Objective:To investigate the effect and prognostic factors of rituximab-containing chemotherapy regimen in treatment of patients with mantle cell lymphoma (MCL).Methods:The clinical data of 56 patients aged ≤65 years in the First Affiliated Hospital of Soochow University from June 2007 to November 2018 were retrospectively analyzed. Rituximab-containing chemotherapy regimen was used, and the effects of clinical features, treatment regimen and biological indexes on overall survival (OS) and progression-free survival (PFS) were observed.Results:The median age of 56 patients was 57 years old, including 43 males and 13 females. Among these cases, 24 patients received R-CHOP chemotherapy regimen; 29 patients received cytarabine-containing chemotherapy regimen, including R-hyper CVAD/R-MA regimen used in 15 patients and R-CHOP alternating with R-DAHP regimen used in 14 patients; and 3 patients received other treatment regimens. Among 56 patients, 19 patients received autologous hematopoietic stem cell transplantation (ASCT) consolidation therapy. The median OS time was 74 months, 2-year OS rate was 83.8%, 3-year OS rate was 70.9%, 2-year PFS rate was 72.0% and 3-year PFS rate was 49.7%. International prognostic index (IPI) high-risk and receiving ASCT or not during the treatment were independent influencing factors of OS and PFS in MCL patients. The overall response rate (ORR) in cytarabine-containing regimen group was higher compared with that in R-CHOP regimen group (93.1% vs. 83.3%), and there was no statistically significant difference ( χ2=0.465, P=0.495). In addition, there were no significant differences between two groups in both OS ( χ2=0.291, P=0.590) and PFS ( χ2=0.912, P=0.339). ASCT consolidation prolonged the median OS time (72 months vs.124 months, χ2=3.973, P=0.040) and the median PFS time (34 months vs. 90 months, χ2=3.984, P=0.046) in MCL patients achieving remission after induction therapy. Among patients in simplified MCL IPI (sMIPI) score middle-high risk group, compared with those not receiving ASCT, patients receiving ASCT therapy could obtain better OS and PFS (OS: χ2=5.037, P=0.025; PFS: χ2=6.787, P=0.009); among patients of sMIPI score low risk, there were no statistically significant differences in OS and PFS between the group receiving ASCT and not (all P > 0.05). Conclusions:Cytarabine-containing chemotherapy regimen has no predicatively satisfactory value in improving the prognosis and survival for MCL patients. For MCL patients who have achieved remission after reduction therapy and those in sMIPI score middle-high risk group, ASCT consolidation therapy can improve the prognosis and can be taken as the first-line consolidation treatment in young patients.

The first-generation Bruton tyrosine kinase inhibitor (BTKi) ibrutinib significantly improved the survival and prognosis of patients with chronic lymphocytic leukemia (CLL), but its adverse reactions such as bleeding, infection, cardiovascular events, etc., limited the long-term compliance of patients. It has been considered that the new generation of BTKi could significantly reduce the adverse reactions caused by ibrutinib because of their higher selectivity and specificity. Among them, the efficacy and safety of acalabrutinib in untreated and relapsed/refractory patients with CLL have been confirmed in phase Ⅲ clinical trials. In addition, zanubrutinib and orelabrutinib, which were independently developed in China, have also been proven their preliminary safety and therapeutic effects in pre-clinical and phase Ⅰ and Ⅱ clinical trials, while the data from large phase Ⅲ clinical trials are still lacking. Currently, more BTKi are also under active exploration. The future therapeutic strategies of CLL may be converted to combining with a wide range of drugs to achieve the goal of drug discontinuation when minimal residual disease (MRD) is negative, or use MRD to guide the treatment. In this trend, the new generation of BTKi will provide more optimized options for the combination therapy regimens.

Objective The optimal access for natural orifice transluminal endoscopic surgery is still uncertain .This study was designed to compare the practicability and maneuverability of transgastric ,transunmbilical ,and transrectal approach in abdominal surgery in a canine model .Methods Three dogs were used in this research .Three approach :trangastric ,transunmbilical and tran-srectal approach were carried out for abdominal exploration ,liver biopsy ,bladder biopsy and an attempted cholecystectomy .The ma-neuverability ,endoscopic image ,performer′s perception ,and spatial orientation were evaluated .Results The maneuverability of trangastric ,and transrectal approach NOTES were better than transunmbilical NOTES .Abdominal exploration ,live biopsy ,and bladder biopsy were completed successfully .The cholecystectomy was failed because of poor exposure and difficulty of separating the around tissure .Conclusion The optimal approach for upper abdomen NOTES is transrectal route .For lower abdomen NOTES , the trangastric approach is superior to other accesses .Further study is needed to develop more flexible and precise equipment for NOTES and to evaluate more feasible access approach .

