Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

IgH translocation with undefined partners is associated with superior outcome in multiple myeloma patients.

BACKGROUND: In multiple myeloma (MM), impact of specific chromosomal translocations involving IgH (14q21 locus, including t(4;14), t(11;14), and t(14;16)) has been explored extensively. However, over 15% MM patients harboring IgH translocation with undefined partners have long been ignored. METHODS: A prospective non-randomized cohort study with a total of 715 newly-diagnosed MM cases was conducted, 13.6% of whom were t(14;undefined) positive. The whole cohort was divided into four groups: no IgH split (47.7%); t(14;undefined) (13.6%); t(11;14) (17.6%); and t(4;14) or t(14;16) group (21.1%). RESULTS: Median OS for the four groups was 84.2, not reached (NR), 58.7, and 44.2 months, respectively, with P values for t(14;undefined) vs no IgH split, t(11;14), and t(4;14)/t(14;16) groups of 0.197, 0.022, and 0.001, respectively. In bortezomib-based group, the survival advantage gained by t(14;undefined) group was much more significant compared to t(11;14) and t(4;14)/t(14;16) groups. Importantly, t(14;undefined) turned out to be an independent predictive factor for longer OS of MM patients in multivariate analysis, especially in the context of bortezomib treatment. Similar results were also observed in the PUMCH external validation cohort. CONCLUSION: Collectively, our data confirmed and externally validated the favorable prognosis of the t(14;undefined) groups, especially in the era of novel agents.

[Clinical Analysis of B-CLPD with Cytopemia as the Predominant Characteristic].

OBJECTIVE: To investigate the clinical characteristics and therapeutic responte of patients with B-CLPD mainly manifested as cytopenia, so as to deeply understand this disease. METHODS: The clinical data of 13 B-CLPD patients with hematocytopenia as main manifestation, and the absolute count of lymphocytes＜5×109/L, absence of hepatosplenic lymph-nodes and extramedullary invasion tin our department fron 2003 to 2018 were analyzed retrospectively. The clinical characteristics, therapeutic efficacy and adverse reactions of 3 patients were summarized. RESULTS: The median age of patients was 59 (43-76) years old, the median of lymphocyte was 1.86 (0.69-4.8) ×109/L, the levels of LDH and ß2-microglubulin were normal in most patients, the monolineage and multilencage hematopoietic failure of different degrees existed in most all patients. The lymphocyte ratio in patients was 18.5%-94.0%, CD20 was positive in all patients, and yet the CD5-positive and CD-negative existed in 7 and 6 cases respectively. There was no significant difference in ratio of lymphocyte invasion among different immunophemtype. The FISH detection showed that there were no high risk genetic types. 92.3% of patients received rituximab treatment, most of them received chemotherapy of rituximab combined with C0P/CHOP like regimen, only 2 patients received fludarabine for comparatively short course. The analysis indicated that 8 out of 13 patients showed a certain theropeutic efficacy, however the drug-related hematopoietic suppression occurred in both 2 patients treated with fludarabin. CONCLUSIONS: The B-CLPD accompanied with hematocytopenia often displays bone marrow hypohematopoiesis of different degree and easily confuses with the congenital and acquired hemotopoietic faiture diseases. The rituximab treatment may be more appropreate for these patients, but for patients received chemotherapy containing fludarabin, the persistant hematopoietic failure must be especially watched out.

Secretory status of monoclonal immunoglobulin is related to the outcome of patients with myeloma: a retrospective study.

