Humans ; Lymphohistiocytosis, Hemophagocytic ; Herpesvirus 4, Human ; Interleukin-2 ; Epstein-Barr Virus Infections/complications* ; T-Lymphocytes

OBJECTIVE: To investigate the cytokine/chemokine profile in patients with Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH), and assess the prognostic value of survival. METHODS: Serum levels of thirty-eight cytokines/chemokines were measured by multiple cytokine assay kit in EBV-related HLH patients, EBV-infected patients, and controls. The expression profile of cytokines/chemokines was compared among groups. The changes of cytokine/chemokine expression in active and remission stage of EBV-related HLH patients were also compared, and the prognostic values for survival were evaluated. RESULTS: Serum levels of interferon-α2 (IFN-α2), interleukin (IL)-6, and IL-7 in EBV-related HLH patients were 33.67(23.23-68.78) pg/ml, (74.95±25.53) pg/ml, and 35.35(19.50-63.55) pg/ml, respectively, which were significantly higher than those in EBV-infected patients［IFN-α2: 16.07(9.87-29.63); IL-6: 55.91±20.29; IL-7: 20.40(13.35-31.40)］ and controls ［IFN-α2: 11.02(4.67-21.25); IL-6:42.64±13.41; IL-7: 16.95(14.95-33.78)］(all P<0.05). Serum levels of IL-8, IL-9, and marcophage-derived chemokine (MDC) in EBV-related HLH patients were 11.00(7.50-15.27) pg/ml, 81.30(40.79-111.0) pg/ml, and (512.6±128.7) pg/ml, respectively, which were significantly higher than those in controls ［IL-8: 6.80(5.56-8.38); IL-9: 41.30(29.82-67.91); MDC: 384.1±156.6］(all P<0.05), but there was no remarkable differences compared with EBV-infected patients (P>0.05). Serum IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC in survival and death groups of EBV-related HLH patients were analyzed by receiver operating characteristic curve with area under curve of 0.781, 0.778, 0.633, 0.805, 0.562, and 0.657, respectively (P=0.019, 0.021, 0.269, 0.015, 0.607, and 0.190). IFN-α2, IL-6, and IL-8 had good predictive effect on survival. Serum level of IFN-α2, IL-6, and MDC of EBV-related HLH patients in remission stage were significantly lower than those in active stage (P<0.05), while IL-7, IL-8, and IL-9 were not different (P>0.05). CONCLUSION IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC may take part in the pathogenesis of EBV-related HLH.
Humans ; Lymphohistiocytosis, Hemophagocytic/complications* ; Herpesvirus 4, Human ; Cytokines/metabolism* ; Epstein-Barr Virus Infections/complications* ; Interleukin-6 ; Clinical Relevance ; Interleukin-7 ; Interleukin-8 ; Interleukin-9 ; Chemokines ; Interferons

Humans ; Herpesvirus 4, Human ; Wiskott-Aldrich Syndrome ; Epstein-Barr Virus Infections/complications* ; Smooth Muscle Tumor/therapy* ; Hematopoietic Stem Cell Transplantation

Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications* ; Multiple Myeloma/complications* ; Lymphoma, Large B-Cell, Diffuse/pathology*

OBJECTIVE: To compare the clinical characteristics of children with hemophagocytic lymphocytosis (HLH) associated with primary Epstein-Barr virus (EBV) infection and EBV reactivation, and explore the effects of different EBV infection status on the clinical indexes and prognosis of HLH. METHODS: The clinical data of 51 children with EBV associated HLH treated in Henan Children's Hospital from June 2016 to June 2021 were collected. According to the detection results of plasma EBV antibody spectrum, they were divided into EBV primary infection-associated HLH group (18 cases) and EBV reactivation-associated HLH group (33 cases). The clinical features, laboratory indexes and prognosis of the two groups were analyzed and compared. RESULTS: There were no significant differences in age, gender, hepatomegaly, splenomegaly, lymphadenopathy, neutrophil count in peripheral blood, hemoglobin content, platelet count, plasma EBV-DNA load, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, albumin, fibrinogen, triglyceride, ferritin, hemophagocytosis in bone marrow, NK cell activity and sCD25 between the two groups(P>0.05). The central nervous system involvement and CD4/CD8 in EBV reactivation-associated HLH group were significantly higher than those in primary infection-associated HLH group, but the total bilirubin was significantly lower than that in primary infection-associated HLH group (P<0.05). After treatment according to HLH-2004 protocol, the remission rate, 5-year OS rate and 5-year EFS rate of patients in EBV reactivation-associated HLH group were significantly lower than those in EBV primary infection-associated HLH group (P<0.05). CONCLUSION EBV reactivation-associated HLH is more likely to cause central nervous system involvement and the prognosis is worser than EBV primary infection-associated HLH, which requires intensive treatment.
Child ; Humans ; Epstein-Barr Virus Infections/complications* ; Lymphohistiocytosis, Hemophagocytic/complications* ; Herpesvirus 4, Human ; Retrospective Studies ; Prognosis

