B-cell lymphoma with cytokine storm in serosal effusion: A case report and literature review.

RATIONALE: Cytokine storm is now considered to be a systemic inflammatory response, but local cytokine storm may exist in systemic diseases of the blood system. Monitoring of regional cytokine storm is an important clue for the diagnosis of systemic diseases. PATIENT CONCERNS: A 72-years-old male presented to our hospital with multiple serosal effusion without solid mass or enlarged lymph nodes. We found that the level of cytokines in ascites was tens to hundreds of times higher than that in plasma, mainly IL-6 and IL-8. DIAGNOSES: The patient was diagnosed with multiple serous effusion, hemophagocytic syndrome, B-cell lymphoma, Epstein-Barr virus infection, and hypoproteinemia. INTERVENTIONS: During hospitalization, the patient was treated with 5 courses of R-CVEP therapy and supportive treatment. OUTCOMES: After the first R-CVEP regimen, the patient's condition was evaluated as follows: hemophagocytic syndrome improved: no fever; Serum triglyceride 2.36 mmol/L; Ferritin 70.70 ng/L; no hemophagocyte was found in the bone marrow; the lymphoma was relieved, ascites disappeared, and bone marrow cytology showed: the bone marrow hyperplasia was reduced, and small platelet clusters were easily seen. Bone marrow flow cytometry showed that lymphocytes accounted for 13.7%, T cells increased for 85.7%, CD4/CD8 = 0.63, B cells decreased significantly for 0.27%, and NK cells accounted for 10.2%. Blood routine returned to normal: WBC 5.27 × 109/L, HB 128 g/L, PLT 129 × 109/L; Epstein-Barr virus DNA < 5.2E + 02 copies/mL; correction of hypoproteinemia: albumin 39.7 g/L. LESSONS: Cytokines in ascites are significantly higher than those in plasma by tens to hundreds of times, suggesting that "regional cytokine storms" may cause serosal effusion.

[Inhibitory Effect of Cinobufotalin on Macrophage Inflammatory Factor Storm and Its Mechanism].

OBJECTIVE: To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism. METHODS: THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot. RESULTS: 1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1ß, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway. CONCLUSION: Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.

[Establishment of a Patient-Derived T-Cell Acute Lymphoblastic Leukemia Xenograft Model in Novel Immunodeficient NCG Mice].

OBJECTIVE: The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model. METHODS: Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model. RESULTS: On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks. CONCLUSION: Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.

Philadelphia chromosome-positive acute lymphoblastic leukemia: a case report.

Prognosis of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph-ALL) relapsing after allogeneic hematopoietic stem cell transplantation (HSCT) is extremely poor. Therefore, effective alternative therapeutic measures are urgently needed. Recently, the use of antigen receptor-modified T cells holds great promise for relapsed and refractory ALL treatment. Prior to chimeric antigen receptor T-cell (CAR-T) infusion conditioning chemotherapy is used routinely to establish a favorable in vivo environment for CAR-T expansion, which has mostly involved fludarabine and cyclophosphamide. We report on a patient presented with extreme fatigue and anemia and was diagnosed with relapsed and refractory acute lymphoblastic leukemia (ALL) harbored T315I-BCR-ABL mutation, who had undergone allogeneic HSCT and multiple reinducing chemotherapy, but achieved complete hematologic remission (CHR) with CAR -T infusion as a later salvage treatment. Prior to CAR-T infusion there was no conditioning chemotherapy, but a bone marrow suppression period induced by ponatinib. CAR-T cell infusion was well tolerated and the patient achieved a CHR and maintained it for three months. At present, there is no relevant report on the use of tyrosine kinase inhibitors (TKI) as preconditioning protocols before CAR-T cells infusion. Our case indicated ponatinib not only reduces tumor burden but may also serve as a conditioning regimen for CAR-T therapy in the treatment of relapsed and refractory Ph-ALL.

[Curative Efficacy and Survival Analysis of Low-Intensity Traditional Chemotherapy Regimen in the Elderly Patients with Acute Myeloid Leukemia (non-M3)].

OBJECTIVE: To investigate the short-term and long-term curative efficacy of low-intensity traditional chemotherapy regimen for elderly patients with acute myeloid leukemia (AML, non-M3) and related adverse reactions, in order to explore whether low-intensity traditional chemotherapy regimen still has application value in the treatment of elderly AML patients today. METHODS: The clinical characteristics, treatment response and prognosis of 67 elderly patients with AML (non-M3) admitted to our hospital from June 2008 to December 2018 were retrospectively analyzed. All patients received low-intensity conventional chemotherapy (i.e. lower standard dose, and without new drugs listed in China since the 21st century), including DA, HA, CAG, etc. The CR rate, median survival time and 5-year cumulative survival rate of patients were evaluated, and the related indexes were compared with the data reported in domestic and foreign literatures at the same time. RESULTS: The CR rate was 55.2% (37/67), the median survival time was 13.7 months, and the 5-year cumulative survival rate was (24.4±6.3)% in patients received low-intensity tradional chemotherapeutic regimens. The CR rates of high-risk group and non-high-risk group were 38.7% (12/31) and 69.4% (25/36), respectively; the median survival time of high-risk group and non-high-risk group was 8.9 months and 25.2 months respectively; the 5-year cumulative survival rate of high-risk group was (10.2±6.6)% and that of non-high-risk group was (36.0± 9.4)%. Compared with the data reported in the literature at the same time, the data obtained from the low-intensity traditional chemotherapy regimen for the elderly AML did not have an obvious disadvantage, morever had relatively short bone marrow suppression time, low induction early mortality rate and low incidence of severe infection. CONCLUSION: At present, the low-intensity traditional chemotherapy regimen still has good curative effect and survival advantages for elderly AML patients, especially for non-high-risk patients. The adverse reactions are controllable, and the physical and economic conditions of the vast majority of patients can bear the treatment regimen.

