氟达拉滨联合地塞米松治疗血管免疫母细胞性T细胞淋巴瘤继发噬血细胞综合征1例

噬血细胞综合征（hemophagocytic syndrome，HPS）又称噬血细胞性淋巴组织细胞增生症（hemophagocytic lymphohistio—eytosis，HLH），是一种良性单核细胞、巨噬细胞、组织细胞系统性增生疾病，骨髓或淋巴组织／器官中出现异常增生的组织细胞，吞噬自身血细胞，进而引起多脏器浸润及全血细胞臧少。临床表现为高热、肝脾和（或）淋巴结肿大，全血细胞减少，肝功能异常和凝血功能障碍Ⅲ。病情常发展迅速，若不及时诊断及治疗，预后很差。我们近期应用氟达拉滨联合地塞米松治疗1例血管免疫母细胞性T细胞淋巴瘤伴发HLH患者．取得良好效果，现报道如下。     

免疫治疗相关噬血细胞综合征诊疗进展

噬血细胞综合征又称噬血细胞性淋巴组织细胞增多症（hemophagocytic lymphohistiocytosis,HLH），是一种罕见的、危及生命的临床综合征。由于淋巴细胞及巨噬细胞失控性增殖并分泌大量细胞因子，导致多器官、多系统受累。免疫治疗是肿瘤和自身免疫性疾病治疗的重要组成部分，改变了传统治疗模式，提高了患者的生存率。随着免疫治疗的广泛应用，免疫治疗相关HLH因其病情凶险、进展迅速引起研究者关注。目前，这一类HLH多以病例报告形式出现，缺乏统一的诊疗标准。本文将从免疫治疗相关HLH的发病机制、诊断及治疗进展展开综述，以提高医务工作者对此类疾病的认知。     

噬血细胞性淋巴组织细胞增生症的临床进展

<正>噬血细胞性淋巴组织细胞增生症(hemophagocytic lymphohistiocytosis,HLH)亦称噬血细胞综合征(hemophagocytic syndrome,HPS)。HLH并非单一疾病,而是一组临床综合征,以高热、肝脾肿大、血细胞减少、病情凶险和死亡率高为其临床特征。近年免疫化学治疗和异基因造血干细胞移植的     

噬血细胞性淋巴组织细胞增多症六例并文献复习

 目的　探讨噬血细胞性淋巴组织细胞增多症（HLH）的临床特点、病因、发病机制及治疗和预后。方法　对2010年1月至9月收治的6例HLH患者的临床资料进行回顾性分析并进行文献复习。结果　6例患者中有3例死亡；2例接受地塞米松（DXM）+依托泊苷（VP16）治疗，早期疗效明显；1例疟原虫感染患者治疗后明显好转。结论　HLH病情凶险，死亡率高，早期积极免疫-化疗及基础疾病的治疗可以改善预后。     

恶性肿瘤相关噬血综合征的研究进展

噬血综合征（hemophagocytic lymphohistiocytosis,HLH）是一种少见的疾病，由于机体分泌大量细胞因子产生过度炎症反应，进而导致多器官、多系统受累的临床综合征。恶性肿瘤相关噬血综合征（malignancy-associated hemophagocytic lymphohistiocytosis,MA-HLH）患者多数病情危重、误诊率、延诊率和死亡率较高，对其认识不断被重视和深化。尤其是在免疫检测点抑制剂的广泛应用之后，MA-HLH的发生越来越多。本文结合近年来这一领域相关研究进展，从流行病学、易患因素、病理生理、诊断标准及治疗等方面进行综述。     

ALK阳性间变性大细胞淋巴瘤合并噬血细胞综合征1例

噬血细胞综合征(hemophagocytic syndrome,HPS),又称噬血细胞性淋巴组织细胞增多症(hemophagocyt ic lympho-histiocytosis,HLH),是一组罕见的、致命的以细胞因子风暴为特征的临床综合征,常以发热、脾大、血细胞减少、铁蛋白升高和肝功能受损等为主要特征[1] . ...     

