The molecular landscapes of diffuse large B-cell lymphoma (DLBCL) remained to be comprehensively investigated with an urgent need to identify novel prognostic biomarkers guiding prognostic stratification and disease monitoring. Baseline tumor samples of 148 DLBCL patients were analyzed using targeted next-generation sequencing (NGS) for mutational profiling, whose clinical reports were retrospectively reviewed. In this cohort, the subgroup of old DLBCL patients (age at diagnosis > 60, N = 80) exhibited significantly higher Eastern Cooperative Oncology Group scores and International Prognostic Index than their young counterparts (age at diagnosis ≤ 60, N = 68). As revealed by the NGS results, PIM1 (43.9%), KMT2D (31.8%), MYD88 (29.7%), and CD79B (27.0%) were identified as the most frequently mutated genes. Aberrations of genes of the immune escape pathway were significantly enriched in the young subgroup, while the altered epigenetic regulators were more abundant in the old patients. FAT4 mutation was identified as a positive prognostic biomarker, associated with longer progression-free survival and overall survival in the entire cohort and the old subgroup, using the Cox regression analyses. However, the prognostic function of FAT4 was not reproduced in the young subgroup. We comprehensively analyzed the pathological and molecular characteristics of old and young DLBCL patients and demonstrated the prognostic value of FAT4 mutation, which requires further validation with sizable cohorts in future research.

Women and girls with haemophilia (WGH) may have spontaneous/traumatic bleeding similar to that in males with haemophilia, and in addition excessive bleeding during menstruation and delivery.

Background: Bleeding episodes in hemophiliacs with inhibitors are difficult to control. Staidson protein-0601 (STSP-0601), a specific factor (F)X activator purified from the venom of Daboia russelii siamensis, has been developed. Objectives: We aimed to investigate the efficacy and safety of STSP-0601 in preclinical and clinical studies.Methods: In vitro and in vivo preclinical studies were performed. A phase 1, first -in-human, multicenter, and open-label trial was conducted. The clinical study was divided into parts A and B. Hemophiliacs with inhibitors were eligible for this study. Patients received a single intravenous injection of STSP-0601 (0.01 U/kg, 0.04 U/kg, 0.08 U/kg, 0.16 U/kg, 0.32 U/kg, or 0.48 U/kg) in part A or a maximum of 6 4-hourly injections (0.16 U/kg) in part B. The primary endpoint for each part was the number of adverse events (AEs) from baseline to 168 hours after administration. This study was registered at clinicaltrials.gov (NCT-04747964 and NCT-05027230).Results: Preclinical studies showed that STSP-0601 could specifically activate FX in a dose-dependent manner. In the clinical study, 16 patients in part A and 7 patients in part B were enrolled. Eight (22.2%) AEs in part A and 18 (75.0%) AEs in part B were reported to be related to STSP-0601. Neither severe AEs nor dose-limiting toxicityevents were reported. There were no thromboembolic event. The antidrug antibody of STSP-0601 was not detected.Conclusion: Preclinical and clinical studies showed that STSP-0601 had a good ability to activate FX and had a good safety profile. STSP-0601 could be used as a hemostatic treatment in hemophiliacs with inhibitors.

Objective: To detect the chromosomal abnormalities in patients with multiple myeloma (MM) by fluorescence in situ hybridization (FISH) and to explore their correlation with clinical significance and prognostic value.Methods: 83 MM patients who were treated in our hospital from April 2015 to January 2017 were selected as the observation group, and 12 patients with non-hematological malignant diseases who provided bone marrow specimens were selected as the control group. The IGH, 1q21, RB1, D13S319, and p53 probes were used to detect FISH in MM patients and observe chromosomal abnormalities. Correlation with clinical data (age, R-ISS stage, bone loss, white blood cells, platelets, hemoglobin, erythrocyte sedimentation, creatinine, globulin, albumin, and C-reactive protein (CRP)), clinical significance, and prognostic value were analyzed.Results: Among 83 patients with MM, 64 (77.11%) had chromosomal abnormalities, and 19 patients had negative test results. Among those with abnormalities, 8 cases (12.50%) had all four of the chromosomal abnormalities tested for via FISH, 17 cases (26.56%) had three kinds of abnormalities, and 16 cases (25.00%) had two kinds of abnormalities. There were 23 cases (35.94%) with only one chromosome abnormality. We found that IGH rearrangement was related to bone damage and albumin, 1q21 amplification was related to CRP, and 13q14 deletion was related to hemoglobin, albumin and globulin levels, and R-ISS stage. 17p13 deletion was significantly correlated with albumin, platelet, albumin, and globulin levels and R-ISS stages. Among the positive and negative FISH test results, the CR, PR, SD, and PD patients were significantly different in the T-VAD group (P<0.05), but not significantly different in the PAD group (P>0.05). Among the patients with chromosomal abnormalities, the treatment effect was worse than that of patients with negative results. Patients with IGH rearrangement and 17p13 deletion had significantly lower survival time. Patients with normal chromosomes had a significantly negative correlation with prognosis (P<0.05), while 1q21 amplification and 13q14 deletion had no significant correlation with patient prognosis. IGH rearrangement and 17p13 deletion are independent risk factors that affect the prognosis of this group of MM patients.Conclusions: Most patients with MM have chromosomal abnormalities, which are related to some specific clinical measurements. FISH test can identify patients with these abnormalities, who have poorer treatment effect and poor prognosis.

