儿童中枢神经系统白血病的诊治进展

鉴于急性白血病联合化疗时血脑屏障的作用,白血病细胞逃避化疗药物的杀伤最终导致中枢神经系统白血病(central nervous system leukemia,CNSL)发生.目前诊断CNSL的标准主要是依赖于脑脊液(carebrospinal fluid,CSF)检查、临床表现和影像学检查,早期诊断方法有CSF细胞形态学检查、CT和MRI等影像学检查、CSF微小残留病的检测、检测CSF硫化氢含量、分子生物学指标的检测.CNSL的预防主要包括直接鞘内注射药物、可透过血脑屏障的全身化疗药物和放射疗法.CNSL的治疗主要包括化疗放疗、异基因造血干细胞的移植和靶向治疗.     

以肥胖为首发症状的复发性中枢神经系统白血病

目的分析罕见的以肥胖为首发症状的中枢神经系统白血病(CNSL)的诊断。方法 1例6岁4个月男孩,近3个月来进行性肥胖伴性格改变,以往患急性淋巴细胞白血病(ALL,普通B细胞,BCR-ABL阴性,中危),经化疗后持续缓解超过2年。根据临床表现做一系列的实验室和影像学检查进行诊断和鉴别诊断,并进行相关中英文文献复习。结果脑脊液(CSF)白细胞中度升高,以单个核细胞为主,伴少量可疑的幼稚淋巴细胞,葡萄糖和氯化物低,蛋白稍高,MRI示脑膜、大脑皮质、下丘脑和垂体柄以及桥脑等中线结构、颅神经根等信号异常。临床检查分析排除单纯肥胖、Cushing综合征等继发性肥胖和结核性脑膜炎;CSF流式细胞术检查发现65%的有核细胞符合ALL细胞的特征而诊断为CNSL复发,经化疗和头颅放疗后缓解。目前中、英文文献只检索到3篇相似病例的个案报道。结论肥胖和性格改变可以是CNSL的首发症状,但由于罕见,需注意与其他疾病鉴别,传统的CSF细胞形态学结合流式细胞术检查将提高CNSL诊断的可靠性。     

小儿中枢神经系统白血病45例临床分析

本文报告了 45例小儿中枢神经系统白血病 (CNSL) ,分析了CNSL的隐匿性及二次复发 ,提出鞘内注射仍是预防和治疗CNSL的有效手段。主张在仅有脑脊液 (CSF)检查发现 1～ 2个幼稚细胞时 ,可观察 1～ 2周再做CSF检查 ,以确定治疗方案     

流式细胞术在诊断儿童中枢神经系统白血病中的意义

目的 探讨流式细胞术(FCM)在诊断儿童中枢神经系统白血病(CNSL)中的意义.方法 分别采用FCM及细胞形态学(CC)检测急性淋巴细胞白血病(ALL)患儿脑脊液(CSF),对比这两种方法诊断儿童CNSL的敏感度.结果 脑脊液FCM检出67例异常表型细胞,检出率为20.36％;脑脊液CC检出6例异常细胞,检出阳性率1....     

脑脊液可溶性细胞粘附分子的检测及其临床意义

目的　 检测脑脊液中sICAM 1与sL 选择素水平 ,探讨其在小儿中枢神经系统白血病中的临床意义。 方法 　采用双抗体夹心方法检测 43例ALL小儿血清、脑脊液中sICAM -1与sL -选择素水平。 结果 　合并CNSL时 ,sICAM -1与sL -选择素较对照组升高、甚至在诊断CNSL之前 12周时已经较对照组升高。且CSF中sICAM -1与sL -选择素升高出现在CSF常规检查改变之前。 结论 　检测ALL患儿脑脊液中sICAM -1与sL -选择素水平 ,并结合细胞学等其他检查 ,有助于早期诊断CNSL ,有助于判断ALL疗效及预后     

