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.

中文翻译：

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同种异体HSCT用于成人发作的白细胞性脑病伴球体和色素性胶质细胞。

具有球状体和色素性胶质细胞的成人发作性白质脑病（ALSP）是由集落刺激因子1受体（CSF1R）突变引起的常染色体显性白质脑病。在这里，我们报告了2016年1月至2017年12月间在加利福尼亚大学旧金山分校的两名ALSP患者进行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岁时与单倍体同胞进行了移植捐赠者。患者2（其姐妹和母亲均死于该疾病）在49岁时接受了与12/12人类白细胞抗原匹配的无关供体的移植。两名患者均接受了强度降低的调理方案。分别在HSCT术后28个月和26个月，两名患者均存活，没有移植物抗宿主病的证据，一年中有一次重大感染，而另一年则是新发作。在这两种情况下，HSCT后神经系统疾病继续恶化。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持续发展。在脑部MRI上，在1年内T2 / FLAIR异常得以稳定，并且在2年后完全消除了多灶性减少的弥散性异常。总之，经过2年以上的随访，ALSP中的同种异体HSCT导致了弥散性MRI异常的间隔解决，T2 / FLAIR MRI异常的稳定以及部分临床稳定，从而支持了治疗反应。