严重过敏症诱发的噬血细胞综合征临床分析

目的：对噬血细胞性淋巴组织细胞增生症（ haemophagocytic lymphohistiocytosis,HLH）临床特点及相关基因突变进行研究,推测可能的发病原因。方法3月龄患儿,发热皮疹起病,临床表现符合HLH,进行骨髓细胞学检查,并用聚合酶链反应及Sanger直接测序法对患儿进行HLH相关基因突变检测。结果患儿影像学以急性坏死性脑病为特征性表现,骨髓学检查显示大量噬血组织细胞;HLH相关基因测序发现PRF1基因有1个突变位点,UNC13D基因10个突变位点,STXBP2基因存在8个突变,XIAP基因存在2个突变,诊断继发性噬血细胞综合征,按照HLH-2004方案治疗,病情控制良好。结论患儿以坏死性脑病为特征性表现,严重超敏反应可能是导致噬血细胞综合征的病因之一,早诊断早治疗对于超敏反应引起的噬血细胞综合征及脑损伤预后非常重要。     

儿童噬血细胞综合征临床分析

噬血细胞综合征(hemophagocytic syndrome,HPS)又名噬血细胞性淋巴组织细胞增生症(he-mophagocytic lymphohistiocytosis,HLH),表现为发热、肝脾肿大和全血细胞减少,高甘油三酯和低纤维蛋白原血症等[1]。病情重,发展快,病死率高,需要早发现,早治疗。对我科收治的15例患儿进行分析。资料与方法1对象2004年1月至2006年5月间首都儿科研究所血液科收治的15例HLH患儿,15例中男10例,女5例,无明显地理分布区别。2诊断标准参见国际组织细胞协会提出的2004年诊断标准[2]15例患儿均符合诊断指标。结果1临床特点15例噬血细胞综合征的中白血病合并H…     

HLH-2004方案诊治儿童噬血细胞综合征临床分析

噬血细胞综合征(hemophagocytic syndrome,HPS)又称噬血细胞淋巴组织细胞增生症(hemophagocytic lymphohistiocytosis,HLH),是以发热、肝脾淋巴结肿大、全血细胞减少、肝功能受损、凝血功能障碍、骨髓噬血现象等为特征的一组临床综合征。临床经过凶险,病情发展迅速,如不及时诊断并进行治疗,大多数患儿病情进行性恶化,病死率高。     

噬血细胞综合征患儿的临床诊断与骨髓细胞学特点分析

目的探讨儿童噬血细胞综合征的临床诊断标准及其骨髓细胞学检查结果对于临床诊断的意义。方法回顾分析2008年5月-2011年5月于我院确诊为噬血细胞综合征的22例患儿的病历资料及骨髓细胞学特点。结果 22例患儿均符合国际组织细胞协会HLH-2004方案诊断标准。均有发热、脾大及血清铁蛋白增高,18/22例(82%)伴外周血至少两系减低,15/19例(79%)伴低纤维蛋白原血症,14/20例(70%)伴高三酰甘油血症,14/22例(64%)患儿在初诊时骨髓中找到噬血细胞。结论骨髓涂片见到噬血细胞不是儿童噬血细胞综合征临床诊断的必备条件,初诊时进行骨髓细胞学检查有助于噬血细胞综合征的诊断与鉴别诊断,在治疗过程中复查骨髓有助于指导治疗。     

小儿噬血细胞综合征10例临床分析

小儿噬血细胞综合征是一组组织细胞疾病,表现组织细胞在骨髓或其他淋巴组织中异常增多,并伴有活跃的吞噬自身血细胞的行为.临床表现为持续高热,肝脾肿大,血象2系以上减低,肝功能异常,凝血障碍,高甘油三脂血症,骨髓涂片可见组织细胞增多并可见吞噬血细胞现象.该病进展快,预后差,病死率高.而早期诊断治疗很关键.现对我院2000年至2004年收治的10例噬血细胞综合征做回顾性分析.     

