Hepatitis B virus reactivation and hepatitis in diffuse large B-cell lymphoma patients with resolved hepatitis B receiving rituximab-containing chemotherapy: risk factors and survival / 癌症

<p><b>INTRODUCTION</b>Hepatitis B virus (HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B (hepatitis B surface antigen [HBsAg]-negative and hepatitis B core antibody [HBcAb]-positive). This study aimed to assess HBV reactivation and hepatitis occurrence in diffuse large B-cell lymphoma (DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reactivation and hepatitis occurrence and to analyze whether HBV reactivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis B.</p><p><b>METHODS</b>We reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center, China. Predictive factors for HBV reactivation, hepatitis development, and survival were examined by univariate analysis using the chi-square or Fisher's exact test and by multivariate analysis using the Cox regression model.</p><p><b>RESULTS</b>Among the 278 patients, 165 were HBsAg-negative. Among these 165 patients, 6 (10.9%) of 55 HBcAb-positive (resolved HBV infection) patients experienced HBV reactivation compared with none (0%) of 110 HBcAb-negative patients (P = 0.001). Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients (21.8% vs. 8.2%, P = 0.013). HBcAb positivity and elevated baseline alanine aminotransferase (ALT) levels were independent risk factors for hepatitis. Among the 55 patients with resolved hepatitis B, patients with elevated baseline serum ALT or aspartate aminotransferase (AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels (P = 0.037, P = 0.005, respectively). An elevated baseline AST level was an independent risk factor for hepatitis in these patients. Six patients with HBV reactivation recovered after immediate antiviral therapy, and chemotherapy was continued. HBcAb positivity, HBV reactivation, or hepatitis did not negatively affect the survival of DLBCL patients.</p><p><b>CONCLUSIONS</b>DLBCL patients with resolved hepatitis B may have a higher risk of developing HBV reactivation and hepatitis than HBsAg-negative/HBcAb-negative patients. Close monitoring and prompt antiviral therapy are required in these patients.</p>

EGFR inhibitors sensitize non-small cell lung cancer cells to TRAIL-induced apoptosis / 癌症

Apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can be regulated by the epidermal growth factor (EGF) signaling pathway. In this study, recombinant adenoviral vectors that encode TRAIL gene from the hTERT/RGD promoter (AdTRAIL) was combined with drugs including gefitinib, elotinib, and cetuximab that inhibit EGFR and the EGF signaling pathway in non-small cell lung cancer (NSCLC) cell lines to investigate their antitumor activity. In vitro, compared to single reagent, AdTRAIL combined with EGFR inhibitors reduced proliferation and enhanced apoptosis in H460, A549, and SW1573 cell lines. Western blot results suggested that these effects were relative to up-regulation of pro-apoptosis protein BAX and down-regulation of p-AKT. In vivo, AdTRAIL combined with cetuximab resulted in a significant growth reduction in H460 xenografts without damage to the main organs of nude mice. Histological examination and TUNEL analyses of xenografts showed that cetuximab enhanced cell apoptosis induced by AdTRAIL. These results indicate that EGFR inhibitors enhanced AdTRAIL anti-tumor activity in NSCLC cell lines and that inhibiting the AKT pathway played an important role in this enhancement.

Cyclosporine, prednisone, and high-dose immunoglobulin treatment of angioimmunoblastic T-cell lymphoma refractory to prior CHOP or CHOP-like regimen / 癌症

Angioimmunoblastic T-cell lymphoma (AITL) is a rare, distinct subtype of peripheral T-cell lymphoma, possessing an aggressive course and poor prognosis with no standard therapy. Twelve patients who have failed at least two initial CHOP or CHOP-like regimens were enrolled in this study and treated with individualized cyclosporine (CsA), prednisone (PDN), and monthly, high-dose intravenous immunoglobulin (HDIVIG). The dose of CsA was adjusted individually based on the blood trough concentration of CsA and renal function. All patients were examined for response, toxicity and survival. The most significant toxicities (≥ grade 2) were infection (16.7%), renal insufficiency (8.3%), hypertension (8.3%), diabetes (8.3%) and insomnia (16.7%). Discontinuation of treatment occurred in one patient (8.3%) due to grade 3 renal toxicity and subsequent grade 4 pulmonary infection. Treatment-related death was not observed. The overall response rate was 75.0% (complete response, 33.3%; partial response, 41.7%). With a median follow-up of 25.5 months, the median duration of response was 20 months (range, 12 to 49 months) and the median progression-free survival (PFS) was 25.5 months (range, 10 to 56 months). The 2-year PFS rate was 81.5%. Our findings indicate the combination of CsA, PDN and HDIVIG is an effective salvage regimen for refractory or relapsed AITL with predictable and manageable toxicity.

