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The over-activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamcyin (mTOR) pathway is closely related to the occurrence, development and clinical prognosis of malignant tumors. Taking this signal pathway as a target can effectively inhibit tumor progression. At present, the Food and Drug Administration of the United States has approved three drugs (CAL-101, BAY80-6946, IPI-145) for the treatment of recurrent and refractory indolent non-Hodgkin lymphoma, which demonstrates significant efficacy and a manageable safety profile.
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Objective:To investigate the prognostic significance of D-dimer level in patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 70 newly diagnosed DLBCL patients who were admitted to Tianjin People's Hospital from January 2015 to June 2019 were retrospectively analyzed. The optimal cut-off value of D-dimer for survival was determined according to the receiver operating characteristic (ROC) curve, and the patients were grouped. The differences of coagulation related indexes and clinicopathological features between patients with different D-dimer levels were compared. Kaplan-Meier method was used for univariate analysis of overall survival (OS), and Cox regression model was used for multivariate analysis of OS.Results:According to ROC curve, the best cut-off value of D-dimer for survival was 0.75 mg/L. The proportion of patients with different clinical staging, international prognostic index score, lactate dehydrogenase level had statistically significant differences between the D-dimer ≥0.75 mg/L group (36 cases) and <0.75 mg/L group (34 cases) (all P < 0.05). The prothrombin time of D-dimer ≥ 0.75 mg/L group and < 0.75 mg/L group were (13.5±0.9) s and (13.0±0.8) s, respectively, and the activated partial thromboplastin time were (37±5) s and (34±6) s, respectively,and the differences were statistically significant (all P < 0.05). Univariate analysis showed that the 5-year OS rates of DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ, international prognostic index score > 2, lactate dehydrogenase level > 240 U/L, B symptoms, D-dimer level ≥0.75 mg/L were decreased (all P < 0.05). Multivariate Cox regression analysis showed that D-dimer ≥0.75 mg/L was an independent risk factor for OS of DLBCL patients ( HR=0.368, 95% CI 0.144-0.944, P= 0.038). Conclusion:The level of D-dimer can be used as a clinical indicator to judge the prognosis of DLBCL patients, and the prognosis of patients with high D-dimer level is poor.
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At present, there are few treatment protocols with limited efficacy for relapsed and refractory non-Hodgkin lymphoma (NHL). Histone deacetylase inhibitors (HDACi) exert anti-tumor effects by inhibiting the activation of histone deacetylase (HDAC) and regulating gene expression. HDACi alone or combined with other anti-tumor drugs have shown good efficacy in the treatment of relapsed and refractory NHL. This article reviews the progress of HDACi in the treatment of NHL.
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Objective: To investigate the prognostic value of prognostic nutritional index (PNI) in patients with diffuse large B-cell lym-phoma (DLBCL). Methods: We retrospectively reviewed the medical records of 82 patients with DLBCL treated at Tianjin Union Medi-cal Center between June 2010 and June 2016. The optimal cutoff value of PNI was determined using a receiver operating characteristic (ROC) curve and the Youden index. The relationship of high and low PNI with the clinical characteristics of the patients, therapeutic ef-ficacy, and prognosis were analyzed. Results: Overall, mean PNI of the patients was 46.17±8.8. When the PNI was 44.15, the Youden in-dex was found to be maximal, with a sensitivity of 74.6% and specificity of 67.2%. There were 38 patients (46.3%) in the low PNI group (<44.15) and 44 patients (53.7%) in the high PNI group (≥44.15). Data analysis showed that PNI was correlated with Eastern Coopera-tive Oncology Group performance status (ECOG PS), Ann Arbor stage, international prognostic index (IPI) score, and lactic acid dehydro-genase (LDH) level (P<0.05). The total effective rate of the low PNI group was significantly lower than that of the high PNI group (65.8% vs. 86.4%; χ2=4.848; P=0.028). The 3-year overall survival (OS) rate of the entire group of patients was 69.1%. The 1-, 2-, and 3-year OS rates of the low PNI group (86.8%, 67.8%, and 56.9%, respectively) were significantly lower than that of the high PNI group (96.7%, 89.5%, and 80.2%, respectively; χ2=9.421, P=0.002). Univariate analysis showed that PNI<44.15, ECOG PS≥2, IPI>2, stageⅢ/Ⅳ, and lymphocyte count<1.0×109/L had a significant impact on predicting OS (P<0.05). Multivariate analysis showed that PNI<44.15 (P=0.006) and stageⅢ/Ⅳ(P=0.011) were independent factors for predicting OS. Conclusions: PNI might be used as a simple and feasible clinical prognostic indicator in patients with DLBCL.
