Despite the growing evidence supporting the existence of CNS involvement in acute and chronic graft-versus-host disease (CNS-GvHD), the characteristics and course of the disease are still largely unknown. In this multicenter retrospective study, we analyzed the clinical, biological, radiological, and histopathological characteristics, as well as the clinical course of 66 patients diagnosed with possible CNS-GvHD (pCNS-GvHD), selected by predetermined diagnostic criteria. Results were then contrasted depending on whether pCNS-GvHD occurred before or after day 100 following allogeneic hematopoietic stem cell transplantation. Median time between hematopoietic stem cell transplantation and pCNS-GvHD onset was 149 days (IQ25-75 48-321), and pCNS-GvHD onset occurred before day 100 following transplantation in 44% of patients. The most frequent findings at presentation were cognitive impairment (41%), paresis (21%), altered consciousness (20%), sensory impairment (18%), and headache (15%). Clinical presentation did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Brain MRI found abnormalities compatible with the clinical picture in 57% of patients, while CT detected abnormalities in only 7%. Seven patients had documented spinal cord MRI abnormalities, all of them with pCNS-GvHD occurring after day 100 following transplantation. In the cerebrospinal fluid, white blood cell count was increased in 56% of the population (median 18 cells/μL). Histopathological analyses were performed on 12 specimens and were suggestive of pCNS-GvHD in 10. All compatible specimens showed parenchymal and perivascular infiltration by CD3+ and CD163+ cells. Immunosuppressive therapy was prescribed in 97% of patients, achieving complete clinical response in 27%, partial improvement in 47% and stable disease in 6%. Response to immunosuppressive therapy did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Clinical relapse was observed in 31% of patients who initially responded to treatment. One-year overall survival following pCNS-GvHD onset was 41%. Onset before day 100 following hematopoietic stem cell transplantation (HR [95%CI]: 2.1 [1.0-4.5]; P=0.041) and altered consciousness at initial presentation (HR [95%CI]: 3.0 [1.3-6.7]; P=0.0077) were associated with a reduced one-year overall survival probability. Among surviving patients, 61% had neurological sequelae. This study supports that immune-mediated CNS manifestations may occur following allo-HSCT. These can be associated with both acute and chronic GvHD and carry a grim prognosis. The clinical presentation as well as the radiological and biological findings appear variable.

中文翻译：

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急性和慢性移植物抗宿主病的中枢神经系统表现。


尽管越来越多的证据支持 CNS 参与急性和慢性移植物抗宿主病 （CNS-GvHD），但该疾病的特征和病程在很大程度上仍然未知。在这项多中心回顾性研究中，我们分析了 66 例诊断为疑似 CNS-GvHD （pCNS-GvHD） 的患者的临床、生物学、放射学和组织病理学特征，以及根据预定诊断标准选择的临床病程。然后根据同种异体造血干细胞移植后 pCNS-GvHD 是发生在第 100 天之前还是之后对结果进行对比。造血干细胞移植与 pCNS-GvHD 发病之间的中位时间为 149 天 （IQ25-75 48-321），44% 的患者在移植后第 100 天之前发病。就诊时最常见的发现是认知障碍 （41%） 、麻痹 （21%）、意识改变 （20%）、感觉障碍 （18%） 和头痛 （15%）。移植后 100 天之前或之后发生的 pCNS-GvHD 患者的临床表现没有显著差异。脑部 MRI 发现 57% 的患者出现与临床表现相符的异常，而只有 7% 的患者 CT 检测到异常。7 例患者记录了脊髓 MRI 异常，所有患者均在移植后 100 天后发生 pCNS-GvHD。在脑脊液中，56% 的人群白细胞计数增加 （中位数 18 个细胞/μL）。对 12 个标本进行了组织病理学分析，其中 10 个标本提示 pCNS-GvHD。所有相容标本均显示 CD3 + 和 CD163 + 细胞的实质和血管周围浸润。 97% 的患者接受了免疫抑制治疗，27% 的患者达到完全临床缓解，47% 的患者达到部分改善，6% 的患者病情稳定。移植后 100 天之前或之后发生的 pCNS-GvHD 患者对免疫抑制治疗的反应没有显著差异。在最初对治疗有反应的患者中，有 31% 的患者观察到临床复发。pCNS-GvHD 发病后的 1 年总生存率为 41%。造血干细胞移植后第 100 天前发病 （HR [95%CI]： 2.1 [1.0-4.5];P=0.041） 和初始表现时意识改变 （HR [95%CI]： 3.0 [1.3-6.7];P=0.0077） 与一年总生存概率降低相关。在幸存的患者中，61% 有神经系统后遗症。本研究支持免疫介导的 CNS 表现可能发生在同种异体 HSCT 之后。这些可能与急性和慢性 GvHD 有关，并且预后很严峻。临床表现以及放射学和生物学发现似乎各不相同。