The treatment of multiple myeloma (MM) with proteasome inhibitor (PI) bortezomib has significantly improved the survival of patients with MM. The 26S proteasome inhibitor targets the unfolded protein response (UPR) by inhibiting proteasome degradation of ubiquitinated paraprotein, subsequently leading to the lethal accumulation of paraprotein within the endoplasmic reticulum. According to secretory status of monoclonal immunoglobulin, newly diagnosed MM (NDMM) is divided into measurable and unmeasurable disease, which includes oligosecretory, nonsecretory, and nonproducer myeloma. The present study analyzed the clinical characteristics of 822 patients with NDMM who had either measurable or unmeasurable diseases and received bortezomib- or thalidomide-based therapies. Our results showed that the median progression-free survival (PFS) and overall survival (OS) of patients with MM was significantly longer in patients with measurable disease than those in oligosecretory, nonsecretory, and nonproducer MM (PFS: 27, 18, 19, and 2.0 months, respectively [P < .001]; OS: 51, 30, 22, and 2.0 months, respectively [P < .001]). Within the unmeasurable group, patients with nonproducer myeloma showed the shortest PFS and OS. Importantly, compared with thalidomide treatment, bortezomib significantly improved the PFS and OS of patients with MM with measurable disease (PFS: 25 and 33 months [P = .022], respectively; OS: 41 and 58 months [P < .001], respectively), but not those with unmeasurable disease (PFS: 18 and 16 months [P = .617], respectively; OS: 22 and 27 months [P = .743], respectively). Our results indicate that bortezomib-based therapy performed no better than thalidomide-based treatment in patients with unmeasurable MM. The results need to be confirmed in other patient cohorts, preferably in the context of a prospective trial.

Octreotide treatment of cancer chemoradiotherapy-induced diarrhoea: a meta-analysis of randomized controlled trials.

BACKGROUND: Patients receiving radiotherapy and chemotherapy have a high risk developing to an acute chemoradiotherapy-induced diarrhea (RID). The clinical efficacy of octreotide in controlling chemoradiotherapy-induced diarrhea remains controversial. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of octreotide for treatment the chemoradiotherapy-induced diarrhoea. METHODS: Relevant RCTs studies assessing the effect of octreotide on clinical outcomes compared with placebo were searched in Cochrane Library, PubMed, EMBASE and Web of Science (up to December 2018). Heterogeneity was assessed with I2, and publication bias was evaluated using sensitive analysis. RESULTS: Eight trials, a total of 594 participants. We found octreotide was significantly effective compared with the control group (OR =3.17; 95% CI, 1.28-7.85; P<0.0001). The overall effect of octreotide was 62.5% (220/352), while that of the control group was 49.3% (168/341). We found octreotide group was effective compared with the control group in 24, 48, and 96 h (OR =16.02; 95% CI, 3.51-73.15; P=0.0003), (OR =4.70; 95% CI, 1.65-13.42; P=0.004) and (OR =14.49; 95% CI, 6.24-33.65; P<0.00001). CONCLUSIONS: Octreotide is superior to conventional therapy in the duration and effectiveness for chemoradiotherapy-induced diarrhea.

c.1439delA frameshift deletion mutation in familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is a rare autosomal dominant genetic disease related to germline mutations of the APC gene. The clinical features of this disease most commonly include hundreds of adenomas or polyps. If not treated in a timely fashion, FAP can eventually result in colorectal carcinoma. In this report, clinical manifestations, family history, relevant auxiliary examinations and gene detection from patient blood led us to discover a novel frameshift mutation in exon 12 of the APC gene. The deletion of adenine in c.1439 resulted in the formation of codon 480. The occurrence of this frameshift deletion may lead to inexpressibility of the main functional regions in APC and may affect gene function. In addition, colonoscopy and histopathology showed malignant changes in the colon and rectum. There have been no reports of this frameshift mutation, but it can be considered in case of APC mutations and FAP in patients with clinical manifestations; auxiliary examination may be related, and it may be used as a reference for preventive clinical treatment in the future.

Chronic Lymphocytic Leukemia Prognostic Index: A New Integrated Scoring System to Predict the Time to First Treatment in Chinese Patients with Chronic Lymphocytic Leukemia.

