Objective: A major cause of hemophagocytic lymphohistiocytosis (HLH) is malignant neoplasms of the blood system, among which NK/T cell lymphoma is one of the most common risk factors. Patients with NK/T cell lymphoma hemophagocytic lymphohistiocytosis (NK/T-LAHS) have a worse prognosis and higher mortality. We aimed to explore the factors that affect the prognosis of NK/T-LAHS. Methods: Clinical data of 42 patients with NK/T-LAHS diagnosed by Beijing Friendship Hospital from June 2008 to June 2016 were analyzed retrospectively. The survival time was counted until 1 August 2016. Results: For the 42 NK/T-LAHS patients, 1-month survival rate was 48.9%, 2-month survival rate was 36.7%, 3-month survival rate was 28.8%, 6-month survival rate was 23.0%, and 12-month survival rate was 15.4%. NK/T-LAHS patients who underwent allogeneic hematopoietic stem cell transplantation (Allo-HSCT) (p = 0.000), exhibited peripheral blood Epstein-Barr virus (EBV)-positivity (p = 0.004), and achieved overall response (OR) remission after initial induction therapy (p = 0.007) had statistical significance. Conclusion: NK/T-LAHS is a disease of poor prognosis and high mortality. NK/T-LAHS patients who achieved OR remission after the initial induction therapy had a better prognosis than non-remission patients and Allo-HSCT was an effective way to prolong the survival of NK/T-LAHS patients. However, EBV positivity in peripheral blood was a poor prognostic factor in NK/T-LAHS patients.

Low or absent natural killer (NK) cell activity is included as one of the HLH-2004 diagnostic criteria. To improve the diagnosis of HLH, we aimed to establish a rapid and reliable NK cell activity assay that avoids the use of radioactivity. The K562 cell line, as standard NK target cells, was engineered to stably express enhanced green fluorescent protein (EGFP), which can be quantified by flow cytometry. The EGFP-flow cytometry method for measuring NK cell activity was improved by double staining of early and late apoptotic target cells. Whole-blood samples from healthy volunteers were assessed with this method, which demonstrated that optimal conditions were effector–target ratio of 10:1 and incubation time of 4 h. This method was further evaluated for samples from 113 HLH patients and 64 healthy volunteers. Mean NK cell activity in either primary or secondary HLH patients was significantly lower (P < 0.001) than in healthy individuals (20.23 ± 4.12%). Furthermore, primary HLH patients (10.76 ± 2.54%) exhibited even lower (P < 0.001) NK cell activity compared with secondary HLH patients (15.01 ± 3.62%). We have optimized and implemented this method in clinically relevant samples.

OBJECTIVE:To investigate the significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis (HLH).METHODS:Four cases of primary HLH patients with PRF1, UNC13D and SH2D1A gene mutations were conducted pedigree investigation, including family genetic screening and detections of immunological parameters (NK cell activity, CD107a degranulation and expression of HLH related defective protein), to evaluate the significance of these different indicators in the diagnosis of primary HLH and explore their correlations.RESULTS:The DNA mutations of the four families included missense mutation c.T172C (p.S58P) and non- frameshift deletions c.1083_1094del (p.361_365del), missense mutation c.C1349T (p.T450M) and frameshift mutation c.1090_1091delCT (p.T364fsX93) in PRF1 gene, missense mutation c.G2588A (p.G863D) in UNC13D gene and hemizygous mutation c.32T>G (p.I11S) in SH2D1A gene. The patients and their family members presented decreased NK cell activities. Individuals who carried mutations of PRF1 gene and SH2D1A gene showed low expression of perforin (PRF1) and signaling lymphocytic activation molecule associated protein (SAP). And the patient with UNC13D gene mutation and his family member with identical mutation showed significant reducing cytotoxic degranulation function (expression of CD107a).CONCLUSION:Pedigree genetic screening and rapid detection of immunological parameters might play an important role in the diagnosis of primary HLH, and both of them had good consistency. As an efficient detection means, the rapid immunological detection indicators would provide reliable basis for the early diagnosis of the primary HLH.

