Infection is among the most common causes of death in patients with acute myeloid leukemia (AML) after chemotherapy. The anti-tumor effect of the intestinal microbiota in patients with AML is increasingly being recognized. Tigecycline, a broad-spectrum antibiotics, plays a vital role in the anti-infection treatment of AML patients with neutropenia and accompanying infections. Previously, this group reported that long-term use of tigecycline caused coagulation dysfunction in patients with hematological malignancies, increasing the risk of casualties. RNA sequencing was performed on CHO cells before and after tigecycline treatment. Further, the combined analysis of AML prognostic differentially expressed genes revealed 13 genes affected by tigecycline and closely related to AML prognosis. These genes were used for modeling analysis, and the results showed that the prepared model significantly improved the prognostic prediction efficiency for AML patients. The model also explored the correlation between prognosis score and immune cells infiltrating tumors and immune therapy targets. Moreover, 16S sequencing was performed on fecal samples from AML patients before and after tigecycline treatment. The results revealed that tigecycline significantly altered the distribution of intestinal microbiota in AML patients - These changes in microbiota are related to chemotherapy resistance. This study emphasizes the importance of intestinal microbiota in AML prognosis. Thus, the findings of this study show that the long-term use of antibiotics can not only cause dysbiosis of the intestinal microbiota but also indirectly affect the sensitivity of chemotherapy drugs, affecting the prognosis of AML patients.

Objective: To evaluate the reliability of flow cytometry (FCM) for diagnosing lymphoma associated hemophagocytic syndrome (LAHS). Method: The clinical data in 57 patients with hemophagocytic lymphohistiocytosis (HLH)were retrospective analyzed at Peking University Shenzhen Hospital from July 2010 to July 2019. All patients were performed bone marrow FCM and bone marrow pathological examination before final diagnoses were made. The golden diagnosis criterion was based on clinical, biochemical and histopathological evidence, which was regarded as the standard to evaluate the sensitivity and specificity of FCM analysis in diagnosing LAHS. Results: Among 57 cases, 36 cases were eventually diagnosed with LAHS, including 15 B-cell lymphoma(14 diffuse large B-cell lymphoma, 1 B-cell lymphoma with reactive T-cell hyperplasia), 13 aggressive NK/T cell lymphoma/leukemia, 2 cases of gamma-delta T-cell lymphoma, 4 angioimmunoblastic T-cell lymphoma, 1 enteropathy-associated peripheral T-cell lymphoma and 1 anaplastic T-cell lymphoma. Lymphoma cells in bone marrow were detected in all patients by FCM except one ENTCL patient. The sensitivity and the specificity of FCM in LASH compared to bone marrow biopsy were 97.2%(P=0.014)and 90.5%(P=0.488) respectively. In the other 21 non-LAHS patients, T cell receptor Vβ (TCRVβ) rearrangement was detected in 2 patients with Epstein-Barr virus (EBV) associated primary HLH. Conclusions: FCM effectively detects lymphoma cells in bone marrow of lymphoma patients with LHL, suggesting that FCM could be an important indicator for the diagnosis of LAHS. FCM also has the advantage in differentiating LAHS from other HLH.

Epstein-Barr virus (EBV) primary infection is usually asymptomatic, but it sometimes progresses to infectious mononucleosis (IM). Occasionally, some people develop chronic active EBV infection (CAEBV) with underlying immunodeficiency, which belongs to a continuous spectrum of EBV-associated lymphoproliferative disorders (EBV+ LPD) with heterogeneous clinical presentations and high mortality. It has been well established that T cell-mediated immune response plays a critical role in the disease evolution of EBV infection. Recently, high-throughput sequencing of the hypervariable complementarity-determining region 3 (CDR3) segments of the T cell receptor (T cell receptor β (TCRβ)) has emerged as a sensitive approach to assess the T cell repertoire. In this study, we fully characterized the diversity of peripheral blood TCRβ repertoire in IM (n = 6) and CAEBV patients (n = 5) and EBV-seropositive controls (n = 5). Compared with the healthy EBV-seropositive controls, both IM and CAEBV patients demonstrate a significant decrease in peripheral blood TCRβ repertoire diversity, basically, including narrowed repertoire breadth, highly expanded clones, and skewed CDR3 length distribution. However, there is no significant difference between IM and CAEBV patients. Furthermore, we observed some disease-related preferences in TRBV/TRBJ usage and combinations, as well as lots of T cell clones shared by different groups (unique or overlapped) involved in public T cell responses, which provide more detailed insights into the divergent disease evolution.

