The objective of this study is to determine the effect of hematopoietic stem cell transplantation (HSCT) on disease progression in patients with CSF1R-related leukoencephalopathy.

CSF1R-related leukoencephalopathy is an autosomal dominant disease that typically presents in adulthood as combinations of frontal-predominant cognitive impairment with pyramidal and extrapyramidal tract dysfunction. Treatment of this disease is symptomatic with an average disease duration of seven years. There are a few case reports suggesting a role for HSCT in patients with this disease with patients showing stability or even improvement post-transplant.

We performed HSCT on seven patients with genetically-confirmed CSF1R-related leukoencephalopathy and monitored their clinical outcomes with routine neurological examination, neuropsychological evaluation and radiographic assessments.

Our patients had an average disease duration of 2.2 (0.8-3.3) years at the time of transplant with varying degrees of white matter change and cortical atrophy on pre-transplant neuroimaging. Our average follow-up time is 9.5 months (range 2-19). Most of our patients experienced no transplant-related complications and are demonstrating slowing or stability of neurological symptoms and disease-related radiographic abnormalities.

This is the largest series of CSF1R-related leukoencephalopathy receiving HSCT. We conclude that HSCT effectively stabilizes the disease in some patients. Variability in patient responsiveness suggests that there may be measures of disease progression that should be considered when evaluating a patient’s candidacy for transplant. HSCT appears to be the first disease-modifying therapy for CSF1R-related leukoencephalopathy. This milestone may serve as a foothold towards a better understanding of the disease’s pathomechanism, thus providing new opportunities for better disease-specific therapies.