目的:探究血清铁蛋白升高是否对成人噬血细胞综合征(HLH)的诊断具有重要作用.方法:对411例成人患者的临床信息进行回顾性研究.结果:血清铁蛋白高于5 000 μg/L的患者中确诊HLH的比例为36.25％;血清铁蛋白高于10000 μg/L的患者中确诊HLH的比例为55.04％;血清铁蛋白高于15000 μg/L的患者中确诊HLH的比例为63.92％.在血清铁蛋白高于5000 μg/L同时出现发热、全血细胞减少、脾大和(或)肝功损害的成人患者中,确诊为HLH的比例为62.23％;在血清铁蛋白高于10 000 μg/L同时出现发热、全血细胞减少、脾大和(或)肝功损害的成人患者中,诊断为HLH的比例为81.33％;在血清铁蛋白高于15 000 μg/L同时出现发热、全血细胞减少、脾大和(或)肝功损害的成人患者中,诊断为HLH的比例为86.89％.按照血清铁蛋白水平分组,≥15 000 μg/L组与5 000～10 000 μg/L组、10 000～15 000 μg/L组比较,HLH患者比例存在显著差异,≥15000 μg/L组中HLH患者的比例明显高于其他2组(P＜0.05).结论:血清铁蛋白升高对成人HLH的诊断可能具有重要作用.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome. Central nervous system (CNS) involvement is a severe complication, which can lead to rapid disease development and higher morality. However, this has not been given enough attention in adult HLH. Therefore, we carried out this study to analyze the clinical features, laboratory findings, treatment outcomes, and other characteristics of adult HLH with CNS involvement. Methods: A retrospective analysis of 96 adult patients with HLH combined with CNS involvement between June 2003 and December 2016 was conducted. Clinical features, cerebrospinal fluid (CSF) features, image changes, and therapeutic outcomes were analyzed. Results: Among the 96 patients, 86 had various CNS symptoms and 33 (38.4%) had already presented symptoms before the HLH diagnosis was confirmed. A total of 59 patients received CSF examinations and showed abnormalities in 23 patients (39.0%). Seventy patients received imaging examinations and the results showed fifty patients with imaging changes (71.4%). Fifty-seven patients received multiple rounds of repeated intrathecal injection therapy and 35 patients improved (61.4%). As for the multiple analyses of effective factors on survival time, the results showed that the effects of combined Epstein–Barr virus (EBV) infection (P = 0.026, Exp(B) = 2.309, 95% confidence interval [CI] [1.108, 4.823) and intrathecal injection therapy (P = 0.013, Exp(B) = 0.422, 95% CI [0.214, 0.831]) on the survival time of the CNS-HLH patients were significant. Conclusions: Complication with EBV infection is a risk factor, and intrathecal injection is a protective factor. CNS involvement in HLH is not rare, which can result in a poor prognosis. Multiple rounds of repeated intrathecal injection therapy can improve the prognosis of CNS-HLH patients.

目的 探究自体造血干细胞移植(AHSCT)治疗复发难治性朗格汉斯组织细胞增多症(LCH)的疗效。 方法 报道1例AHSCT治疗复发难治性LCH患者的治疗经过，并复习相关文献。 结果 患者经过多次化疗后疗效欠佳，进行AHSCT治疗后完全缓解。 结论 AHSCT治疗可作为复发难治性LCH的有效治疗方案。

OBJECTIVE:To investigate the outcomes, survival status, and the prognostic factors of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) patients.METHODS:A retrospective study was carried out to analyze the clinical data of 61 EBV-HLH cases, from January 2008 to July 2014. Prognostic factors were analyzed through COX model (single factor and multiple factors).RESULTS:A total of 246 patients with HLH were diagnosed, among which 102 cases were with EBV infection (including 61 EBV-HLH, 36 lymphoma associated HLH, 5 primary HLH. Among the 61 cases, 40 were male and 21 were female, with a ration of 1.9:1. The median age was 28 years (range, 12-78). 1, 3, 6 and 12-month overall survival rates of 61 EBV-HLH were 65.6%, 47.5%, 32.4%, and 25.0%, respectively. The median follow-up time was 3 (0.5-28) months. 12 patients didn't use etoposide within 4 weeks after diagnosis, while HLH-94 protocol was used in 33 patients and HLH-2004 protocol was used in 16 patients. Response rates of theses three groups were 33.3%, 51.5%, and 43.8%, respectively (P=0.401). There was statistically difference between the group without etoposide and the HLH-94/ HLH-2004 group in the overall survival rate (P=0.033). Serum albumin level (P=0.033) and whether EBV could became negative (P=0.010) were independent predictors for EBV-HLH.CONCLUSION:EBV-HLH patients have severe clinical feature and poor prognosis. Early application of immune chemotherapy based on etoposide can improve survival. Serum albumin level and whether EBV can become negative are independent prognostic factors for survival.