OBJECTIVETo investigate the clinical and laboratory features of patient with B cell lymphoma associated hemophagocytic syndrome(B-LAHS).METHODSThe clinical data of 10 cases of B-LAHS were retrospectively analysed and the relevant literatures were reviewed.RESULTSThe median age of 10 cases diagnosed as B-LAHS was 55.5 (31-88) years old, and median time from attack to diagnosis was 2 months (2 weeks-4 months). The diagnosis can be made histopathologically and immunohistochemically by bone marrow biopsy. Among them 7 cases were diagnosed as large B cell lymphoma, 2 cases as mantle cell lymphoma and 1 case as small B cell lymphoma. The prominent clinical symptoms and signs were persistent fever (100%) and splenomegaly(90%), and the involvements with respiratory and digestive system were common. Another 1 case had systemic muscle pain and lactic acidosis as the first onset. Laboratory studies showed hepatic dysfunction, significantly elevated ferritin and lactate dehydrogenase, abnormal lymphocytes in peripheral blood smear, and hemophagocytosis in bone marrow smear. The FSC/SSC abnormalities of cloned B lymphoma cells were detected through flow cytometry (FCM). The complete remission (CR) was maintained in 4 cases receiving immunochemotherapy based on rituximab.CONCLUSIONB-LAHS possesses heterogeneous clinical manifestations and rapid deterioration. Bone marrow biopsy and immunohistochemical examination can confirm the diagnosis. FCM may improve the early diagnosis of B-LAHS.

OBJECTIVE:To explore the lymphocytic clonal expansion in adult patients with Epstein-Barr virus-associated lymphoproliferative diseases (EBV+LPD), and to investigate the experimental methods for EBV+LPD cells so as to provide a more objective measure for the diagnosis, classification and prognosis in the early stage of this disease.METHODS:Peripheral blood samples from 5 patients with EBV+LPD, 4 patients with adult infectious mononucleosis(IM) as negative control and 3 patients with acute NK-cell leukemia(ANKL) as positive control were collected. Prior to immunochemotherapy, viral loads and clonality were analysed by flow cytometry (FCM), T cell receptor gene rearrangement (TCR) was detected by real-time polymerase chain reaction (RT-PCR), and diversity of EB virus terminal repeat (EBV-TR) was detected by Southern blot.RESULTS:FCM showed only 1 case with clonal TCRVβ in 5 patients with EBV+LPD, TCR clonal expansion could be detected both in patients with IM(4 of 4) and 4 patients with EBV+LPD(4 of 5), Out of patients with EBV+LPD, 1 patient displayed a monoclonal band and 2 patients showed oligoclonal bands when detecting EBV-TR by southen blot.CONCLUSION:Detecting the diversity of EBV-TR by Southern blot may be the most objective way to reflex clonal transformation of EBV+LPD, which is of great benefit to the diagnosis, classification and prognosis in the early stage of this disease.

After infecting cells,EBV-encode microRNA (miRNA),a short,non-coding RNA,negatively regulates gene expression through attenuating target mRNA translation and stability.It is now apparent that many viral miRNAs may contribute to immortalization and immune evasion by targeting viral and cellular factors involved in host cell proliferation,apoptosis and immune responses.This article sums up the known target genes of EBV-encoded miRNAs and their functions,as well as their potential clinical value.