Aim: To investigate the targets of miR-181b in patients with chronic lymphocytic leukemia (CLL). Materials & methods: The bioinformatic softwares were used to indicate the key target genes associated with miR-181b, and the results were verified in CLL patient samples and 293T cells. Results:CARD11 is a potential target gene of miR-181b, an inverse relationship was revealed between the expression of CARD11 and miR-181b in 104 CLL patients, and it was confirmed in vitro with luciferase assays and western blotting. Kaplan-Meier analysis showed that CLL patients with high CARD11 expression demonstrated poor survival. Conclusion:CARD11 is a novel target of miR-181b that is upregulated, which could be a poor prognostic indicator for CLL patients.

SummaryThe development of alloantibodies (inhibitors) against coagulation factor VIII (FVIII) is the most serious complication of FVIII replacement therapy in patients with haemophilia A (HA). We carried out a nationwide study focussing on patients with HA with inhibitors in China to evaluate the condition and management of this population. The study retrospectively analysed patient characteristics, clinical history, manifestation, treatment strategy as well as individual haemophilia care of 493 patients with inhibitors (466 with severe HA and 27 with non‐severe HA) registered all over China. The median (interquartile range) age at diagnosis of FVIII inhibitors was 13 (5–28) years in patients with severe HA and 24 (10·5–39·5) years in patients with non‐severe HA. Most patients (85%) had high‐titre inhibitors. Prothrombin complex concentrate and recombinant activated coagulation factor VII were used respectively in 76·2% and 29·2% of patients for acute bleeding. Only 22·3% of patients underwent immune tolerance induction (ITI) treatment, of whom 64·9% achieved negative inhibitor titre. In patients who did not undergo ITI, the inhibitors turned negative in 17·7%, and patients with low peak inhibitor titre were more likely to acquire negative titre spontaneously (odds ratio 11·524, 95% confidence interval 5·222–25·432; P = 0·000). We recorded that 3·2% of the patients died from haemophilia‐related life‐threatening bleeding.

OBJECTIVE:To explore the value of CpG-oligonucleotide(CpG-ODN) immunostimulatory method in chromosome culture of chronic lymphocytic leukemia (CLL) cells and to compare the differences between related studies at home and abroad, so as to improve the success rate of CLL karyotype culture and the detection rate of abnormal karyo-types.METHODS:Bone marrow samples from 82 CLL patients were collected and cultured with phytohemagglutinin (PHA), CpG-oligonucleotide plus interleukin-2 (CpG-ODN DSP30+IL-2) for 72 hours. Chromosomes were prepared and analyzed by conventional cytogenetics (CC). Meanwhile, D13S25, Rb1, ATM, p53 and CSP12 probes were used for interphase fluorescence in situ hybridization (iFISH) test. The differences of chromosome culture and iFISH test results between two cell stimulants were compared.RESULTS:The success rate of karyotype culture in PHA and CpG-ODN DSP30+IL-2 immunostimuli (analyzable mitotic t >20) was 90.2% (74 cases), 68.3% (56 cases) respectively, and the detection rate of abnormal karyotype was 13.5% (10 cases) and 46.4% (26 cases), respectively. The success rate of karyotype culture in PHA group was significantly higher than that in CpG-ODN DSP30+IL-2 group (P=0.01). The detection rate of abnormal karyotypes in CpG-ODN DSP30+IL-2 group was significantly higher than that in PHA group, and the difference was statistically significant (P=0.003). The detection rate of abnormal karyotypes in iFISH group was 74.4% (61 cases), which was significantly higher than that in CpG-ODN DSP30+IL-2 group (P=0.000). iFISH detection could verify the abnormalities detected by CC analysis.CONCLUSION:Application of CpG-ODN DSP30+IL-2 immunostimulation method in culture of CLL cells can enhance the detection rate of abnormal karyotypes, especially the detection of various translocations suggesting poor prognosis.

