Development and validation of a novel risk stratification model and a survival rate calculator for diffuse large B-cell lymphoma in the rituximab era: a multi-institutional cohort study.

BACKGROUND: This study aimed to develop and validate a novel risk stratification model and a web-based survival rate calculator to improve discriminative and predictive accuracy for diffuse large B-cell lymphoma (DLBCL) in the rituximab era. METHODS: We retrospectively collected pre-treatment data from 873 primary DLBCL patients who received R-CHOP-based immunochemotherapy regimens at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 1, 2005, to December 31, 2018. An independent cohort of 175 DLBCL patients from Fujian Cancer Hospital was used for external validation. FINDINGS: Age, ECOG PS, number of extranodal sites, Ann Arbor stage, bulky disease, and LDH levels were screened to develop the nomogram and web-based survival rate calculator. The C-index of the nomogram in the training, internal validation, and external validation cohorts was 0.761, 0.758, and 0.768, respectively. The risk stratification model generated based on the nomogram effectively stratified patients into three distinct risk groups. K-M survival curves demonstrated that the novel risk stratification model exhibited a superior level of predictive accuracy compared to IPI, R-IPI, and NCCN-IPI both in training and two validation cohorts. Additionally, the area under the curve (AUC) value of the novel model (0.763) for predicting 5-year overall survival rates was higher than those of IPI (0.749), R-IPI (0.725), and NCCN-IPI (0.727) in the training cohort. Similar results were observed in both internal and external validation cohort. CONCLUSIONS: In conclusion, we have successfully developed and validated a novel risk stratification model and a web-based survival rate calculator that demonstrated superior discriminative and predictive accuracy compared to IPI, R-IPI, and NCCN-IPI in the rituximab era.

Sequential P-GEMOX and radiotherapy for early-stage extranodal natural killer/T-cell lymphoma: A multicenter study.

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma and most of the patients presented localized disease. Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with early-stage ENKTL. However, the optimal CMT has not been fully clarified. This study reports the efficacy and toxicity of sequential P-GEMOX (pegaspargase, gemcitabine and oxaliplatin) and radiotherapy in a large Chinese cohort comprising of 202 patients diagnosed with early-stage ENKTL from six medical centers. The observed best overall response rate was 96.0% and 168 (83.2%) patients achieved complete remission. With a median follow-up of 44.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 74.6% and 85.2%, respectively. Multivariate analysis suggested that extensive primary tumor (PFS, hazard ratio [HR] 3.660, 95% CI 1.820-7.359, p < 0.001; OS, HR 3.825, 95% CI 1.442-10.148, p = 0.007) and Eastern Cooperative Oncology Group performance status ≥ 2 (PFS, 3.042, 95% CI 1.468-6.306, p = 0.003; OS, HR 3.983, 95% CI 1.678-9.457, p = 0.02) were independent prognostic factors for survival outcomes. Among the established prognostic models for ENKTL, the nomogram-revised risk index model had optimal prognostic risk stratification ability (PFS, p < 0.001; OS, p < 0.001) and relatively balanced population distribution. The adverse events of this CMT were well-tolerated and manageable. In conclusion, sequential P-GEMOX and radiotherapy showed favorable efficacy with acceptable toxicity, and could be an effective treatment option for early-stage ENKTL patients.

[Analysis of the Predictive Value of EZH2 Expression Level on the Clinical Efficacy and Long-term Prognosis of Patients with Primary Gastrointestinal Diffuse Large B-cell Lymphoma].