Long-term results of rituximab-based salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the efficacy and toxicity of rituximab-based salvage chemotherapy in the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>Sixty-nine patients with relapsed or refractory DLBCL were treated by rituximab-based salvage chemotherapy, including 40 male and 29 female patients with a median age of 51.5 years (range 17 to 82 years). All the patients had prior treatments including of EPOCH, ICE, DHAP, GEMOX, and GDP. Twenty-seven patients also received rituximab treatment as the first-line regimen.</p><p><b>RESULTS</b>The objective response (OR) rate was 73.4% (47/64) in these patients with a complete response (CR) rate of 45.3%. The major adverse effects included bone marrow suppression, fatigue, and gastrointestinal toxicity. The side effects of rituximab were mild, including chill, fever and fatigue. The median follow-up was 40.6 (3.7-179.9) months. Twenty-eight patients died of tumor progression and two died from grade 4 myelosuppression accompanied by severe systemic infection. The median survival was 51.6 (3.7-179.9) months in this group. The 1, 3 and 5-year overall survival was 92%, 62% and 37%, respectively, and in patients without rituximab as the first line treatment, the overall survival at 1 and 3 years (97.4% and 73.5%) was much better than that in rituximab-treated patients (83.1% and 42.8%) (P=0.001). The patients of GCB subtype had better survival compared to the non-GCB subtype, with the 5-year overall survival of 42.3% and 21.4%, respectively (P=0.005).</p><p><b>CONCLUSION</b>Rituximab-based salvage regimens are effective and well tolerable, but further clinical trial is warranted.</p>

Clinicopathologic study of 963 cases of mature T-cell and natural killer/T-cell lymphoma with respect to 2008 WHO classification of lymphoid neoplasms / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of various types of mature T-cell and natural killer (NK)/T-cell lymphoma in Guangdong, China, with respect to the 2008 WHO classification of lymphoid neoplasms.</p><p><b>METHODS</b>Eleven hundred and thirty-seven (1137) cases of mature T-cell or NK/T-cell lymphoma diagnosed during the period from 2002 to 2006 in Guangzhou area were retrieved. The clinical data, histologic features and immunohistochemical findings were reviewed by a panel of experienced hematopathologists. Additional immunostaining was performed if indicated. The cases were re-classified according to the 2008 WHO classification of lymphoid neoplasms.</p><p><b>RESULTS</b>Nine hundred and sixty-three (963) cases fulfilled the diagnostic criteria of mature T-cell or NK/T-cell lymphoma and accounted for 20.1% of all cases of lymphoma encountered during the same period (963/4801). A predominance of extranodal involvement was noted in 644 cases (66.9%), while 319 cases (33.1%) showed mainly nodal disease. The prevalence of various lymphoma subtypes was as follows: peripheral T-cell lymphoma, unspecified (PTCL, NOS) 293 cases (30.4%), extranodal NK/T-cell lymphoma, nasal type 281 cases (29.2%), anaplastic large cell lymphoma (ALCL) 198 cases (20.6%), and angioimmunoblastic T-cell lymphoma (AILT) 46 cases (4.8%). The male-to-female ratio was 1.99. The median age of the patients was 44 years, with the peak age of PTCL, NOS, extranodal NK/T-cell lymphoma, nasal type and AILT being 55 to 64 years, 25 to 54 years and 65 to 74 years, respectively. ALK-positive ALCL occurred more frequently in young age, while the ALK-negative ALCL cases occurred mainly in the elderly.</p><p><b>CONCLUSIONS</b>Extranodal lesions predominate in mature T-cell and NK/T-cell lymphomas occurring in Guangzhou area. There is a male predominance and the overall incidence shows no increasing trend with age of the patient. The peak age of various subtypes however varies. The most common subtype was PTCL, NOS, followed by extranodal NK/T-cell lymphoma, nasal type, ALCL and AILT. The relatively frequent occurrence of extranodal NK/T-cell lymphoma, nasal type in Guangdong area is likely associated with the high incidence of Epstein-Barr virus infection there.</p>

