Allogeneic HSCT for adult-onset leukoencephalopathy with spheroids and pigmented glia
Allogeneic HSCT for adult-onset leukoencephalopathy with spheroids and pigmented glia
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DOI：
10.1093/brain/awz390
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发表时间：
2020-02-01
期刊：
影响因子：
14.5
通讯作者：
Mannis, Gabriel N.
中科院分区：
文献类型：
--
作者：
Gelfand, Jeffrey M.;Greenfield, Ariele L.;Mannis, Gabriel N.
成人发病脑白质病伴球样细胞和色素胶质（ALSP）是一种常染色体显性脑白质病，由集落刺激因子1受体（CSF1R）突变引起。在此，我们报告了2016年1月至2017年12月期间，加州大学旧金山分校的两名ALSP患者接受同种异体造血干细胞移植（HSCT）后的临床和影像学结果。患者1在53岁时接受了单倍同卵兄弟姐妹供体的移植。患者2，其姐姐和母亲都死于该疾病，在49岁时接受了12/12人类白细胞抗原匹配的非亲属供体的移植。两名患者均接受了低强度调理方案。分别在移植后28个月和26个月，两名患者都存活，没有移植物抗宿主病的证据，其中一名患者在1年出现严重感染，另一名患者出现新发作。在这两种情况下，hsct后神经系统继续恶化；然而，认知缺陷、整体功能状态和步态障碍的进展逐渐稳定。两名患者的帕金森病都有持续的进展。在脑MRI上，1年内T-2/FLAIR异常稳定，2年后异常多灶性弥散减弱完全消退。总之，经过50年的随访，ALSP的同种异体造血干细胞移植导致弥散性MRI异常的间歇消退，T-2/FLAIR MRI异常的稳定，以及部分临床稳定，支持治疗反应。同种异体造血干细胞移植可能对ALSP有益，因为它提供了骨髓来源的脑移植骨髓细胞和供体野生型CSF1R，以重新填充小胶质细胞生态位。
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 T-2/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 T-2/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.