[Clinicopathological Characteristics of Patients with Intestinal Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the clinicopathological features of intestinal diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical features, pathological morphology, immunophenotype, and EBER in situ hybridization of 136 DLBCL patients diagnosed in Jinan People's Hospital Affiliated to Shandong First Medical University from January 2007 to October 2014 were analyzed retrospectively. A total of 136 DLBCL samples were obtained, the DLBCL sites were categorized as: duodenum (n=23), ileocecal region (n=63), other small intestine (n=29), rectum (n=7), and other large intestine (n=14). Survival curves for the DLBCL patients were plotted using the Kaplan-Meier method and judged by the Log-rank test. RESULTS: Patients with DLBCL of the ileocecal region and other small intestine except duodenum were mainly male (P=0.042), and had a higher proportion of limited-stage tumors(P=0.015), and lower International Prognostic Index (IPI) (P=0.001). Patients with DLBCL of ileocecal region had higher incidence of lactate dehydrogenase elevation (P=0.007), and higher incidence of intestinal obstruction or perforation (P<0.001) than those with DLBCL of other regions. The 5-year overall survival and 5-year progression-free survival of patients with DLBCL in ileocecal and other small intestine sites were higher than those in other sites, but the differences were not statistically significant (P=0.135, 0.459). Fifty percent of intestinal DLBCL were germinal center B cell-like (GCB) subtypes. A low-grade B-cell lymphoma was found in 21% of 136 tumor samples. In ileocecal and other small intestinal specimens, the proportion of low-grade B-cell lymphoma was 29%, and the difference was statistically significant(P=0.025). About 16% of 136 DLBCL samples expressed follicular lymphoma while no mucosa-associated lymphoid tissue lymphoma . The Epstein-Barr virus-encoded RNA-1 (EBER1) positive rate of duodenal DLBCL was significantly higher than that of other sites (5/23, 22% vs 2/63, 3%, P=0.001). CONCLUSION: The intestinal DLBCL is commonly observed in male, and ileocecal is the most primary site. Patients with DLBCL of the ileocecal region and small intestine except duodenum have low IPI, high proportion of limited-stage tumors, low level of lactate dehydrogenase, high incidence of intestinal obstruction or perforation, and low incidence of inert lymphoma. The EBER1 positive rate of DLBCL in duodenal is higher.

[Clinical Comparation of Two Kinds of Chemotherapy Regimens in the Treatment of Patients with MDS-RAEB/AML-MRC].

OBJECTIVE: To investigate the influence of conventional CAG regimen and decitabine + decreased dose CAG (D+dCAG) regimen on the clinical efficacy and safety of patients with MDS-RAEB/AML-MRC. METHODS: The clinical data of 67 patients with MDS-RAEB/AML-MRC hospitalized in our hospital from March 2012 to July 2017 were analyzed retrospectively. According to chemotherapecctic regimens, 76 patients were divided into 2 groups: 37 patients treated with conventional CAG regimen were enrolled in control group, 30 patients treated with decitabine + decreased dose CAG regimen were enrolled in D+dCAG group. The complete remission (CR) rate, overall remission rate (ORR), OS and PFS time and incidence of adverse reactions in 2 groups were compared. RESULTS: The CR in D+dCAG group was significantly higher than that in control group (P＜0.05). ORR was not significanly different between 2 groups (P＞0.05). There was no significant difference in the cumulative OS rate between 2 groups (P＞0.05). There was no significant difference in the cumulative OS rate and PFS rate in nonimplantation between 2 groups (P＞0.05). The incidence of adverse reactions of hematological system, pulmonary infection, skin and soft tissue infection, agranulocytosic fever and mycotic infection was not significanly different between 2 groups (P＞0.05). The duration of granulocyte deficiency and platelet count less than 20×109/L were not significanly different between 2 groups (P＞0.05). CONCLUSION: Compared with conventional CAG regimen, decitabine + decreased dose CAG regimen in the treatment of patients with MDS-RAEB/AML-MRC can efficiently improve the remission effects and showed the well overall safety, but can not increase the survival rate.

[Correlation of Early Minimal Residual Disease Level with Prognosis in AML Patients with NPM1 Mutation Positive after Chemotherapy].

OBJECTIVE: To analyze the correlation of the minimal residual disease level with the prognosis of the AML patients with NPM1 gene mutation positive after chemotherapy. METHODS: The clinical data of 112 newly diagnosed adult AML patients with positive NPM1 gene were collected and retrospectively analyzed. The correlation of the transcripts of NPM1 gene mutation with prognosis of patients was analyzed. RESULTS: In 112 AML patients, the median transcript level of NPM1 gene mutation accounted for 83.68% (5.86%-486.57%), FLT3-ITD mutation positive was found in 44 cases (39.29%), chromosomal abnormalities in 22 cases (19.64%) and complete remission in 96 cases (85.71%). Multivariate logistic regression analysis showed that the initial induction therapy and white blood cell count closely related with complete remission (P＜0.05). The median follow-up time was 22 (3-36) months, and the 3-year overall survival rate was 66.07% in 112 patients. Multivariate logistic regression analysis showed that both the high level of minimal residual disease at the initial complete remission and the high level of minimal residual disease after consolidation therapy were the independent risk factors for overall survival (P＜0.05). CONCLUSION: In newly diagnosed adult AML patients with NPM1 mutation positive, the early high level of minimal residual disease after chemotherapy closely relates with poor prognosis.