The role of Skp2 in extranodal NK/T-cell lymphoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Expression of Skp2 was related with the prognosis of several tumors. However, there was no intensive study on the relationship between Skp2 and extranodal NK/T cell lymphoma. This study was to explore the role of Skp2 in extranodal NK/T cell lymphoma.</p><p><b>METHODS</b>The clinicopathological data of 39 patients with extranodal NK/T cell lymphoma were analyzed. The expression of Skp2 was examined by immunohistochemistry on formalin fixed, paraffin embedded tissue sections.</p><p><b>RESULTS</b>Among the patients with high expression of Skp2, complete remission (CR) rate was only 14.3% (2/14). However, CR rate among the patients with low expression of Skp2 was 68.0% (17/25). Significant difference was shown between these two groups (P < 0.001). In the group of low expression, the median overall survival (OS) was 85.59 months (95% CI: 35.83 135.34 months), the 1 and 2 year OS rates were 81% and 71%, respectively. However, in the group of high expression, the median OS was only 9.73 months (95% CI: 2.05-17.40 months), the 1 and 2 year OS rates were 42% and 14%, respectively. There was statistical difference between these two groups (P < 0.001). Multivariate analysis showed that Skp2 expression (P <0.001), LDH (P = 0.026) and ECOG PS (P = 0.003) were dependent prognostic factors of extranodal NK/T cell lymphoma.</p><p><b>CONCLUSION</b>High expression of Skp2 is an independent unfavorite adverse prognostic factor of extranodal NK/T cell lymphoma.</p>

5-Fluorouracil upregulates the activity of Wnt signaling pathway in CD133-positive colon cancer stem-like cells / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>CD133-positive colon cancer stem like cells (CSLCs) are resistant to the conventional cytotoxic drug 5-fluorouracil (5-FU). Wnt signaling pathway plays important roles in colon cancer carcinogenesis and metastasis, and regulates the self-renewal capacity of CSLCs. In the present study, we explored the impact of 5-FU on Wnt signaling pathway of CD133-positive colon CSLCs, and the relation between Wnt signaling pathway and drug resistance of CD133-positive colon CSLCs.</p><p><b>METHODS</b>Magnetic activation cell separation was used to collect CD133-positive cells from colon cancer cell line DLD1, which was transfected with luciferase reporter for Wnt signaling activity. The activity of Wnt signaling pathway was compared between CD133-positive and CD133-negative cells. After the treatment with 1 μg/mL of 5-FU, the cell proliferation rates of DLD1 cells, CD133-positive cells, and CD133-negative cells were compared. After the treatment with 1 μg/mL and 10 μg/mL of 5-FU for 48 h, Wnt activity was compared between CD133-positive and CD133-negative cells. The expression of CD133 and cell apoptosis of CD133-positive cells was detected after exposure to 50 ng/mL of dickkopf (DKK)-1, a Wnt pathway inhibitor.</p><p><b>RESULTS</b>After the treatment with 5-FU, the cell proliferation rate of CD133-positive cells was higher than that of CD133-negative cells and the sensitivity of CD133-positive cells to 5-FU decreased. Wnt activity was higher in CD133-positive cells than in CD133-negative cells [(46.3 ± 0.3)% vs. (33.9 ± 2.7)%, P = 0.009]. After the treatment with 1 μg/mL and 10 μg/mL of 5-FU, Wnt activity of CD133-positive cells was (90.1 ± 10.0)% (P = 0.012) and (52.9 ± 2.5)% (P = 0.047), respectively, whereas that of CD133-negative cells was (35.5 ± 3.3)% (P = 0.434) and (26.5 ± 0.4)% (P = 0.046), respectively. CD133 expression in CD133-positive cells decreased from (87.2 ± 5.3)% to (60.6 ± 3.1)% (P = 0.022) after treatment with DKK-1, whereas the cell apoptosis rate increased from (11.8 ± 0.2)% to (28.3 ± 0.6)% (P = 0.013).</p><p><b>CONCLUSIONS</b>Wnt activity is higher in CD133-positive DLD1 cells than in CD133-negative DLD1 cells. 5-FU can upregulate Wnt activity of CD133-positive colon CSLCs. Blocking Wnt activity may reverse drug sensitivity of CD133-positive cells to 5-FU.</p>