BACKGROUND: The established clinical staging systems (Rai/Binet) of chronic lymphocytic leukemia (CLL) cannot accurately predict the appropriate treatment of patients in the earlier stages. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated more markers together. To predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index (CLL-PI). METHODS: Taking advantage of a population of 406 untreated Chinese patients with CLL at early and advanced stage of disease, we identified the strongest prognostic markers of TTFT and, subsequently, in a cohort of 173 patients who had complete data for all 3 variables, we integrated the data of traditional staging system, cytogenetic aberrations, and mutational status of immunoglobulin heavy chain variable region (IGHV) in CLL-PI. The median follow-up time was 45 months and the end point was TTFT. RESULTS: The median TTFT was 38 months and the 5-year overall survival was 80%. According to univariate analysis, patients of advanced Rai stages (P < 0.001) or with 11q- (P = 0.002), 17p- (P < 0.001), unmutated IGHV (P < 0.001), negative 13q- (P = 0.007) and elevated lactate dehydrogenase levels (P = 0.001) tended to have a significantly shorter TTFT. And subsequently, based on multivariate Cox regression analysis, three independent factors for TTFT were identified: advanced clinical stage (P = 0.002), 17p- (P = 0.050) and unmutated IGHV (P = 0.049). Applying weighted grading of these independent factors, a CLL-PI was constructed based on regression parameters, which could categorize four different risk groups (low risk [score 0], intermediate low [score 1], intermediate high [score 2] and high risk [score 3-6]) with significantly different TTFT (median TTFT of not reached (NR), 65.0 months, 36.0 months and 19.0 months, respectively, P < 0.001). CONCLUSIONS: This study developed a weighted, integrated CLL-PI prognostic system of CLL patients which combines the critical genetic prognostic markers with traditional clinical stage. This novel modified PI system could be used to discriminate among groups and may help predict the TTFT and prognosis of patients with CLL.

Efficacy of Rituximab for Patients with Chronic Lymphocytic Leukemia.

Objective To evaluate the efficacy of rituximab in treating chronic lymphocytic leukemia (CLL). Methods The clinical data of CLL patients receiving fludarabine,cyclophosphamide±rituximab (with or without rituximab) regimen or cyclophosphamide,vincristine,and prednisone±doxorubicin±rituximab regimen in our hospital from March 2000 to February 2015 were analyzed retrospectively. Therapeutic efficacies and survivals of patients treated with different regimens were evaluated and compared. Results The complete response (CR) rate and the overall response rate (ORR) in 72 patients (43.6%) treated with rituximab were significantly higher than those treated without rituximab (38.9% vs. 21.5%,P=0.015;83.3% vs. 60.2%,P=0.001). The median PFS and OS for patients treated with rituximab were 53.0 (27.0-79.0) months and 112.0 (81.1-142.9) months,and the median PFS and OS for patients treated without rituximab were 28.0 (18.3-37.7) months and 89.0(72.0-106.0),but the results were not statistically significant (P=0.094,P=0.109). According to the cytogenetic features,patients were further divided into high-risk subgroup (with chromosome 17p deletion or 11q deletion) and non-high-risk subgroup. And in the high-risk subgroup,the ORR of patients treated with rituximab was 86.4%,which was significantly higher than that in patients treated without rituximab (53.3%)(P=0.012);in the non-high-risk subgroup,the PFS was marginally prolonged in patients treated with rituximab,but the difference was not statistically significant(P=0.050). Conclusions Compared with traditional chemotherapy,the chemoimmunotherapies with rituximab result in higher CR rate and ORR in CLL patients. In patients without 17p deletion or 11q deletion,the use of rituximab can marginally prolong PFS.

[Divergence Analysis of Hepatitis Virus Infection between Aggressive and Indolent B Cell Non-Hodgkin's Lymphoma].