[Clinical Efficacy and Safety of R-CDOP Regimen for Treatment of Newly Treated DLBCL Patients with Adverse Prognostic Factors].

OBJECTIVE: To investigate the clinical efficacy and Safety of R-CDOP regimen for treatment of newly diagnosed DLBCL patients with adverse prognostic factors. METHODS: The clinical data of 94 patients who suffered from DLBCL and received treatment with R-CDOP regimen, from October 2013 to February 2018 were collected and analyzed retrospectively. The clinical efficacy, survival benifits and safety, as well as the OS and PFS were compared according to clinical features. RESULTS: After treatment of 94 cases with R-CDOP regimen, 73 cases reachived CR, 14 cases reachived PR, 2 cases were in SD and 4 cases were in PD, the ORR was 92.55% (87/94). The OS rate and PFS rate in followed-up 1 year were 94.68%（89/94） and 85.11%（80/94） separately, However, the median OS and PFS were not reached. There was no significant difference in the followed-up cumulative OS rate and PFS rate between patients with different Age, Ann-Arbor stage, IPI score, number of extranodal tumors, tumor diameter, expression of Ki-67 and LDH level and tissue involvement status（P>0.05）. There was no significant difference in the 1 years PFS rate and OS rate between patients with number of extranodal tumors for 0-1 and ≥2（P>0.05）. There was no significant difference in the 1 years PFS rate and OS rate between patients with tumor diameter for <7.5 cm and ≥7.5 cm（P>0.05）. CONCLUSION: The R-CDOP regimen in the treatment of newly diagnosed DLBCL patients with poor prognostic factors can efficiently improve the early clinical efficacy, prolong the survival time and possess good safety, but the clinical prognosis for long-term remains to be observed.

[The Clinical Efficacy of Small Dose CAG Program in Comparison with MA Program in Senile Patients with Acute Myeloid Leukemia].

OBJECTIVE: To compare the clinical efficacy of small dose CAG regimen and MA regimen in the senile patients with acute myeloid leukemia(AML). METHODS: The clinical data of 83 senile patients with AML from Sep. 2012 to Sep. 2016 in our Hospital were analyzed retrospectively. According to the chemotherapy regimens, the patients were divided into CAG group and MA group; 36 patients in CAG group were treated with small dose CAG, while 47 patients in MA group were treated with MA. The curative efficiency(CR rate, PR rate,NR rate and OR rate), side effect (myelosuppression,infection,intestinal discomfort and hemorrage), serum cytokines(IL-6，IL-17，TGFß）, and prognosis(survival rate in 2 years, MST and SST) were observed, compared and studied in these 2 group. RESULTS: The curative efficiency, CR rate and PR rate of the CAG group were not significantly different from that of the MA group (P>0.05）. The side effect in CAG group was significantly lower than that in the MA group (P<0.05）. The levels of serum cytokines of the MA group were lower than those of the CAG group. Additionally, the prognosis was not significantly different between 2 groups(P>0.05）. CONCLUSION: For senile patients with acute myeloid leukemia, compared with traditional MA regimen, the small dose CAG has a certain curative efficacy and survival rate, and the incidence of side effect reduced. Therefore, the small dose CAG is superior to MA for the senile patients with acute myeloid leukemia.

[Ratio of Primary Bone Marrow Cells after Induction Chemothrapy for Two Weeks in the Patients with Ph- ALL and Its Influence on Complete Remission and Overall Progrosis].

OBJECTIVE: To investigate the influence of bone marrow blasts ratio after induction chemotherapy for 2 weeks in patients with Ph- ALL, and it's influence on complete remission (CR) and overall prognosis. METHODS: A total of 172 patients with Ph- ALL in our hospital from March 2012 to February 2016 were selected. The bone marrow blast ratio was analyzed by the receiver-operating characteristic curve (ROC) in patients after induction chemotherapy for 2 weeks, at same time its influence on CR and overall prognosis of Ph- ALL patients was evaluated. RESULTS: The cutoff value of CR was 0.075, its area under ROC was 0.763; the comparison of area under ROC with Az=0.5 showed statistically significant difference, therefore 172 patients with Ph- ALL were grouped according to bone marrow blast ratio after induction chemotherapy for 2 weeks: 104 cases (60.5%) with bone marrow blast ratio <0.075, 68 cases (39.5%) with bone marrow blast ratio ≥0.075. The Ph- ALL patinets with bone marrow blast ratio <0.075 who achieved CR and finally achieved CR after induction chemotherapy for 4 weeks acconnted for 89 (85.6%) and 99(95.2%) respectively, which were significantly higher than those in Ph- ALL patients with bone marrow blast ratio≥0.075, [29(42.6%) and 52 (76.5%)](P<0.05). In addition, the influencing factor clinically reducing the OS and DFS rate of patients and enhancing the ralapse rate of patients were mainly chemotherapy, the failure of induction chemotherapy (patients did not achieve CR after induction therapy for 4 weeks), the bone marrow blast ratio≥0.075 after induction treatment for 2 weeks, and CNSL at diagnosis and so on, while the enhaced WBC count at diagnosis was poor factor affecting the DFS rate of patients. CONCLUSION: After induction chemotherapy for 2 weeks, the elevated bone marrow blast ratio in Ph- ALL patients will be infavourable to CR, and the overall prognosis is poor.

