Clinical Significance of EBV-DNA Copy Number in EBV Positive Lymphoma Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of EBV-DNA copy number on the prognosis of patients with EBV positive lymphoma.@*METHODS@#Clinical data of 109 patients diagnosed as EBV positive lymphoma in Tianjin Medical University Cancer Institute and Hospital from January 2010 to January 2020 were enrolled and analyzed retrospectively. Kaplan-Meier analysis was used for survival analysis, Log-rank was used to compare the clinical characteristics between the patients in different groups, and Cox regression was used for multivariate analysis.@*RESULTS@#Among the 109 patients with EBV-positive lymphoma, the medium age were 56 (range 15 to 83) years old. 29 patients at Ann Arbor stage I-II while 80 patients at stage III-IV. The average value of EBV-DNA was 1 023 510 IU/ml, 7 patients were higher than the average value, while 102 patients were lower. KM survival analysis showed that OS and PFS in patients with EBV-DNA above average level were shorter than those in patients with EBV-DNA below average level (OS: P=0.048, PFS: P=0.001), EBV-DNA copy number was a factor affecting the prognosis of patients. In addition, LDH level showed positive correlation with EBV-DNA copy number (r=0.650), which was also one of the factors affecting OS (P=0.053).@*CONCLUSION@#EBV-DNA copy number and LDH level can influence the prognosis of EBV positive lymphoma patients. Therefore, detection of EBV-DNA copy number in peripheral blood is important for evaluate the prognosis the patients.

Clinical Characteristics of 219 Patients with Primary Gastrointestinal Non-Hodgkin's Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical and pathological characteristics of primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL) patients, and to explore the factors affecting the patients' survival and prognosis.@*METHODS@#The clinical data of 219 patients with PGI-NHL diagnosed in our hospital from March 2009 to April 2016 was collected and retrospectively analyzed. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison among the groups, and Cox regression was used for multivariate analysis.@*RESULTS@#Among the 219 patients with PGI-NHL, 126 patients were males and 93 patients were females. 182 patients were IPI 0 to 2 and 37 patients were IPI 3 to 5. There were 205 cases (93.6%) of B cell phenotype and 14 cases (6.4%) of T cell phenotype. 140 patients (63.9%) were patients with primary gastric NHL, including 85 DLBCL and 19 MALT. 79 cases (36.1%) were patients with primary intestinal NHL, including 46 DLBCL, 4 MALT, 7 FL, 3 MCL and 4 Burkitt lymphoma. 23 cases were HP positive and received anti-HP therapy. 57 cases and 32 cases received surgery and chemotherapy respectively. 84 cases received combination treatment of surgery and chemotherapy and 11 cases received combination treatment of radiotherapy and chemotherapy. Overall survival (OS) of indolent B-cell non-Hodgkin's lymphoma was longer than that of invasive B-cell non-Hodgkin's lymphoma, which shows better prognose. Kaplan-Meier analysis showed that there was no difference between progression-free survival (PFS) and OS in the patients with different origin sites, age and sex. There was no significant difference in PFS between B-cell and T-cell-derived patients, whereas OS of B-cell-derived PGI-NHL patients was longer than that of T-cell-derived PGI-NHL patients. The OS and PFS of patients with IPI 0-2 were longer than those of patients with IPI 3-5. According to Lugano and Ann Arbor staging systems, there was no difference in prognosis of patients between phase I/II and III/IV. The prognosis of patients treated with surgery alone was worse than that of patients treated with combination therapy, and the prognosis of patients with surgery combined with chemotherapy was not significantly different from that of patients with chemotherapy alone.@*CONCLUSION@#B-cell phenotype, indolent and low IPI score lymphoma indicate better prognosis, while that of different origin site, sex and age shows no different in prognosis. Surgery is used only for emergency case or pathological materials, and these patients should be treated with chemotherapy-based combined treatment.