OBJECTIVE: To investigate the predictive value of methyltransferase EZH2 expression level on the clinical efficacy and long-term prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL). METHODS: 161 patients with newly treated PGI-DLBCL in our hospital from August 2013 to July 2019 were selected. The expression level of EZH2 protein was detected by immunohistochemistry, and the short-term efficacy and long-term survival differences of patients with different levels of EZH2 were compared. The predictive values of EZH2 expression level on the short-term efficacy and long-term prognosis of PGI-DLBCL patients were analyzed by Log-rank test and COX risk proportional regression model. Chi-square test and Logistic regression analysis were used to analyze the influencing factors of EZH2 expression level. RESULTS: The complete response (CR) and overal response(OR) rates of those with high EZH2 expression were significantly lower than those with low EZH2 expression (P<0.001). The median OS and PFS of EZH2 high-level and low-level expression group was 37, 31 months and 49, 42 months, respectively. The cumulative OS and PFS rates of the high-level expression group were significantly lower than those of the low-level expression group, and the differences were statistically significant (P<0.05). The high expression levels of H3K27me3, EZH2, BCL-2, BCL-6, c-MYC were closely related to the shortening of OS and PFS, while the high expression level of Ki-67 was closely related to the shortening of OS (P<0.05), of which the high expression levels of H3K27me3, EZH2, BCL-2, and BCL-6 were independent risk factors for shortening of OS and PFS. The expression level of EZH2 was positively correlated with the expression level of H3K27me3, BCL-6, c-MYC and Ki-67 (r=0.741, r=0.837, r=0.809, r=0.772), and the high expression levels of H3K27me3, BCL-6 and Ki-67 were independent factors influencing the high expression of EZH2. CONCLUSION: In patients with PGI-DLBCL, the high expression of EZH2 significantly reduces the short-term CR and OR rates, which is an independent risk factor for the shortening of long-term OS and PFS rates, and it is independently related to the high expression of H3K27me3 and BCL6.

Latent Epstein-Barr virus infection status and prognosis in patients with newly diagnosed Hodgkin lymphoma in Southeast China: a single-center retrospective study.

PURPOSE: This study aimed to investigate the latent Epstein-Barr virus (EBV) infection status of patients with newly diagnosed Hodgkin lymphoma (HL) and to discuss the relationship between tumor cell EBV status and the prognosis of HL patients. PATIENTS AND METHODS: A total of 134 previously untreated HL patients were analyzed in the study. Epstein-Barr virus encoded RNAs (EBERs) in situ hybridization was performed to detect the EBV status of tumor cells. RESULTS: EBV positive status correlated with sex (p=0.046) and the proportion of extranodal lesions(p=0.037). There was no obvious correlation between EBV status and overall survival (OS) or failure-free survival (FFS) in all cases, but in cases over 50 years old, EBV positive group had an inferior 5-year FFS compared with EBV negative group (38.5%±13.5% vs 90.9%±8.7%, p=0.012). In FFS multivariate analysis of this age subgroup, EBV positive status was associated with significantly inferior survival (HR, 10.10; 95% CI, 1.26-81.08; p=0.030). CONCLUSION: This study demonstrates positive tumor cell EBV status is an unfavorable prognostic factor in elder HL patients.

Clinicopathological and prognostic features of hepatitis B virus-associated diffuse large B-cell lymphoma: a single-center retrospective study in China.

BACKGROUND: While the epidemiologic association between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) is established, little is known about the pathological characteristics and outcome of DLBCL arising in patients with HBV infection. METHODS: We retrospectively studied a cohort of 420 patients with DLBCL for the incidence of HBV infection, and the clinicopathologic features and prognostic factors in HBsAg-positive DLBCL patients in China, a hepatitis B endemic area. RESULTS: In our study, 127 (30.2%) patients were HBsAg-positive. HBsAg-positive DLBCL displayed a younger median onset age (50 vs. 54 years, P = 0.002), more frequent involvement of the spleen (19.7% vs. 6.1%, P < 0.001), less frequent involvement of the small and large intestine (2.3% vs. 11.2%, P = 0.003), more advanced disease (stage III/IV: 56.7% vs. 45.1%, P = 0.028), and lower expression rate of MYC (49.1% vs. 66.7%, P = 0.026). The median follow-up time was 61.9 months. Univariate analysis showed that there was no significant difference in overall survival (OS) between HBsAg-negative and -positive DLBCL (P = 0.577). In the HBsAg-positive DLBCL subgroup, age older than 60 years, advanced disease, elevated lactate dehydrogenase (LDH), spleen involvement, B symptoms (fever, night sweats, weight loss), and double expressers of MYC and BCL2 had a significantly worse outcome, and patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) had a better prognosis. Multivariate analysis further confirmed that spleen involvement and rituximab use were independent prognostic factors in HBsAg-positive DLBCL patients. CONCLUSIONS: Our study indicates that HBsAg-positive DLBCL has unique clinicopathological features and independent prognostic factors. Moreover, under antiviral prophylaxis, the survival of DLBCL patients with HBV infections was comparable to that of HBV-negative patients, and the use of rituximab significantly improved OS in HBsAg-positive DLBCL patients.

