Allogeneic HSCT for adult-onset leukoencephalopathy with spheroids and pigmented glia
| Autor: | Keith Van Haren, Christopher P. Hess, Ariele L. Greenfield, Matthew J. Barkovich, Jeffrey M. Gelfand, Bryce A. Mendelsohn, Gabriel N. Mannis |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Male medicine.medical_specialty medicine.medical_treatment Hematopoietic stem cell transplantation Fluid-attenuated inversion recovery Colony stimulating factor 1 receptor Leukoencephalopathy 03 medical and health sciences 0302 clinical medicine Leukoencephalopathies Internal medicine medicine Humans business.industry Parkinsonism Leukodystrophy Brain Middle Aged medicine.disease Transplantation 030104 developmental biology Graft-versus-host disease Receptors Granulocyte-Macrophage Colony-Stimulating Factor Mutation Disease Progression Female Neurology (clinical) Microglia business Cognition Disorders Neuroglia 030217 neurology & neurosurgery |
| Zdroj: | Brain : a journal of neurology. 143(2) |
| ISSN: | 1460-2156 |
| Popis: | Adult-onset leukoencephalopathy with spheroids and pigmented glia (ALSP) is an autosomal dominant leukoencephalopathy caused by mutations in colony stimulating factor 1 receptor (CSF1R). Here we report clinical and imaging outcomes following allogeneic haematopoietic stem cell transplantation (HSCT) in two patients with ALSP at the University of California, San Francisco between January 2016 and December 2017. Patient 1 proceeded to transplantation at age 53 with a haplo-identical sibling donor. Patient 2, whose sister and mother had died of the disease, proceeded to transplantation at age 49 with a 12/12 human leukocyte antigen-matched unrelated donor. Both patients received reduced intensity conditioning regimens. At 28 and 26 months post-HSCT, respectively, both patients were alive, without evidence of graft-versus-host disease, with major infection at 1 year in one and new-onset seizures in the other. In both cases, neurological worsening continued post-HSCT; however, the progression in cognitive deficits, overall functional status and gait impairment gradually stabilized. There was continued progression of parkinsonism in both patients. On brain MRI, within 1 year there was stabilization of T2/FLAIR abnormalities, and after 2 years there was complete resolution of abnormal multifocal reduced diffusion. In summary, after >2 years of follow-up, allogeneic HSCT in ALSP led to interval resolution of diffusion MRI abnormalities, stabilization of T2/FLAIR MRI abnormalities, and partial clinical stabilization, supportive of treatment response. Allogeneic HSCT may be beneficial in ALSP by providing a supply of bone marrow-derived brain-engrafting myeloid cells with donor wild-type CSF1R to repopulate the microglial niche. |
| Databáze: | OpenAIRE |
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