噬血细胞性淋巴组织细胞增生症六例

 目的　提高对噬血细胞性淋巴组织细胞增生症（HLH）诊断及治疗的认识。方法　总结6例HLH患者的临床特征、诊断依据、治疗方案及疗效,并进行分析讨论。结果　HLH常见的临床表现包括发热、肝脾大及血细胞减少,实验室检查异常包括高三酰甘油血症、低纤维蛋白原血症、肝功能异常、黄疸、转铁蛋白升高、低钠血症,骨髓涂片可见噬血细胞。接受包含依托泊苷的化疗方案在疗程的早期有效,但疗效短暂。结论　HLH病情凶险,预后差,提高对HLH的临床表现及实验室特征的认识,有利于加强HLH的早期诊断和治疗,依据HLH-2004治疗指南可以提高患者生存率,但造血干细胞移植仍是目前唯一能使患者获得长期缓解及治愈的有效措施。     

成人噬血细胞性淋巴组织细胞增生症21例临床分析

目的:探讨成人噬血细胞性淋巴组织细胞增生症(HLH)的临床特点。方法:对2005年1月－2015年1月在南京医科大学第二附属医院血液科收治的21例成人HLH患者的临床资料进行回顾性分析。结果:21例患者初治时均表现为高热、肝脾肿大、凝血功能异常、血常规三系或二系受累。病因分析中7例（33.3%）为血液肿瘤相关性;10例（47.6%）为感染,其中3例确诊为发热伴血小板减少综合征（新型布尼亚病毒核酸检测阳性）;1例（4.8%）肿瘤相关性（骨髓活检示转移癌）;3例（14.3%）原因不明。随访中死亡16例,存活3例（最长至今已5年7个月）,2例失访;生存时间为4天～5.7年（中位生存时间183天）。结论:HLH为罕见的致死性疾病,成人更为少见。临床表现复杂,常伴有多脏器受损,病情凶险,进展迅速。预后大多不良。发病机制和治疗手段有待进一步研究。     

伴噬血细胞综合征EB病毒阳性T细胞淋巴瘤患者临床特征及疗效分析

目的:探讨噬血细胞综合征[又称噬血细胞性淋巴组织细胞增多症（HLH）]对EB病毒（EBV）阳性T细胞淋巴瘤（TCL）患者临床特征及治疗效果的影响。方法:回顾性分析2015年11月至2020年8月于广州医科大学附属第一医院经病理检查确诊的23例EBV-TCL患者临床资料。按发病时是否伴HLH分为HLH组（10例）和非HLH组（13例）,比较两组患者临床特征及预后。比较不同治疗方式、血浆EBV-DNA定量患者的疗效。结果:23例患者中,Ann Arbor分期Ⅰ~Ⅱ期3例（13.0%）,Ⅲ~Ⅳ期20例（87.0%）;国际预后指数（IPI）评分1分3例（13.0%）,2分4例（17.4%）,3分8例（34.8%）,4分8例（34.8%）。HLH组中侵袭性NK细胞白血病2例,儿童系统性EBV-TCL 3例,非HLH组无这两种病理类型患者。HLH组中发热、骨髓侵犯、IPI评分>2分、EBV-DNA>10 4拷贝/ml患者均多于非HLH组（均 P<0.05）。所有患者化疗后客观缓解（完全缓解+部分缓解）率为47.8%（11/23）;HLH组和非HLH组均有3例行造血干细胞移植,且均获得客观缓解;HLH组和非HLH组未行造血干细胞移植的7例和10例患者经过淋巴瘤方案化疗后,客观缓解分别为0例和5例,差异有统计学意义（ P＝0.044）。单纯化疗组17例患者中客观缓解5例,化疗+移植组6例患者均客观缓解,差异有统计学意义（ P＝0.039）。血浆EBV-DNA定量转阴的16例患者中客观缓解11例,持续阳性的7例患者均未客观缓解,差异有统计学意义（ P＝0.001）。所有患者1年总生存率为69.3%,2年总生存率为52.0%。HLH组中7例单纯化疗患者和3例化疗+移植患者的1、2年总生存率均分别为42.9%和66.7%。非HLH组中10例单纯化疗患者和3例化疗+移植患者的1年总生存率分别为80.0%和100.0%,2年总生存率分别为26.7%和100.0%。两组中化疗+移植患者的总生存均优于单纯化疗患者,差异均有统计学意义（均 P<0.05）。 结论:EBV-TCL患者总体临床分期较晚,伴HLH的患者预后更差,治疗效果可能与血浆EBV-DNA定量相关。造血干细胞移植能提高缓解率。     

