Risk factors and prognosis of early death in secondary hemophagocytic lymphohistiocytosis.

The aim of our study was to summarize the clinical characteristics of early death patients with newly diagnosed secondary hemophagocytic lymphohistiocytosis (sHLH), analyze the risk factors of early death, and analyze the survival of patients. The clinical characteristics of 324 newly diagnosed sHLH patients admitted to the First Affiliated Hospital of Zhejiang University Medical College and Zhejiang Provincial Cancer Hospital from January 2014 to February 2021 were analyzed retrospectively. Analyze the independent risk factors of early death, compare the secondary diseases and treatment methods of patients with early death group and non early death group, and analyze the survival of all patients with sHLH. Among the 324 newly diagnosed patients with sHLH, 134 died early, with an early mortality rate of 41.4%. Comparing the clinical characteristics of patients with early death group and patients with non early death group, logistic regression model was used to conduct multifactor analysis. Age > 60 years, Plt ≤ 20.0 × 109/L, APTT > 36.0 s and LDH > 1000.0 U/L were independent risk factors for early death of newly diagnosed sHLH patients (P < 0.05). Comparing the secondary diseases and treatment methods between early death group and non early death group, the proportion of sHLH patients secondary to lymphoma was higher in early death group than that in non early death group (P < 0.05). The proportion of sHLH patients secondary to connective tissue disease and infection was lower in early death group than that in non early death group (P < 0.05), and the proportion of sHLH patients used hormone combined chemotherapy was lower in early death group than that in non early death group (P < 0.05). The median follow-up time of all patients was 12.0 (1-65) months. The 5-year OS rates of patients with age > 60 years and age ≤ 60 years were 25.8% and 49.6% respectively (P < 0.001); The 5-year OS rates of patients with Plt > 20.0 × 109/L and Plt ≤ 20.0 × 109/L were 52.5% and 25.5% respectively (P < 0.001); The 5-year OS rates of patients with APTT > 36.0 s and APTT ≤ 36.0 s were 34.5% and 57.4% respectively (P < 0.001); The 5-year OS rates of patients with LDH > 1000.0 U/L and LDH ≤ 1000.0 U/L were 23.3% and 56.3% respectively (P < 0.001). Age > 60 years, Plt ≤ 20.0 × 109/L, APTT > 36.0 s and LDH > 1000.0 U/L are independent risk factors for early death of sHLH patients. The early mortality of lymphoma associated HLH (LA-HLH) patients is high, and early use of hormone combined chemotherapy can reduce the early mortality.

Activated microglia promote invasion and barrier dysfunction of brain endothelial cells via regulating the CXCL13/CXCR5 axis.

The blood brain barrier (BBB) is a protective border that prevents noxious substances from gaining access to the central nervous system (CNS). CXCL13 is a chemokine from the CXC chemokine family, which has been shown to destroy the barrier function of umbilical vein endothelial cells with its receptor CXCR5. Here, we aimed to investigate the role of CXCL13/CXCR5 signaling axis in BBB. The invasive ability of bEnd.3 cells was determined by the Transwell invasion assay. The barrier integrity of bEnd.3 cells was assessed by detecting trans-endothelial electrical resistance, the permeability to fluorescein isothiocyanate-dextran, and the expression levels of the tight junction protein E-cadherin. Lipopolysaccharide (LPS)-activated microglia promoted invasion and barrier dysfunction, and upregulated CXCR5 and p-p38 expression levels in cocultured bEnd.3 cells. However, the effects of activated microglia were alleviated by knocking down CXCR5 in cocultured bEnd.3 cells. Furthermore, recombinant CXCL13 promoted invasion and barrier dysfunction, and upregulated the expression levels of p-p38 in bEnd.3 cells; however, its effects were abolished by treating bEnd.3 cells with the p38 inhibitor SB203580. Our data tentatively demonstrated that LPS-activated microglial cells may promote invasion and barrier dysfunction in bEnd.3 cells by regulating the CXCL13/CXCR5 axis and p38 signaling.

Clinical features and prognostic analysis of lymphoma-associated hemophagocytic syndrome: A report of 139 cases.

