Retrospective analysis of the clinical features and prognostic factors of 370 patients with advanced-stage diffuse large B-cell lymphoma / 中华肿瘤杂志

Objective@#The clinical features and prognosis of diffuse large B-cell lymphoma (DLBCL) were analyzed to optimize the treatment.@*Methods@#We retrospectively collected the clinical data of patients with advanced-stage DLBCL from January 2006 to December 2012 in National Cancer Center/Cancer Hospital. The demographic characteristics, clinical stage, histological diagnosis, treatment and prognostic characteristics of these patients were analyzed.@*Results@#A total of 370 patients with median age of 55 years old were recruited in the study. The male-to-female ratio was 1.3∶1. Among the 361 patients who underwent therapy, 280 cases received chemotherapy alone, 65 cases received chemoradiotherapy, and 16 cases received chemotherapy combined with autologous hematopoietic stem cell transplantation (AHSCT). The median follow-up period was 89 months, the 5-year overall survival (OS) rate of the entire cohort was 42.9%. The 5-year OS rate of chemotherapy alone, chemoradiotherapy and chemotherapy combined with AHSCT were 36.8%, 58.5%, 87.5%, respectively. The 5-year OS rate were significantly different between chemoradiotherapy and chemotherapy alone (P=0.001), and between chemotherapy combined with AHSCT and chemoradiotherapy (P=0.040). Univariate analysis showed that the age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, Ann Arbor stage, B symptom, bulky disease, number of extranodal sites, Ki-67 index, lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), international prognostic index (IPI), therapeutic manner and chemotherapy combined with rituximab were significantly associated with the prognosis of advanced DLBCL patients (all P<0.05). Multivariate analysis demonstrated that the age >60 years, Ann Arbor stage IV, with B symptom, with bulky disease, ECOG PS≥1, Ki-67 index > 90%, CD5 expression, up-regulation of serum LDH and β2-MG, and chemotherapy without rituximab were related with the poor prognosis of patients with advanced-stage DLBCL (all P<0.05).@*Conclusions@#Chemotherapy combined with rituximab can improve the outcome of patients with advanced-stage DLBCL. The age, stage, B symptom, bulky disease, ECOG PS score, Ki-67 index, CD5 expression, LDH, β2-MG and chemotherapy combined with rituximab are associated with the prognosis of these patients.

Duration of filgrastim prophylaxis for chemotherapy-induced neutropenia and its predictors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the duration of preventive filgrastim administration as support for chemotherapy and its affecting factors.</p><p><b>METHODS</b>Single institutional data from a phase Ⅱ clinical trial and a phase Ⅲ clinical trial of pegylated filgrastim were combined. In the two randomized cross-over trials, patients with previously untreated cancer received two cycles of chemotherapy of the same regimen. In the study group, the patients received a single subcutaneous injection of 100 μg/kg pegylated filgrastim, and in the control group, they received daily subcutaneous injections of 5 μg/kg filgrastim.</p><p><b>RESULTS</b>In 53 chemotherapy cycles, the median duration of filgrastim administration was (9.57±2.10)d. 83.0% (44/53) of them received filgrastim for 7-11 days. Patients with baseline absolute neutrophil count of <4×10(9)/L or body mass index less than 22 received a longer filgrastim prophylaxis(P<0.05). RESULTS of multivariate analysis showed that the baseline absolute neutrophil count is associated with the time of filgrastim administration(P=0.019). The most common adverse event of rhG-CSF was skeletal pain, generally mild and no treatment-related death occurred.</p><p><b>CONCLUSIONS</b>The median duration of filgrastim support for chemotherapy was 10 days. Patients with lower baseline neutrophil count require a longer filgrastim prophylaxis.</p><p><b>TRIAL REGISTRATION</b>: ClinicalTrials.gov identifier, NCT01285219.</p>

Retrospective analysis of the clinical features and prognostic factors of 126 patients with primary gastric diffuse large B-cell lymphoma / 中国肿瘤临床