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Objective To investigate the correlation between baseline serum lipid levels and hematoma enlargement in patients with acute intracerebral hemorrhage (ICH). Methods From October 2013 to January 2018, patients with ICH admitted to the Department of Neurosurgery, Heze Municipal Hospital, were enrolled retrospectively. The first CT scan was completed within 6 h after onset, and the second one was completed at 48 h after onset. Hematoma enlargement was defined as an increase >33 % in the volume of hematoma on CT. The demographic and baseline clinical data in the hematoma enlargement group and the non -hematoma enlargement group were compared. Multivariate logistic regression analysis was used to identify the independent risk factors for hematoma enlargement. Results A total of 470 patients with acute ICH were enrolled, including 187 females (39.8%) and 283 males (60.2%), aged 47-81 years. Seventy-nine patients (16.8%) had hematoma enlargement. The proportion of patients with atrial fibrillation and who used warfarin before onset, as well as age, baseline National Institutes of Health Stroke Scale score, baseline hematoma volume, international normalized ratio, prothrombin time, activated partial thromboplastin time, and thrombin time of the hematoma enlargement group were significantly higher than those of the non -hematoma enlargement group ( all P< 0.05 ), while from the onset to the first CT scan time, total cholesterol, triglyceride, low-density lipoprotein cholesterol levels were significantly lower than those in the non- hematoma enlargement group (all P<0.05). Multivariate logistic regression analysis showed that baseline total cholesterol <3.20 mmol/L (odds ratio [ OR] 1.32, 95% confidence interval [ CI] 1.08-1.83; P=0.004), baseline hematoma volume≥30 ml (1.76,95% CI 1.30-2.15; P<0.001), and using anticoagulant before onset ( OR 2.37, 95% CI 1.81-3.02; P<0.001 ) had significantly independent correlation with hematoma enlargement. Conclusion Baseline total cholesterol <3.20 mmol/L, hematoma volume ≥30 ml, and using anticoagulant before onset were the independent risk factors for hematoma enlargement in patients with acute ICH.
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Objective To evaluate the efficacy and safety of neurokinin1 (NK1) receptor antagonist aprepitant combined with prednisone and tropisetron in prevention of nausea and vomiting (CINV) induced by R-CHOP or CHOP regimen. Methods A total of 90 patients with diffuse large B-cell lymphoma (DLBCL) who accepted R-CHOP or CHOP regimen in the People''s Hospital of Tianjin from October 2015 to January 2016 were divided into aprepitant group (45 cases) and the control group (45 cases) according to the random number table. In aprepitant group, day 1: aprepitant 125 mg 1 h before chemotherapy, prednison 100 mg, tropisetron 10 mg, and tropisetron 5 mg 2 hours after chemotherapy;day 2-3:aprepitant 80 mg and prednison 100 mg, tropisetron 10 mg; day 4-5: prednison 100 mg. In the control group, day 1: prednison 100 mg 1 h before chemotherapy, tropisetron 10 mg, and tropisetron 5 mg 2 h after chemotherapy; days 2-3: prednison 100 mg, tropisetron 10 mg; day 4-5: prednison 100 mg. Data on nausea, vomiting and remission treatment were collected every day. The complete remission (CR) rates of CINV without vomiting and remission drugs in the whole cycle were recorded. Functional living index-emesis questionnaire (FILE) was used to assess the effect of CINV on the life quality of the patients. Results CR in aprepitant group was higher than that in the control group (77.8 ％ vs. 55.6 ％, χ2= 5.000, P= 0.025). The rate of no vomiting in aprepitant regimen was higher than that in the control regimen (82.2 ％ vs. 62.2 ％, χ2 = 4.486, P= 0.034). The average scores of FILE between the two groups were (113 ±10) and (100 ±11) scores respectively, and there was a significant difference (t=12.437, P<0.001). The related adverse reactions of vomiting-stopping drugs in both groups had no statistical difference. Conclusion The aprepitant combined with tropisetron and prednisone can improve effectively nausea and vomiting induced by R-CHOP or CHOP chemotherapy regimen for DLBCL patients.