Tenacigenin B Has Anti-Tumor Effect in Lymphoma by In Vitro and In Vivo Study.

BACKGROUND The aim of this study was to examine the effects and mechanisms of tenacigenin B in lymphoma treatment by in vitro and in vivo experiment. MATERIAL AND METHODS Raji cells were treated by difference methods. Measuring the cell proliferation of difference groups was done by MTT assay; cell apoptosis and cell cycle of difference groups were evaluated by flow cytometer; relative mRNA expression was evaluated by real-time polymerase chain reaction (RT-PCR), and relative protein expressions were measured by western blot assay in an in vitro study. In an in vivo study, we used a nude mice model to explore the anti-tumor effects and mechanism of tenacigenin B. Cell apoptosis was measured by TUNEL assay; relative protein expressions were evaluated by immunohistochemistry assay, and relative mRNA expression was evaluated by RT-PCR. In addition, the blood components of difference groups were measured. RESULTS Compared with the Normal control group, the cell proliferation rate was significantly downregulated, with cell apoptosis significantly increasing with G1 phase in the Drug group and the si-Aurora-A group (P<0.05, respectively). The PTEN, PI3K, AKT, P53, and P21 mRNA and protein expressions of the Drug group, the si-Aurora-A group, and the si-Aurora-A+Drug group were significantly different (P<0.01, respectively), The tumor volume and weight of the Drug group, the si-Aurora-A group, and the si-Aurora-A+Drug group were significantly suppressed compared with the Normal group (P<0.01, respectively). The positive apoptosis cell number in the Drug group, the si-Aurora-A group, and si-Aurora-A+Drug group were increased compared with that of Normal group (P<0.01, respectively). CONCLUSIONS Tenacigenin B had anti-tumor effects on lymphoma via regulation of Aurora-A in vitro and in vivo.

Screening and predication on tumor neoantigen for primary plasma cell leukemia / 中国肿瘤生物治疗杂志

@#Objective:To investigate the tumor-specific neoantigen for primary plasma cell leukemia (PCL) using gene sequencing technology combined with bioinformatic analysis. Methods: Peripheral blood samples of one patient with primary PCL during relapse and remission periods were collected. HLA molecular typing was performed using polymerase chain reaction with sequencing-based typing; whole-exome and transcriptome were sequenced by next-generation sequencing method; and bioinformatics software NetMHCpan was used to predict neoantigens. Results: Six tumor-specific missense mutations were found in the patient's peripheral blood during relapse period, located in genes FRG1, MLL3, SVIL, MYOM1, ZDHHC11 and RFPL4A.Considering patient's HLA sub-types, 43 neoantigens were predicted via bioinformatics. Considering that FRG1 and MLL3 had relatively high gene expression levels, 20 neoantigens derived from mutations of the two genes were preferentially selected, among which four neoantigens had high affinity with the patient's HLA molecules and thus had potential clinical application value. Conclusion: The study has completed a tumor neoantigen screen and prediction for primary PCL. This practice demonstrates that predicting neoantigen based on tumor-specific somatic mutation is feasible for primary PCL.

Transfusion-associated graft-versus-host-disease: case report and review of literature.

Transfusion-associated graft-versus-host disease (GVHD) is a rare condition that can occur after receipt of any cellular blood component with viable lymphocytes. Pathogenesis depends on immunocompetent donor T lymphocytes and a host immune system unable to clear donor cells before they proliferate, engraft, and attack host cells. Unlike bone marrow transplantation-associated GVHD, transfusion-associated disease destroys marrow stem cells early in the course of the disease, resulting in pancytopenia contributing to a fulminant clinical course and nearly 100% mortality. Transfusion-associated disease may be diagnosed late or completely missed; thus, true incidence rates are uncertain. We report our experience with an oncology patient who developed transfusion-associated GVHD. This report also reviews the literature to discuss established GVHD risk factors as well as provide recommendations for standardized reporting to better understand incidence rates and possible risk factors. This information would allow individual physicians and blood bank associations to make more informed decisions on the use of irradiated blood products.

[New insight into pathogenesis of idiopathic myelofibrosis--review].

Idiopathic myelofibrosis is a type of chronic myeloproliferative disorders characterized by splenomegaly, a leukoerythroblastic blood picture, teardrop poikilocytosis, in various degrees of bone marrow fibrosis and extramedullary hematopoiesis. In this paper, the biological characters and pathogenesis of idiopathic myelofibrosis such as mutation of tyrosine kinase receptor, mutation of GABA transporter 1, JAK2 mutation and c-MPl mutation, as well as other pathogenesis related with idiopathic myelofibrosis were reviewed.