The abnormal expression of miRNAs may play critical roles in the occurrence, development and prognosis of chronic lymphocytic leukemia (CLL), with potential ethnic differences being involved. p53 and immunoglobulin heavy chain variable region gene (IGVH) mutations were monitored and miRNA profile screening of CD19 + cells from Uygur CLL patients was performed, analyzed by miRNA arrays and verified using real-time PCR. There were 68 differentially expressed miRNAs in CD19 + B lymphocytes obtained from 6 Uygur CLL patients, of which miR-1295, miR-29b, miR-34a, miR-21 and miR-29c were the 5 most upregulated, and miR-181a, miR-126, miR-181b, miR-125a-5p and miR199b the 5 most downregulated miRNAs. miR-15a/miR-16-1 which might be important drivers of the disease, were not eliminated by profile screening. From the 68 differentially expressed miRNAs, 5 previously-reported CLL-related miRNAs were selected for further confirmation analyses, from which expression levels of miR-29b, miR-34a and miR-155 were found to be increased while miR-181a and miR-181b decreased. However, there were no differences in the expression levels of miR-15a/miR-16-1 between CLL patients and healthy donors, but the expression levels of miR-15a/miR-16-1 in CLL patients with a 13q deletion was depressed. In addition, there was no difference in the expression level of the above 7 miRNAs between 44 Han and 40 Uygur CLL patients. The expression levels of miR-29b, miR-181a and miR-181b correlated with IGVH mutations, while the expression levels of miR-34a, miR-29b and miR-181b correlated with a p53 abnormality in 84 Uygur and Han CLL patients. Taking p53 abnormality as the cut-off value criteria, low expression levels of miR-34a (cut-off value 4.65, P = 0.02) and miR-29b (cut-off value 4.71, P = 0.009) hinted at a poor treatment-free survival (TFS) prognosis for all CLL patients. Thus miR-34a and miR-29b may represent useful indicators for the prognosis of both Uygur and Han CLL patients.

Background Genetic factors play a role in the etiology of BCR-ABL-negative myeloproliferative neoplasms (MPNs). This study explored the relationship between mutations in the Janus kinase 2 gene (JAK2), MPL, and the calreticulin gene (CALR) in Uygur and Han Chinese patients with BCR-ABL fusion gene-negative MPN and corresponding clinical features. Methods A total of 492 BCR-ABL-negative MPN patients treated in our hospital from May 2013 to August 2016 were enrolled. Genomic DNA was extracted from peripheral blood and used for PCR amplification and DNA sequencing. Mutations including JAK2 V617F, MPL W515L/K, and those in JAK2 exon 12 and CALR were analyzed and compared with patient clinical characteristics. Results Of the 492 MPN patients, 169 were Uygur and 323 were Han. In these two patient groups, JAK2 mutations were detected in 39.64% and 52.63%, respectively, CALR mutations were detected in 10.06% and 20.43%, respectively, and MPL mutations were detected in 0.93% of Han patients. The age, white blood cell count, platelet levels, and hemoglobin levels in JAK2 in Han patients were higher than those in Uygur patients. Conclusion Han MPN patients harboring JAK2 mutations had higher level of age, WBC, PLT, and Hb than Uyghur patients with the same mutations.

