Haddad E, Sulis M L, Jabado N, Blanche S, Fischer A, Tardieu M
Unité d'Immuno-Hématologie et Unité INSERM 429, Hôpital Necker-Enfants Malades, Paris, France.
Blood. 1997 Feb 1;89(3):794-800.
We have retrospectively assessed the neurological manifestations in 34 patients with hemophagocytic lymphohistiocytosis (HLH) in a single center. Clinical, radiological, and cerebrospinal fluid (CSF) cytology data were analyzed according to treatment modalities. Twenty-five patients (73%) had evidence of central nervous system (CNS) disease at time of diagnosis, stressing the frequency of CNS involvement early in the time course of HLH. Four additional patients who did not have initial CNS disease, who did not die early from HLH complications, and who were not transplanted, also developed a specific CNS disease. Therefore, all surviving and nontransplanted patients had CNS involvement. Initially, CNS manifestations consisted of isolated lymphocytic meningitis in 20 patients and meningitis with clinical and radiological neurological symptoms in nine patients. For these nine patients, neurological symptoms consisted of seizures, coma, brain stem symptoms, or ataxia. The outcome of patients treated by systemic and intrathecal chemotherapy and/or immunosuppression exclusively (n = 16) was poor, as all died following occurrence of multiple relapses or CNS disease progression in most cases. Bone marrow transplantation (BMT) from either an HLA identical sibling (n = 6) or haplo identical parent (n = 3) was performed in nine patients, once first remission of CNS and systemic disease was achieved. Seven are long-term survivors including three who received an HLA partially identical marrow. All seven are off treatment with normal neurological function and cognitive development. In four other patients, BMT performed following CNS relapses was unsuccessful. Given the frequency and the poor outcome of CNS disease in HLH, BMT appears, therefore, to be the only available treatment procedure that is capable of preventing HLH CNS disease progression and that can result in cure when performed early enough after remission induction.
我们回顾性评估了单中心34例噬血细胞性淋巴组织细胞增生症（HLH）患者的神经系统表现。根据治疗方式分析了临床、影像学和脑脊液（CSF）细胞学数据。25例患者（73%）在诊断时有中枢神经系统（CNS）疾病证据，突出了HLH病程早期CNS受累的频率。另外4例最初没有CNS疾病、未因HLH并发症过早死亡且未接受移植的患者，也出现了特定的CNS疾病。因此，所有存活且未接受移植的患者均有CNS受累。最初，CNS表现包括20例单纯淋巴细胞性脑膜炎和9例伴有临床及影像学神经症状的脑膜炎。对于这9例患者，神经症状包括癫痫发作、昏迷、脑干症状或共济失调。仅接受全身和鞘内化疗及/或免疫抑制治疗的患者（n = 16）预后较差，因为大多数病例在多次复发或CNS疾病进展后均死亡。9例患者在CNS和全身疾病首次缓解后，接受了来自HLA相同同胞（n = 6）或单倍体相同父母（n = 3）的骨髓移植（BMT）。7例为长期存活者，其中3例接受了HLA部分相同的骨髓。所有7例均已停止治疗，神经功能和认知发育正常。另外4例在CNS复发后进行BMT的患者未成功。鉴于HLH中CNS疾病的频率和不良预后，因此，BMT似乎是唯一能够预防HLH CNS疾病进展且在缓解诱导后尽早进行可实现治愈的可用治疗方法。
