this high-risk patient population.