Objective To analyze the clinical characteristics,treatment and prognosis of primary lymphoma of bone (PLB).Methods Retrospective analysis of 9 cases with newly diagnosed PLB was performed.The primary lesion was located in bone and no evidence of lesion was found in other tissues.All the lesions were confirmed by histological examination and immunohistochemical staining.The clinical manifestation and radiological appearance of all cases were non-specific.Results 9 patients were enrolled in the current study including 6 males and 3 females with average age of 34 years old (15-71 years old).All cases had suffered local pain or edema as initial symptom.Single bone infiltration was detected in 7 patients,while multiple bones infiltration was noticed in 2 patients.The lesion distribution was as follows:4 lesions were situated in pelvis (3 in ilium and 1 in sacral),1 in femur,1 in humerus,1 in scapula,and 2 in spine.2 cases were treated with radiotherapy and chemotherapy,3 cases were treated with chemotherapy and hematopoietic stem cell transplantation,1 case was treated with chemotherapy and surgery,and 3 cases received chemotherapy alone.With in a median follow-up of 8 months,6 patients showed overall response (including 5 cases of complete response and 1 case of partial response).Conclusions PLB is a rare condition,and the diagnostic criteria and treatment are still not well defined.Early diagnosis and prompt treatment usually achieves satisfactory prognosis.The possibility of PLB must be concerned for patients with bone pain,soft tissue swelling or unexplained fractures,and pathological examination should be carried on as soon as possible.

OBJECTIVE To investigate the prevalence and etiology of hemophagocytic lymphohistiocytosis (HLH) in different age groups. METHODS Clinical data of patients with HLH were retrospectively collected from June 2005 to March 2014 in 49 hospitals in China. These patients were divided into child, youth, middle-aged and elderly groups according to the age of onset; meanwhile divided into primary HLH group, infection-associated HLH group, tumor-associated HLH group, rheumatic disease-associated HLH group according to the etiology. Prevalence rates, gender and underlying diseases of each group were retrospectively analyzed. RESULTS A total of 601 patients were included in the study, age ranging from 1 month to 82 years. The median age of onset was 27 years and 26 years respectively in males(316 cases) and females (285 cases) without statistical significance (P=0.622). There were 171 in child group (28.5%); 262 in youth group(43.6%); 104 in middle-aged group(17.3%); 64 in elderly group(10.6%). The most common causes were infections in child group, malignancies and infections in youth group, malignancies in middle-aged group as well as elderly group. There were 48 patients in primary HLH group(8.0%), 197 in infection-associated HLH group(32.78%), 208 in tumor-associated HLH group(34.61%), 56 in rheumatic disease-associated HLH group(9.32%). Patients with primary HLH were significantly younger than those with secondary HLH (P<0.001), however the tumor-associated HLH group was the eldest. Primary HLH, infection-associated HLH and tumor-associated HLH had more male patients but without statistical significance (P=0.196), while rheumatic disease-associated HLH was mostly female patients (P<0.001). CONCLUSIONS HLH is not a disease peculiar to children, instead, it may occur in all ages. There are a variety of etiology in different age groups, and a possible link between sex and HLH development. In clinical practice, due attention should be paid to the patients with suspected HLH. Positive relevant inspections may aid in the final diagnosis.

目的:探讨皮下脂膜炎样T细胞淋巴瘤(SPTCL)合并噬血细胞综合征(HPS)的诊断及治疗.方法:报道2例SPTCL合并HPS患者并进行文献复习.结果:2例患者治疗过程中HPS反复发作,经多次病理检查最终确诊为SPTCL,给予原发病治疗后长期生存.结论:SPTCL合并HPS少见,原发病诊断困难,病情反复.尽早且多次进行淋巴结、骨髓或病变部位组织病理检查以寻找原发病,给予原发病治疗,是控制SPTCL合并HPS的关键.