Objective: To analyze the detection rate, clinical significance, and prognosis of Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of patients following allogeneic hematopoietic stem cell transplantation. Methods: A retrospective analysis was performed on 1100 patients who underwent the CSF virus test after allogeneic hematopoietic stem cell transplantation in Peking University People's Hospital between January 2017 and June 2022. Among them, 19 patients were screened positive for EBV in their CSF, and their clinical characteristics, treatment, and prognosis were analyzed. Results: Among 19 patients with EBV-positive cerebrospinal fluid, 12 were male and 7 were female, with 5 patients aged <18 years and 12 aged ≥18 years, with a median age of 27 (5-58) years old. There were 7 cases of acute myeloid leukemia, 8 of acute lymphocytic leukemia, 2 of aplastic anemia, 1 of Hodgkin's lymphoma, and 1 of hemophagocytic syndrome. All 19 patients underwent haploid hematopoietic stem cell transplantation, including 1 secondary transplant. Nineteen patients had neurological symptoms (headache, dizziness, convulsions, or seizures), of which 13 had fever. Ten cases showed no abnormalities in cranial imaging examination. Among the 19 patients, 6 were diagnosed with EB virus-related central nervous system diseases, with a median diagnosis time of 50 (22-363) days after transplantation. In 9 (47.3%) patients, EBV was detected in their peripheral blood, and they were treated with intravenous infusion of rituximab (including two patients who underwent lumbar puncture and intrathecal injection of rituximab). After treatment, EBV was not detected in seven patients. Among the 19 patients, 2 died from EBV infection and 2 from other causes. Conclusion: In patients who exhibited central nervous system symptoms after allogeneic hematopoietic stem cell transplantation, EBV should be screened as a potential pathogen. EBV detected in the CSF may indicate an infection; however, it does not confirm the diagnosis.
Humans ; Male ; Female ; Adolescent ; Adult ; Middle Aged ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications* ; Rituximab/therapeutic use* ; Retrospective Studies ; Clinical Relevance ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Lymphoproliferative Disorders/drug therapy*

Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications* ; Cholangiocarcinoma/pathology* ; Carcinoma, Squamous Cell ; Bile Ducts, Intrahepatic/pathology* ; Bile Duct Neoplasms/pathology*

OBJECTIVES: To study the value of metagenomic next-generation sequencing (mNGS) in detecting intracranial Epstein-Barr virus (EBV) infection in children with hemophagocytic syndrome (HPS) with central nervous system involvement. METHODS: A retrospective analysis was performed for the cerebrospinal fluid mNGS results of 30 HPS children with central nervous system involvement, which were compared with the results of cerebrospinal fluid EBV-DNA detection and serum EBV antibody profile. The change in serum EBV-DNA copy number after treatment was used to evaluate the efficacy of targeted therapy. RESULTS: The positive rate of EBV in cerebrospinal fluid determined by mNGS was significantly higher than that of EBV-DNA in cerebrospinal fluid (100% vs 10%, P<0.001) and had no significant difference from the positive rate of serum EBV antibody profile (100% vs 93%, P>0.05). The median number of sequences determined by mNGS was 2 400, and serum EBV-DNA copy number before treatment was moderately positively correlated with the number of EBV sequences (r_s=0.693, P<0.001). The multiple linear regression analysis showed that the number of sequences determined by mNGS in cerebrospinal fluid increased with the increase in serum EBV-DNA copy number before treatment (P<0.05). CONCLUSIONS EBV-associated HPS often results in EBV-infected viral encephalitis, and mNGS can significantly increase the detection rate of EBV in cerebrospinal fluid, which may help with clinical diagnosis.
Child ; Humans ; Lymphohistiocytosis, Hemophagocytic/genetics* ; Epstein-Barr Virus Infections/complications* ; Herpesvirus 4, Human/genetics* ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Central Nervous System