Preclinical study of apoptosis of B-NHL cell lines induced by anti-CD20 monoclonal antibody / 中国实验血液学杂志

The aim of this study was to investigate the effect of anti-CD20 monoclonal antibody (McAb) on induction of apoptosis in malignant B cell lines in vitro and to explore its possible mechanism. The human Burkitt's lymphoma cell lines (Daudi, Namalwa, Raji and Ramos cells) were cultured in vitro. The inhibitory rate of cell proliferation was detected by XTT assay, the apoptosis of cells was determined by flow cytometry. The expression of BCL-2 in human Burkitt's lymphoma cell lines (Daudi, Namalwa, Raji and Ramos cells) treated with rituximab (20 microg/ml) for 24 hours was analyzed by Western blot. The results showed that the anti-CD20 McAb had a slight anti-proliferation effect on the Daudi, Namalwa, Raji cell lines and no effect on the Ramos cell line. There is no correlation between the effect and the concentration of anti-CD20 McAb. Anti-CD20 McAb as a single agent could weakly induce the apoptosis of four cell lines. The inhibitory rate of cell proliferation ranged from 3% to 10%. Expression of BCL-2 protein was down-regulated after treated by anti-CD20 McAb for 24 hours in Raji and Namalwa cell lines. It is concluded that the anti-CD20 McAb as a monomer can slightly inhibit the proliferation of Daudi, Namalwa and Raji cell lines, the inhibition does not dependent on the treating time and the concentrations of anti-CD20 McAb. Anti-CD20 McAb as a monomer can weakly induce the apoptosis of four cell lines. Expression of BCL-2 in Raji and Namalwa cell lines is down-regulated after the cells were treated by anti-CD20 McAb for 24 hours. Down-regulation of BCL-2 expression may be one of the mechanisms enhancing the cytotoxicity of cytotoxic drugs.

Effect of KRAS mutation on efficacy of Cetuximab combined with chemotherapy in advanced colorectal cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the relationship between KRAS gene status and efficacy of Cetuximab (C225) combined with chemotherapy on advanced colorectal cancer in Chinese patients, and to evaluate the safety of C225.</p><p><b>METHODS</b>From May 2006 to March 2009, 81 patients with advanced colorectal cancer received Cetuximab combined with chemotherapy were enrolled in this study. The rate of KRAS mutation and the relationship of KRAS with response rate (RR), progression-free survivor (PFS), overall survival (OS) and adverse reaction of C225 were analyzed retrospectively.</p><p><b>RESULTS</b>All the 81 patients received C225 therapy, and the overall RR was 33.3%. The RR of initiate therapy was 57.1%; of the second line and over the third line therapy was 38.5% and 22.0% respectively. KRAS gene phenotype examination was performed in 44 patients whose tumor samples were available. KRAS mutation was found in 20 cases (45%). Out of 44 patients, 43 were evaluable for response. RR was 5% and 43.48% in KRAS mutation and wild KRAS patients respectively (P =0.002). The median PFS was 7.0 weeks and 18.6 weeks in mutational KRAS patients and wild KRAS patients, reaching statistical significance (P =0.003). The median OS was 15.2 months and 17.3 months in mutational KRAS patients and wild KRAS patients respectively without statistical significance (P =0.463). The common adverse reactions were leucopenia, nausea, vomiting and rash. All the adverse reactions were tolerated. The incidence of skin rash in patients with mutational KRAS and patients without KRAS mutation was 40% and 42% respectively, without statistical significance (P =0.91).</p><p><b>CONCLUSION</b>C225 combined with chemotherapy is well-tolerated in Chinese patients with advanced colorectal cancer, and it can significantly prolong PFS of patients with wild KRAS as compared to patients with KRAS mutation.</p>