Prognostic evaluation of P53 and BCL2 proteins in MYC/BCL2 double expression DLBCL / 中华血液学杂志

Objective: To investigate the strong expression (S+) of P53 and BCL2 proteins in MYC/BCL2 double-expression DLBCL (DEL) and whether they can be used for the prognostic evaluation and stratified diagnosis of DELs. Methods: Tissue microarray were made by filed FFPE blocks of 174 DLBCL cases. The translocation of MYC, BCL2 and BCL6 genes were detected by FISH, and the proteins were detected by IHC. Data of clinicopathologic features and follow up of patients were collected and OS (overall survival) and PFS (progression free survival) were analyzed by statistics. Results: Eight double-hit lymphomas (DHLs) were identified in all cases, and 45 DELs were selected from 166 remaining cases, which have no significant difference in OS and PFS compared with non-DEL cases (P=0.668 and P=0.790) . Of 42 DEL-cases with follow up data, 24 cases with P53+ or/and BCL2 (S+) are significantly shorter OS and PFS than others (P=0.003 and P=0.000) , in which the cases with P53+/BCL2 (S+) co-expression were the worst prognosis, and P53/BCL2 co-weaker positive DEL cases even have superior OS and PFS than those non-DELs. Although statistics showed that the cases of P53+ or/and BCL2 (S+) have a lower OS and PFS in total cases (P=0.063 and P=0.024) , it is not the case when the DEL-cases take out from total cases, that is the cases with P53+ or/and BCL2 (S+) are as similar OS and PFS as others in non-DEL group (P=0.590 and P=0.550) . Conclusion: The strong expression of P53 and BCL2 proteins can be used as indicators of stratified diagnosis and poor prognosis of DEL.

Expression and prognostic value of regulatory T cells and M2 macrophages in diffuse large B-cell lymphoma tissues / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the prognostic value of regulatory T cells (Tregs) and M2 macrophages in diffuse large B-cell lymphoma (DLBCL) tissues.</p><p><b>METHODS</b>The expression of CD163 and Foxp3 was detected by immunohistochemistry in 92 cases of DLBCL, and it was statistically analyzed whether their expressions correlate with clinical data and prognosis in patients with DLBCL.</p><p><b>RESULTS</b>The density of M2 macrophage and regulatory T cells in DLBCL tumor tissues was significantly higher than that in the adjacent tissues (P = 0.02, P = 0.04). The expression of M2 macrophages was significantly positively correlated with regulatory T cells expression (r = 2.012, P < 0.05). High density of M2 or Tregs had a relationship with extranodal involvement (P < 0.05). Cox regression analysis showed that the expressions of CD163 and Foxp3 were independent prognostic factors of DLBCL (P < 0.05).</p><p><b>CONCLUSIONS</b>Combined detection of the expression of CD163 and Foxp3 proteins and then evaluation of the amount of M2 macrophages and Tregs can be used to more closely predict the prognosis for DLBCL patients.</p>

Prognostic factors of nasal NK/T-cell lymphoma / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the prognostic predictors of nasal NK/T cell lymphoma.</p><p><b>METHODS</b>Records of 80 patients with nasal NK/T cell lymphoma were analyzed retrospectively. The correlation between clinical and haematological factors and prognosis was analyzed with univariate and multivariate analysis.</p><p><b>RESULTS</b>After treatment, 33 of 80 patients achieved complete response, the 5-year overall survival and progression free survival were 52.5% and 32.5%, respectively. In univariate analysis, Eastern Cooperative Oncology Group performance status, Ann Arbor stage, local tumor invasion out of the nasal cavity, international prognostic index, complete response rate to the primary treatment, treatment model, lactate dehydrogenase (LDH),β2-microglobulin level, globulin and white blood cell were found to be the prognostic factors. Multivariate analysis indicated that unfavorable prognostic factors included complete response rate to the primary treatment (χ(2) = 17.109, P < 0.01), LDH(χ(2) = 15.695, P < 0.01), and local tumor invasion out of the nasal cavity (χ(2) = 13.503, P < 0.01).</p><p><b>CONCLUSION</b>Complete response rate to the primary treatment, elevated plasma LDH and tumor invasion out of the nasal cavity may be independent prognostic factors for NK/T cell lymphoma.</p>