Lymphoma-associated hemophagocytic syndrome (LAHS) is characterized by rapid onset, rapid progression and a poor prognosis, and is easy to misdiagnose. In order to improve the clinical understanding, diagnosis and treatment of LAHS, the clinical characteristics and risk factors of LAHS were discussed by retrospective data analysis in the present study. The clinical characteristics of 324 patients with newly diagnosed hemophagocytic syndrome (HPS) were retrospectively investigated. The patients were divided into two groups: The LAHS group comprising 139 patients with LAHS and the non-LAHS group comprising 185 patients with HPS that was not associated with lymphoma. The clinical features and prognosis of the two groups were compared. Patients in the LAHS group had higher levels of total bilirubin (P=0.005) and indirect bilirubin (P=0.006). In addition, patients in the LAHS group had a higher early mortality rate (50.4 vs. 34.6%; P=0.004), higher recurrence rate (30.2 vs. 15.1%; P=0.001), reduced 5-year overall survival rate (OS; 21.5 vs. 52.4%; P<0.001) and reduced relapse-free survival rate (RFS; 7.7 vs. 48.3%; P<0.001) compared with those in the non-LAHS group. If patients with early mortality in the two groups were excluded, the 5-year OS rates were improved and also significantly different (43.3 vs. 80.2%; P=0.041). The 5-year OS and RFS of patients in the LAHS group who had received chemotherapy were significantly superior compared with those who had not received chemotherapy (P<0.001). Multivariate analysis showed that an activated partial thromboplastin time of >36.0 sec (P=0.020) and serum lactate dehydrogenase level of >1,000 U/l (P=0.045) were independent risk factors for a poor LAHS prognosis. The outcomes of the patients with LAHS were worse than those of those with other types of HPS due to the higher early mortality rate. Therefore, it may be concluded that the reduction of the early mortality rate of patients with LAHS is of great importance.

Acute Mast Cell Leukemia Preceded by Malignant Mediastinal Germ Cell Tumor: A Case Report and Literature Review.

Background: Mast cell leukemia (MCL) is a highly life-threatening and extremely rare subtype of systemic mastocytosis (SM). MCL often genetically contains one or more somatic mutations, particularly activating mutations of KIT. This study reported on an acute MCL patient who had a rare phenotype and genetic mutants with a history of primary malignant mediastinal germ cell tumor (GCT). Case Presentation: A 30-year-old Asian male patient who underwent two rounds of surgery and chemotherapy with a history of primary mediastinal GCT (PM-GCTs) was admitted to our hospital due to persistent chest pain and severe fatigue. The diagnosis of acute MCL was confirmed via morphology analysis and chemical staining of marrow aspirate, as well as via marrow biopsy, with the addition of C-findings that included splenomegaly and cytopenia. The atypical MCs were phenotypically positive for CD117 and CD9 but weakly positive for CD2 and negative for CD25. Next-generation sequencing of the marrow aspirate identified heterozygous mutations in TP53 P301Qfs*44, FLT3 R973X, SETBP1 N272D, and JAK3 I688F, whereas mutations in KIT were not found. Although the initial therapy of corticosteroids, ruxolitinib, and dasatinib-based regimens was effective, he died of acute respiratory distress syndrome after the first cycle of chemotherapy with cladribine and cytarabine. The patient's survival time was 2.4 months after the initial presentation of MCL. Conclusion: In this case, MCL preceded by PM-GCTs had similar clinical symptoms and morphological manifestations but distinctly different genetic profiles than primary MCL. The characteristic morphology of MCL provides the most pivotal evidence that led our diagnosis in the correct direction. A competing hypothesis is that there is a common embryonal cancer stem cell between PM-GCTs and secondary MCL, and the latter is gradually developed in the context of additional "driver mutations".

Analysis of Prognostic Risk Factors and Establishment of Prognostic Scoring System for Secondary Adult Hemophagocytic Syndrome.

INTRODUCTION: The objective of this paper is to identify the prognostic risk factors of secondary adult hemophagocytic syndrome (HLH) in hospitalized patients and establish a simple and convenient prognostic scoring system. METHOD: We reviewed 162 adult patients secondary with HLH treated in Zhejiang Cancer Hospital and the First Affiliated Hospital of Medical College of Zhejiang University from January 2014 to December 2018 were enrolled to form the test group; from January 2019 to February 2021, 162 adult patients in the hospitals constituted the validation group. The HLH prognosis scoring system was constructed according to the risk factors, and the patients were divided into three risk groups: low risk, medium risk, and high risk. The scoring system was verified by Kaplan-Meier method and log rank test survival analysis. The discrimination ability was evaluated according to the receiver operating characteristic (ROC) curve. RESULTS: Univariate and multivariate analysis showed that the independent risk factors for the prognosis of HLH were male sex, activated partial prothrombin time (APTT) greater than 36 s, lactate dehydrogenase (LDH) greater than 1000 U/L, and C-reactive protein (CRP) greater than 100 mg/L. The area under the ROC curve was 0.754 (95% Cl: 0.678-0.829). The patients were divided into a low-risk group (0-1), a medium-risk group (2-4), and a high-risk group (5-6). The 5-year overall survival (OS) rate were 87.5%, 41.8% and 12.8%, respectively (p < 0.001). The area under ROC curve was 0.736 (95% Cl: 0.660-0.813) in the validation group, and the 2-year OS of patients in low-risk, medium-risk and high-risk groups were 88.0%, 45.1% and 16.7%, respectively (p < 0.001). CONCLUSION: The new prognostic scoring system can accurately predict the prognosis of secondary adult HLH and can further provide basis for the accurate treatment of secondary adult HLH.

