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Hematopoietic Stem Cell Transplantation in CSF1R-Related Leukoencephalopathy: Retrospective Study on Predictors of
Jarosław Dulski1,2,3, Michael G Heckman4, Launia J White4
1Department of Neurology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA.
Insights
For CSF1R-ALSP patients undergoing hematopoietic stem cell transplantation (HSCT), initial gait problems predict good outcomes, while cognitive impairment suggests a poor response to HSCT.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Mutations in the CSF1R gene cause adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a severe neurodegenerative disease.
- Hematopoietic stem cell transplantation (HSCT) is a potential treatment for CSF1R-ALSP, but outcomes vary significantly.
- Identifying predictors for HSCT success in CSF1R-ALSP is crucial for patient selection.
Purpose of the Study:
- To determine predictors of favorable and unfavorable outcomes following HSCT in patients with CSF1R-ALSP.
- To elucidate which patients with CSF1R-ALSP are most likely to benefit from HSCT.
Main Methods:
- Retrospective analysis of 15 patients with CSF1R-ALSP who underwent HSCT.
- Evaluation of clinical manifestations, age at onset, and age at HSCT.
- Correlation of initial symptoms and demographic factors with HSCT outcomes.
Main Results:
- Good HSCT outcomes were associated with gait problems as the initial and predominant manifestation (p=0.041, p=0.017) and younger age at HSCT (p=0.044).
- Cognitive impairment as the first manifestation predicted poor outcomes (p=0.016) and post-HSCT cognitive decline (p=0.025).
- Median follow-up was 26 months, with a median age of onset of 39 and median age of HSCT of 43 years.
Conclusions:
- Gait problems at onset indicate a milder CSF1R-ALSP phenotype and better response to HSCT.
- Patients presenting with significant cognitive impairment may not benefit from HSCT and are at risk for further cognitive deterioration.
- These findings aid in selecting appropriate candidates for HSCT in CSF1R-ALSP.
Abstract:
Mutations in the CSF1R gene are the most common cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a neurodegenerative disease with rapid progression and ominous prognosis. Hematopoietic stem cell transplantation (HSCT) has been increasingly offered to patients with CSF1R-ALSP. However, different therapy results were observed, and it was not elucidated which patient should be referred for HSCT. This study aimed to determine predictors of good and bad HSCT outcomes in CSF1R-ALSP. We retrospectively analyzed 15 patients, 14 symptomatic and 1 asymptomatic, with CSF1R-ALSP that underwent HSCT. Median age of onset was 39 years, and the median age of HSCT was 43 years. Cognitive impairment was the most frequent initial manifestation (43%), followed by gait problems (21%) and neuropsychiatric symptoms (21%). Median post-HSCT follow-up was 26 months. Good outcomes were associated with gait problems as initial (p = 0.041) and predominant (p = 0.017) manifestation and younger age at HSCT (p = 0.044). Cognitive impairment as first manifestation was a predictor of a bad outcome (p = 0.016) and worsening of cognition post-HSCT (p = 0.025). In conclusion, gait problems indicated a milder phenotype with better response to HSCT and good therapy outcomes. In contrast, patients with a higher burden of cognitive symptoms were most likely not to benefit from HSCT.
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