OBJECTIVE: To investigate the prevalence rate of hepatitis B virus(HBV)and hepatitis C virus(HCV)between aggressive and indolent B cell non-Hodgkin's lymphoma (B-NHL), and to compare the different infection rate of Hepatifis Virus between the 2 groups. METHODS: Integrated clinical information of 733 newly diagnosed indolent B-NHL patients and 148 aggressive B-NHL patients from January 1994 to January 2014 was retrospectively analyzed. The difference of hepatitis virus infection was compared between the 2 groups. RESULTS: The positive rate of HCV-Ab was 1.8% in 881 newly diagnosed B-NHL patients. The HCV prevalence was 1.9% and 1.35% in the indolent and aggressive B-NHL group respecitvely. Compared with general population, the HCV positive rate was significantly higher in the whole B-NHL group and the indolent group(1.8% vs 0.4%,1.9% vs 1.4%)(P<0.01), while it was not significantly different in the aggressive group (1.35% vs 0.4%)(P=0.068). The positive rate of HCV-Ab was not significantly different between the indolent and the aggressive group (1.9% vs 1.35%)(P=0.639). The HBs-Ag positive rate in the whole B-NHL group was 9.0%, which was significantly higher than that in the general population (9.0% vs 7.2%)(P<0.05). The positive rate of HBs-Ag in the indolent and aggressive B-NHL group was 7.9% and 14.2%, respectively. It was significantly higher in the aggressive group than that in the indolent one (14.2% vs 7.2%)(P<0.01). Compared with the general population, the aggressive group had significantly higher prevalence rate of HBV. However, it was not significantly different between the indolent group and the general population (7.9% vs 7.2%)(P>0.05).In the aggressive B-NHL group,the co-expression of HBs-Ag,HBe-Ag and anti-HBc-Ab was 4.4%, which was higher than that in the indolent one (4.7% vs 1.2%)(P<0.01). However, compared with the indolent group, the co-expression of HBs-Ag, anti-HBe-Ab and anti-HBc-Ab was not significantly different in the aggressive group (5.5% vs 6.1%)(P>0.05). CONCLUSION: The HCV is more relevant with indolent B-NHL, the HBV has more relevance with the aggressive patients.

[Analysis of Clinical Curative Efficacy for 91 Cases of Splenic Marginal Lymphoma].

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of splenic marginal zone lymploma (SMZL). METHODS: A total of 91 cases of SMZL admitted in our hospital from January 2002 to March 2013 were enrolled in this study. The clinical characteristics and immunophenotypes were summarized, and the clinical therapeute response and prognostic factors were analyzed statistically. RESULTS: The median age of 91 patients was 56 (28-79); all the patients displayed splenomegaly with 73.6% of large spleen, hepatomegaly (14.6%) and lymphadenophathy (28.2%); the bone marrow involvement was observed in 98.9% patients, the B symptom was found in 47.1% patients. The positive expression of CD20 was observed in 100% patients, the positive expression of CD5 was in 8.3% patients, the positive expression of CD23 was found in 47.6% patients, no specific antigen was observed by now for SMZL. The clinical treatment showed that total ORR was 87.7%, CRR was 53.8% in chemotherapy group, chemotherapy combined with rituximab showed a better response than that of chemotherapy alone, which ORR was 100%, CRR was 72.4%, the difference between them was statistically significant. The Hb < 120 g/L, elevated LDH level and treatment without rituximab were the poor prognostic factors for PFS, while the elevated LDH level was related with OS of patients. CONCLUSION: The patients with SMZL often display splenomegaly, involvement in bone marrow and absence of specific immunophenotypes. Chemotherapy combined with rituximab can definitely improve the outcome of SMZL. The Hb level, LDH level and treatment combined with or without rituximab seem to be related to the prognosis of the disease.

A novel spherical magnetic compression device for colorectal anastomosis in a Swine model.

