Clinical Efficacy and Prognostic Factors of Autologous Hematopoietic Stem Cell Transplantation for Hodgkin's Lymphoma in 38 Cases / 肿瘤防治研究

Objective To investigate the clinical efficacy and prognostic factors of autologous hematopoietic stem cell transplantation (ASCT) for Hodgkin's lymphoma (HL). Methods We retrospectively analyzed the data of 38 patients with HL who underwent ASCT. Kaplan-Meier and Cox methods were used to analyze the curative effect and prognostic factors after transplantation. Results All 38 transplanted patients obtained hematopoietic reconstitution. The CR rates before and after transplantation were 55.3% and 81.6%, respectively, and the 5-year PFS and OS were 76.1% and 79.0%, respectively. Univariate analysis showed that B symptoms, IPS score, pre-transplant remission status, extranodal invasion, and pretreatment regimen were the factors affecting the prognosis of ASCT in patients with HL. Multivariate analysis showed that B symptom was an independent risk factor affecting 5-year PFS. Conclusion ASCT is effective in the treatment of high-risk, relapsed, and refractory patients with HL. B symptom is an independent risk factor affecting the prognosis of transplantation.

Progress of drug resistance mechanism of ibrutinib / 白血病·淋巴瘤

As a novel molecular targeted anti﹣tumor drug, it has been proved that ibrutinib has remarkable anti﹣tumor activity and is characterized by high efficiency and low toxicity. However, the risks of drug resistance, safety, and disease transformation are gradually concerned. This review focused on the research progress of ibrutinib′s drug resistance mechanism in various B﹣cell non﹣Hodgkin lymphomas.

Prognostic significance of miRNA-223 targeting SOX11 in mantle cell lymphoma / 中华血液学杂志

Objective@#To explore the expression and prognostic significance of miR-223 in patients with mantle cell lymphoma (MCL) and to investigate the possible mechanism.@*Methods@#Twenty-one newly diagnosed MCL patients with bone marrow involvement were enrolled in the present study, 20 healthy donors as normal control. The expression level of miR-223 and SOX11 mRNA was determined by RQ-PCR. CCK-8 and flow cytometer assays were used to analyze cell proliferation, cell cycle and apoptosis of the constructed miR-223 overexpressing MCL cell line, Granta519 cells. SOX11 protein expression level was determined by Western blot. The target gene of miR-223 was confirmed by dual luciferase reporter assay.@*Results@#①Of the 21 newly diagnosed MCL patients, 15 were male and 6 female, the median age was 58 (37-72) years. The expression level of miR-223 was significantly down regulated in MCL patients compared with that of healthy donors (14.7±10.5 vs 1 244.1±1 935.2, P<0.001). The lower expression of miR-223 was inversely correlated with high-risk mantle international prognostic index (P=0.001), elevated LDH (P=0.001), ECOG score ≥2 (P=0.035). ②Using the median relative expression level of miR-223 as the cutoff value, 21 MCL patients were divided into high-expression group (n=10) and low-expression group (n=11) and found that the high-expression group had a significantly superior OS (median OS: 36 vs 12 months, P=0.021). ③In vitro results showed that compared with the control group, the proliferation of miR-223 overexpressed Granta519 cells was inhibited (the most significant reduction on 96h, P<0.001), manifested by lower proportion of cells in G2/M phase (P<0.001) and increased apoptosis (P<0.001), and the expression level of SOX11 protein in Granta519 cells was significantly lower than that of the control group. ④miR-223 could inhibited the 3′ untranslated region of SOX11, and the expression level of miR-223 was significantly negatively correlated with mRNA level of SOX11 in MCL patients (r=-0.81, P<0.001).@*Conclusions@#The expression of miR-223 was repressed in MCL and was associated with poor clinical outcomes, which may be probably attributed to its direct targeting SOX11.

Study on the expression of TRIP13 mRNA in chronic lymphocytic leukemia B lymphocyte and the molecular mechanism of TRIP13 mediated JVM-2 cell proliferation and apoptosis / 中华血液学杂志

Objective@#To investigate the clinical significance of expression level of thyroid hormone receptor interactors 13 (TRIP13) gene to probe its function and downstream molecular mechanism in chronic lymphocytic leukemia (CLL) .@*Methods@#Real-time quantitative PCR method was used to detect the expression levels of TRIP13 mRNA of CD19+ B lymphocytes in 30 cases of patients with CLL and 12 cases of peripheral blood hematopoietic stem cell donors (normal control group) . Lentivirus mediated shRNA was used to interference the mRNA and TRIP13 protein in CLL cells JVM-2. Scramble sequence was used as control. Methyl thiazolyl tetrazolium colorimetric assay (MTT) and flow cytometry was used to detect the cell proliferation and apoptosis in TRIP13 knocked-down and negative control JVM-2 cells.@*Results@#TRIP13 mRNA level was significantly higher in 30 cases of CLL patients (2-△Ct= 0.014 89) compared with 12 healthy donors (2-△Ct= 0.000 19) (P<0.001) . Validated TRIP13 shRNA target was achieved in JVM2 cell. Compared with the control group, down-regulation of TRIP13 expression could significantly inhibit the proliferation of JVM-2 cells and induce apoptosis. The expressions of Myc and Bcl-2 protein in JVM-2 cells decreased significantly after interference with TRIP13 (P<0.001) , and the expressions of Bax, caspase 3 and Bad protein increased significantly (P<0.001) .@*Conclusion@#TRIP13 mRNA significantly over-expressed in CLL patients CD19+ B lymphocytes. TRIP13 could influence JVM2 cell proliferation and apoptosis through proliferation- and apoptosis-related proteins.