Expressions of epidermal growth factor receptor in primary nasopharygeal carcinoma and lymph node metastases / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expressions of epidermal growth factor receptor (EGFR) in primary nasopharygeal carcinoma (NPC) and lymph node metastases.</p><p><b>METHODS</b>Archived samples of primary NPC and paired lymph node metastases from 86 patients were examined immunohistochemically for the protein expression of EGFR.</p><p><b>RESULTS</b>EGFR expression positivity was detected in the primary NPC and lymph node metastases at the rate of 73.3% and 60.5%, respectively, and primary and metastatic foci showed significant difference in the expression levels (P=0.001). A discrepancy of EGFR expression between the primary and metastatic foci was found in 25 patients, with a discrepancy rate of 29.1% (25/86).</p><p><b>CONCLUSION</b>The difference in EGFR expression between the primary and lymph node metastastic foci of NPC needs to be evaluated when performing EGFR-targeted therapies especially in advanced NPC cases.</p>

Relationship between clinopathological features and outcome of rituximab treatment for diffuse large B-cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship of clinopathological features and outcome of rituximab treatment for diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>Sixty-nine patients with DLBCL received intravenous infusion of rituximab in combination with different chemotherapy regimens have been retrospectively analyzed. The influencing factors such as age, stage, serum level of lactate dehydrogenase (LDH) and bulky disease were analyzed retrospectively in terms of the response. The anti-/ pro-apoptosis proteins were detected by immunohistochemistry (SP methods). The correlation of protein expression with efficacy of rituximab treatment was also analyzed.</p><p><b>RESULTS</b>In the patients with previously untreated aggressive B-NHL, the combination of rituximab with chemotherapy achieved an overall response rate (ORR) of 90.7% and CR of 69.8%, while in the patients with relapsed disease, that was 80.8% (ORR) and 30.8% (CR). The disease stage (P = 0.046), serum lactate dehydrogenase (LDH) (P = 0.024), physical status (P = 0.009) and bulky disease (P = 0.013) were found to be unfavorable factors for the immunochemotherapy. The treatment efficacy in the patients with Bcl-2 overexpression was better than that in cases with negative one. No correlation of the bax and survivin expression with immunochemotherapy efficacy was observed.</p><p><b>CONCLUSION</b>The immunochemotherapy regimen (rituximab plus chemotherapy) can improve the response rate and CR rate without significant increase in toxicity in patients with diffuse large B-cell lymphoma. The advanced stage, high serum LDH level, relapsed disease, bulky disease and negative Bcl-2 expression are unfavorable factors affecting the therapeutic efficacy.</p>

FOLFOX versus PLF regimen in treatment of advanced gastric adenocarcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the efficacy and tolerability of the regimen FOLFOX [1eucovorin (LV), 5-fluorouracil (5-Fu) and oxaliplatin] and the regimen PLF (Paclitaxel, leucovorin and 5-Fu) for treatment of advanced gastric adenocarcinoma.</p><p><b>METHODS</b>We retrospectively studied the clinical data of 132 patients with stage IV gastric adenocarcinoma treated by FOLFOX (group A, n=60) or PLF (group B, n=72). The tumor response rate, toxicity, time to progress (TTP) and overall survival (OS) were compared between the two groups.</p><p><b>RESULTS</b>A total of 544 cycles were administrated in these patients. The overall response rate was 35.0% with FOLFOX regimen and 41.7% with PLF regimen, showing no significant difference between them (P>0.05). The TTP was 6.13-/+1.26 (95%CI, 3.65-8.61) months in group A, and 5.92-/+0.49 (95%CI, 4.97-6.87) months in group B; the OS was 10.67-/+1.55 (95%CI, 7.63-13.71) months in group A, and 10.8-/+3.07 (95%CI, 4.78-16.82) months in group B. Neither TTP or OS showed significant differences between the two groups (P>0.05). Five patients in group A (8.33%) and 8 in group B (11.11%) had grade 3 and 4 leukopenia. The non-hematological toxicities were mostly mild, including nausea, vomiting, stomatitis, diarrhea and alopecia. The main adverse effects were grade 1 or 2 sensory neuritis in FOLFOX group, and alopecia in PLF group, without significant difference between the two groups (P<0.05).</p><p><b>CONCLUSION</b>Both FOLFOX and PLF can serve as effective first-line treatment of stage IV gastric adenocarcinoma with good tolerance.</p>