BACKGROUND: We designed a novel, spherical magnetic compression colorectal anastomosis device and established a swine model to assess the feasibility and safety, as well as advantages, of the device. METHODS AND MATERIALS: Fifteen animals were divided into five groups (sacrificed on Days 3, 5 7, 9, and 14) with 3 in each group. In each group, a magnetic compression device was used in 2 animals (experimental animals), and a stapled device was used in 1 animal (control animal). Feeding status, bowel movements, the discharge time of the magnetic anastomosis device, burst pressure, and magnetic field strength were recorded. Gross anatomical and histological examinations were performed. RESULTS: The average device discharge time was 7.5 days. The burst pressure increased over time for both the experimental and control animals. Both the gross anatomical and histological examinations suggested that the inflammatory reaction was milder. Healing occurred more quickly, and the incidence of complications was lower for the experimental animals than for the control animals. CONCLUSIONS: The potential benefits of the spherical magnetic compression colorectal anastomosis device, relative to the stapled device, were in terms of effectiveness and complication incidence, which encourages us to further study its application in gastrointestinal anastomosis.

[Clinical and laboratory features of T-cell prolymphocytic leukemia in China].

OBJECTIVE: To investigate the clinical and laboratory characteristics and survival of Chinese patients with T- cell prolymphocytic leukemia (T-PLL). METHODS: Eleven patients with T-PLL admitted in our hospital from Jan 2006 to Oct 2012 were retrospectively analyzed. RESULTS: Of the 11 patients, nine were males and two females, with the median age of 56.0(19-69) years old. All the patients, except for three, presented with leukocytosis. The incidence of hyperleukocytosis (1/11) was less frequent than that in the British series (75%) (P=0.000). Lymphocyte counts in peripheral blood were increased in 9 of the 11 patients with the median absolute lymphocyte count (ALC) of 17.22(0.58-148.83)×109/L. Superficial lymphadenopathy and splenomegaly were the most common physical signs. It was common that serum lactate dehydrogenase (LDH) and beta 2 microglobulin(ß2-MG)were higher than normal level. All cases were positive for CD2/CD3/CD5/TCRαß, negative for CD1a /HLA-DR and TdT, and most of them were strong positive for CD7 expression. By chromosome analyses, most cases. (9/10) have normal chromosome. This rate is significantly higher than that of the British and American series (3% and 25%, respectively) (P=0.000, P=0.001). The 14q11 abnormality and trisomy 8q, which are common among Western cases, were not observed in any of our cases. With a median follow-up of 23.0 months, three patients died. Two year progress free survival (PFS) and overall survival (OS) were 53.3% and 50%, respectively. There were 3 patients with PFS over a number of years, whether it should be considered as the T-chronic lymphocytic leukemia (T-CLL) is worthy of further studies. CONCLUSION: The common clinical manifestations of T-PLL patients were increased lymphocyte counts and lymphadenopathy as well as splenomegaly. And most cases have high level of blood LDH and ß2- MG and normal chromosome karyotype.

[The prognostic impact of 1p21 deletion on newly diagnosed multiple myeloma patients receiving thalidomide-based first-line treatment].