Effect of ERK1/2 inhibitor AZD8330 on human Burkitt's lymphoma cell line Raji cells and its mechanism / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of ERK1/2 inhibitor AZD8330 on human Burkitt's lymphoma cell line Raji cells and its mechanism.</p><p><b>METHODS</b>Raji cells were treated with different concentrations of AZD8330. CCK-8 was used to detect the cell viability. The apoptosis rate of Raji cells was detected by flow cytometry using Annexin V/PI-staining. Real-time PCR was used to assess the expression of Bcl-2, Bcl-xl, caspase-3 and VEGF genes. The protein expression level of Bcl-2, Bcl-xl, caspase-3 and p-ERK1/2 was tested with Western blot.</p><p><b>RESULTS</b>The cell survival rate decreased to(62.09±0.86)%,(50.06±1.33)% and (39.13±2.34)% respectively after cells were treated with AZD8330 at 1.00 μmol/L in vitro for 24 h, 48 h and 72 h, and statistically significant differences were observed in groups with different time of treatment(P<0.05). Apoptosis of cells treated with AZD8330 at 0.10, 1.00, 10.00 μmol/L in vitro for 24 h, 48 h and 72 h was analyzed, and the statistically significant differences were observed in groups of different time and concentration treatment (P<0.05). AZD8330 induced Raji cell apoptosis and upregulated expression of Bcl-2, Bcl-xl, VEFG and decreased the expression of caspase-3 in a dose and time dependent manner, and statistically significant differences were observed in groups of different time and concentration treatment (P<0.05). At the same time, the Bcl-2, Bcl-xl and p-ERK1/2 proteins expression is suppressed obviously, but the expression of caspase-3 protein increased.</p><p><b>CONCLUSION</b>AZD8330 induces cell apoptosis by down-regulating the activation of ERK1/2 signal transduction pathway in Burkitt's lymphoma cell line Raji cells in a dose and time dependent manner.</p>

Clinical analysis of 18 adult patients with hemophagocytic syndrome / 肿瘤研究与临床

Objective To analyze the adult hemophagocytic syndrome' s pathogeny,clinical features,prognostic factors and therapeutic options.Methods 18 cases of adult hemophagocytic syndrome were analyzed,the Kaplan-Meier analysis was used to investigate the total survival rate,and 17 clinical pathological factors and clinical treatment methods which may influence survival were analyzed by Log-rank test in the univariate analysis.Results In this group of patients,EBV infection and malignant lymphoma were the most common initiating diseases.The most common clinical features were peripheral cytopenia in two or three lineages (100 ％),fever (83 ％),splenomegaly (78 ％),swollen lymph nodes (56 ％).The mortality rates as high as 66.7 ％.The median survival time was 7.4 weeks.One-way ANOVA results showed that the initial symptoms as fever (P =0.039),age ＞ 30 years old (P =0.031),enlargement of the liver (P =0.041),Hb ＜ 100 g/L and Ph ＜ 50 g/L (P =0.039) were relevant prognostic factors.Conclusion Adult hemophagocytic syndrome patients with fever as the initial symptoms,age ＞ 30 years old,liver enlargement,Hb ＜ 100 g/L,Plt ＜ 50 g/L indicates poor prognosis,thus these patients having HPS risk factors should be given active chemotherapy and supportive therapy.

Investigation of long-term follow-up results of 135 patients with chronic myeloid leukemia receiving imatinib / 白血病·淋巴瘤

Objective To evaluate the efficacy and safety of imatinib in chronic myeloid leukemia (CML) patients and analyse the factors affecting the survival. Methods 135 CML patients receiving imatinib were evaluated for hematologic, cytogenetic, and molecular responses and adverse events. Results The median follow-up was 20 (range 3-67) months. The rate of cumulative complete hematological response (CHR), major cytogenetic response (MCyR), complete cytogenetic response( CCyR ) and complete molecular response (CMoR) in chronic phase CML patients were 97.9 %, 78.3 %, 72.2 % and 35.1%, respectively.These rates were significantly higher in chronic phase than in accelerated phase and blastic phase (P ＜0.001).The rate of CCyR in low-risk patients was significantly higher than high-risk patients (P =0.048). The estimated overall survival (OS) rate at 1, 3 and 5 year for chronic phase patients were (97.8±1.5) %, (95.2±2.4) % and (91.9±3.2) %, respectively. The estimated progression-free (PFS) survival rate at 1, 3 and 5 year were (92.6±2.7) %, (85.5±3.7) % and (81.3±4.3) %, respectively. The OS rate for accelerated phase patients at 6, 12 and 24 month were (93.8±6.1) %, (72.5±11.8) % and (64.5±12.9) %, the PFS rate were (92.3±7.4) %,(64.5±14.7) %, (53.7±15.7) %, respectively. The OS rate for blastic phase patients at 6, 12 and 19 month were (86.4±7.3) %, (45.4±11.4) %, (19.4±9.8) %, the PFS rate were (70.1±12.6) %, (37.6±15.6) % and (18.8±15.4) %, respectively. The OS and PFS of patients in chronic phase who achieved CCyR or CMoR were better than patients only achieved CHR (P ≤0.001). Multivariate analysis for survival of chronic phase patients indicated that imatinib resistance was the unfavourable factor for PFS (P =0.000, RR =46.744) and OS(P =0.007, RR =20.270). The non-hematological toxicity of imatinib was slight and tolerable, severe hematological toxicity was the major reason for dose reduction or drug discontinuation. Conclusion The efficacy of imatinib in chronic phase CML patients is significantly superior to which in accelerated phase and blastic phase; Achieving CCyR even CMoR is the most important thing for longer survival, iinatinib resistance is the major problem in the treatment with imatinib.