Objective To analyze the clinical characters,treatment and prognosis of autoimmune disease-associated hemophagocytic syndromes (AAHS).Methods A retrospective study was carried out to analyze the clinical features,laboratory tests,diagnosis,treatments and clinical outcomes of 29 patients with AAHS from Apr.2004 to Apr.2014.Results Among the 29 cases,22 were female while the other 7 were male.The median age was 31 years old (16-70 years old).The initiating diseases consisted of 17 adult onset still's disease,5 sicca syndrome,4 systemic lupus erythematosus,1 polymyositis,primary,1 biliary cirrhosis,1 undifferentiated connective tissue disease.19 patients of them were diagnosed as hemophagocytic syndromes (HPS) in the treatment of autoimmune disease while the other 10 patients were diagnosed as autoimmune disease and HPS at the same time.The most common clinical features were persistent fever (100.0 ％,29/29),respiratory symptom (79.3 ％,23/29),splenomegaly (72.4 ％,21/29),rash (65.5 ％,19/29),arthralgia (62.1％,28/29).Among the 29 patients,13 patients had acquired clinical effective and 8 patients had acquired clinical alleviate within 8 weeks treatment.Among the 29 cases,1-month,3-month and 1-year overall survival rates were 93.1％,82.3 ％ and 72.0 ％ respectively.Conclusions The initiating diseases of AAHS mainly consist of adult onset still's disease,sicca syndrome and systemic lupus erythematosus.HPS can not only onset at the same time with autoimmune disease,but also onset in the treatment of autoimmune disease.Autoimmune disease should be considered when HPS patients complicated by rash and arthralgia.Compared with other types of HPS patients,the prognosis of AAHS is better relatively.

多发性骨髓瘤(multiple myeloma,MM)是浆骨髓浆细胞异常增生导致的溶骨性骨质破坏,血清中出现单克隆免疫球蛋白或轻链(M蛋白),引起反复感染、贫血和肾功能损害的一种常见的血液系统恶性肿瘤,起源于前B细胞和/或浆细胞.MM治疗后继发急性白血病的临床报道多为个案报道.现回顾性分析我院收治的1例继发于MM的急性髓系白血病(acute myelomonocytic leukemia,AML),并回顾相关文献,报道如下.

OBJECTIVE:To analyze the clinical characteristics, treatment and prognosis of hemophagocytic lymphohistiocytosis (HLH) patients with Epstein-Barr viremia (EBV).METHODS:A retrospective study was conducted to analyze the clinical data of 80 HLH patients aged ≥ 14 years with EBV-DNA >1 000 copies/ml in peripheral blood from 2008 to 2013.RESULTS:There were EBV-HLH (n = 46), HLH-associated lymphoma (n = 30) and primary HLH (n = 4). Among the relevant laboratory parameters, inter-group statistical differences existed only in alanine transaminase (ALT) and aspartate aminotransferase (AST) (P = 0.021, 0.035). The median follow-up period was 2.0 (0.5-20.0) months. And the 1-month, 3-month, 6-month and 12-month overall survival rates were 58.8%, 37.5%, 29.7% and 19.6% respectively.CONCLUSIONS:HLH patients with EBV have a pernicious clinical course with a poor prognosis. And it makes little sense for distinguishing HLH-associated lymphoma from EBV-HLH through routine laboratory tests.

OBJECTIVE To analyze the clinical manifestations, laboratory data, therapy, and prognosis in patients with hemophagocytic lymphohistiocytosis (HLH). METHODS A retrospective study was carried out in 192 adult patients with HLH between 2003 and 2013. RESULTS Of the 192 cases, 70 cases were secondary to cancer and 64 cases secondary to infection. According to HLH-2004 criteria, the coincidence rate of indices were: fever (98.96%), high level of serum ferritin (94.27%), increased level of soluble interleukin- 2 receptor(sCD25) (94.79%), decreased or absent activity of NK cells (94.27%), cytopenias (80.73%), splenomegaly (80.21%), emophagocytosis in bone marrow, spleen or lymph nodes (74.48%), hypofibrinogenemia (50.52%), hypertriglyceridemia (37.50%). In addition, 94.27% of patients were presented with liver dysfunction, 96.35% with infections, and 75.52% with coagulopathy. Incidences of central nervous system symptoms and rash were 19.27% and 20.31%, respectively. Among cancer, infection and rheumatic group, there were statistically differences on white blood cells (WBC), platelet (PLT), sCD25, alanine aminotransferase, aspartate aminotransferase, total bilirubin and globulin(GLO) (P<0.05). The differences of WBC, PLT, albumin (ALB), GLO, brain natriuretic peptide, creatinine, urea nitrogen between survival group and death group had statistical significance. CONCLUSION The secondary HLH occurs from various underlined diseases. Cancer, especially T- cell lymphoma, is the main cause, Secondly, it is EB virus infection. The diagnostic sensitive indicators are Persistent fever, higher level of serum ferritin, low or absent NK-cell activity, and increased sCD25 were the most valuable parameters for diagnosis. Cytopenias were not common in early phase of HLH secondary to rheumatic diseases. WBC, PLT, ALB, GLO could be used as the preliminary parameters for diagnosis. Cardiac insufficiency, renal insufficiency and coagulation dysfunction play important roles in prognosis.