Adult onset haemophagocytic lymphohistiocytosis prognosis is affected by underlying disease: analysis of a single-institution series of 174 patients.

BACKGROUND: Haemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterised by activation of the mononuclear phagocytic system, and often leads to progressive multiple organ failure. The diagnosis of HLH is made late by most physicians. METHODS: To confirm the diagnosis of acquired HLH made in a single-institution series of adult patients with HLH-04 criteria, we applied the HScore and evaluated prognostic factors associated with clinical outcome. RESULTS: A total of 174 patients with a median age of 51 years (range 17-90) were included. Male/female ratio was 111/63. In 92/174 (52.9%) patients, there were potential haematological diseases (4 acute leukaemia, 1 thrombotic thrombocytopenic purpura, 3 Hodgkin's lymphoma [HL], 17 B-cell non-Hodgkin's lymphoma [NHL], 67 T-cell NHL including 22 natural killer / T-cell NHL [NK/t-cell NHL). Six (3.4%) patients had autoimmune disease and 76 (43.7%) undiagnosed underlying disease. There were 44 (25.3%) patients with Epstein-Barr virus infection, 11 (6.3%) with cytomegalovirus, 1 (0.5%) syphilis, 9 (5.2%) hepatitis B virus and 3 (1.7%) human immunodeficiency virus. More than 95% of patients had hyperferritinaemia, high lactate dehydrogenase, fever and low albumin, whereas 89.1% of patients had bone marrow phagocytosis. By the HScore, 4/174 patients had a >50% and 16/174 patients had a >90% probability of not having HLH. All 174 patients fulfilled more than five of the HLH-04 diagnostic criteria, but 16 of them had a low probability of HLH by the HScore. In a multivariate analysis, lymphopenia and hypofibrinogenaemia were independent prognostic factors for death. CONCLUSION: In our study, viral infection was not an independent prognostic factor. NK/T-cell -NHL was associated with worse prognosis compared with B-cell NHL and T-cell NHL (p = 0.036) and similar to other aetiologies.

Risk factors and clinical characteristics of non-promyelocytic acute myeloid leukemia of intracerebral hemorrhage: A single center study in China.

BACKGROUND: Although high mortality in patients with acute leukemia (AL) is associated with intracranial hemorrhage (ICH), the clinical features and pathogenesis of AL patients with cerebral hemorrhage are not well known. METHODS: We diagnosed 90 patients with ICH from a total of 1467 patients with non-promyelocytic AL who had been hospitalized in the First Affiliated Hospital of Medical School of Zhejiang University from January 2010 to October 2015. Moreover, the risk factors of ICH death were evaluated. RESULT: Median age at ICH was 51years old, in which men accounted for 52.2%. They also accounted for 85.6% of acute myeloid leukemia. The relative incidence of ICH was the highest in M2 and M5 (60.1%). ICH presented with higher peripheral blood white blood cell count (WBC) (P<0.001), lower peripheral platelet counts (P<0.001), lower albumin (P<0.001), lower fibrous protein (P<0.001) and prolongation of prothrombin time (P<0.001) compared to those observed in the patients of NICH group; multivariate analysis, independent risk factors for death in patients with ICH include: WBC≥30.00×109/l and prothrombin time≥12.91 s. CONCLUSIONS: Leukocytosis and coagulation dysfunctions might be the main pathogenesis of acute leukemia complicated with cerebral hemorrhage.

A Case of Primary Hepatic Lymphoma and Related Literature Review.

Objective. Primary hepatic lymphoma is a rare disease. And the clinical manifestations of this disease are nonspecific. The objective of this paper is to improve clinicians' understanding of this disease. Methods. We analyzed the clinical characteristics of a case of primary hepatic lymphoma in association with hepatitis B virus infection and reviewed the literature. Conclusion. The clinical manifestations of primary hepatic lymphoma are nonspecific. And it is easily misdiagnosed. Postoperative radiotherapy of patients with early stage was previously speculated to achieve favorable improvement. The application of targeted therapeutic drugs, chemotherapy, or combined local radiotherapy has become the first-line treatment strategy.