Objective:Primary gastric diffuse large B-cell lymphoma (PGLBCL) is a highly common subtype of extranodal non-Hodgkin lymphoma. We analyzed the disease's clinical features and prognosis to guide better treatment. Methods:We retrospectively collect-ed data from PGLBCL cases seen from January 1999 to March 2012 in one cancer center. We then analyzed the demographic character-istics, clinical stage, histological diagnosis, complications, treatment, and prognostic characteristics of such patients. Results:A total of 126 patients with median age of 49 years old (range:16-81 years) were included in the study. The male-to-female ratio was 68:58. A to-tal of 96 patients were pathologically diagnosed with pure diffuse large B-cell lymphoma (DLBCL), 27 with mucosa-assouated lymphoid (MALT) component, and 3 with plasmacytoid differentiation. Meanwhile, 90%of the patients were in the early stage of the disease. For the early-stage patients, treatment strategy included surgery+chemotherapy ± radiotherapy for 38 cases, chemoradiotherapy for 39 cases, chemotherapy alone for 37 cases, and surgery alone for 1 case. Under a median follow up of 48 months, the 4-year progres-sion free survival (PFS) and overall ourvival (OS) rate of the whole group were 75.6%and 82.7%, respectively. PFS rates for early and advanced stage patients were 77%and 41.7%(P=0.005), respectively. For the early-stage patients treated with chemotherapy alone, chemoradiotherapy, and surgery with therapy, the PFS rates were 67.3%, 77.8%, and 77.8%(P=0.588), respectively. The patients with international prognostic index (IPI) score of 0, 1, and>1 achieved PFS of 85.4%, 74.4%, and 55.6%(P=0.011), respectively. The PFS rates were 81.2%and 66.1%(P=0.018) for stagesⅠandⅡ, respectively, and 86.6%and 63.3%(P=0.006) for the normal and elevated LDH levels, respectively. The pathological type of pure DLBCL or a MALT component, GCB or non-GCB origin, and age more than 60 years old were not associated with prognosis. Conclusion:The majority of the PGLBCL patients were in the early stage of disease, but the outcome of early-stage disease was favorable. Surgery did not improve outcomes. Univariate analysis demonstrated that IPI score>1, stageⅡdisease, and elevated LDH levels were associated with poor prognosis in the early-stage patient.

Efficacy and safety evaluation of gemcitabine combined with ifosfamide in patients with advanced nasopharyngeal carcinoma after failure of platinum-based chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of gemcitabine combined with ifosfamide (GI regimen)in patients with recurrent or metastatic nasopharyngeal carcinoma after failure of platinum-based chemotherapy.</p><p><b>METHODS</b>The clinical data of 27 nasopharyngeal carcinoma patients, who received GI regimen between April 2005 and March 2014 after failure of prior platinum-based chemotherapy, were retrospectively reviewed,and relevant prognostic factors were explored.</p><p><b>RESULTS</b>All patients were evaluable for efficacy and toxicity. No patient achieved complete response (CR). Partial response (PR) was achieved in ten patients, stable disease (SD) in thirteen patients, progressive disease (PD) in four patients, with a response rate of 37.0% and an overall disease control rate (PR+SD) of 85.2%. For ten PR patients, the median duration of response was 5.5 months. The median progression-free survival of the whole group was 6.7 months, and the Kaplan-Meier estimate of median overall survival was 17.4 months. The 1-year survival rate was 72.6%. Toxicity was mainly hematological: Grade III or IV anemia, neutropenia and thrombocytopenia were found in 3.7%, 37.0% and 18.5% of all patients, respectively. Univariate and multivariate analyses indicated that dose intensity of gemcitabine was a significant prognostic factor for PFS, whereas salvage treatment after failure of GI regimen was a significant prognostic factor for OS.</p><p><b>CONCLUSIONS</b>Gemcitabine and ifosfamide combination is effective and well tolerated by patients with advanced nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Further clinical study is warranted.</p>

Autologous peripheral blood stem cell mobilization following dose-adjusted cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy alone or in combination with rituximab in treating high-risk non-Hodgkin's lymphoma / 癌症