噬血细胞综合征的骨髓像特征分析

噬血细胞综合征(hemophagocytic syndrome,HPS),或称噬血细胞性淋巴细胞组织细胞增生症(hemophagoeytic lymphohistocytosis,HLH),亦称噬血细胞性网状细胞增生症(hemophagocytic reticulo-is),是一组以在骨髓或淋巴组织/器官中出现异常增生的组织细胞,伴活跃吞噬自身血细胞现象特征的病症。其临床特征为发热,肝、脾、淋巴结肿大,外周血细胞减少,肝功能异常和凝血障碍,骨髓可见噬血细胞等,可分为特发性和继发性两类,由于其病因复杂、临床表现缺乏特异性而常易导致误诊和漏诊,而HPS临床进展迅速,病死率高,故其早期诊断、及时治疗尤为重要,…     

噬血性淋巴组织细胞增生症20例

目的 探讨噬血性淋巴组织细胞增生症(HLH)的临床特点.方法回顾性分析2009年4月-2010年5月本院血液科收治的20例HLH患儿临床表现及血常规、肝功能、血液生化、病原学、免疫学检测、血清铁蛋白及骨髓涂片检查等实验室指标,参照HLH-2004治疗方案治疗.结果患儿主要表现为持续发热,肝、脾、淋巴结大,全血细胞减少,肝功能受损,凝血障碍,低纤维蛋白血症,高三酯甘油血症,自然杀伤细胞比例降低.12例中性粒细胞＜1.0×109 L-1,16例Hb<90 g·L-1,18例血小板<100×109 L-1,血细胞二系降低者18例,三系同时降低12例.ALT升高20例,AST升高18例,LDH升高20例,胆碱酯酶升高13例.三酰甘油升高18例,血清铁蛋白＞1 500 μg·L-1 8例,ESR增快9例;CRP增高11例,自然杀伤细胞比例降低12例,骨髓增生活跃17例,增生低下3例,12例骨髓涂片找到噬血细胞.20例发病与感染相关者中,与EB病毒感染相关性噬血细胞综合征3例,巨细胞病毒感染相关4例,铜绿假单胞菌感染1例.治愈3例,好转15例,疗效不佳自动出院2例.结论 HLH临床表现多样,及时诊治可改善预后.     

HLH-2004方案诊断治疗噬血细胞综合征10例

噬血细胞综合征(hemophagocytic syndrome,HPS),又称噬血细胞淋巴组织细胞增生症(hemophagocytic lymphohistocytosis,HLH),是一类由多种不同疾病引起的T细胞介导的组织细胞反应性增生、以高细胞因子血症、噬血细胞大量增生为特征的疾病.其本质是细胞因子病(cytokine disease)或巨噬细胞活化综合征(MAS).本病处理不当病死率很高.文献报道应用国际组织细胞协会HLH-2004方案(简称HLH-04方案)已使本病的预后有了明显的改善[1].现将我院2007年1月1日-2008年12月30日应用HLH-04方案治疗10例儿童HLH的情况总结如下.     

噬血细胞性淋巴组织细胞增生症研究进展

噬血细胞性淋巴组织细胞增生症 (HLH)是一组以淋巴细胞、巨噬细胞非恶性增生伴噬血细胞增多引起多脏器浸润及全血细胞减少为特征的疾病。HLH分为两种亚型 :原发性HLH和继发性HLH。其临床表现相同 ,主要有持续发热、肝脾肿大以及神经系统受累的症状和体征。实验室检查可见全血细胞减少、高脂血症、低纤维蛋白原血症、血浆铁蛋白增多、肝功异常 ,骨髓、肝、脾、淋巴结活检可见明显的组织细胞增生伴吞噬血细胞现象。目前HLH的治疗仍采用化疗与免疫抑制治疗相结合的方法 ,骨髓移植更为有效。HLH预后差 ,病死率高。     

