Philip W Tipton1, Daniel Kenney-Jung2, Beth K Rush3, Erik H Middlebrooks4, David Nascene5, Balvindar Singh2, Shernan Holtan6, Ernesto Ayala7, Daniel F Broderick4, Troy Lund8, Zbigniew K Wszolek1. 1. Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA. 2. Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USA. 3. Department of Psychiatry & Psychology, Mayo Clinic, Jacksonville, Florida, USA. 4. Department of Radiology, Mayo Clinic, Jacksonville, Florida, USA. 5. Department of Radiology, University of Minnesota, Minneapolis, Minnesota, USA. 6. Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA. 7. Department of Hematology Oncology, Mayo Clinic, Jacksonville, Florida, USA. 8. Department of Pediatrics, Division of Blood and Marrow Transplant, University of Minnesota, Minneapolis, Minnesota, USA.
Abstract
BACKGROUND: Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy is a rapidly progressive neurodegenerative disease for which there is currently no cure. Hematopoietic stem cell transplantation (HSCT) has been proposed as a disease-modifying treatment. OBJECTIVE: The objective of this study was to determine the effect of HSCT on disease progression. METHODS: We collected all available clinical data from a cohort of 7 patients with CSF1R-related leukoencephalopathy who underwent HSCT at our institutions. Clinical data included detailed neurological examination by a board-certified neurologist, serial cognitive screens, formal neuropsychological evaluations, and serial brain magnetic resonance imaging (MRI). RESULTS: Our patients had an average disease duration of 27.6 months at the time of transplant, and we have 87 months of total posttransplant follow-up time (median, 11; range, 2-27). One patient died in the periprocedural period. The remaining patients showed a variable response to treatment, with 6 of 7 patients trending toward stabilization on motor examination, cognitive scores, and/or MRI abnormalities, especially with white matter lesion burden. CONCLUSIONS: This is the largest series of patients with CSF1R-related leukoencephalopathy receiving HSCT. We conclude that HSCT can stabilize the disease in some patients. Variability in patient responsiveness suggests that measures of disease heterogeneity and severity need to 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 toward better understanding the disease's pathomechanism, thus providing new opportunities for better disease-specific therapies.
BACKGROUND: Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy is a rapidly progressive neurodegenerative disease for which there is currently no cure. Hematopoietic stem cell transplantation (HSCT) has been proposed as a disease-modifying treatment. OBJECTIVE: The objective of this study was to determine the effect of HSCT on disease progression. METHODS: We collected all available clinical data from a cohort of 7 patients with CSF1R-related leukoencephalopathy who underwent HSCT at our institutions. Clinical data included detailed neurological examination by a board-certified neurologist, serial cognitive screens, formal neuropsychological evaluations, and serial brain magnetic resonance imaging (MRI). RESULTS: Our patients had an average disease duration of 27.6 months at the time of transplant, and we have 87 months of total posttransplant follow-up time (median, 11; range, 2-27). One patient died in the periprocedural period. The remaining patients showed a variable response to treatment, with 6 of 7 patients trending toward stabilization on motor examination, cognitive scores, and/or MRI abnormalities, especially with white matter lesion burden. CONCLUSIONS: This is the largest series of patients with CSF1R-related leukoencephalopathy receiving HSCT. We conclude that HSCT can stabilize the disease in some patients. Variability in patient responsiveness suggests that measures of disease heterogeneity and severity need to 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 toward better understanding the disease's pathomechanism, thus providing new opportunities for better disease-specific therapies.
Authors: Adit Friedberg; Eliana Marisa Ramos; Zhongan Yang; Luke W Bonham; Jennifer S Yokoyama; Peter A Ljubenkov; Kyan Younes; Daniel H Geschwind; Bruce L Miller Journal: Front Neurol Date: 2022-06-22 Impact factor: 4.086
Authors: Spyros Papapetropoulos; Angela Pontius; Elizabeth Finger; Virginija Karrenbauer; David S Lynch; Matthew Brennan; Samantha Zappia; Wolfgang Koehler; Ludger Schoels; Stefanie N Hayer; Takuya Konno; Takeshi Ikeuchi; Troy Lund; Jennifer Orthmann-Murphy; Florian Eichler; Zbigniew K Wszolek Journal: Front Neurol Date: 2022-02-03 Impact factor: 4.003