OBJECTIVE: To analyze the clinical characteristics of SAA patients with post-transplantation lymphoproliferative disease (PTLD) after allogeneic hematopoietic stem cell transplantation, and to improve diagnosis and treatment of PTLD. METHODS: The clinical data of 192 patients with SAA patients who underwent HSCT in a single center from September 2010 to September 2017 were analyzed retrospectively. All patients were received antithymocyte globulin（ATG） conditioning regimen and mesenchymal stem cell(MSC) infusion. RESULTS: Among 192 cases, PTLD occurred in 14 cases, the incidence was 7.29％， 9 of them were diagnosed by pathology， and 5 were diagnosed clinically. EBV infection occurred with a median time of 72（35-168） days, Viral load higher than 1×10⁴ copies/ml occured in all PTLD patients. The incidence of probable PTLD in patients ≤12 years old and ＞12 years old was 11.11%, 2.38%, respectively (P<0.01）. Univariate and multivariate analysis that the EBV infection, patients age≤12 years old, HLA-mismatch in URD-HSCT, grade II to IV aGVHD were the independent risk factors for PTLD. All PTLD patients were treated with rituximab(RTX) when EBV-DNA load higher than 1×10⁴ copies/ml, or reducted the use of immunosuppression(RIS), patients with poor therapeutic effect were treated combined with EBV-specific CTLs(EBV-CTL) and chemotherapy. All patients were treated effectively, and the total effective rate was 100％. The median follow-up time was 65(62-115) months, and the overall survival rate was 92.85%. One patients died of cerebral hemorrhage, 7 months after PTLD curred. CONCLUSION The incidence of PTLD after HSCT with SAA who used ATG and MSC in conditioning regimen closely relates to EBV infection, age of patients≤12 years, HLA-mismatch in URD-HSCT, grade II to IV GVHD. Rituximab combined with RIS may reduce the incidence of PTLD, combined EBV-CTL and chemotherapy may be the useful and most important treatment for PTLD.
Anemia, Aplastic/therapy* ; Child ; Epstein-Barr Virus Infections/complications* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Lymphoproliferative Disorders/therapy* ; Retrospective Studies ; Rituximab/therapeutic use*

Objective: To investigate the clinicopathological features and prognosis of cytotoxic T-cell lymphoma (CTL). Methods: The clinicopathological data of 134 CTL patients in Beijing Friendship Hospital Affiliated to Capital Medical University, the 989 Hospital of PLA Joint Logistics Support force (formerly the 152 Hospital) and the Fourth Hospital of Hebei Medical University from 2008 to 2020 were retrospectively collected. Immunophenotype, Epstein-Barr virus infection status and T cell receptor (TCR) clonality of tumor cells were assessed, and clinicopathological features and prognosis of patients were analyzed. Results: Among the 134 CTL patients, the male to female ratio was 1.7∶1.0, the median age was 49.5 years (range 3-83 years), and 100 cases (74.6%) were under 60 years old. Forty-six point nine percent of the patients (53/113) had B symptoms. Most of the patients presented with systemic superficial lymphadenopathy. According to the Ann Arbor staging system, 36.8% (39/106) of the patients were in stage Ⅰ-Ⅱ, and 63.2% (67/106) in stage Ⅲ-Ⅳ. The rate of extranodal involvement was 51.6% (66/128). Spleen was involved in 24.2% (31/128) of the cases. Morphology showed diffuse growth of abnormal lymphocytes, infiltrating and destroying normal tissue structure. Immunohistochemical staining showed that tumor cells expressed T cell antigens (CD2, CD3, CD5, and CD7), and 72.0% (77/107) of them had decreased or lost expression of one or more antigens. According to the numbers of CD4 and CD8 expression in tumor cells, 70 cases (52.2%) were grouped into CD8⁺>CD4⁺group. The expression rates of TIA-1 and granzyme B were 99.2% (119/120) and 79.8% (95/119), respectively. CD20 abnormal expression rate was 27.6% (37/134) and CD56 was negative in all cases. The median Ki-67 proliferative index was 45.0% (range 5%-80%). In situ hybridization of small RNA encoded by Epstein-Barr virus was negative. Clonal TCR gene rearrangement analysis was performed on 49 cases and was positive in all cases. Ninety-one patients were followed up for a median of 36 months (range, 1 to 240 months), and 40 of the 91 patients (44.0%) died. The twenty-three patients were in complete remission (including 13 cases with localized single extranodal mass). The 3-year and 5-year overall survival rates were 53.5% and 49.4%, respectively. Univariate analysis showed that B symptom, spleen involvement, extranodal involvement, clinical stage, CD8⁺>CD4⁺phenotype, abnormal expression of CD20 and Ki-67 proliferation index (>60%) were associated with overall survival (P<0.05). The multivariate Cox regression analyses showed that spleen involvement and CD8⁺>CD4⁺ phenotype were independent prognostic factors for overall survival in CTL patients. Conclusions: CTL are more commonly found in adult males under 60 years old, often accompanied by B symptom, with a high proportion of extranodal involvement and more CD8 positive phenotypes. Spleen involvement and CD8⁺>CD4⁺phenotype are independent predictors of CTL overall survival. Some patients with localized extranodal CTL may have a good prognosis.
Epstein-Barr Virus Infections/complications* ; Female ; Herpesvirus 4, Human/genetics* ; Humans ; Lymphoma, T-Cell/pathology* ; Male ; Prognosis ; Retrospective Studies