CNS-directed Prophylactic Approach to Langerhans Cell Histiocytosis.
CNS-directed Prophylactic Approach to Langerhans Cell Histiocytosis.
复制标题
中枢神经系统导向的朗格汉斯细胞组织细胞增多症预防方法。
DOI：
10.1097/mph.0000000000000781
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Morimoto A.
中科院分区：
文献类型：
--
作者：
Imashuku S;Shioda Y;Morimoto A.
由BhDMf 5ePHKbH 4 TTImqenVA + lpWIIBvonhQl 60 EtgtdlLYrLzSPu + hQedJnbNaXBf于12/01/2023组织细胞增多症（LCH）下载。正如我们所知，多系统LCH疾病的患者在结局方面分为低风险和高风险器官组（RO +/RO+）。此外，LCH是一种CNS导向的疾病，其中垂体柄的肿块病变可引起中枢性尿崩症和垂体前叶功能障碍。此外，CNS疾病高风险患者可能会发生令人沮丧的神经退行性疾病（ND）作为晚期并发症。2目前，LCH病例中CNS疾病的危险因素已得到充分认识。3特别是，发展为ND的高风险患者倾向于在年轻时（<3岁）经历多系统LCH病变，其可以涉及颅面骨。他们也可能在5.2（范围，3.5至10.0）岁的中位年龄发展LCH相关的ND。4我们以前主张，对于中枢神经系统疾病（包括ND）高危的LCH患者，应考虑进行中枢神经系统预防。5，6当LCH细胞通过微血管或淋巴途径亚临床接种CNS时，应在早期和关键阶段采取预防措施。1，6在CNS疾病高危的LCH患者中，在治疗的初始诱导期或再激活时缺乏CNS导向的预防可能是LCH相关ND后期发生的原因之一。1，5，6由于鞘内注射甲氨蝶呤治疗CNS LCH病例的报道很少，7其作为CNS疾病高危患者预防药物的有效性尚不清楚。Krenova和Sterba 1建议必须考虑长春新碱/阿糖胞苷（因为AraC穿过血脑屏障）以减少或消除LCH细胞接种CNS的可能性;然而，我们之前发现长春新碱/阿糖胞苷联合治疗方案（如日本LCH研究组研究中所用）不足以降低日本LCH相关ND的发生率。8 Krenova和Sterba 1以及我们自己6都强调了对LCH患者进行脑脊液（CSF）研究的必要性，这是确定适当的CNS导向预防措施的重要步骤。LCH相关ND的几种CSF生物标志物可用，包括骨桥蛋白、NF-L、IL-17 A+单核细胞和CD 207 + LCH细胞。6，9在LCH治疗的早期阶段检查CSF对于识别CNS疾病的高风险群体至关重要。建议在诊断时进行CSF/血清谷氨酰胺蛋白质组学评估、CSF/血浆基因突变分析（包括BRAFV 600 E突变）和神经认知/神经学/心理学评估。6然而，在过去（与急性白血病儿童患者相反），在LCH的早期治疗中，CSF研究/鞘内化疗并不常规使用。这可能是因为LCH被认为是一种反应性和良性疾病。然而，我们对这种疾病的认识发生了重大变化。最近，BRAFV 600 E突变在LCH中的发现阐明了LCH的肿瘤特征。10，11我们假设LCH相关ND病变的可能发病机制涉及LCH细胞/T细胞和CNS微血管周围神经胶质细胞之间的颅内免疫相互作用和炎症机制，这可能受到免疫球蛋白的调节或抑制。5如果我们的假设是正确的，那么可以实现预防神经退行性过程发展的CNS导向疗法，例如，通过用...
Downloaded from by BhDMf5ePHKbH4TTImqenVA+ lpWIIBvonhQl60EtgtdlLYrLzSPu+ hQedJnbNaXBf on 12/01/2023 histiocytosis (LCH). As we know, those with multisystem LCH disease fall into low-risk and high-risk organ groups (ROÀ/RO+) with respect to outcome. Also, LCH is a CNS-oriented disease in which mass lesions in the pituitary stalk may cause central diabetes insipidus and anterior pituitary dysfunction. In addition, patients at high risk for CNS disease may develop dismal neurodegenerative disease (ND) as a late complication. 2 Currently, risk factors for CNS diseases in cases of LCH are well recognized. 3 In particular, patients at high risk for developing ND tend to experience multisystem LCH lesions, which can involve the craniofacial bones, at a young age (< 3y). They may also develop LCH-related ND at a median age of 5.2 (range, 3.5 to 10.0) years. 4 We previously advocated that CNS prophylaxis should be considered for patients with LCH at high risk of CNS disease, including ND. 5, 6 Prophylactic measures should be given at the early and critical stage, when subclinical seeding of the CNS by LCH cells occurs through the microvessel or lymphoid routes. 1, 6 It is possible that the absence of CNS-directed prophylaxis during the initial induction phase of treatment, or at the time of reactivation, in LCH patients at high risk of CNS disease might be one reason for the later occurrence of LCH-related ND. 1, 5, 6 Since treatment with intrathecal methotrexate is rarely reported for cases of LCH in the CNS, 7 its effectiveness as a prophylactic agent in patients at high risk of CNS disease is unclear. Krenova and Sterba1 suggest that vincristine/cytosine arabinoside must be considered (because AraC crosses the blood-brain barrier) to reduce or eliminate the possibility of CNS seeding by LCH cells; however, we previously found that the combination of vincristine/cytosine arabinoside as an initial treatment regimen (as used in the Japan LCH Study Group study) was not sufficient to reduce the incidence of LCH-related ND in Japan. 8 Both Krenova and Sterba1 and ourselves6 underscore the necessity of cerebrospinal fluid (CSF) studies in those with LCH as an important step in determining appropriate CNS-directed prophylactic measures. Several CSF biomarkers for LCH-related ND are available, including osteopontin, NF-L, IL-17A+ monocytes, and CD207+ LCH cells. 6, 9 Examination of the CSF during the early stage of LCH treatment is critical for identifying groups at high risk of CNS disease. CSF/serum cytokine-proteomic assessments, CSF/plasma gene mutation analyses (including BRAFV600E mutation), and neurocognitive/neurological/psychological assessments at the time of diagnosis are recommended. 6 However, in the past (and in contrast to pediatric patients with acute leukemia), CSF studies/intrathecal chemotherapy was not routinely employed during early treatment of LCH. This is probably because LCH was thought to be a reactive and benign disease. However, our understanding of the disease has changed significantly. More recently, the discovery of the BRAFV600E mutation in LCH has clarified the neoplastic characteristics of LCH. 10, 11 We hypothesized that the probable pathogenesis of LCH-related ND lesions involves intracranial immune interactions and inflammatory mechanisms between LCH cells/T cells and glial cells around microvessels in the CNS, which may be modulated or suppressed by immunoglobulins. 5 If our hypothesis is correct, then CNS-directed therapies that prevent development of neurodegenerative processes could be achieved, for example, by killing of neoplastic LCH cells with …