Cerebral hemodynamic changes after haploidentical hematopoietic stem cell transplant in adults with sickle cell disease.

Preliminary evidence from four adults with sickle cell disease (SCD) suggests that hematopoietic stem cell transplant (HSCT) improves cerebral hemodynamics. HSCT largely normalizes cerebral hemodynamics in children with SCD. We tested the hypothesis in adults with SCD that cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) measured using MRI, normalized to healthy values, comparing measurements approximately one month before to 12-24 months following HSCT (n=11; age=33.3±8.9 years; 389±150 days post-HSCT) to age-, race- and sex-matched values from healthy adults without sickle trait (n=28; age=30.2±5.6 years). Prior to transplant, 7 patients had neurological indications for transplant (e.g., overt stroke) and 4 had non-neurological reasons for haploidentical bone marrow transplant (haploBMT). All received haploBMT from first-degree relatives (parent, sibling, or child donor) with reduced-intensity preparation and maintained engraftment. Pre-transplant, CBF was elevated (CBF=69.1124.7 ml/100g/min) compared to controls (p = 0.004). Mean CBF declined significantly following haploBMT (post-transplant CBF=48.2±13.9 ml/100g/min, p=0.003). OEF was not different from controls at baseline and did not change significantly following HaploBMT (pre-transplant: 43.16.7%; post-transplant: 39.67.0%, p=0.34). Post-transplant, CBF and OEF were not significantly different from controls (CBF=48.213.4 ml/100g/min; p=0.78, and OEF=39.67.0%; p>0.99). CMRO2 did not change significantly following haploBMT (pre-transplant=3.180.87 ml O2/100g/min; post-transplant: 2.950.83; p=0.56). Major complications of haploBMT included one infection-related death and one severe chronic graft versus host disease. HaploBMT in adults with SCD reduces CBF to control values and maintains OEF and CMRO2 on average at levels observed in healthy adult controls.