<p><b>BACKGROUND</b>The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is an efficient treatment of non-Hodgkin's lymphoma (NHL). This study aimed to assess the efficacy and toxicity of dose-adjusted CHOP alone or in combination with rituximab (R-CHOP) by examining the stem cell mobilization in NHL patients. Factors affecting the collection of CD34+ cells were also explored.</p><p><b>METHODS</b>Our retrospective study included 39 patients eligible for autologous stem cell transplantation: 14 patients who expressed CD20 and were financially eligible received R-CHOP for autologous peripheral blood stem cell (APBSC) mobilization; the remaining 25 patients received CHOP.</p><p><b>RESULTS</b>The median CD34+ cell yield was 7.01×10(6) cells/kg body weight (range 1.49-28.39×10(6) cells/kg body weight), with only two patients failing to meet the target CD34+ cell harvest of ≥2.0×10(6) cells/kg body weight. The median number of apheresis procedures per patient was 1 (range 1-3). The APBSC mobilization yield of the CHOP group appeared to be higher than that of the R-CHOP group (P=0.005), whereas the success rate was similar between groups. R-CHOP elevated the complete response (CR) rate in B cell lymphoma patients as compared with CHOP (P=0.01). No significant differences in toxicity or engraftment were observed between the two groups.</p><p><b>CONCLUSION</b>The present study demonstrated that dose-adjusted CHOP chemotherapy effectively mobilized APBSCs in NHL patients and that the addition of rituximab to dose-adjusted CHOP chemotherapy elevated the CR rate for patients with B-cell lymphoma.</p>

Efficacy analysis of pegylated filgrastim as prophylaxis for chemo-therapy-induced neutropenia / 中国肿瘤临床

Objective:To compare the efficacy of a single injection of pegylated filgrastim with daily doses of filgrastim as pro-phylaxis for chemotherapy-induced neutropenia in Chinese cancer patients. Methods:Single-institution data from a phase 2 study and a phase 3 trial on pegylated filgrastim were combined to analyze the efficacy and safety parameters. In the two randomized crossover tri-als, patients with previously untreated cancers received two cycles of chemotherapy with identical regimen. In the study cycle, the pa-tients received a single subcutaneous injection of pegylated filgrastim (100 μg/kg), whereas those in the control cycle received daily subcutaneous injections of filgrastim (5μg/kg). Results:Among the 56 patients enrolled, 53 were evaluable for efficacy. These patients received one cycle with pegylated filgrastim prophylaxis and one cycle with filgrastim support each. Results indicated that 94.3%(50/53) of the cycles with pegylated filgrastim or filgrastim support did not develop grade 4 neutropenia. Moreover, febrile neutropenia did not occur in the cycles. The incidence rates of antibiotic administration were 7.5%(4/53) and 3.8%(2/53) in the pegylated filgrastim and filgrastim cycles, respectively (P=0.678). The median duration of filgrastim administration was 10 days (3-14 days). Generally, the safety profile of pegylated filgrastim is similar to that of filgrastim, including skeletal pain, pain at the injection site, palpitation, fever, and fatigue. Conclusion:A single dose of pegylated filgrastim demonstrated comparable efficacy with 10 consecutive doses of filgras-tim as prophylaxis for chemotherapy-induced neutropenia.

Clinical features and prognostic analysis of mantle cell lymphoma patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinical features, therapeutic outcome and prognostic factors of mantle cell lymphoma (MCL).</p><p><b>METHODS</b>Clinical data of a total of 68 patients with MCL admitted from August 2003 to June 2013 in our department were retrospectively analyzed.</p><p><b>RESULTS</b>Of all the patients, the median age was 58.5 years, with marked male predominance (2.8:1), 59 patients (86.8%) were in Ann Arbor stage III/IV. 56 cases (82.4%) primarily showed lymph node involvement, 49 cased showed extranodal involvement and 19 cases (38.8%) had bone marrow involvement. Patients were followed up for 4 to 122 months with a median follow up time of 35 months. The 3- and 5-year overall survival (OS) rates were 78.5% and 64.1%, respectively. The 2- and 3-year progression-free survival (PFS) rates were 41.3% and 23.7%, respectively, and the median time to progression was 20.0 months. The overall response rate (ORR) of CHOP regimen was superior to that of intense regimens (P = 0.036). Univariate analysis showed that stage III/IV,IPI score of 3-5, expression of Ki-67 higher than 30%, elevated LDH, elevated β2-MG, blastic variant, more than 5 lymph nodes involved, and failure to chemotherapy were the negative factors. Multivariate analysis showed that Ki-67 index, LDH and the response to chemotherapy were independent factors affecting survival.</p><p><b>CONCLUSIONS</b>Most patients with MCL were elderly males with advanced stage and usually had bone marrow involvement. Although ORR of CHOP regimen is superior to intense regimens, the prognosis of MCL remains poor.</p>

