Hematopoietic Stem Cell Transplantation in an International Cohort of Colony Stimulating Factor-1 Receptor (CSF1R)-Related Disorder

Abstract

Background: Colony stimulating factor-1 receptor (CSF1R)-related disorder (CSF1R-RD) is an autosomal dominant, rapidly progressive, demyelinating disease leading to death usually within a few years. Because of the central role of CSF1R in microglia functions, allogeneic hematopoietic stem cell transplantation (HSCT) has been suggested as a therapy for CSF1R-RD.

Objectives: To report multicenter clinical (Expanded Disability Scoring Scale [EDSS]), neurocognitive), neuroimaging (Sundal score), and biological (neurofilament light chain [NfL]) outcomes after HSCT in CSF1R-RD.

Methods: We report an international cohort of 17 adult patients (8 females/9 males, 43.3 ± 9.4 years) who were treated in seven transplant centers. Patients were evaluated for a median of 2.5 years post-HSCT, including one patient with follow-up of 8 years. We also report neurological outcomes of the first child transplanted to date with biallelic CSF1R variants.

Results: In the first 6 months post-HSCT, 2 patients died from early complications of myeloablative transplantation, and clinical and radiological severity scores worsened in most surviving adult patients. At 12 months post-HSCT, most patients completely stabilized or improved in certain clinical domains. Radiological scores fully stabilized or slightly improved in all but one of the patients. Plasma/serum NfL sharply decreased in most patients after transplantation. Notably, 7/8 adult patients who received a reduced-intensity conditioning regimen displayed similar neurological outcomes as patients who underwent myeloablative transplantation.

Conclusions: After an initial clinical and radiological deterioration in the first 6 months post-transplantation, HSCT can halt disease progression in patients with CSF1R-RD, regardless of their presenting clinical symptoms. The possibility of reduced conditioning regimens in CSF1R-RD opens the way to treat older patients. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: CSF1R‐RD; adult‐onset leukoencephalopathy with axonal spheroids and pigmented glia; demyelination; hematopoietic stem cell transplantation; neurofilament light chain; neuroinflammation.

FIG. 1

Clinical, neuroradiological, and biological evolution of 17 patients with CSF1R‐RD with hematopoietic stem cell transplantation (HSCT). T = 0 represents time of transplantation. (A) Clinical evolution with Expanded Disability Scoring Scale (EDDS). Besides the 2 patients who died a few months after transplant, the EDSS increased for 9/15 patients during the first 6 months post‐HSCT but then stabilized (10/15) or improved (5/15) – nonetheless, Patient‐8 returned to his baseline score at 4 years post‐HSCT. (B) Neuroradiological evolution with the Sundal score. The total Sundal score increased in 12/13 patients during the first 6 months post‐HSCT but then stabilized in 10/13 patients. (C) Plasma/serum neurofilament light chain (NfL) (pg/mL) is presented on the y‐axis. NfL increased slightly in 4/12 patients shortly after transplantation but decreased afterwards in all patients.

FIG. 2

Changes in white matter lesions in CSF1R‐RD patients with transplantation. (A) Patient‐14 presented with extensive fluid‐attenuated inversion recovery (FLAIR) hyperintensities in the frontal and parietal white matter at baseline. Lesions decreased in size from 1 year onwards after transplantation, in parallel with atrophic evolution. (B) Diffusion weighted imaging (DWI) of the same patient, exhibiting restricted diffusion in callosal lesions at baseline, that disappeared early after transplantation. (C) Patient‐13 presented with areas of FLAIR hyperintensity in the centra semiovalia at baseline. Lesions progressively decreased in thickness and extent over a period of 7 years, in parallel with atrophic evolution. (D) DWI of the same patient, exhibiting restricted diffusion in lesions of the centra semiovalia at baseline. Diffusion abnormalities progressively decreased over time and disappeared at 7 years post‐HSCT.