目的 探讨成人急性髓系白血病(非APL)预后相关因素.方法 回顾性分析北大深圳医院血液内科116例初发AML患者临床特征:年龄、初发WBC水平、骨髓细胞免疫表型特征与预后关系.结果 完全缓解(CR)率:总CR率70.7％ (82/116),≥60岁组58.6％(17/29),显著低于＜60岁组74.7％ (65/87);初发WBC≥30×109/L组52.2％ (25/48),显著低于＜30×109/L组83.8％(57/68);CD34阳性组59.7％(40/67),低于CD34阴性组85.7％(42/49);2年复发率:CD34阳性组76.0％(19/25),显著高于CD34阴性组14.3％(3/18).多因素分析:≥60岁、初发WBC≥30 × 109/L是CR率的独立危险因素;CD34阳性是2年复发率的独立危险因素;CD34阳性是长期生存的独立危险因素.结论 CD34阳性是复发率、长期生存的独立危险因素.

目的:通过观察非霍奇金淋巴瘤(NHL)患者调节性T淋巴细胞(Treg)及白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α在疾病不同阶段的水平,探索这些免疫因素在NHL预后中的作用.方法:将87例NHL患者按临床预后分为无事件存活组64例、复发组14例、难治组9例,另设健康对照20例,动态观察Treg细胞及IL-6、TNF-α在疾病不同阶段的水平.结果:初治时NHL患者外周血Treg细胞比例、IL-6、TNF-α较对照者显著升高(P＜0.05);其中难治组和复发组在起病时的Treg及IL-6水平较无事件存活组更高(P＜0.05),而TNF-α水平差异无统计学意义.停止治疗时所有NHL患者外周血Treg、IL-6、TNF-α的水平与对照者比较差异无统计学意义;停止治疗后3个月及6个月时Treg、CD4+T淋巴细胞比例有升高趋势,复发组IL-6、TNF-α较无事件存活组升高,但差异无统计学意义.结论:Treg细胞可能在NHL发病及疾病进展中起促进作用,监测IL-6及TNF-α的表达水平对早期判断难治患者和预测复发可能有重要的临床意义.

Adult EBV associated T/NK-cell lymphoproliferative disease is a rare disease, the majority of patients with fulminant course and poor prognosis.Because of the lack of characteristics clinical manifestations and pathological histology change,it is not easy to diagnosis. The article discuss the diagnosis of adult EBV associated T/NK-cell lymphoproliferative disease,reviews the EBV infection sign,cytokine and EBV cloned amplification.

Objective To investigate the cytogenetic and immunological phenotypes of acute myeloid leukemia (AML) with t(8;21), and explore the risk stratification and risk-adapted treatments. Methods The chromosomal karyotype of bone marrow was detected and analyzed in 22 newly diagnosed patients with t(8;21) AML by direct culture and G banding technique. Patients were divided into two groups according to the chromosomal karyotypes. Clinical characteristics and immunological phenotypes were compared between patients with isolated t(8;21) and those with additional aberrations. A follow-up study with median time 30 months (4-68 months) was conducted to analyze prognostic factors. Results 13 cases (59.1 [) were isolated t(8;21) AML, while 9 (40.9 [) had additional aberrations. Loss of sex chromosome was found in 3 cases and complex variant translocation in 2. The 10q-, 9q-, -18 and +10 were found in single cases. Overall survival of patients with additional aberrations was significantly poorer than those with isolated t (8;21) (P-0.0176). Analysis of prognostic factors showed that t(8;21) chromosomal karyotype, initial white blood cells at diagnosis, and treatment regimen (chemotherapy alone or plus hematopoietic stem cell transplantation) had effects on overall survival. Conclusion Patients with t (8;21) AML are frequently associated with additional chromosomal aberrations. The latter indicates a poorer outcome and can be one of the bases of risk stratification. Hematopoietic stem cell transplantation might help to improve the overall survival.