Efficacy and survival status of retuximab-NCE regimen treatment in patients with relapsed or refractory B cell non-Hodgkin's lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to analyze the efficacy and toxicity of RNCE regimen in the treatment of relapsed or refractory B cell non-Hodgkin's lymphoma (NHL).</p><p><b>METHODS</b>From January 2000 to December 2005, 46 patients with relapsed or refractory B cell NHL were treated by RNCE regimen with or without radiotherapy for the involved field. The clinical characteristics, response, toxicity and long-term survival results were analyzed retrospectively.</p><p><b>RESULTS</b>A total of 46 patients were eligible. The complete response rate of second-line therapy was 52.17% (24/46), and the overall response rate was 82.61% (38/46). The median follow-up duration in this series was 69 months (range:6 to 102 months). The overall 1, 3, 5-year survival rate was 74.8%, 48.3%, 40.1%, respectively, with a median survival time of 30.2 months (5 to 65 months), and median progression free survival time of 10.9 months (2 to 31 months). The major toxicities were myelosuppression, GI toxicity, fatigue, fever and alopecia.</p><p><b>CONCLUSION</b>Our data show that RNCE regimen treatment is effective and well tolerated in patients with relapsed or refractory B cell non-Hodgkin's lymphoma.</p>

Expression of Cdc7 and mcm2 as a marker for proliferation and prognosis in diffuse large B cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to assess the expression of cell division cycle 7 (Cdc7) kinase and minichromosome maintenance protein 2 (MCM2) in diffuse large B cell lymphoma (DLBCL) and explore their relationship with prognosis of DLBCL patients.</p><p><b>METHODS</b>Clinical data of 60 DLBCL patients treated in our hospital from 2008.1 to 2010.1 were collected. The expression levels of Cdc7 and MCM2 in peripheral blood and bone marrow were determined by real-time PCR. A statistical analysis was carried out to evaluate their association with prognosis in DLBCL patients.</p><p><b>RESULTS</b>The 2-year survival rate of patients with high expression of peripheral blood Cdc7 was 38.3% and those with low expression 65.4% (P = 0.001). The 2-year survival rate of patients with high expression of bone marrow Cdc7 was 37.2% and those with low expression was 75.5% (P = 0.032). The 2-year survival rate of patients with high expression of MCM2 in peripheral blood was 44.0% and those with low expression was 68.2% (P = 0.025). The 2-year survival rate of patients with high expression of MCM2 in bone marrow was 39.0% and those with low expression was 63.4% (P = 0.007). A poor disease specific survival was observed in DLBCL patients with high level expression of Cdc7 and MCM2.</p><p><b>CONCLUSIONS</b>Cdc7 and MCM2 expression can be used to assess tumor proliferation and may be useful as an additional marker in combination with conventional markers in prediction of the outcome of DLBCL patients. Moreover, the Cdc7 and MCM2 signal pathway might be useful as a new approach in the treatment of refractory DLBCL lymphoma patients.</p>

Nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the role of nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>The clinical data of 37 NSCLC patients who received nimotuzumab in combination with chemotherapy in Tianjin Medical University Cancer Hospital from January 2009 to October 2010 were retrospectively reviewed. Of the thirty-seven patients, 12 patients were in stage III B, 25 patients in stage IV. Twenty-four patients recived platinum-based chemotherapy in combination with nimotuzumab, 13 patients recived nonplatinum-based chemotherapy in combination with nimotuzumab. Ten patients received nimotuzumab in combination with chemotherapy as first-line regimen, 23 patients as second-line regimen, 4 patients as third-line regimen.</p><p><b>RESULTS</b>Of the 37 advanced NSCLC patients who received nimotuzumab in combination with chemotherapy, the total number of chemotherapy were 137 cycles, the mean number was 3.7 cycles. One patient had complete remission (CR), 9 patients had partial remission (PR), 16 cases had stable disease (SD), and 11 patients had progressive disease (PD). The response rate (RR) was 27% and clinical benefit rate (CBR) was 70.3%. The main side effects were bone marrow suppression and gastrointestinal reactions. Grade I acneiform rash was found in one patient.</p><p><b>CONCLUSION</b>The regimen of nimotuzumab in combination with chemotherapy can improve the response rate and was well tolerated in patients with advanced non-small cell lung cancer.</p>