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Objective:To compare the therapeutic efficacy and safety of Hyper-CVAD/MA regimen and CHOP/CHOP-like regimen in the treatment of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Methods:The 78 primary PTCL-NOS patients who were initially diagnosed and treated in Tianjin Medical University Cancer Institute and Hospital and Tianjin Union Medical Center from June 2004 to June 2012 were retrospectively analyzed. The patients were then divided into two groups:Hyper-CVAD/MA group (n=21) and CHOP/CHOP-like group (n=57). Curative efficacies and toxicities were analyzed by Chi-square test, and survival was estimated by Ka-plan-Meier method. Results: In the Hyper-CVAD/MA group, complete response (CR) was 42.9%, overall response rate (ORR) was 85.7%, median progression-free survival (PFS) was 20 months, and the three-year overall survival (OS) was 56.9%. In the CHOP/CHOP-like group, the CR, ORR, and three-year OS were 28.1%, 59.6%, and 49.6%, respectively, and the median PFS was 13 months. Compara-tive analysis showed that the ORR and three-year OS were statistically significant (P0.05). The incidence rates ofⅢ/Ⅳneutrocytopenia and thrombocytopenia in Hyper-CVAD/MA group (66.7%and 61.9%, respectively) were significantly higher than those of the CHOP/CHOP-like group (22.8%and 14.0%, respec-tively) (P<0.05). Conclusion:Hyper-CVAD/MA regimen can achieve satisfactory efficacy in parents with PTCL-NOS, and toxicity can be controlled with granulocyte colony stimulating factor (G-CSF).
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Indolent B-cell lymphomas constitute a slow growing cancer of the lymphatic system. These lymphomas mainly include fol-licular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenstom macroglobulinemia, marginal zone lym-phoma, and low malignant mantle cell lymphoma. These lymphomas are sensitive to chemotherapy and/or immunochemotherapy, but they cannot be cured. Furthermore, patient age at diagnosis, patient age at time of first onset or subsequent relapses, and compli-cations often influence the chemotherapy curative effect. At present, recent progress has been achieved in our understanding of dys-regulated pathways and immunologic anti-tumor responses in indolent lymphoma. In particular, the breakthrough of non-cytotoxic drugs renderschemo-freetreatment a near-future reality. In this review, we highlight these promising approaches, such as the com-bination of anti-CD20 antibodies with immunomodulatory drugs, mAbs directed against other surface antigens, and programmed cell death 1 (PD-1) receptor inhibitor or B-cell receptor signaling pathway inhibitors. Future phase III studies will evaluate the efficacy of these drugs in the context of non-chemotherapy and further clarify treatment status.
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The standard therapy for relapsed/refractory Hodgkin lymphoma (RR-HL) consists of salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT). Salvage therapy is not obviously superior to commonly used regimens such as BEAM, CBV, and IGEV. Functional imaging with 18F-fluoro-2-deoxy-D-glucose positron emission tomogra-phy scanning is a critical predictor of the outcome after the completion of salvage chemotherapy and before ASCT. Meanwhile, re-duced-intensity conditioning allogeneic stem cell transplantation may induce a strong response in some patients with relapsing or pro-gressing HL after ASCT. In this study, we reviewed some problems in hematopoietic stem cell transplantation for treating RR-HL.
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Objective:To evaluate the efficacy and toxicity of single-agent bendamustine in patients with indolent B-cell non-Hodgkin's lymphoma (NHL) refractory to rituximab. Methods:Between April 2010 and April 2013, 100 patients with rituximab-refrac-tory indolent B-cell NHL from 8 institutions were enrolled. Bendamustine was administered at 120 mg/m2 on days 1 and 2 every 21 days for 6-8 cycles. The primary endpoint was the overall response rate (ORR). The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results:One hundred patients with a median age of 56 (rang-ing from 28 to 74) years were recruited in this clinical study. The total number of chemotherapy was 447 cycles, and the median number was 4 cycles. Ninety-three patients could be evaluated for efficacy. Fifteen patients (16.1%) had complete remission (CR), 52 (55.9%) had partial remission (PR), 22 (23.7%) had stable disease (SD), and 4 (4.3%) had progression disease (PD). The ORR and DCR were 72%and 95.7%, respectively. After a median follow-up of 26.6 months (ranging from 2 to 48.4 months), 59 patients (63.4%) had PD.The median PFS was 8.53 (95%CI:6.518-10.542) months, and PFS rate for 1 year was (40.6±5.3)%. Forty-eight patients (48%) had 3/4 grade adverse events, including leucopenia (26%), neutropenia (24%), and anemia (11%). Conclusion:Single-agent bendamustine produced a high rate of objective responses in patients with rituximab-refractory indolent B-cell NHL and could be one of the new op-tions for second-line treatment of these patients. The most common adverse event is hematologic toxicity.