Blinatumomab, as a novel bispecific antibody targeting CD19 and CD3, can induce T lymphocytes to precisely target CD19 positive B lymphocytes to apoptosis. At present, it is the only bispecific antibody approved for the treatment of hematological malignancies in China. Blinatumomab is effective in the treatment of newly diagnosed, relapsed/refractory, minimal residual disease positive patients with B-cell acute lymphoblastic leukemia (B-ALL) . It can improve the survival of the patients and is well tolerated. The further study of blinatumomab can provide theoretical basis and new ideas for induction therapy, salvage therapy and subsequent hematopoietic stem cell transplantation in patients with B-ALL.

Objective: To investigate the efficacy of first-line administration of generic dasatinib or first-generation TKI (imatinib) in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph⁺ ALL) treated by hematopoietic stem cell transplantation (HSCT). Methods: Clinical features and prognoses of 63 newly diagnosed Ph⁺ ALL patients from Jan 2014 to June 2017 treated by HSCT combined with first-line administration of generic dasatinib or imatinib were retrospective analyzed. Results: Of 63 Ph⁺ ALL patients, 31 cases were administered generic dasatinib, and the other 32 ones imatinib. Complete remission (CR) rates at the fourth week of induction therapy in generic dasatinib and imatinib groups were 96.8% and 93.8% (P=1.000) , respectively. Meanwhile major molecular response (MMR; BCR-ABL/ABL reduce 3log) rates were 41.9% and 43.8% (χ²=0.021, P=0.884), respectively. Relapse rates before transplantation were 6.5% and 12.5% (P=0.672), respectively. MMR rates before HSCT were 83.9% and 68.8% (χ²=1.985, P=0.159), respectively. The 20-monthes overall survival (OS) rates of generic dasatinib and imatinib groups were 95.5% and 76.5% (χ²=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ²=5.926, P=0.015), respectively. Statistically significant differences of EFS were reached. Multiple factors analysis showed that generic dasatinib (HR=0.201, 95% CI 0.045-0.896, P=0.035) and MMR before transplantation (HR=0.344, 95% CI 0.124-0.956, CI=0.041) could improve EFS. Conclusions First-line administration of generic dasatinib could improve EFS for Ph⁺ALL patients treated by HSCT when compered with imatinib.

Objective To describe the demographic and clinical characteristics of patients with the diagnosis of multiple myeloma(MM)and to analyse the outcome of difierent regimens for the treatment of MM.Methods The study reviewed 332 MM cases diagnosed within the period from January 1,2002 to December 31,2002.These patients were tracked via their records to a total period of three years.Results First-line treatment:Totally 332 patients were included,among them 325(97.9%)patients received chemotherapy and 7(2.1%)patients received stem cell transplantation(SCT);Second-line treatment:197 patients were included,among them 190(96.5%)patients received chemotherapy and 7(3.6%)patients received SCT;Third-line treatment:92 patients were included,among them 88(95.7%)patients received chemotherapy and 4(4.4%)patients received SCT.Major adverse effects were follows:severe infection 19.3%,severe anaemia 19.3%,phlebothrombosis 1.2%,thrombocytopenia 16.9%,fever associated with neutropenia 18.1%.Conclusions Some curative effects can be achieved by using traditional treatment plans to treat patients suffering from MM,but new methods are expected to improve the prognosis.

Objective: To study the specific killing effect of CD4 membrane protein targeted chimeric antigen receptor modified T (CAR-T) cell. Methods: The second generation CD4 targeted chimeric antigen receptor containing 4-1BB costimulation domain was insert into lentiviral vector through recombinant DNA technology. Lentivirus was prepared and packaged by 293T cells with four plasmids. Beads activated T cells were transduced with lentivirus and the transduction efficiency was checked with Protein L and flow cytometry. T cell subsets and IFN-γ concentrations were detected with probe-tagged antibody and cytometric bead assay. Results: ①The transduction efficiency of activated T cells with prepared lentivirus were 50.0%-70.0%. A subset of CD8⁺ T cell acquired dim expression of CD4 membrane protein after activation. CD4⁺T cell and CD8⁺CD4^dim T cell were gradually killed by CD4 targeted CAR-T post lentivirus transduction. ②The kill efficacy of CD4 targeted CAR-T cell and control T cell toward KARPAS 299 T cell at an E∶T ratio of 8∶1 for 24 h was (96.9±2.1)% and (11.2±3.1)%, CAR-T cell has a higher killing efficacy than control T cell (t=7.137, P=0.028). The IFN-γ concentrations in culture supernatant of CAR-T cell with K562-CD4 cell, CAR-T cell with K562 cell and CAR-T cell alone were (15 648±2 168), (1 978±354) and (1 785±268) pg/ml, CAR-T cell cocultured with K562-CD4 cell produced more IFN-γ than the other two controls (P<0.01). Conclusions CD4 targeted CAR-T has an immunophenotype of CD8⁺CD4^-T cell. CD4 targeted CAR-T cell has killing efficacy toward normal CD4⁺T cell and CD4⁺T lymphoma cell. CD4 targeted CAR-T cell also has a killing efficacy toward CD4^dim target cell.