OBJECTIVE: To explore the deletion rate, clinical correlation and prognostic significance of 1p21 deletion, a novel genetic prognostic index, in patients with multiple myeloma (MM). METHODS: The interphase fluorescence in situ hybridization (I-FISH) was performed on purified CD138⁺ plasma cells from 78 newly diagnosed patients from Sep 2007 to Sep 2012 receiving thalidomide-based chemotherapy by using BAC probe covered 1p21.2 region that contains the human cell division cycle 14A (HCDC14A) gene. Deletion rate, the cell percentage of deletion, clinical relevance and prognostic significance were analyzed in myeloma patients. RESULTS: Among 78 patients, there were 51 males and 27 females, the median age was 59(42-81). The deletion rate of 1p21.2 was 23.1%. Some patients had amplification (amp) of 1p with amp rate of 5.1% in 1p21.2, the amp rate was significantly lower than the deletion rate (P=0.001). 1p21.2 deletion was positively correlated with renal lesion (Cr≥177 µmol/L), high percentage of plasma cells in bone marrow, high LDH (≥220 U/L) and high ß2-MG (P=0.014, 0.000, 0.010 and 0.022, respectively). With a median follow-up time of 15.0(1.0-53.5) months, the estimated median progressionfree survival (PFS) and overall survival (OS) time for patients with 1p21 deletion was (12.0±2.7) and (14.0±3.4) months, however those were (30.0±8.0) and (38.5±1.8) months in patients without 1p21 deletion, respectively (P=0.000). On multivariate analysis, which included complex karyotype, LDH≥220 U/L, renal lesion and del(17p13), 1p21 deletion remained as an independent risk factor for PFS (HR: 3.312, 95% CI: 1.095-10.017, P=0.034) and OS (HR: 4.961, 95% CI: 1.487-16.552, P=0.009). CONCLUSION: 1p21 deletion is an important genetic prognosis indicator in multiple myeloma patients.

The -842G/C polymorphisms of PIN1 contributes to cancer risk: a meta-analysis of 10 case-control studies.

BACKGROUND: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) plays an important role in cancer development. The relationship between PIN1 -842G/C (rs2233678) polymorphism and cancer risk was inconclusive according to published literature. METHODOLOGY/PRINCIPAL FINDINGS: A literature search, up to February 2013, was carried out using PubMed, EMBASE and the China National Knowledge Infrastructure (CNKI) database. A total of 10 case-control studies including 4619 cases and 4661 controls contributed to the quantitative analysis. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association. Overall, individuals with the variant CG (OR = 0.728, 95% CI: 0.585,0.906; Pheterogeneity<0.01) and CG/CC (OR = 0.731, 95% CI: 0.602,0.888; Pheterogeneity<0.01) genotypes were associated with a significantly reduced cancer risk compared with those with wild GG genotype. Sub-group analysis revealed that the variant CG (OR = 0.635, 95% CI: 0.548,0.735; Pheterogeneity = 0.240) and CG/CC (OR = 0.645, 95% CI: 0.559,0.744, Pheterogeneity = 0.258) genotypes still showed an reduced risk of cancer in Asians; while no significant association was observed in Caucasians (CG vs.GG: OR = 0.926, 95% CI: 0.572,1.499, Pheterogeneity<0.01; CG/CC vs. GG: OR = 0.892, 95% CI: 0.589,1.353; Pheterogeneity<0.01). Furthermore, sensitivity analysis confirmed the stability of results. Begg's funnel plot and Egger's test did not reveal any publication bias. CONCLUSIONS: This meta-analysis suggests that the PIN1 -842G/C polymorphism is associated with a significantly reduced risk of cancer, especially in Asian populations.

[Inhibitory effect of silencing of HMGB1 gene expression on the invasive and metastatic abilities of MGC-803 gastric cancer cells].

OBJECTIVE: To investigate the effect of high mobility group box-1 (high mobility group box B 1, HMGB1) on the invasive and metastatic abilities of gastric cancer cell line MGC-803 and analyze the possible mechanisms. METHODS: HMGB1 gene targeting siRNA was designed and synthesized, and HMGB1 siRNA oligonucleotides were transfected into the MGC-803 cells with Lipofectamine 2000. The invasive and migratory abilities were detected by transwell assay and scratch assay. The Matrigel matrix glue adhesive ability of MGC-803 cells was evaluated by MTT assay. NF-κB activity was detected by electrophoretic mobility shift assay. The mRNA and protein levels of HMGB1 and MMP-9 were determined by RT-PCR and Western blot, respectively. RESULTS: The siRNA down-regulated the levels of HMGB1 mRNA and protein. Compared with that of the control group, the number of invasive (142.7 ± 3.4 /view vs. 303.5 ± 4.3/view) and migratory (293.7 ± 4.4/view vs. 445.5 ± 5.6/view) cells was significantly increased (P < 0.05) and the adhesive ability of MGC-803 cells to Matrigel was significantly elevated (33.4 ± 0.03% vs. 57.4 ± 4.2%, P < 0.05). In addition, silencing of HMGB1 gene significantly inhibited the activity of NF-κB and the relative expression folds of mRNA (0.2 ± 0.1 vs. 1.4 ± 0.4, P < 0.05)and protein (0.4 ± 0.1 vs. 2.3 ± 0.7, P < 0.05) of MMP-9. CONCLUSION: Silencing of HMGB1 can effectively inhibit the invasion and migration of gastric cancer cells and this effect of HMGB1 may be partly due to its regulation of NF-κB and MMP-9 expressions.