The aim of this study was to analyze the clinical features and laboratory findings of adult Epstein-Barr virus associated T/NK cell lymphoproliferative disease (EBV+T/NK-LPD) and to investigate the early diagnosis and prognosis of EBV+T/NK-LPD. The clinical data of 19 adult patients with EBV+T/NK-LPD were retrospectively analyzed. The results indicated that there were 11 males and 8 females. The median age was 32 years (range: 20-70 years). The average duration from onset of symptoms to diagnosis was 3.5 months. The median survival time was 2.5 months. Unkown fever, hepatosplenomegaly, liver dysfunction and interstitial pneumonia were the main clinical features. High levels of β2-MG, LDH, TNF, IL-6 and significantly increased EBV-DNA level (median level > 10(6) copies/ml) were occurred in all the patients. Cytopenia was seen in 18 cases. Morphologically, atypical large granular lymphocytes and hemophagocytosis were common in bone marrow smears. Deletion of CD5 or CD7 were frequently observed in T/NK lymphocytes in bone marrow cells by flow cytometry. Bone marrow biopsy showed atypical lymphocyte interstitial infiltrated in 10 cases, while a few large cells infiltrated in 6 cases. Immunohistochemistry showed the expression of CD3(+)CD56(+) were seen in 2 cases, CD3(+)CD8(+) in 11 cases and CD3(+)CD4(+) in 3 cases. TIA-1 and EBER were positive in all biopsy specimens. Three cases underwent biopsy of lymph nodes showed reactive proliferations of lymphocytes. All the patients died of multiorgan failure. It is concluded that the fever, hepatosplenomegaly are the most common clinical features in adult EBV+T/NK-LPD, the bone marrow infiltration of EBV-infected T/NK lymphocytes and significantly increased EBV-DNA level can be observed in all cases, the clinical outcome of this disease is poor, these clinical and experimental features can be served as a reliable marker for the timely diagnosis of adult EBV+T/NK-LPD.

Objective To investigate the cytogenetic and immunological phenotypes of acute myeloid leukemia (AML) with t(8;21),and explore the risk stratification and risk-adapted treatments.Methods The chromosomal karyotype of bone marrow was detected and analyzed in 22 newly diagnosed patients with t(8;21) AML by direct culture and G banding technique.Patients were divided into two groups according to the chromosomal karyotypes.Clinical characteristics and immunological phenotypes were compared between patients with isolated t(8;21) and those with additional aberrations.A follow-up study with median time 30 months (4-68 months) was conducted to analyze prognostic factors.Results 13 cases (59.1％) were isolated t(8;21) AML,while 9 (40.9 ％) had additional aberrations.Loss of sex chromosome was found in 3 cases and complex variant translocation in 2.The 10q-,9q-,-18 and +10 were found in single cases.Overall survival of patients with additional aberrations was significantly poorer than those with isolated t (8;21) (P =0.0176).Analysis of prognostic factors showed that t(8;21) chromosomal karyotype,initial white blood cells at diagnosis,and treatment regimen (chemotherapy alone or plus hematopoietic stem cell transplantation) had effects on overall survival.Conclusion Patients with t (8;21) AML are frequently associated with additional chromosomal aberrations.The latter indicates a poorer outcome and can be one of the bases of risk stratification.Hematopoietic stem cell transplantation might help to improve the overall survival.

Objective To explore the efficiency and safety of velcade regimen treating multiple myeloma (MM).Methods Totally 11 MM patients during August 2008 to May 2011 treated with VD regimen were analyzed retrospectively.VD regimen was adopted.Then VAD regimen was used.Halidomide combined with prednisone and mafalan were given during stable stage.Results The median follow-up period was 24 months.After one VD course,the main side effects were as follow:one peripheral nerve numbness,two restless multilingual,two lung infection (bacter and fungal),one diarrhea and two zoster.Conclusions VD regimen can be used to treat MM.

To explore the clinical characteristics, diagnosis, treatment outcome and prognosis of de novo CD5 positive diffuse large B cell lymphoma (CD5(+)DLBCL), clinical data of 10 patients with pathologically confirmed CD5(+)DLBCL were retrospectively analyzed. The results indicated that 9 out of 10 patients were older than 60 years. All cases were in III/IV stages according to Ann-Arbor Staging System. Bone marrow biopsy with immunohistochemistry showed lymphoma involvement in 5 cases. Nine patients received chemotherapy with anti-CD20 monoclonal antibody (Rituximab) except one. Five cases achieved CR, two cases achieved PR, two cases achieved SD, one case achieved PD. Eight cases died within 2 years because of relapse or disease progression, in which 3 cases developed central nervous system lymphoma. The median survival time was 16 (1-23) months, 2-year survival rate was 20.40%. It is concluded that de novo CD5(+) DLBCL is rare in clinic, but it is a kind of highly aggressive lymphoma with poor prognosis. So, new treatment strategy should be explored.