[Clinicopathological Features and Prognostic Factors of DLBCL].

OBJECTIVE: To analyze the clinicopathological features and prognostic factors of patients with diffuse large B-cell lymphoma(DLBCL). METHODS: Ninety-four cases of DLBCL followed up were selected in Fujian Tumor Hospital. The immunohistochemistry method was used to detect the protein expressions of BCL-2 BCL-6, MYC, CD10 and MUM-1, the gene abnormalities of MYC and BCL-2 were analyzed by fluorescence in situ hybridization, and the clinical pathological features and the related factors affecting prognosis in the patients with DLBCL were analyzed. RESULTS: The protein positive rates of BCL-2, BCL-6, MYC, CD10 and MUM-1 in 94 patients were 75.53% (71/94), 58.51% (55/94), 52.13% (49/94), 15.96% (15/94) and 34.04% (32/94) respectively. The detection rate of MYC gene abnormality was 20.93% (9/43) and the detection rate of BCL-2 gene abnormality was 44% (22/50); 2 kinds of gene abnormalities were of multiple copies, and 2 cases (2.13%) were abnormal in MYC and BCL-2 genes simultaneously. The median survival time of 3 years in 94 patients was 21.79 months (2-36 months), and the overall survival rates of 1 and 3 years were 82.98% and 64.89% respectively. Single factor analysis revealed that the high ECOG score (≥ 2), high international prognostic index (IPI) classification, positive expression of BCL-6 protein, and MYC and BCL-2 gene simultaneously abnormal were the risk factors influencing the prognosis (all P<0.05). COX regression analysis showed that IPI classification, ECOG score and treatment methods were independent factors influencing the prognosis (all P<0.05). CONCLUSION: IPI classification, ECOG score and treatment methods have greater impacts on the prognosis of patients with DLBCL. Chemotherapy combined with radiotherapy or surgical treatment can significantly improve the prognosis of patients.

[Primary mediastinal large B-cell lymphoma:a report of 24 cases with literature review].

BACKGROUND & OBJECTIVE: Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon subtybe of diffuse large B-cell lymphoma (DLBCL). This study was to investigate optimal treatment and prognostic factors of PMBCL by analyzing its clinical features. METHODS: Clinical records of 24 PMBCL patients, treated in Fujian Provincial Tumor Hospital from 1995 to 2005, were reviewed. RESULTS: Of the 24 patients, 16 were men and 8 were women, aged from 12 to 81; 20 were at stage I-II, 1 at stage III, and 3 at stage IV; 13 had bulk disease; 10 had superior vena cava syndrome; 14 had contiguous infiltration; 15 had lacate dehydrogenase elevation; 11 received chemoradiotherapy, 10 received chemotherapy alone, and 3 received radiotherapy alone; 10 achieved complete remission (CR) after scheduled treatment, 12 achieved partial remission (PR), 1 had stable disease and 1 had progressive disease. The median survival time was 89 months; the 3-year overall survival rate was 69%. At the end of follow-up, the patients initially achieved CR were all alive. International prognostic index (IPI) did not predict survival in this analysis, while bulk disease predicted poor survival. CONCLUSIONS: PMBCL has a male dominance in this analysis. Its clinical presentation is critical. Prompt diagnosis is needed. Anthracycline-based chemotherapy with radiotherapy may lead to favorable outcome. The patients with bulk disease have poor survival.