High-dose chemotherapy/autologous stem cell transplantation for nasopharyngeal T cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the role of high-dose chemotherapy (HCT)/autologous stem cell transplantation (ASCT) for nasopharyngeal T cell lymphomas.</p><p><b>METHODS</b>A retrospective review of 51 patients who underwent HCT/ASCT between January 1995 and January 2007.</p><p><b>RESULTS</b>Of the 51 patients who underwent ASCT, no treatment-related death was seen; sixteen patients relapsed after transplant, two patients are still alive through salvage chemotherapy 91 months and 56 months after relapse, the other fourteen patients died in tumor progression. 1-year, 3-year and 5-year overall survival (OS) rates were 98.0%, 84.0% and 72.0%, respectively. 1-year, 3-year and 5-year progression-free survival (PFS) rates were 90.2%, 78.4%and 66.7%, respectively. Univariate analysis showed that clinical stage, B symptom and IPI were prognostic factors for patients with nasopharyngeal T cell lymphomas, the P value being 0.041, 0.036 and 0.031, respectively.</p><p><b>CONCLUSION</b>High-dose therapy/autologous stem cell transplantation can improve cure rate and prolong survival time significantly in patients with nasopharyngeal T cell lymphomas.</p>

Killing effect of interleukin-18-enhanced FasL-expressing colon cancer cells on human hepatocytes in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the influence of mutual interactions between FasL expressed by colon carcinoma cells and endogenous cytokines interleukin-18 on liver metastasis and invasion of human colon cancer cells.</p><p><b>METHODS</b>Using immunohistochemical streptavidin-biotin complex (SABC) method, the expressions of Fas receptor and Fas ligand in SW620 colon carcinoma cells and Chang liver cells were observed so as to provide morphological evidence for the functions of Fas receptor and Fas ligand. In an effort to examine the cytotoxicity of effector cells, CytoTox(96) Non-Radioactive Cytotoxicity Assay was adopted to measure the LDH releasing value after the SW620 cells were co-cultured with Chang liver cells.</p><p><b>RESULTS</b>It was shown that the Fas ligand of colon carcinoma SW620 cells was positive and the positive substances were distributed in the cell membrane and cytoplasm, and the Fas receptor of colon carcinoma SW620 cells was negative. The Fas receptor of Chang liver cells turned out to be positive and the positive substances were distributed in the cell membrane, and the Fas ligand of Chang liver cells was negative. At 6 hours after co-culture of IFN-γ-stimulated Chang liver cells with interleukin-18-stimulated (for 36 h) SW620 cells or unstimulated SW620 cells, the cytotoxicity of SW620 cells to IFN-stimulated Chang liver cells at effector-to-target ratios of 10:1, 5:1, 2.5:1 and 1.25:1 was 68.3%, 49.8%, 21.1%, 9.7% (F = 76.87, P < 0.05) and 32.7%, 21.8%, 11.1%, 6.7% (F = 7.27, P < 0.05), respectively. The non-radioactive cytotoxicity assay showed that the apoptotic rate of Chang liver cells was remarkably increased with the increase of planting concentration of SW620 after the SW620 cells were co-cultured with Chang liver cells. The cytotoxicity was significantly enhanced by interleukin-18.</p><p><b>CONCLUSION</b>The FasL expression of human colon cancer cells may be regulated by endogenous interleukin-18 in the host microenvironment and enhance the liver colonization competence of colon cancer cells through induction of apoptosis in the Fas-expressing hepatocytes.</p>

Capecitabine combined with weekly docetaxel in Chinese patients > 65 years with anthracycline-resistant metastatic breast cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel for the treatment of anthracycline-resistant metastatic breast cancer (MBC) in older Chinese patients.</p><p><b>METHODS</b>MBC patients aged > 65 years pretreated with 1 - 5 prior chemotherapy regimens, including an anthracycline, received oral capecitabine 825 mg/m(2) twice daily, days 1 - 14, plus docetaxel 30 mg/m(2) on days 1 and 8 every 21 days. All 41 enrolled patients received at least 1 dose of treatment and were evaluable for safety; 38 received at least 2 cycles (median 4, range 2 - 8) and were evaluable for efficacy.</p><p><b>RESULTS</b>The overall objective response rate was 47%, including complete responses in 8% of patients. Median time to progression was 8.9 months. Median overall survival was 17.6 months. The most common side effects were haematological and gastrointestinal toxicities and hand-foot syndrome. The only grade 3/4 adverse events were neutropenia (12%), alopecia (7%), grade 3 nausea and vomiting (2%) and grade 3 nail toxicity (2%).</p><p><b>CONCLUSIONS</b>Capecitabine 825 mg/m(2) twice daily plus weekly docetaxel is active with an acceptable safety profile in Chinese women > 65 years with anthracycline-resistant MBC. Efficacy and tolerability compare favourably with previously reported trials evaluating higher capecitabine doses in combination with 3-weekly or weekly docetaxel.</p>