[Outcomes of younger than 60 years old adults with Ph/BCR-ABL positive acute lymphoblastic leukemia: a single center clinical trial of BDH ALL 2000/02].

OBJECTIVE: To explore the treatment options for younger than 60 years old adults with Ph /BCR-ABL positive acute lymphoblastic leukemia (Ph⁺ ALL). METHODS: From January 2001 to June 2012, 42 adult patients were enrolled in the study. All patients received standard VDCP±L ±imatinb (IM) as induction therapy followed by intensive consolidation of modified Hyper-CVAD/MA±IM. At complete remission 1 (CR1), patients with appropriate donor received allogeneic hematopoietic stem cell transplantation (allo-HSCT), the others sequentially received intensive consolidation ±IM and autologous HSCT (ASCT) at molecular CR (MCR), then MM±VP±IM as maintenance therapy. Overall survival (OS), disease free survival (DFS) and relapse rate (RR) were analyzed. RESULTS: CR rate after 1 cycle of induction chemotherapy was 83.3%. 39(92.9%) patients achieved CR. The median DFS and OS were (22.0±3.5) and (37.0±5.3) months respectively, with cumulative RR of (43.7±9.7)% during a median follow-up of 26.5(8-75) months. All 7 patients in CT group relapsed. Two patients received IM pre- and post-ASCT maintained MCR for 35 and 12 months after ASCT. But the other 3 ASCT recipients without IM died of relapse within 1 year. The transplant-related mortality rate in allo-HSCT group was 12.5%. The estimated 3-year OS in allo-HSCT (n=16), ASCT (n=5) and CT (n=7) groups were (66.7±12.2)%, (25.0±21.7)% and (16.7±15.2)%, respectively (P=0.014); meanwhile, the estimated 3-year DFS in those groups were of (56.3±12.4)%, (26.7±22.6)% and 0, respectively (P=0.002). CONCLUSION: IM combined with intensive chemotherapy significantly increased the CR rate with the improved quality of CR, which highlighted the feasibility of SCT. Allo-HSCT could decrease relapse to produce favorable OS and DFS in CR1 of young adults with Ph⁺ ALL. ASCT combined IM might be the treatment of choice for those achieved MCR but without donors.

[Research progression of extralevator abdominoperineal excision].

The application of extralevator abdomino-perineal excision (ELAPE) and total mesorectal excision has improved the prognosis of rectal cancer. However, compared with anterior resection for rectal cancer, the circumferential resection margin (CRM) positive rate and intraoperative perforation (IOP) rate are still high. The ELAPE can reduce the CRM positive rate and IOP rate, therefore reduce postoperative local recurrence rate and increase the survival rate of patients. The disadvantage of its trauma, longer operative time, and higher perineum complication in ELAPE is controversial. This review mainly discusses the key points of operative procedure, advantages and disadvantages, research status and development prospects of ELAPE.

[Clinical efficacy and safety of chemoimmunotherapy with rituximab,fludarabine and cyclophosphamide for chronic lymphocytic leukemia].

