Objective:To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in CHOP regimen for un-treated elderly patients with advanced diffuse large B-cell lymphoma (DLBCL). Methods:In a prospective phase II study, we analyzed the feasibility of PLD-modified CHOP regimen in elderly patients with advanced stages of DLBCL. PLD was administered at 30 mg/m2 in combination with cyclophosphamide, vincristine, and prednisone at standard doses every 21 d for six cycles. CD20 positive patients were given option for rituximab treatment. Results:From November 2011 to March 2014, 30 patients with a median age of 70 years (range:63 to 80) were enrolled in this study. Up to 24 cases (80.0%) obtained an International Prognostic Index of≥3. The overall re-sponse rate was 86.7%, and the complete remission rate was 66.7%. With a median follow-up of 20.1 months, the 18-month overall and progression-free survival rates were 82.4%and 70.1%, respectively. The main toxicity was neutropenia, reaching grades 3 to 4 in the 24 cases (80.0%). No significant changes existed in patients' left ventricular ejection fraction and serum troponin-T during the study. Four patients (13.3%) showed asymptomatic abnormal changes in electrocardiogram after PLD infusion. Conclusion:CHOP regimen with PLD is an effective alternative for the treatment of DLBCL in elderly patients, exhibiting an acceptable toxicity.

Roles of sympathicus, sensory neuropeptides (SNP), metabolites of cyclooxygenase, metabolites of lipoxygenase, endothelium derived relaxing factor (EDRF), reactive oxygen (ROS) and potassium channels (PC) in the hypoxic pulmonary vasoconstriction (HPV) and hypoxic cerebral vasodilation (HCVD) were studied in intact rats, rabbits and dogs. Results were as follows: during hypoxia, the excitation of sympathicus results in a constriction of both pulmonary and cerebral vessels; SNP, EDRF and the opening of 4-AP sensitive PC caused the dilation of both of them; metabolites of lipoxygenase mediated HPV and HCVD, whereas metabolites of cyclooxygenase were their modulators; hypoxia induced blockade of the ATP sensitive PC mediated HPV, but had no effect on HCVD; reduction of O_2~+ in the lung might potentiate HPV, but had no effect on HCVD. It is suggested that the alteration of lipoxygenase metabolites, ROS and ATP sensitive PC are factors accounting for the difference in response of pulmonary and cerebral vassels to hypoxia.

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.

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.

OBJECTIVETo analyze the clinical features, therapeutic outcome and prognostic factors of mantle cell lymphoma (MCL).

METHODSClinical data of a total of 68 patients with MCL admitted from August 2003 to June 2013 in our department were retrospectively analyzed.

RESULTSOf 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.

CONCLUSIONSMost 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.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide ; Disease Progression ; Disease-Free Survival ; Doxorubicin ; Female ; Humans ; Lymphoma, Mantle-Cell ; diagnosis ; Male ; Middle Aged ; Multivariate Analysis ; Prednisolone ; Prognosis ; Retrospective Studies ; Survival Rate ; Vincristine

OBJECTIVETo analyze the duration of preventive filgrastim administration as support for chemotherapy and its affecting factors.

METHODSSingle 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.

RESULTSIn 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.

CONCLUSIONSThe median duration of filgrastim support for chemotherapy was 10 days. Patients with lower baseline neutrophil count require a longer filgrastim prophylaxis.

TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01285219.

Antineoplastic Agents ; adverse effects ; Cross-Over Studies ; Filgrastim ; adverse effects ; therapeutic use ; Hematologic Agents ; adverse effects ; therapeutic use ; Humans ; Induction Chemotherapy ; Injections, Subcutaneous ; Multivariate Analysis ; Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; prevention & control ; Time Factors

OBJECTIVETo evaluate the efficacy and safety of gemcitabine combined with oxaliplatin (GEMOX) in lymphoma patients after failure of multiple chemotherapy regimens.

METHODSThe 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.

RESULTSThe 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).

CONCLUSIONSGEMOX 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.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Deoxycytidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Follow-Up Studies ; Hodgkin Disease ; drug therapy ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Lymphoma, Mantle-Cell ; drug therapy ; Lymphoma, Non-Hodgkin ; drug therapy ; Lymphoma, T-Cell, Peripheral ; drug therapy ; Male ; Middle Aged ; Neutropenia ; chemically induced ; Organoplatinum Compounds ; adverse effects ; therapeutic use ; Remission Induction ; Salvage Therapy ; Thrombocytopenia ; chemically induced ; Young Adult

OBJECTIVEThis 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.

METHODSWe 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.

RESULTSAmong 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%).

CONCLUSIONSMost 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.

Follow-Up Studies ; Humans ; Lymphoma ; diagnosis ; Neoplasm Recurrence, Local ; Neoplasms ; Remission Induction ; Retrospective Studies

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.

BACKGROUNDThe 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.

METHODSOur 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.

RESULTSThe 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.

CONCLUSIONThe 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.

Antibodies, Monoclonal, Murine-Derived ; Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide ; Doxorubicin ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, B-Cell ; Lymphoma, Non-Hodgkin ; Prednisolone ; Prednisone ; Remission Induction ; Retrospective Studies ; Rituximab ; Vincristine