病例报告：人类移植物抗宿主病的中枢神经系统受累：7例报告及文献复习
Case report: Central nervous system involvement of human graft versus host disease: Report of 7 cases and a review of literature.
作者信息
Ruggiu Mathilde, Cuccuini Wendy, Mokhtari Karima, Meignin Véronique, Peffault de Latour Régis, Robin Marie, Fontbrune Flore Sicre de, Xhaard Aliénor, Socié Gérard, Michonneau David
机构信息
Service d'Hématologie Greffe, Hôpital Saint Louis, APHP Université Paris Diderot, Sorbonne Paris Cité Laboratoire de Cytogénétique, Hôpital Saint Louis Laboratoire d'anatomie pathologique, Hôpital La Pitié Salpétrière, APHP Université Pierre et Marie Curie, Sorbonne Paris Cité Laboratoire d'Anatomie Pathologique, Hôpital Saint Louis, APHP EA3518, Université Paris Diderot INSERM U1131, Université Paris Diderot INSERM UMR1160, Institut Universitaire d'Hématologie, Centre Hayem, Paris, France.
出版信息
Medicine (Baltimore). 2017 Oct;96(42):e8303. doi: 10.1097/MD.0000000000008303.
RATIONALE
Central nervous system (CNS) involvement of graft versus host disease (GvHD) is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Chronic CNS GvHD symptoms are heterogeneous and include cerebrovascular manifestations, demyelinating disease and immune-mediated encephalitis. CNS-Acute GvHD is not formally defined in literature.
PATIENTS CONCERNS AND DIAGNOSES
We report 7 cases of CNS-GvHD among which two had histological-proven disease. We reviewed 32 additional cases of CNS GvHD published in literature since 1990. In this cohort, 34 patients were transplanted for hematologic malignancies, and 5 for non-malignant hematopoiesis disorders. Of these patients, 25 had a history of chronic GvHD and immunosuppressive treatment had been decreased or discontinued in 14 patients before neurological symptoms onset. Median neurological disorder onset was 385 days [7-7320]. Patients had stroke-like episodes (n = 7), lacunar syndromes (n = 3), multiple sclerosis-like presentations (n = 7), acute demyelinating encephalomyelitis-like symptoms (n = 4), encephalitis (n = 14), mass syndrome (n = 1), and 3 had non-specific symptoms. Median neurological symptoms onset was 81.5 days [7-1095] for patients without chronic GVHD history versus 549 days [11-7300] for patients with chronic GVHD (P = 0.001). Patients with early involvement of CNS after allo-HSCT and no chronic GVHD symptoms were more frequently suffering from encephalitis (64% versus 28%, P = 0.07), whereas stroke-like episodes and lacunar symptoms were less frequent (9% versus 36%, P = 0.13).
INTERVENTIONS
34 patients with CNS-GvHD were treated with immunosuppressive therapy, including corticosteroids for 31 of them. Other treatments were intravenous immunoglobulin, plasmapheresis, cyclophosphamide, calcineurin inhibitors, mycophenolic acid, methotrexate and etoposide.
OUTCOMES
27 patients achieved a response: 10 complete responses, 15 partial responses and 2 transient responses. Of 25 patients with sufficient follow-up, 7 were alive and 18 patients deceased after CNS-GvHD diagnosis.
LESSONS
CNS-related GvHD is a rare cause of CNS disorders after allo-HSCT and is associated with a poor prognosis.
理论依据
移植物抗宿主病（GvHD）累及中枢神经系统（CNS）是异基因造血干细胞移植（allo - HSCT）后中枢神经系统疾病的罕见病因。慢性中枢神经系统移植物抗宿主病症状多样，包括脑血管表现、脱髓鞘疾病和免疫介导的脑炎。中枢神经系统急性移植物抗宿主病在文献中尚无正式定义。
患者情况与诊断
我们报告了7例中枢神经系统移植物抗宿主病病例，其中2例经组织学证实。我们还回顾了自1990年以来文献中发表的另外32例中枢神经系统移植物抗宿主病病例。在这个队列中，34例患者因血液系统恶性肿瘤接受移植，5例因非恶性造血系统疾病接受移植。这些患者中，25例有慢性移植物抗宿主病病史，14例在神经症状出现前免疫抑制治疗已减少或停用。神经功能障碍发作的中位时间为385天[7 - 7320天]。患者出现类中风发作（n = 7）、腔隙综合征（n = 3）、多发性硬化样表现（n = 7）、急性脱髓鞘性脑脊髓炎样症状（n = 4）、脑炎（n = 14）、肿块综合征（n = 1），3例有非特异性症状。无慢性移植物抗宿主病病史患者的神经症状中位发作时间为81.5天[7 - 1095天]，而有慢性移植物抗宿主病患者为549天[11 - 7300天]（P = 0.001）。异基因造血干细胞移植后早期累及中枢神经系统且无慢性移植物抗宿主病症状的患者更常患脑炎（64%对28%，P = 0.07），而类中风发作和腔隙症状较少见（9%对36%，P = 0.13）。
干预措施
34例中枢神经系统移植物抗宿主病患者接受了免疫抑制治疗，其中31例使用了皮质类固醇。其他治疗包括静脉注射免疫球蛋白、血浆置换、环磷酰胺、钙调神经磷酸酶抑制剂、霉酚酸、甲氨蝶呤和依托泊苷。
结果
27例患者有反应：10例完全缓解，15例部分缓解，2例短暂缓解。在25例有足够随访时间的患者中，中枢神经系统移植物抗宿主病诊断后7例存活，18例死亡。
经验教训
中枢神经系统相关移植物抗宿主病是异基因造血干细胞移植后中枢神经系统疾病的罕见病因，且预后不良。
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