DNCE regimen for treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of DNCE [DXM, navelbine (NVB), DDP and Vp-16] regimen and DICE [dexamethasone (DXM), ifosfamide (IFO), cisplatin (DDP) and etoposide (Vp-16)] regimen in the treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma (NHL).</p><p><b>METHODS</b>A total of 69 patients with histopathologically proved advanced aggressive and highly aggressive NHL were randomized into trial group (32 patients treated with DNCE regimen) and control group (37 patients treated with DICE regimen). The control group was given DICE regimen: DXM 20 mg, iv d1 approximately d4; IFO 1 g/m2), iv d1 approximately d4; Mesna 400 mg, iv q8h, d1 approximately d4; DDP 25 mg/m2, iv d1 approximately d4; Vp-16 100 mg/m2, iv d1 approximately d4; one cycle for 21 approximately 28 days. The trial group was given DNCE regimen: DXM 20 mg, iv d1 approximately d4; NVB 25 mg/m2, iv d1 and d5; DDP 25 mg/m2, iv d1 approximately d4; Vp-16 100 mg/m2, iv d1 approximately d4; one cycle for 21 approximately 28 days. Each patient completed at least 2 cycles of treatment.</p><p><b>RESULTS</b>A better efficacy was shown in the complete response rate, partial response rate, and total response rate between DNCE and DICE groups (18.8% vs. 10.8%, 37.5% vs. 35.1%, and 56.3% vs. 45.9%, respectively), but the differences were statistically non-significant (P > 0.05). The 1-, 3-, and 5-year survival rates were not significantly increased in DNCE group compared with that in DICE group (86.5% vs. 87.5%, 58.3% vs. 63.2%, 42.9% vs.38.5%, respectively, P > 0.05). The major side effects were leucopenia, thrombocytopenia, and nausea in both groups. The bone marrow depression in DNCE group was significantly slighter than that in the DICE group (P < 0.05).</p><p><b>CONCLUSION</b>The efficacy of DNCE regimen is as good as DICE regimen, and the bone marrow toxicity is less severe in DNCE group than that in DICE regimen. Therefore, the DNCE regimen is an effective second-line salvage regimen for the treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma.</p>

Treatment outcome and prognosis of autologous hematopoietic stem cell transplantation combined with high dose radiotherapy/chemotherapy in 22 patients with nasal NK/T cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the outcome and prognosis of autologous hematopoietic stem cell transplantation (AHSCT) combined with high dose radiotherapy/chemotherapy in 22 patients with nasal NK/T cell lymphoma.</p><p><b>METHODS</b>From July 1992 to December 2005, 22 patients with nasal NK/T cell lymphoma were diagnosed pathologically. Immunophenotyping was performed in 13 cases. The patients were classified by Ann Arbor staging system and international prognosis index (IPI). The patients received cycles of chemotherapy every other two weeks or combined with radiotherapy for remission induction, followed high dose radiotherapy/chemotherapy, combined with autologous peripheral blood stem cell transplantation (APBSCT), or autologous bone-marrow transplantation (ABMT). Patients were given complementary radiotherapy after transplantation if they did not have it before. Twelve patients of IPI 3 -4 received consolidation chemotherapy, and one of them received the second transplantation.</p><p><b>RESULTS</b>The median follow-up duration was 64 (12 - 168) months. The 5 and 8-year overall survivals (OS) were 79.3% and 64.1%, and disease free survivals (DFS) were 36.4% and 27.3%, respectively. The 5-year OS were as follows: for stage I - II and III - IV disease were 90.0% and 70.0% (P = 0. 041); for patients without and with B symptom were 100.0% and 70.7% (P = 0.045); and for IPI 1 - 2 and 3 - 4 were 100.0% and 60.0% (P = 0.035), respectively. Multivariate analysis by COX regression revealed that disease stage, B symptom and IPI were independent prognostic factors.</p><p><b>CONCLUSION</b>AHSCT combined with high dose radiotherapy/chemotherapy is an effective treatment for patients with poor prognosis nasal NK/T cell lymphoma.</p>