Hematopoietic Stem Cell Transplantation in an International Cohort of Colony Stimulating Factor‐1 Receptor (<scp>CSF1R)</scp>‐Related Disorder
Hemmo A. F. Yska, Marianne Golse, Shanice Beerepoot, Stefanie N. Hayer, Caroline Bergner, Anderson Rodrigues Brandão de Paiva, Cécilia Marelli, Natalia Juliá Palacios, Yudy Llamas Osorio, Camille Huiban, Georg‐Nikolaus Franke, Friederike Wortmann, Udo Holtick, Xavier Ayrignac, Marjo S. van der Knaap, Lüdger Schöls, Vincent Perlbarg, Damien Galanaud, Moniek A. de Witte, Nicole I. Wolf, Stéphanie Nguyen, Fanny Mochel, and the International CSF1R‐RD Working Group
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.