OBJECTIVE: To evaluate the efficacy and safety of a chemoimmunotherapy regimen of rituximab, fludarabine and cyclophosphamide (FCR) for patients with chronic lymphocytic leukemia(CLL). METHODS: The clinical data of 26 CLL patients receiving FCR regimen in our hospital from April 2003 to January 2012 were analyzed retrospectively. Patients were grouped according to indicators including Rai risk stratification, ß(2)-MG, LDH, ZAP-70, CD38, cytogenetics and immunoglobulin heavy chain variable region gene (IgVH) mutation status. Therapy efficacy and survival were evaluated and the safety of FCR regimen was assessed. RESULTS: Among 26 patients, the overall response rate ( ORR ) was 76.9%, 10 patients (38.5%) achieved complete remission(CR) and 10(38.5%) partial remission(PR). With a median follow-up time of 30 ( 3-98 ) months, the median estimated progression-free survival(PFS) for all patients was 42(16-68) months and median overall survival(OS) was 63(41-85)months. Clinical parameters associated with higher CR rates were ＜2 courses of prior treatment regimens, proportions of bone marrow lymphocytes declining ≥ 50% after 2 courses of FCR, low LDH, low ß(2)-MG and ZAP-70 negative (P = 0.014, 0.008, 0.027, 0.035 and 0.013, retrospectively). PFS and OS time in minimal residual disease(MRD)-negative, normal LDH and proportions of bone marrow lymphocytes declining ≥ 50% after 2 courses of FCR patients were significantly better than that of the control group (P＜0.05), PFS in the non-high-risk genetics group was significantly better than that in the high-risk genetics group (P = 0.005), while OS between two groups showed no statistically significant difference. The most common toxicities were gastrointestinal reactions (88.5%), followed by bone marrow suppression (80.8%): including neutropenia, anemia and thrombocytopenia. Infections accounted for 30.8%, mainly lung infection. CONCLUSION: FCR is an effective and well-tolerated therapy for patients with CLL. Patients with MRD-positive, elevated LDH, proportions of bone marrow lymphocytes declining＜50% after 2 courses of FCR and high risk genetics patients are suitable for more effective treatment after achieving treatment response.

[Analysis of the efficacy and prognosis on first-line autologous hematopoietic stem cell transplantation of patients with multiple myeloma].

OBJECTIVE: To explore the efficacy and prognosis of first-line autologous hematopoietic stem cell transplantation (ASCT) for newly diagnosed patients with multiple myeloma(MM). METHODS: From January 2005 to December 31, 2012, 60 patients with MM were enrolled. All patients received thalidomide or/and bortezomib-based induction therapy, then received high-dose melphalan (200 mg/m²) and autologous stem cell support to get a ≥ partial response (PR), and followed by thalidomide-dexamethasone (TD) ±bortezomib as consolidation or maintenance treatment. With the follow up to December 31, 2012, the overall survival (OS), progression free survival (PFS) and the prognostic factors, including ISS stage, response and fluorescent in situ hybridization (FISH) data of cytogenetics were analyzed. RESULTS: With a median follow up of 36.8 (12.0-102.5) months, the median OS and PFS estimate were not reached and 86.5 months, respectively. After transplantation, all (100%) patients received very good partial response (VGPR), and 34 (56.7%) patients achieved complete response (CR) after consolidation or maintenance treatment. The patients that achieved CR resulted in long term PFS (P=0.030), with no difference in OS (P=0.942). The univariate analysis showed that the abnormalities, including 13q14 deletion, 1q21 gain, IgH location and p53 deletion had the prognostic impacts. If the t(4;14) or p53 deletion was excluded, there would be no correlation between 13q14 deletion or 1q21 gain with PFS and OS. The patients with p53 deletion had a worst survival. CONCLUSION: There has been significant improvement in the outcome for young MM patients by using ASCT and novel drugs. Cytogenetic abnormalities and response to therapy are the main factors affecting the survival of patients.