Subgrouping and outcome prediction of diffuse large B-cell lymphoma by immunohistochemistry / 中华病理学杂志

<p><b>OBJECTIVE</b>To categorize diffuse large B-cell lymphoma (DLBCL) into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subgroups by immunohistochemistry; and to investigate the underlying prognostic significance.</p><p><b>METHODS</b>Immunohistochemical study for CD10, bcl-6 and MUM1 was performed on 133 cases of DLBCL. The cases were then categorized into GCB and non-GCB subgroups. The 5-year overall survival and 5-year progression-free survival rates were compared between the GCB and non-GCB groups, and among the cases with different immunohistochemical expression or with different IPI.</p><p><b>RESULTS</b>Amongst the 133 case studied, CD10 was expressed in 33.1%, while bcl-6 was positive in 34.6% and MUM1 in 45.1%. CD10 expression had a favorable impact on 5-year overall survival (P=0.041) and 5-year progression-free survival (P=0.031). On the other hand, bcl-6 expression had a favor able impact on 5-year progression-free survival (P=0.044). Expression of MUM1 carried an adverse effect on 5-year overall survival (P=0.031) and 5-year progression-free survival (P=0.028). GCB immunophenotype was demonstrated in 40.6% of the cases, while 59.4% showed a non-GCB profile. GCB DLBCL had a significantly longer 5-year overall survival (P=0.004) and 5-year progression-free survival (P=0.003), as compared with the non-GCB group. When dividing the cases into two groups according to their IPI score (IPI=0 to 1 and IPI=2 to 5), it turned out that the 5-year overall and progression-free survival rates of the GCB group were significantly higher than those of the non-GCB group (P=0.019 and 0.014 respectively in cases with IPI of 0 to 1 and P=0.006 and 0.009 respectively in cases with IPI of 2 to 5). The non-GCB cases with a IPI of 2 to 5 had the poorest prognosis.</p><p><b>CONCLUSION</b>DLBCL subgrouping by immunohistochemistry and analysis of the subgrouping with IPI is feasible and useful in predicting clinical outcome.</p>

Significance of EGFR and p-ERK expression in nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of EGFR and p-ERK in nasopharyngeal carcinoma (NPC) and investigate their clinical significance.</p><p><b>METHODS</b>Immunohistochemistry LSAB method was adopted to detect the expression of EGFR and p-ERK. Statistical analysis was performed using SPSS statistical software package (10.0) to correlate their expression with clinical characteristics and prognosis.</p><p><b>RESULTS</b>Positive staining for EGFR was observed in 39 of 55 cases (70.9%). The EGFR expression was correlated with clinical stage and gender. EGFR expression was correlated with poorer overall survival (OS) and shorter time to progression (TTP). Positive staining for p-ERK was observed in 29 of 55 cases (52.7%). There was a statistically significant association between positive p-ERK expression and advanced clinical stage. Positive p-ERK expression was correlated with poorer OS, disease-free survival (DFS) and TTP. EGFR expression was correlated with the expression of p-ERK. On multivariate analysis, age over 50 years was an independent poor prognostic factor for NPC. Both EGFR and p-ERK were not independent prognostic factors for NPC.</p><p><b>CONCLUSION</b>Expressions of EGFR and p-ERK are detected in NPC. Their abnormally high expression signifies poor prognosis in NPC patients.</p>

Treatment outcome and prognosis of 112 patients with nasal and nasopharyngeal peripheral T cell lymphomas / 中华血液学杂志