噬血细胞综合征13例临床分析

噬血细胞综合征１３例临床分析王岐山，赵刚云，李梅生噬血细胞综合征（Ｈｅｍｏｐｈａｇｃｉｔｉｃｓｙｎｄｒｏｍｅ简写ＨＳ）是组织细胞异常增生并大量吞噬血细胞而引起一系列临床表现的综合征。往往继发于其它疾病。临床表现多以发热、肝脾肿大为特征，骨髓组织细胞增...     

成年人嗜血细胞性淋巴组织细胞增多症研究进展

嗜血细胞性淋巴组织细胞增多症（HLH）是一种以免疫功能极度活化导致病理性炎症反应的临床综合征。目前广泛使用的诊断标准是来源于儿童患者数据的 HLH-2004诊断标准。成年人 HLH 和儿童 HLH 相比,在病因、临床表现、实验室指标上存在不同,有学者提出了针对成年人 HLH 独特的诊断评分系统。 HLH 在成年人中表现多样化,需要根据诱发因素、疾病严重程度、遗传背景等制定个性化的治疗方案。     

Hemophagocytic lymphohistiocytosis after allogeneic bone marrow transplantation during chronic norovirus infection

Hemophagocytic lymphohistiocytosis (HLH) is a macrophage activating syndrome that is known to develop in patients with autoimmune disease, malignancies or infection, for example with Epstein–Barr virus, cytomegalovirus or varicella zoster virus. We describe a 24‐month old boy with acute myelogenous leukaemia relapse and allogeneic bone marrow transplantation, who developed HLH on day +40 during chronic infection with norovirus. Here, we report for the first time the development of HLH in combination with chronic norovirus infection after allogeneic bone marrow transplantation in a hematopoietic malignancy. Copyright © 2013 John Wiley & Sons, Ltd.     

Interleukin-18 in hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by dysregulated hyperactivation of macrophages and T helper 1 (Th1) cells accompanied by excessive secretion of inflammatory cytokines. Although TNF-alpha and IFN-gamma are known to be important factors for the development of the disease, the mechanism of their overproduction has not been clarified, yet. We measured serum IL-18 levels of patients with HLH to investigate the possible significance of IL-18 in its pathophysiology, especially in IFN-gamma production. IL-18 levels were significantly increased in all patients with HLH compared with healthy controls. A significant correlation was observed between IL-18 and IFN-gamma levels. In addition to IFN-gamma and soluble Fas ligand (sFasL), IL-18 levels significantly correlated with disease activity. IL-18 may play important roles in the pathogenesis of HLH, particularly through induction of Th1 cells. In addition, IL-18 measurement may not only be useful for the diagnosis, but also for the evaluation of disease activity.     

B-cell lymphoma-associated hemophagocytic lymphohistiocytosis: A case report

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by an exaggerated but dysregulated immune response resulting in hyperinflammation, with a potential for progression to multiple organ dysfunction and failure. Infectious diseases, inflammatory disorders, malignancies and immunodeficiency syndromes are known triggers of HLH in adults. The present study reported the case of a middle-aged man with HLH triggered by B-cell lymphoma who was successfully treated with dexamethasone; etoposide, prednisone, vincristine, cyclophosphamide, hydroxy-doxorubicin and rituximab chemotherapy; and multiple intrathecal methotrexate with a good outcome.     

An exclusive case of juvenile myelomonocytic leukemia in association with Kikuchi's disease and hemophagocytic lymphohistiocytosis and a review of the literature

We present a case of juvenile myelomonocytic leukemia (JMML) accompanied by immune-mediated hemophagocytic lymphohistiocytosis (HLH) and Kikuchi's disease, both as a paraneoplastic phenomenon. As this combination, to the best of our knowledge, has not been described before, consensus on preferable treatment is lacking. Our patient was treated with prednisolone according to the few described cases of HLH and Kikuchi's disease in non-JMML patients, resulting in disappearance of the clinical symptoms.     