Grb2-associated binder 2 silencing impairs growth and migration of H1975 cells via modulation of PI3K-Akt signaling.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death and often has a poor prognosis. Investigation of NSCLC cancer cell migration, invasion and development of strategies to block this process is essential to improve the disease prognosis. In this study, we tested our hypothesis that Grb2-associated binder 2 (Gab2) regulate NSCLC cancer cell H1975 malignant biological behaviors, and silencing Gab2 reduced H1975 cellular colony forming ability, migration and invasion. Moreover, silenced cells present defects in phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (Akt) signaling, and reduced expression/activity of matrix metallopeptidase (MMP)-2/9. Furthermore, in Gab2 siRNA-transfected cells, we detected a decrease in signal transducer and activator of transcription 3 (STAT3) phosphorylation and nuclear translocation. In vivo, Gab2 siRNA cells inoculated subcutaneously in nude mice demonstrated decreased tumor growth and PI3K-Akt signaling inhibition. These results indicate that Gab2 is a key factor in H1975 tumor migration, invasion, suggesting that Gab2 can be a novel therapeutic target in NSCLC.

Longitudinal study of smoking patterns in relation to the development of smoking-related secondary primary tumors in patients with upper aerodigestive tract malignancies.

BACKGROUND: The authors set out to assess the correlation between smoking-related second primary tumor (SPT) development and cigarette smoking habits after diagnosis and definitive treatment in patients with early-stage head and neck squamous cell carcinoma who were enrolled in a placebo-controlled randomized chemoprevention trial of 13-cis-retinoic acid. METHODS: Longitudinal data collected for 10 years after the index diagnosis are presented for 1190 patients. Cox proportional hazards regression models were used to examine the effects of changes in smoking behavior on smoking-related SPT development. RESULTS: One-third of all patients who quit smoking within 12 months before randomization experienced recurrence, compared with 6.9% and 10.4% of all never-smokers and former smokers, respectively. Approximately 16% of all current smokers stopped smoking, and nearly 22% of current smokers developed SPTs, compared with 14.5%, 13.2%, and 8.8% of all recent smokers, former smokers, and never-smokers, respectively. The probability of developing a smoking-related SPT was highest among patients who were current smokers at randomization. These patients, regardless of whether they ceased smoking during follow-up, were nearly three times more likely than patients who had never smoked to develop a smoking-related SPT. In contrast, former smokers and recent quitters who continued to abstain from smoking during follow-up were approximately 1.5 times more likely to develop an SPT compared with patients who had never smoked. CONCLUSIONS: Patients who continue to smoke after the successful treatment of their index head and neck malignancies have a substantially higher risk of developing smoking-related SPTs.

Second primary tumors in patients with upper aerodigestive tract cancers: joint effects of smoking and alcohol (United States).

OBJECTIVE: This study evaluated the joint effects of tobacco smoking and alcohol consumption on the risk of second primary tumors (SPT) in patients with early-stage head and neck squamous cell carcinoma (HNSCC). METHODS: Data are presented for 1181 patients enrolled in a placebo-controlled chemoprevention trial of 13-cis-retinoic acid. Nearly 17% of patients presented with a SPT. The log rank test and Cox proportional hazards model were used to examine risk factors for SPT development. RESULTS: After adjusting for the time from the index diagnosis to randomization, age at diagnosis, stage, and site of the primary cancer, the factors that emerged as simultaneous predictors of SPT development were continued smoking and alcohol intake after the index diagnosis. Increased SPT risk was associated with older age (RR = 2.1; 95% CI 1.5-2.8); stage II diagnosis (RR = 1.5; 95% CI 1.1-2.1); index diagnosis of pharyngeal cancer (RR = 1.6; 95% CI 1.1-2.5); current smoking at registration (RR = 2.1; 95% CI 1.3-3.6) and continued alcohol consumption post-diagnosis (RR = 1.3; 95% CI 1.0-1.7). CONCLUSION: Important associations exist between SPT development and continued smoking and alcohol consumption after treatment for HNSCC.