Objective: To evaluate the efficacy and safety of generic imatinib (Genike, Chiatai Tianqing Pharmaceutical Group Co., Ltd.) and imatinib (Glevic, Novartis, Switzerland) in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) . Methods: A retrospective study of 323 CML-CP patients (205 in Glivec treatment group and 118 in Genike group) who were ≥ 18 years old receiving imatinib monotherapy over the period of June 2013 to March 2016 was done to compare the differences of cytogenetics, molecular curative effect, survival, and adverse reactions between the two groups. The beginning dosage of imatinib was 400mg per day. There was no statistically difference between the two groups of patients on baseline. Results: ①The median duration of imatinib treatment was 13 (0.5-36) months in Glevic group and 11 (1-31) months in Genike group. ②The rate of complete hematological remission (CHR) had no statistically difference between Glivec and Genike treatment groups[98% (201/205) vs 97.5% (115/118) , χ²=0.123, P=0.725]. ③Cumulative rates of major cytogenetic responses (MCyR) at 3, 6 and 12 months after imatinib treatment in Gleevec and Genike groups were (59.7±3.5) % vs (79.8±3.1) %, (89.2±2.6) % vs (59.1±4.7) %, (80.3±4.1) % vs (87.1±4.3) %, respectively, the difference was not statistically significant (χ²=0.084, P=0.772) . Cumulative rates of complete cytogenetic response (CCyR) at 3, 6 and 12 months after imatinib treatment in Gleevec and Genike groups were (32.9±3.4) % vs (58.3±3.7) %, (87.4±3.0) % vs (35.2±4.5) %, (64.8±4.8) % vs (87.3±4.7) %, respectively, the difference was not statistically significant (χ²=0.660, P=0.417) . ④Cumulative rates of major molecular responses at 6, 12 months after imatinib treatment in Glevic and Genike groups were (24.9±3.3) % vs (57.0±4.1) %, (16.3±4.0) % vs (55.3±7.7) %, respectively, there was no statistical significance (χ²=1.617, P=0.204) . Cumulative rates of molecular response 4.5 (MR4.5) at 12 months after imatinib treatment in Glevic and Genike groups were (14.9±3.2) % vs (8.1±2.1) % (χ²=3.628, P=0.057) , respectively. ⑤At a median follow-up of 12 months, the difference of progression-free survival (PFS) in Glevic and Genike groups had no statistical significance[ (96.6±1.4) % vs (93.3±2.5) %, χ²=2.293, P=0.130]. The difference of event-free survival (EFS) had no statistical significance, either[ (95.6±1.5) % vs (93.3±2.4) %, χ²=2.124, P=0.145]. ⑥Genike was well tolerated in patients with CML-CP and had no statistically significant difference in adverse events compared with Glevic group. Conclusion There were no statistically significant differences in efficacy and safety between Glevic and Genike treatment in newly diagnosed patients with CML-CP.

Objective:To examine the efficacy of haploidentical stem-cell transplantation (haplo-SCT) for patients with refractory relapsed (R/R) non-Hodgkin lymphoma (NHL) by comparing with those contemporaneously undergoing HLA-matched SCT in myeloablative conditioning settings.Methods:Between January 2006 and December 2018, a total of 151 patients undergoing haplo-SCT ( n=81) or HLA-matched SCT ( n=70, sibling or unrelated) were enrolled. Median age of alloSCT was 30(5-59) years. And 150 patients received myeloablative conditioning (MAC) consisting of total body irradiation (12 Gy) plus cyclophosphamide or busulfan plus cyclophosphamide. Only one case had reduced intensity conditioning (RIC) with R-FBA (fludarabine, busulfan & cytarabina). It was followed by an infusion of granulocyte-colony stimulating factor-primed bone marrow (G-BM) and/or peripheral blood stem cells without in vitro T cell depletion. In haplo-SCT and HLA-matched unrelated donor for SCT, GVHD prophylaxis consisted of antithymocyte globulin, cyclosporine A, mycophenolate mofetil and a short course of methotrexate. Clinical efficacy, hematopoietic reconstitution and transplant-related complications were retrospectively analyzed. Results:Among them, 146(96%) patients engrafted with a median time to neutrophil and platelet recovery of 12 and 15 days respectively. During a median follow-up period of 19 months, 66 of them survived (43.7%) and 67 (44.4%) died (39 disease recurrence, 27 transplantation-related mortality). Between haplo-SCT and HLA-matched SCT groups, progression-free survival (PFS) rate was 49.4% and 50.5% ( P=0.577); overall survival (OS) rate 56.7% and 57.4% respectively ( P=0.963). The cumulative incidences of relapse (CIR) were 36.6% and 37.7% ( P=0.836) and those of cumulative incidences of non-relapse mortality (NRM) 22.0% and 24.7% ( P=0.530). And the cumulative incidences of chronic GVHD were 42.3% and 39.6% ( P=0.46) respectively. Conclusions:No inter-group difference exists in each major HSCT endpoint. Multivariate analysis reveals that occurrence of grade Ⅲ-Ⅳ aGVHD has a significantly worse prognosis. And primary chemorefractoriness is a strongest relapsing factor.

Purpose: The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). Materials and Methods: An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. Results: Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. Conclusion Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.