Gastric cancer complicated with hemophagocytic lymphohistiocytosis: case report and a brief review

Hemophagocytic lymphohistiocytosis (HLH) comprises a group of severe immune function disorders that can lead to immune-mediated organ damage. There are two subtypes of HLH: primary and secondary. Secondary HLH is associated with infectious, oncologic, chemotherapeutic, and other underlying causes, and studies on HLH triggered by tumors have mainly focused on hematological malignancies. Secondary HLH in patients with solid tumors is rare. Here, we present two cases of gastric cancer complicated with HLH. The patient 1 was diagnosed as gastric cancer at stage I and got intractable fever after a distal subtotal gastrectomy without any evidence of infections or other complications. The patient 2 suffered from unresectable gastric adenocarcinoma and got fever, hemorrhagic rashes, and petechiae in mouth after six cycles of neoadjuvant chemotherapy. After detailed and comprehensive examinations, HLH was diagnosed in the two patients according to 2004 HLH diagnostic criteria, and the patients received treatment including immunosuppressive agents immediately. After therapy, the two patients showed partial remission, but both eventually died due to HLH relapse or progression of the primary tumor. The treatment regimen for HLH is intricate, and only a few relevant studies have focused on the treatment of cancer patients with HLH. The high mortality associated with this disease calls for more attention and additional research to improve the prognosis for these patients.     

ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology,early and advanced stages,borderline tumours and recurrent disease

The development of guidelines recommendations is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and evidence-based recommendations in several selected areas in order to improve the quality of care for women with ovarian cancer. The ESMO–ESGO consensus conference on ovarian cancer was held on 12–14 April 2018 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of ovarian cancer. Before the conference, the expert panel worked on five clinically relevant questions regarding ovarian cancer relating to each of the following four areas: pathology and molecular biology, early-stage and borderline tumours, advanced stage disease and recurrent disease. Relevant scientific literature, as identified using a systematic search, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. The recommendations presented here are thus based on the best available evidence and expert agreement. This article presents the recommendations of this ESMO–ESGO consensus conference, together with a summary of evidence supporting each recommendation.     

Prognostic factors in patients with bone marrow hemophagocytosis and its association with hematologic malignancies

Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous group of hyperinflammatory statuses that are difficult to diagnose and can be life-threatening. Bone marrow (BM) hemophagocytosis is one of the diagnostic criteria according to HLH 2004 diagnostic criteria and HS score. Limited studies have focused on the prognostic factors of BM hemophagocytosis and its association with hematologic malignancies. We aimed to analyze the clinical significance of BM hemophagocytosis. Patients with BM hemophagocytosis, either by cytology or pathology, were enrolled at Taipei Veterans General Hospital from January 2002 to July 2021. Relevant clinical and laboratory data were extracted from medical records. Of 119 patients with BM hemophagocytosis, 57 were diagnosed with hematologic malignancies. The median age of the patients was 58, ranging from 21 to 90. Splenomegaly (adjusted odds ratio [aOR] 2.96; 95% confidence interval [CI] 1.13–7.79) was a risk factor for hematologic malignancies, while autoimmune disease (aOR 0.07; 95% CI 0.01–0.39) and increased D-dimer (aOR 0.25; 95% CI 0.07–0.92) were protective factors. Risk factors for mortality in patients with BM hemophagocytosis were hematologic malignancies (adjusted hazard ratio [aHR] 2.34; 95% CI 1.24–4.44), Eastern Cooperative Oncology Group score ≥3 (aHR 2.42; 95% CI 1.20–4.89) and thrombocytopenia (aHR 3.09; 95% CI 1.04–9.16). In conclusion, among patients with BM hemophagocytosis, splenomegaly was a predictor of hematologic malignancies. Patients with hematologic malignancies, poor performance status, or thrombocytopenia had a higher mortality risk. Further validation studies are warranted.