Efficacy analysis of different follow-up methods in detecting first recurrence of lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This study aimed to evaluate the value of different follow-up methods for the detection of first recurrence in lymphoma patients in first complete remission (CR), and to find reasonable long-term follow-up strategies.</p><p><b>METHODS</b>We retrospectively analyzed 277 lymphoma patients who achieved CR after first-line therapies and subsequently relapsed. All patients were divided into routine surveillance imaging group (group A) and irregular imaging follow-up visit group (group B). To compare the two groups of patients with tumor burden (tumor diameter and number of tumor invasion areas) at the time of relapse, and the number of imaging scans before the relapse. To analyze the main ways of finding lymphoma relapse in the two groups.</p><p><b>RESULTS</b>Among a total of 277 patients, there were 187 patients in the group A and 90 patients in the group B. The tumor recurrence occurred in 120 cases (43.3%) within the first year, and 76 patients (27.4%) in the second year. At the time of diagnosis of recurrence, the average maximum diameter of tumors in the groups A and B were (3.2 ± 2.2) cm and (3.8 ± 2.9) cm, respectively (P = 0.123). The two groups showed slight difference in number of tumor invasion areas (P = 0.050). At the time of diagnosis of recurrence, there were 3 of 121 patients (2.5%) with maximum diameter of tumors more than 8 cm in the group A and 6 of 49 cases (12.2%) in the group B (P = 0.018). In the group A, the patients had in average 4.9 times of imaging scans before recurrence, significantly more than the 0.22 times in the group B (P < 0.001). Among all patients, the diagnosis of recurrence was based on imaging scans only in 59 patients (21.3%).</p><p><b>CONCLUSIONS</b>Most lymphoma patients do not benefit from routine surveillance imaging to detect the tumor recurrence. It indicates that we should not rely solely on imaging examinations at follow-up visits, and should pay more attention on clinical signs and symptoms.</p>

Efficacy and safety evaluation of gemcitabine combined with oxaliplatin in lymphoma patients after failure of multiple chemotherapy regimens / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of gemcitabine combined with oxaliplatin (GEMOX) in lymphoma patients after failure of multiple chemotherapy regimens.</p><p><b>METHODS</b>The clinical data of 27 lymphoma patients, who received GEMOX regimen after failure of two or more prior chemotherapy regimens, were retrospectively reviewed. The predictive factors related to the clinical efficacy of GEMOX regimen were explored.</p><p><b>RESULTS</b>The efficacy could be evaluated in 24 patients. Complete response was obtained in 4 patients (16.7%), partial response in 7 patients (29.1%), stable disease in 6 patients (25.0%), and progressive disease in 7 patients (29.1%), with an overall response rate of 45.8%. Among the eleven CR and PR patients, four patients were with diffuse large B cell lymphoma, four patients with Hodgkin's lymphoma, one with peripheral T cell lymphoma, one with mantle cell lymphoma and one with gastric mucosa-associated lymphoid tissue lymphoma. The median PFS time of the whole group was 8 months (95%CI, 1.6-14.4 months). For 11 CR and PR patients who had response to the GEMOX regimen, the median PFS time was 19 months (95%CI, 11.1-26.8 months). Major adverse response was hematologic toxicity. Among them, grade III or IV neutropenia appeared in 16 patients (59.3%), and grade III or IV thrombocytopenia appeared in 11 patients (40.7%). The sensitivity to the last chemotherapy was related to the efficacy of GEMOX regimen. The response rate was 83.3% in patients who had response to the last chemotherapy, and only 31.2% in the patients who failed to the last chemotherapy (P = 0.001).</p><p><b>CONCLUSIONS</b>GEMOX regimen can get a better response rate in lymphoma patients after failure of multiple chemotherapy regimens, and with a good tolerance and acceptable safety. Some patients can get long-term survival. Patients sensitive to the last chemotherapy are more likely to benefit from GEMOX regimen.</p>

Separation and identification of flavonoids from fistular onion stalk (Allium fisturosum L. var. Caespitosum Makio) / 华中科技大学学报（医学）（英德文版）

The chemical constituents of fistular onion stalk obtained by supercritical CO(2) extraction were separated and purified by silica gel and sephadex LH-20 gel column chromatography and the preparative TLC method and four flavonoids were obtained. On the basis of the spectral data, they were structurally identified as (+)-catechin, (-)-epicatechin, astragalin, and 3-O-beta-D(2-O-beta-D-glucopyranosyl)-glucopyranosides of kaempferol.