脑脊液可溶性细胞粘附分子的检测及其临床意义

目的 检测脑脊液中sICAM-1与sL-选择素水平，探讨其在小儿中枢神经系统白血病中的临床意义。方法 采用双抗体夹心方法检测43例ALL小儿血清、脑脊液中sICAM-1与sL-选择水平。结果 合并CNSL时，sICAM-1与sL-选择素较对照组升高、甚至在诊断CNSL之前12周时已经较对照组升高。且CSF中sICAM-1与sL-选择素升高出现在CSF常规检查改变之前。结论 检测ALL患儿脑脊液中sICAM-1与sL-选择素水平，并结合细胞学等其他检查，有助于早期诊断CNSL，有助于判断ALL疗效及预后。     

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目的总结170例脑脊液(CSF)细胞学的检查结果,分析其在小儿神经系统疾病或具有中枢神经系统表现疾病诊断中的临床意义。方法2000-06—2004-04河北省儿童医院对170例患儿进行CSF细胞学检查,CSF标本经玻片离心法制片,常规采用迈-格-姬染色后观察。结果CSF细胞学检查结果发现包括特异性病原体与恶性肿瘤,共4例,占全部CSF检查的2.3%,其中新型隐球菌2例,脑膜白血病2例。跟踪观察治疗前后CSF细胞学变化89例,其中结核性脑膜炎20例,化脓性脑膜炎29例,病毒性脑炎40例,治疗前后CSF细胞学检查主要表现为细胞成分及数量的变化。结论CSF细胞学检查对小儿神经系统疾病的临床诊断和治疗有重要意义,其特异性发现恶性肿瘤主要为脑膜白血病,病原体以新型隐球菌多见。脑脊液细胞学检查能直接、客观地评价临床疗效。     

儿童中枢神经系统白血病治疗进展

白血病是全身性疾病 ,各重要脏器均有浸润。血脑脊液屏障使多数药物未能在脑脊液 (CSF)中达到有效浓度 ,从而使中枢神经系统 (CNS)常成为疾病复发的根源。 70年代急性淋巴细胞性白血病 (ALL)的中枢神经系统白血病 (CNSL)发生率约 2 6%～ 3 0 % ,急性非淋巴细胞性白血病 (ANLL)的CNSL发生率约 5 %～ 18%。近年来采用放疗、化疗鞘注等方法使发生率降至 5 %～ 10 %。CNSL可发生在白血病的不同时期 ,约 5 0 %发生在缓解期 (CR) ,3 %发病时有CNSL者[1] 。ALL在CR 2个月内很少发生CNSL ,2个月后发病率开始上升 ,2～ 40个月为发病…     

儿童中枢神经系统白血病22例临床分析

目的分析22例急性白血病合并中枢神经系统白血病(CNSL)患儿的住院资料,为CNSL诊治提供参考。方法分析22例儿童CNSL的临床特征、实验室检查及预后。结果在303例儿童急性白血病中发生CNSL 22例,发生率7.3%,其中急性淋巴细胞白血病(ALL)18例,急性混合型白血病(MPAL)1例,急性髓细胞白血病(AML)3例;在18例ALL中,B-ALL 11例,T-ALL 7例,T-ALL合并CNSL发生率(22.6%)高于B-ALL(5.6%);CNSL常见临床表现有头痛、呕吐、惊厥及瘫痪等;CNSL预后差,死亡率高。结论 CNSL是急性白血病复发的主要原因之一,根据危险度来预防和治疗CNSL是关键。     

小儿中枢神经系统白血病45例临床分析

本文报告了45例小儿中枢神经系统白血病（CNSL），分析了CNSL的隐匿性及二次复发，提出鞘内注射仍是预防和治疗CNSL的有效手段。主张在仅有脑脊液（CSF）检查发现1－2个幼稚细胞时，可观察1－2周再做CSF检查，以确定治疗方案。     

小儿急性白血病脑脊液细胞离心检查

用细胞玻片离心法对７８例急性白血病患儿４１８次脑脊液标本进行了细胞学检查，阳性率分别为６０．３％和３７．８％。这是一种简单、快速、有效的方法，对儿童中枢神经系统白血病检查比传统的测压、白细胞计数、蛋白定量三项指标敏感、可靠，可用于中枢神经系统白血病的早期诊断、疗效观察。     