Objective To explore the differences in expression level of miR-181 b (miR-181 b) in CD19+B lymphocytes in patients with chronic lymphocytic leukemia ( CLL) and analyze its clinical significance. Methods Fifty patients with CLL, and collecting healthy controls 20 cases. All patients took 15 ml of peripheral blood and the total RNA of CD19+B lymphocyte was extracted after sorting with CD19 magnetic beads, and the expression lever of miR-181 b was measured by Taq Man probe. The difference expression lever of miR-181 b in prognostic groups were analyzed, such as clinical stages, Serological indicators, CD38, Zeta chain related protein kinase-70, immunoglobulin heavy chain variable region and Abnormal genetics. Survival analysis was performed on the above indexes. Results (1) The expression lever of miR-181 b in CD19+B lymphocytes in Fifty patients with CLL was significantly lower than the healthy controls ( P ＜ 0. 01). (2) The expression level of miR-181 b in different groups: according to the prognosis of FISH groups, the poor prognosis group was significantly lower than the favorable prognosis group ( P ＜ 0. 05), ATM deletion group was significantly lower than the ATM normal group ( P ＜ 0. 05), There was no statistical difference in the expression level of miR-181 b in other groups (P＞ 0. 05). (3) Survival analysis: The expression level of mir-181 b was divided into low expression group and high expression group by median of 0. 033. The comparison showed that the OS of mir-181 b low expression group was shorter than the mir-181 b high expression group ( P ＜ 0. 05). Combined COX multivariate analysis with poor prognostic factors, the results showed that the high-risk group of FISH prognosis group, P53 deletion, ATM deletion, miR181 b lower expression were all independent prognostic factors affecting survival ( P ＜ 0. 05). Conclusion The expression level of mir-181 b in CLL patients is significantly lower than normal people, and the low expression of mir-181 b is an independent prognostic factor of CLL.

Primary immune thrombocytopenia (ITP) is a bleeding disorder commonly encountered in clinical practice. The International Working Group (IWG) on ITP has published several landmark papers on terminology, definitions, outcome criteria, bleeding assessment, diagnosis, and management of ITP. The Chinese consensus reports for diagnosis and management of adult ITP have been updated to the 4th edition. Based on current consensus positions and new emerging clinical evidence, the thrombosis and hemostasis group of the Chinese Society of Hematology issued Chinese guidelines for management of adult ITP, which aim to provide evidence-based recommendations for clinical decision making.

Introduction: Disseminated intravascular coagulation (DIC) is a severe complication of critical conditions. There are several scoring systems used for the diagnosis of DIC, including the International Society on Thrombosis and Hemostasis (ISTH) Overt-DIC criteria, the Japanese Ministry of Health and Welfare (JMHW) criteria and the Chinese Society of Thrombosis and Hemostasis scoring system for DIC (CDSS). The objective of this prospective study was to evaluate the accuracy and predictive value of the CDSS. Materials and methods: 1318 patients, aged 18-70 years old and suspected of DIC were enrolled from 18 hospitals across China. Participants were divided into two groups for analysis (group 1, non-hematological diseases; group 2, hematological diseases). 242 patients were excluded because of incomplete data collection and failure to follow-up. Results and conclusions: The rates of concordance of diagnosis of DIC between the CDSS and two other scoring systems were close to 80%. The area under ROC curves of CDSS had a slight advantage when using the ISTH, JMHW criteria or prognosis as gold standard, respectively. The CDSS DIC was an independent predictor of mortality, and its odds-ratio was superior or comparable to that of the ISTH and JMHW criteria in the two groups. The CDSS DIC score also had a significant correlation with the APACHE II and SOFA score (p < 0.05). In summary, as a quantification standard of the Chinese experts' consensus, the CDSS is conducive to the standardized diagnosis of DIC because of its favorable diagnostic and prognostic utility.

The nasal type of extranodal natural killer/T‐cell lymphoma is a rare aggressive lymphoma with poor prognosis. To discover a successful treatment, we investigated the efficacy and safety of chemotherapy with methotrexate, etoposide, dexamethasone, and polyethylene glycol‐asparaginase (MESA). Three cycles of MESA were administered to 46 patients with new or relapsed/refractory natural killer/T‐cell lymphoma. Complete response after 3 treatment cycles was 43.5%, the overall response rate was 87%, and 2‐year overall survival was 83.4%. Complete response was significantly better for newly diagnosed patients than for patients with relapsed/refractory disease. Patients with newly diagnosed disease had a significantly better overall response rate after 1, but not after 2 or 3 treatment cycles. Overall survival and progression‐free survival did not differ over 2 years. Grade 1/2 toxicities were frequent, but MESA was associated with fewer grade 3/4 events or treatment‐related deaths. These results will require confirmation in larger prospective trials.