Development and evaluation of the sinomenine transdermal patch

Sinomenine transdermal patch was prepared and its properties were studied. The patches were produced by salivation method. The releasing rate in vitro of the patch was determined by HPLC. Peel test was used to evaluate the adhesion. Acute skin irritation test was performed in comparison with formalin [0.8%] by using mouse model. The Sinomenine TDDS Patch was prepared. The releasing rate in vitro followed the Higuchi equation [r>0.99], the releasing amount was beyond 90% in 24h. The peel adhesion to steel [N/25 mm] is 10 or above. The skin irritation tests showed negligible erythema and edema. The Sinomenine transdermal patch was prepared successfully and it may be beneficial for topical use

Construction and expression of extracellular domain of human death receptor 5 and detection of its biological activity / 中国肿瘤生物治疗杂志

Objective: To construct the expressing vector of the extracellular domain of death receptor 5 (DR5), express it E.coli, identify the purified DR5 protein, and study its biological activity. Methods: The extracellular domain of DR5(eDR5) was assembled by overlapping PCR. The expression vector pET-22b(+)/ DR5 was constructed and transformed into E.coli BL21(DE3). The expression of eDR5 protein was induced by IPTG and purified by Ni 2+ -affinity chromatographic column. The purity and specificities were detected by SDS-PAGE and ELISA, respectively. The blocking effects of purified eDR5 on FMU1.5-induced apoptosis of U343, U373 cells were observed. Results: The extracellular domain of DR5 was obtained by overlapping PCR. The eDR5 protein was expressed in both supernatants and inclusion bodies with a yield more than 30% of total bacterial proteins. The purity of eDR5 was more than 95% and the yield reached 9 mg/ml. The result of ELISA showed the purified protein was eDR5. Purified eDR5 partially blocked the apoptosis of U343 cells induced by FMU1.5 and TRAIL. Conclusion: The successful construction, expression, and purification of the extracellular domain of DR5 protein lays a foundation for further study of DR5 function.

Studies on the chemical constituents of the roots of Rhododendron molle G. Don / 华中科技大学学报（医学）（英德文版）

The compounds from the root of Rhododendron molle G. Don were isolated, purified by various chromatographic techniques, and their structures were identified according to the physical and chemical features and spectral data. Three compounds were separated from the root of Rhododendron molle G. Don and identified as Rhodojaponin-III, taraxerol, beta-sitosterol for the first time.

Studies on the chemical constituents of the roots of Rhododendron molle G. Don / 华中科技大学学报（医学）（英德文版）

The compounds from the root of Rhododendron molle G. Don were isolated, purified by various chromatographic techniques, and their structures were identified according to the physical and chemical features and spectral data. Three compounds were separated from the root of Rhododendron molle G. Don and identified as Rhodojaponin-III, taraxerol, beta-sitosterol for the first time.

Anti-human DR5/DR4 monoclonal antibody induce glioma cell lines apoptosis / 中国免疫学杂志

Objective:To study the cytotoxic effects on three glioma cell lines U343, U138, U373 induced by anti-human DR5/DR4 monoclonal antibodies(FMU1.5/FMU1.4) and the underlying mechanism.Methods:Expression of DR4/DR5 was quantitated by flow cytometry and DR/4DR5 mRNA detected by RT-PCR. Cytotoxicity exerted by FMU1.4/FMU1.5 on three cell lines was measured by MTT colorimetry and the induced apoptosis was determined by agarose gel electrophoresis, DNA ploidy analysis was studied by flow cytometry.Results:The expression of DR5 on U343 cells was higher and the expression of DR4 on U373 cells was lower. Cell line U343 was sensitive to FMU1.5 and in a dose dependent manner, but it was partially sensitive to FMU1.4; Cell line U138 was partially sensitive to FMU1.5 and resistant to FMU1.4; Cell line U373 was insensitive to two antibodies.Conclusion:Apoptosis induced by monoclonal antibodie FMU1.4/FMU1.5 vary among three cell lines. The underlying mechanism may be relevant to DR4/DR5 expression,the release of cytochrome C and FLIP.