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??Objective To explore the differential diagnostic significance of cerebrospinal fluid??CSF?? detection with flow cytometry??FCM?? technology in children with acute lymphoblastic leukemia??ALL?? accompanied by central nervous system diseases. Methods Seven CSF samples of children with ALL were detected by FCM??cell morphology??CSF routine tests and biochemical examination in Department of Pediatrics??the First Affiliated Hospital??Sun Yat-sen University from February 2009 to February 2014. The children were treated and followed-up. The comparison between FCM and traditional methods in the diagnosis of ALL accompanied with encephalopathy was made. Results According to the traditional methods??only two patients were diagnosed reliably with CNSL??and in the other five patients??the initial diagnosis ??CNSL or non-CNSL?? was equivocal. But according to the results of FCM??four patients were diagnosed with CNSL??and three of them had acquired complete remission after systemic and intrathecal chemotherapy. One patient died because of disease progression. Two patients?? who were diagnosed with viral meningitis?? improved rapidly after treatment with acyclovir. One patient was finally diagnosed with reactive meningitis disease?? because the cerebrospinal fluid gradually returned to normal without treatment and the follow-up was uneventful. Conclusion FCM is a highly sensitive technique capable of accurately detecting malignant cells. It is an important supplement to CSF routine detections??and has significant application value in differential diagnosis of ALL children accompanied by central nervous system diseases.     

宏基因组二代测序在伴有中枢神经系统受累儿童噬血细胞综合征中的应用价值

目的 探究宏基因组二代测序(metagenomic next-generation sequencing,mNGS)技术检测伴有中枢神经系统受累的噬血细胞综合征患儿颅内EB病毒(Epstein-Barr virus,EBV)感染的应用价值及临床意义。方法 回顾性分析30例伴有中枢神经系统受累的噬血细胞综合征患儿的脑脊液mNGS结果,与脑脊液EBV-DNA定性检测、血清EBV抗体谱检测结果进行比较,以治疗前后血清EBV-DNA拷贝数变化反映针对性治疗效果。结果 脑脊液mNGS EBV检测阳性率为100%(30/30),高于脑脊液EBV-DNA定性检测阳性率(10%,3/30;P<0.001),与血清EBV抗体谱检测阳性率(93%,28/30)比较差异无统计学意义(P>0.05)。中位mNGS EBV检出序列数为2 400,治疗前血清EBV-DNA拷贝数与EBV检出序列数呈中度正相关(rs=0.693,P<0.001)。多元线性回归分析结果显示,治疗前血清EBV-DNA拷贝数越高,脑脊液mNGS EBV检出序列数越高(P<0.05)。结论 EBV相关噬血细胞综合征容...     

Immunophenotyping of the cerebrospinal fluid as a prognostic factor at diagnosis of acute lymphoblastic leukemia in children and adolescents

This study aimed at evaluating the use of immunophenotyping (IMP) in the identification of blast cells in the cerebrospinal fluid (CSF) of children and adolescents with acute lymphoblastic leukemia (ALL). Sixty-seven patients aged 18 years or younger were included. Fifty-five CSF samples were analyzed at initial diagnosis and 17 at the time of relapse. A cytological analysis (CA) was performed in all 72 samples, while IMP was done in 63. Blasts were identified in only three samples by CA, whereas all three samples were found negative by IMP, one of which had no isolation of nucleated cells after centrifugation. Among the samples analyzed by IMP, 11 showed a positive blast count, two of which had been inconclusive using CA. No equivalence was found between CA and IMP results (p = 0.55). CSF IMP positivity was not associated with other risk factors for ALL relapse. Among the 55 patients included at the time of diagnosis of ALL, eight relapsed during follow-up. Considering the cases of central nervous system (CNS) relapse, one of the patients belonged to the CSF IMP-positive group (11%) at diagnosis, and the other two cases, to the IMP-negative (5%) group. Detection of CSF blast cells using IMP was associated with a worse overall (p < 0.0001) and event-free survival (p < 0.0001). These results show that CSF IMP may be a useful additional method to conventional CA in the diagnosis of CNS involvement in ALL, and for the identification of high-risk subgroups that would benefit from an intensified therapy.     