噬血细胞性淋巴组织细胞增生症研究进展

噬血细胞性淋巴组织细胞增生症(HLH)是一组以淋巴细胞、巨噬细胞非恶性增生伴噬血细胞增多引起多脏器浸润及全血细胞减少为特征的疾病。HLH分为两种亚型：原发性HLH和继发性HLH。其临床表现相同。主要有持续发热、肝脾肿大以及神经系统受累的症状和体征。实验室检查可见全血细胞减少、高脂血症、低纤维蛋白原血症、血浆铁蛋白增多、肝功异常，骨髓、肝、脾、淋巴结活检可见明显的组织细胞增生伴吞噬血细胞现象。目前HLH的治疗仍采用化疗与免疫抑制治疗相结合的方法，骨髓移植更为有效。HLH预后差，病死率高。     

HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS ASSOCIATED WITH VISCERAL LEISHMANIASIS

A 2-year-old child presented with fever and hepatosplenomegaly. Laboratory findings showed pancytopenia, hypertriglyceridemia, hyperferritinemia, and high levels of soluble-IL2 receptors. Initial bone marrow aspiration and biopsy revealed mild hemophagocytosis. A diagnosis of hemophagocytic lymphohistiocytosis was made and appropriate treatment was begun. Repeated marrow aspiration performed because of lack of clinical response revealed Leishmania amastigotes in macrophages in addition to active hemophagocytosis. Treatment with liposomal amphotericin resulted with rapid recovery. Visceral leishmaniasis should be considered in the differential diagnosis of hemophagocytic syndrome.     

Hemophagocytic lymphohistiocytosis associated with visceral leishmaniasis

A 2-year-old child presented with fever and hepatosplenomegaly. Laboratory findings showed pancytopenia, hypertriglyceridemia, hyperferritinemia, and high levels of soluble-IL2 receptors. Initial bone marrow aspiration and biopsy revealed mild hemophagocytosis. A diagnosis of hemophagocytic lymphohistiocytosis was made and appropriate treatment was begun. Repeated marrow aspiration performed because of lack of clinical response revealed Leishmania amastigotes in macrophages in addition to active hemophagocytosis. Treatment with liposomal amphotericin resulted with rapid recovery. Visceral leishmaniasis should be considered in the differential diagnosis of hemophagocytic syndrome.     

Clinical features of measles in immunocompromised children

Measles is often fatal for immunocompromised hosts. Protective immunity against measles has been studied but is still not completely understood. Recently, five cases of measles were encountered in immunocompromised children. Two of these were allogeneic bone marrow transplanted cases (one common variable immunodeficiency and one severe aplastic anemia) in remission, one Wilms' tumor case in remission, one hepatoblastoma case after cytotoxic therapy at disease onset and one exaggerating hemophagocytic syndrome case with suppressed natural killer cell activity. Clinical symptoms, laboratory findings and the immunologic backgrounds of these five patients were investigated. One of the patients, an 8 year old boy with hemophagocytic syndrome, died of giant cell pneumonia which was confirmed in the section of necropsy lung specimen. Two other patients who received allogeneic bone marrow transplants were not immune to measles, despite their own and their donors' immunizations. Their clinical symptoms were rather severe but both patients recovered and have remained seropositive for as long as 13 months. This fatality from measles is the first reported in a patient with hemophagocytic syndrome. Suppressed natural killer cell activity may be a poor prognostic factor. Also, secondary immunization failure for measles can occur in bone marrow transplanted patients with rather severe clinical symptoms.     

