Repair of the Blood Brain Barrier and Neutrophil Recovery Following HSCT in Cerebral Adrenoleukodystrophy

Cerebral leukodystrophy is an X-linked peroxisomal disease characterized by mutations in the ABCD1 gene, resulting in the lack of very long chain fatty acid (VLCFA) transport into peroxisomes. Resultant VLCFA build up in the blood and tissues leads to adrenal gland insufficiency in 95% of boys and a progressive inflammatory cerebral demyelinating process in 40% of patients, which is progressive and most often fatal (cALD). Only hematopoietic stem cell transplant (HSCT) has been shown to halt cerebral disease progression. A key clinical feature of cALD is disruption of the blood brain barrier (BBB) illustrated by gadolinium (gad) contrast enhancement on brain MRI at diagnosis and as an indicator of "active" cerebral disease. Following successful donor neutrophil recovery after HSCT, gad enhancement resolves in the majority of cases by 100 days post HSCT in our experience. A seminal question in the field is how recovery of donor-derived hematopoiesis relates to BBB repair and gad resolution. We evaluated the pre-HSCT characteristics and 1- year post-HSCT outcomes in 78 boys undergoing marrow or umbilical cord blood HSCT for cALD. The median total nucleated cell (TNC) dose was 0.8 x 108cells/kg and CD34+ cell dose was 1.27 x 106cells/kg. Pre-HSCT characteristics included: cALD on MRI quantitated using the Loes scoring system, neurologic disability using the neurologic function scale (NFS), plasma and cerebral spinal fluid (CSF) chitotriosidase level, and intensity of gadolinium ...
Source: Blood - Category: Hematology Authors: Tags: 732. Clinical Allogeneic Transplantation: Results: Poster III Source Type: research