脑脊液流式细胞学检测技术鉴别小儿急性淋巴细胞白血病并发中枢神经系统疾病应用价值探讨（附7例报告）

目的 探讨儿童急性淋巴细胞白血病（ALL）并发中枢神经系统（CNS）疾病时脑脊液流式细胞学（FCM）检测技术的鉴别诊断价值。方法　采用FCM技术、脑脊液常规细胞形态学、脑脊液常规和生化检测对2009年2月至2014年2月在中山大学附属第一医院（包括东院）儿科住院的7例脑脊液淋巴细胞数增多的ALL患儿脑脊液标本进行检测,并对患儿进行治疗追踪,比较FCM与传统方法在诊断ALL并脑病时的差别和准确性。结果　按照传统细胞形态学方法,2例诊断为CNS白血病（CNSL）,其余诊断不确定;依据FCM检测结果,7例患儿中诊断CNSL 4例,诊断非白血病浸润性疾病3例,通过治疗和追踪,后者确诊病毒性脑膜炎2例,反应性脑膜炎1例。确诊CNSL的4例患儿经过全身和鞘注化疗,1例因疾病进展死亡,其余3例均已获得缓解;2例病毒性脑膜炎患儿经阿昔洛韦治疗病情迅速改善;1例反应性脑膜炎患儿未经治疗,脑脊液逐步恢复正常。结论　脑脊液FCM技术敏感度高,可以提供客观、更精确的判断依据,是脑脊液细胞形态学检测方法的重要补充,在儿童ALL并发CNS疾病的鉴别诊断中有重要价值。     

Recurrent central nervous system acute lymphoblastic leukemia associated with cerebrospinal fluid eosinophilia and basophilia: a proposed cytokine-mediated mechanism

The authors describe a case of acute lymphoblastic leukemia with two subsequent isolated central nervous system (CNS) relapses, each accompanied by cerebrospinal fluid (CSF) eosinophilia and basophilia. Despite marked peripheral blood and bone marrow eosinophilia at initial diagnosis, the patient had no blood or bone marrow eosinophilia, basophilia, or leukemic blasts at the time of either CNS relapse. The literature is reviewed and a possible cytokine-based mechanism is proposed for the unusual finding of simultaneous CSF eosinophilia, basophilia, and leukemic blasts.     

急性淋巴细胞白血病并中枢神经系统白血病的诊断与治疗

目的：探讨急性淋巴细胞白血病（ALL）并中枢神经系统白血病（CNSL）的诊断与治疗及影响发病和预后的因素。方法：对1990－1999年收治117例临床资料进行回顾分析。结果：CNSL发生距确诊ALL的中位数时间为8个月,高危型组发生率（54．85）明显高于标危型组（23．7％）。31例CNSL中以脑脊液（CSF）异常作出诊断远比临床症状多。CNSL治疗效果显示,大剂量氨甲喋呤＋三联鞘注＋四组（CR＋IT）相当。结论：为避免诊断假阳性造成的过度治疗,CSF仅有幼稚细胞而白细胞计数政党者诊断CNSL应慎重,HDMTX＋IT＋FC是治疗CNSL的有效措施。     

Cerebrospinal fluid pleocytosis in acute lymphoblastic leukemia without central nervous system relapse: a report of three cases

Three patients with acute lymphoblastic leukemia (ALL) developed mononuclear cells in the cerebrospinal fluid (CSF) after a flu-like history during maintenance treatment. None of the patients showed evidence of central nervous system (CNS) involvement by either clinical or laboratory follow-up. Although the presence of > 5 mononuclear cells/microl in the CSF is important, it may not necessarily indicate CNS disease. Clinical findings, history and cell morphology must be evaluated before deciding on further treatment.