Objective To investigate the prognostic value of interim 18 F-FDG PET/CT scan in pa-tients with natural killer ( NK)/T cell lymphoma. Methods From January 2012 to May 2015, thirteen pa-tients (10 males, 3 females;mean age (43.85±7.66) years) underwent methotrexate+ifosfamide+etoposide+prednisone acetate+L-asparaginase ( SMILE ) chemotherapy. All patients underwent pre-, mid-treatment ( after 3 cycles of SMILE) PET/CT scan, and 9 of them further underwent end-treatment ( after 6 cycles of SMILE) PET/CT scan.View analysis and ΔSUVmax(%) were used to interpret 18F-FDG PET/CT images. Two-sample t test was used to analyze the difference of ΔSUVmax between PET/CT positive group and PET/CT-negative group. Survival curves were obtained using Kaplan-Meier analysis. OS and PFS were calculated and compared with the log-rank test. Results All 13 patients underwent 18 F-FDG PET/CT imaging after 3 chemotherapy cycles and were divided into PET/CT-negative group (7 patients) and positive group (6 pa-tients). ΔSUVmax of the negative group was higher than that of the positive group: (65.73±5. 95)% vs (52. 50±1.49)%;t=4.199, P<0.05. Median follow-up period was 26 (9-48) months. The median PFS and median OS of PET/CT-negative group were higher than those of PET/CT-positive group ( 39 vs 18 months, 44 vs 24 months; χ2=4.521, 4.829, both P<0.05). Conclusion Interim PET/CT scan could predict the outcome of patients with NK/T cell lymphoma.

OBJECTIVE To evaluate the efficacy and safety of high dose dexamethasone combined with recombinant human thrombopoietin (rhTPO) in adults with severe newly diagnosed immune thrombocytopenia (ITP). METHODS Forty-eight adult patients with severe ITP were randomized into two groups, experimental group and control group. The patients in experimental group were given high-dose dexamethasone combined with rhTPO treatment, the patients in control group were given single high-dose dexamethasone treatment. Platelet count, platelet increase, as well as the overall response rate were strictly observed in the process. At the same time, the patient's drug tolerance and any adverse drug reactions were observed. RESULTS The platelet counts and platelet increase of the patients in experimental group were significantly higher than that in control group (P<0.05) at day 3, 7, 14, 30. There was no significant difference in overall response rates between the two groups (34.8% vs 36.0%, 56.5% vs 48.0%, P>0.05) at day 3, 7. The overall response rates of experimental group at day 14, 30 were significantly higher than that of control group (91.3% vs 68.0%, 82.6% vs 52.0%, P<0.05). The muscle aches occurred in one patient in experimental group which was self-recovery without special treatment. CONCLUSION rhTPO combined with high-dose dexamethasone could rapidly increase the platelet count, reduce the risk of bleeding, and prolonge the effect with a low incidence of tolerable adverse events compared to single high-dose dexamethasone. rhTPO combined with high-dose dexamethasone could be a new therapeutic choice for severe primary ITP.

OBJECTIVE:To evaluate the significance of T-cell antigen receptor (TCR) gene rearrangement among patients with acquired pure red cell aplastic anemia (A-PRCA).METHODS:For 16 patients with A-PRCA, an immunosuppressive regimen based on cyclosporin A (CsA) was applied. Rearrangement of the TCR gene was detected by PCR, and T lymphocyte subsets in peripheral blood specimens was detected with flow cytometry.RESULTS:Five patients had presented with TCR clonal rearrangement and were positive for both TCR γ and TCR δ. The blood of 13 patients have returned to normal with the treatment, which included 3 cases with bone marrow returning to normal. In 7 cases, the red cell hyperplasia of bone marrow is still down, but has increased with the treatment. Three patients were close to cure, 7 showed remission, 3 were improved, but 3 were ineffective. The rate of effective treatment in those with TCR rearrangement (2/5) was significantly lower than that those without (11/11, chi-square=8.123, P < 0.05). Compared with those without the TCR gene rearrangement, the Th cells and proportion of Th/Ts were significantly lower, while the Ts cell (CD3+CD8+) were significantly higher in those with the rearrangement (P < 0.05).CONCLUSION:TCR gene rearrangement may play a role in the pathogenesis of A-PRCA. CsA is effective for the treatment of A-PRCA, but patients presenting clonal TCR gene rearrangement may response poorly to the treatment.

Purpose/Background: The nasal type of extranodal natural killer NK/T-cell lymphoma (NKTCL) is a rare aggressive lymphoma with poor prognosis. There is currently no standard treatment. To explore a more effective and feasible treatment for newly diagnosed, relapsed, or refractory NKTCL, we conducted a phase II study of the steroid (Methotrexate, etoposide, dexamethasone, Polyehylene glycol-asparaginase, MESA) regimen and investigated its efficacy and toxicity.