Objective:To explore the effectiveness and side effects of pirarubicin in the consolidation chemotherapy of acute promyelocytic leukemia(APL ).Methods:We retrospectively studied 58 cases of newly diagnosed APL that achieved complete remission( CR ).The patients were divided into two groups,with 26 cases in the TA group(pirarubicin + cytarabin ),and 32 cases in the DA group( daunorubicin + cytarabin ).Results:Of the 58 patients,5 relapsed:1 case in the TA group and 4 cases in DA group.Although no significant difference was observed between the two groups,the 2-year cumulative incidence of relapse was lower in the TA group than the DA group (5.0%vs.13.0%).The 3-year event free survival(EFS ) was higher in the TA group(93.3%vs.76.5%).The incidence and the degree of hematologic toxicity were similar.A mild transient T-wave abnormality was observed in 9.2%of the chemotherapy cycles in the TA group. The TA group had a lower incidence of cardiac toxicity than the DA group.Conclusion:The TA and DA regimens have similar effects on the consolidation chemotherapy of APL.The difference in side effects between the two groups was not significant.Pirarubicin has a lower incidence of cardiac toxicity.The TA regimen(pirarubicin + cytarabin ) may be an alternative to APL consolidation therapy.

目的探讨预防性鞘内注射化疗在急性早幼粒细胞性白血病(APL)患者临床疗效。方法回顾性分析20例预防性鞘注APL缓解患者(鞘注组),与同期未行鞘注治疗27例患者作对照(非鞘注组)。随访中位时间30(6～62)个月。比较两组发生中枢神经系统白血病(CNSL)及复发率。结果鞘注组20例无一例复发,其中鞘注组中3例高危患者CR后首次腰穿检查发现无症状单纯脑脊液压力增高,鞘注治疗后恢复正常,均随访3年以上未发生CNSL。非鞘注组27例4例复发(1例中危,3例高危),其中1例高危患者发生CNSL。结论预防性鞘内注射化疗有益于减少APL患者CNSL发生,可能有助于减少白血病复发。

Objective To explore the clinical significance of fms-like tyrosine kinase3(FLT3) expression in evaluation prognosis of acute myeloid leukemia(AML) prognosis.Methods 50 patients with AML were selected.AML patients with normal karyotype were 20 cases,the abnormal karyotype were 30 cases.3ml bone marrow before themotherapy was aspirated respectively,and the FLT3 gene expression in leukemia cells was detected with polyenzyme chain react(PCR).Results The FLT3 expression rate in AML patients with normal karyotype was 5.0％,and was 26.7％ in AML patients with abnormal karyotype,33.3％ in AML patients with refractory-relapse,and 4.5％ in AML patients with continue remission.The FLT3 expression rate was related with high leukemia cells percentage in bone marrow and high blood cells count in peripheral blood,and was not related with Franch America British(FAB) classification.The free-disease survival(FDS) and overall survived(OS) was shorter in FLT3 expression AML patients than that in no FLT3 expression AML patients.There was a statistical significance between the former and the latter( x2 =4.17,P ＜0.05 ).Conclusion FLT3 was a kind of worse factor in AML patients prognosis,and could guide clinical individual treatment in AML.

目的探讨IA方案治疗急性髓系白血病(AML)的疗效及安全性。方法对2009年8月至2010年4月采用去甲氧柔红霉素(IDA)联合阿糖胞苷(Ara-C)的IA方案治疗的4例AML患者的临床资料进行回顾分析。结果 4例患者经IA方案治疗后达持续缓解。结论 IA方案适用于初发、缓解后AML的治疗,可作为首选方案,安全性较好。

滤泡性淋巴瘤是非霍奇金淋巴瘤中第二常见的病理亚型。传统的治疗方法为放疗及化疗,早期患者有可能通过放疗治愈,但晚期患者很少有治愈的希望。随着新的治疗策略不断涌现,包括单克隆抗体、放射免疫治疗、苯达莫司汀、自体及异体造血干细胞移植、来那度胺、蛋白酶体抑制剂,患者的生存率得到明显的改善。本文作者就滤泡性淋巴瘤的治疗进展作一综述。