<p><b>OBJECTIVE</b>To retrospectively analyze the treatment outcomes and prognostic factors of nasal and nasopharyngeal peripheral T cell lymphomas (PTCL) patients.</p><p><b>METHODS</b>One hundred and twelve patients with pathologically confirmed nasal and nasopharyngeal PTCL were included, among which 39 were CD56(+) NK/T cell lymphomas. The median pre-treatment disease course was 4 months. 84 were males and 28 females median age was 46 years. The tumors mainly involved nasal cavity (88 cases) and/or nasopharynx (50 cases) and adjacent structures, and 83 cases with extra-cavity diseases. 91.1% of the patients had Ann Arbor I(E)/II(E) diseases. The International Prognostic Indices (IPI) were less than 2 scores in 78.8% of the patients. Seventy two patients received combined chemo-radiotherapy, 32 chemotherapy only, 3 radiotherapy only and 5 no any treatment.</p><p><b>RESULTS</b>Median follow-up duration was 42 months. Chemotherapy achieved a complete remission (CR) rate of 34.4% for initial treatment, and of 65.1% after primary treatment. The local tumor controlled rate was 50.5%, and the median time to tumor progression (TTP) was 11 months. There were evidences of systemic relapse in more than 30% of the patients. The extra-cavity tumors usually had a shorter TTP (r(s) = -0.191, P = 0.024). The progress-free survival and overall survival rates were 38.8% and 52.4% at 3 years, and 34.9% and 44.8% at 5 years respectively. Univariate analysis showed that favorable prognostic factors for survival were pre-treatment course > 3 months, earlier clinical stage, non NK/T lymphoma, no skin involvement, lower IPI, CR after initial chemotherapy, radiotherapy, CR after primary treatment and local tumor controlled. Multivariate analysis showed that, pre-treatment course > 3 months (P = 0.011), non NK/T lymphoma (P = 0.007), CR after initial chemotherapy (P = 0.008) and radiotherapy (P = 0.000) were favorable prognostic factors for survival.</p><p><b>CONCLUSIONS</b>Although most nasal and nasopharyngeal peripheral T-cell lymphomas were diagnosed at early stage diseases, some of them were highly aggressive with poor prognosis, particularly CD56(+) NK/T cell lymphomas. Combination chemo/radiotherapy, though remained principal treatments, more effective therapeutic modalities are expected.</p>

Long-term outcomes of 392 non-Hodgkin's lymphoma patients treated with pirarubicin based regimens / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the effectiveness and toxicity of combined chemotherapy regimen containing pirarubicin (THP) in the treatment of non-Hodgkin's lymphoma (NHL).</p><p><b>METHODS</b>Three hundred and ninety two patients with NHL were treated by THP containing regimen with or without involved field radiotherapy. The clinical characteristics, response, toxicity and long-term survival rates were analysed.</p><p><b>RESULTS</b>The median age of the patients was 47 (5 - 87) years and 26.0% aged more than 60 years. 61.0% of the patients were males and 39.0% females. B-cell and T/NK cell NHL accounted for 68.4% and 23.2% respectively with 56.9% of diffuse large B cell lymphoma and 12.5% of peripheral T cell lymphoma. 92.6% of the patients were ECOG < 1, 63.2% in stage I + II, 84.7% with IPI score 0 - 2 and 25% with B symptoms, 93.9% (368/392) of the patients received CTOP (containing THP) regimen chemotherapy and among them 28.5% (112/392) plus involved field radiotherapy. Altogether 1598 courses were administered on 368 patients. The overall response rate was 88.5% (341/385) with a complete remission (CR) rate of 63.6%, major toxicity was myelosuppression with 12.8%, 1.0% and 1.5% of grade III - IV neutropenia, thrombocytopenia and anemia, respectively. G-CSF support was given for 553 courses (34.6%). Alopecia account for 19.8%. The incidence of mild cardiotoxicity was 5.8%. Treatment-related mortality was 1.6% (6/368). Median follow-up was 24 months. The 1, 3 and 5 year actuarial survival rates were 86.4% , 66.5% and 59.2%, respectively. Median survival time has not been achieved.</p><p><b>CONCLUSION</b>The efficacy of THP based regimen CTOP for the treatment of aggressive NHL is promising. Further clinical trial is warranted.</p>