亲体肝移植术后并发噬血细胞综合征的治疗

目的 总结儿童重型肝炎行儿童亲体肝移植术后并发噬血细胞综合征的治疗经验.方法 1例6岁女孩,因不明原因急性进行性黄疸、腹水及全身出血等住院,经化验、彩色多普勒、螺旋CT等确诊为亚急性重型肝炎,于2008年2月26日施行亲体肝移植术,供肝为患儿父亲的左外叶.术后3 d开始出现全血象进行性下降,13 d降至最低,血清铁蛋白升高,EB病毒DNA阳性,骨髓细胞学检查发现噬血细胞,确诊为儿童亲体肝移植术后EB病毒相关性噬血细胞综合征,用环孢素A、地塞米松和静脉注射丙种球蛋白等治疗,并进入层流病房,加强抗感染治疗.结果 术后患儿肝功能恢复顺利,各种酶学指标术后3d各种开始下降,7d接近正常,14d完全正常.术后20 d全血象开始逐渐上升,40 d升至正常水平,准予出院随访,至今无复发,情况良好.结论 儿童亲体肝移植手术后出现不明原因的全血象下降时应想到并发噬血细胞综合征的可能,早期诊断,及时正确的治疗能使患儿顺利康复.     

儿童间变性大细胞淋巴瘤20例临床疗效分析

目的总结分析儿童间变性大细胞淋巴瘤(anaplastic large-cell lymphoma,ALCL)治疗方案的远期疗效及影响预后的因素。方法回顾性分析2002年1月-2010年4月在我院诊断并接受治疗和随访的20例ALCL患儿,采用本院制定的B-NHL 2001方案进行危险度分组和治疗,采用SPSS软件对数据进行处理。结果 ALCL患儿20例,男9例,女11例,诊断时中位年龄8.4(1.9～15.4)岁,>10岁者7例。诊断时Ⅱ期、Ⅲ期和Ⅳ期患儿分别有1例、11例和8例。8例原发于颈部淋巴结,而纵隔、腹腔、腹股沟和腋窝等部位各2例,右腰大肌和左上臂肌各1例,髋骨和右肱骨各1例。15例发病时有B症状,6例ECT显示有骨骼侵润,2例骨髓穿刺见肿瘤细胞,初诊时血清乳酸脱氢酶和铁蛋白增高1倍以上者各6例。病理分析显示17例为T细胞型,16/18例免疫组化间变性大细胞淋巴瘤激酶(ALK)阳性。所有患儿均接受了R3组治疗,有2例初诊为横纹肌肉瘤,其中1例给予AVCP方案一疗程后明确诊断转入R3,1例Ⅱ期患儿接受R2期治疗未缓解转入R3,另有1例初诊T-NHL,以PVDL方案治疗一疗程转入R3。5年无事件生存率和总生存率分别为(69.3±10.5)%和(74.0±10.1)%。单因素分析发现年龄>10岁组患儿复发风险更大,而性别、病理类型、分期、原发部位、是否有骨骼或骨髓侵润、血清乳酸脱氢酶和铁蛋白水平等,对复发风险在统计学上无显著影响。结论儿童ALCL的临床表现多样,其疗效受年龄影响,目前按照B-NHL2001治疗方案能取得较好的远期疗效。     

Kala-azar in a one-year-old Swedish child. Diagnostic difficulties because of active hemophagocytosis

A one-year-old Swedish boy developed kala-azar six months after a holiday in Spain. Upon visiting the hospital after one week of illness he demonstrated clinical and laboratory findings of fever, splenomegaly and cytopenia. A fine-needle aspiration biopsy of the spleen revealed hemophagocytosis and he had increased serum levels of the cytokines tumor necrosis factor-alpha and interferon-gamma. Initially, a diagnosis of hemophagocytic lymphohistiocytosis was made. Re-evaluation of the spleen smears and of the bone marrow aspiration revealed Leishmania parasites and subsequent therapy with sodium stibogluconate was successful. This patient illustrates the interesting similarities between these two disorders involving the mononuclear phagocyte system as well as the problems involved in differential diagnosis. This case also reminds us of the possibility of contracting visceral leishmaniasis in Mediterranean countries.     

Hemophagocytic syndrome associated with neutropenia after chemotherapy]

MATERIAL AND METHODS: This retrospective study reports 15 cases of hemophagocytic syndrome in children treated in our department during a eight-year period. RESULTS: Underlying diseases were acute lymphoblastic leukemia (n = 8) acute myeloblastic leukemia (n = 6) and Burkitt lymphoma (n = 1). Hemophagocytic syndrome was suspected after chemotherapy, in case of an unusual prolonged febrile neutropenia (n = 14) or isolated thrombocytopenia (n = 1). That fever was associated with cutaneous, pulmonary, hematologic, digestive and cardiac signs. Biological disorders included hypoprotidemia, hyponatremia, increased liver enzymes and fibrinopenia. Thrombocytopenia was observed in all patients and was associated with neutropenia for 14 of them. Diagnosis of hemophagocytic syndrome was always confirmed by bone marrow aspiration (infiltration with activated macrophages). Infection was documented in eight children. The treatment of hemophagocytic syndrome relied on steroids and resolution of symptoms occurred within three days of therapy. No recurrence of hemophagocytic syndrome was observed with a median follow up of two years and a half. CONCLUSION: Such complication should be suspected in cases of prolonged febrile neutropenia and/or thrombocytopenia, and confirmed by bone marrow aspiration. Indeed, steroid therapy is effective and chemotherapy can be then pursued.     

TRANSIENT ACUTE LEUKAEMIA IN A NEWBORN WITH DOWN'S SYNDROME

ABSTRACT. A female newborn infant with Down's syndrome presented at birth with clinical and haematologic signs indistinguishable from acute lymphoblastic leukaemia. Specific therapy was withheld, and in contrast to the regular outcome of true congenital leukaemia, complete clinical and haematologic recovery occurred within one month of diagnosis. Cultures of bone marrow cells in the soft agar colony production assay exhibited normal growth pattern, in contrast to the'leukaemic'pattern regularly seen in leukaemic patients and also in patients with Down's syndrome and true leukaemia. In vitro cultures of bone marrow cells can provide useful information about the likelihood of spontaneous resolution in newborns with Down's syndrome and transient acute leukaemia.     

Septo-optic dysplasia and hemophagocytic lymphohistiocytosis in an infant

Macrophage activation in hemophagocytic lymphohistiocytosis (HLH) leads to severe inflammation resulting in cytopenias and multi-organ dysfunction. Septo-optic dysplasia (SOD) is an as-yet unaffiliated disorder that manifests with optic, hepatic, endocrine and/or constitutional defects. We detail the first reported occurrence of both HLH and SOD in one patient. This two-month old patient presented with acute hepatitis, direct hyperbilirubinemia, anemia and thrombocytopenia. Treatment followed standard of care practices for SOD and HLH. The patient subsequently underwent an allogeneic bone marrow transplant within eight months of diagnosis and remained in full remission at day +90. We suggest considering a diagnosis of HLH in patients with SOD who present with severe liver failure refractory to standard therapy.     

Hemophagocytic lymphohistiocytosis following dengue hemorrhagic fever in Hb H/Hb Constant Spring patient

Infection‐associated hemophagocytic syndrome (IAHS), a secondary form of hemophagocytic lymphohistiocytosis (HLH), has been found following several types of infections and can be fatal. We report herein a case of IAHS following dengue infection in a 14‐year‐old patient with underlying α‐thalassemia syndrome (non‐deletional Hb H/Hb Constant Spring disease). He developed prolonged fever, thrombocytopenia, and progressive splenomegaly. Further investigations indicated hyperferritinemia, and increased reactive histiocytes with hemophagocytic activity in the bone marrow. He responded promptly to dexamethasone and i.v. immune globulin. Physicians should be aware of this condition, especially in countries where both dengue hemorrhagic fever and thalassemia are prevalent. The fatal outcome of IAHS can be prevented with prompt appropriate treatment.