Tumor necrosis could reflect advanced disease status in patients with diffuse large B cell lymphoma treated with R-CHOP therapy

Tumor necrosis (TN) can lower responsiveness to chemotherapy and confer basic resistance to anti-cancer therapy. We investigated the association of TN with poor clinical features and outcome in diffuse large B cell lymphoma (DLBCL). We examined the presence or absence of TN in 476 DLBCL patients of who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Eighty-nine (18.7 %) patients had TN at diagnosis. Patients with TN had a progression-free survival (PFS) and overall survival (OS) of 39.3 and 46.7 %, whereas patients without TN had a PFS and OS of 73.4 and 82.6 %. Adverse clinical factors of poor Eastern Cooperative Oncology Group performance status ≥ grade 2 (p?=?0.005), elevated lactate dehydrogenase ratio >1 (p?<?0.001), advanced Ann Arbor stage (p?=?0.002), and bulky disease (p?=?0.026) were more prevalent in the TN group than the non-TN group. Cox regression model analysis revealed TN as an independent prognostic factor for PFS and OS in DLBCL (PFS, hazard ratio [HR]?=?1.967, 95 % confidence interval [CI]?=?1.399–2.765, p?<?0.001; OS, HR?=?2.445, 95 % CI?=?1.689–3.640, p?<?0.001). The results indicate that TN could reflect adverse clinical features and worse prognosis in DLBCL patients receiving R-CHOP therapy.     

The comparison between CHOP and R-CHOP in primary gastric diffuse large B cell lymphoma

The combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) plus rituximab is the standard treatment for patients with primary gastric diffuse large B cell lymphoma (DLBCL). However, a few trials comparing CHOP plus rituximab (R-CHOP) with CHOP have been conducted in primary gastric DLBCL. Among 93 consecutive patients receiving CHOP or R-CHOP as a first-line chemotherapy at our institution, 38 patients received CHOP and 55 patients received R-CHOP. With a median follow-up time of 48?months, the complete response (CR) rate, event-free survival (EFS), and overall survival (OS) did not differ between two treatment groups (P?=?1.000, P?=?0.744, and P?=?0.213, respectively). The CR rates were 93.9?% for patients receiving CHOP and 92.5?% for patients receiving R-CHOP. The 3-year EFS rates were 86.0?% for patients receiving CHOP and 81.7?% for patients receiving R-CHOP; the 3-year OS rates were 94.7 and 84.7?%, respectively. In a multivariate analysis, The CR rate was affected by the number of extranodal involvements (P?=?0.011). The EFS and OS rates were affected by the Lugano stage (P?=?0.067 and P?=?0.008, respectively). High serum level of β₂-microglobulin was associated with worse EFS and OS in patients receiving R-CHOP (P?=?0.018 and P?=?0.015, respectively). In conclusion, the addition of rituximab was not found to have an impact on patients’ outcomes with primary gastric DLBCL. The β₂-microglobulin in primary gastric DLBCL might be able to discriminate the patients’ prognosis who are treated with R-CHOP chemotherapy.     

Treatment of the elderly patient with diffuse large B cell lymphoma

The majority of patients with diffuse large B-cell lymphoma are over the age of 60 years and the management of these patients is often sub-optimal. Intensive therapy with curative intent should be given to all patients who can tolerate such therapy, and this requires very careful evaluation of each patient prior to treatment allocation. A detailed history and examination are required, with attention to concomitant disease and existing drug therapy. A quantitative assessment of comorbidity and a comprehensive geriatric assessment (CGA) are valuable adjuncts to physician judgment. For most elderly patients, the R-CHOP regimen (rituximab, cyclophosphamide doxorubicin, vincristine, prednisolone) remains the standard of care. Granulocyte colony-stimulating factor should be given routinely. Reassessment before each cycle of therapy is essential and interim echocardiography should be performed. In patients with cardiac insufficiency there are a number of alternative regimens but no definitive 'best regimen.' In those patients not treated with curative intent a multi-disciplinary approach is essential.     

EB病毒感染对R-CHOP治疗弥漫大B细胞淋巴瘤影响的Meta分析

目的评价R-CHOP治疗EB病毒(Epstein-Barr virus,EBV)感染弥漫大B细胞淋巴瘤预后的影响。方法检索了PUBMED(1994-04~2017-04)、CNKI(1994-04~2017-04)、Cochrane library(1994-04~2017-04)、Wan Fang Data(1996-12~2017-04)公开发表的关于R-CHOP治疗EBV阳性弥漫大B细胞淋巴瘤的相关研究文献,按照Cochrane质量评价系统评价纳入研究质量后,应用Rev Man 5. 0软件进行Meta分析。结果共纳入7篇队列研究,其中EBV阳性弥漫大B细胞淋巴瘤140例,EBV阴性弥漫大B细胞淋巴瘤1 812例。Meta分析结果显示,EBV阳性弥漫大B细胞淋巴瘤组的总生存期(HR=3. 24,95%CI=1. 88~5. 58,P 0. 0001)、无病生存期(HR=1. 83,95%CI=1. 44~3. 25,P=0. 0002)均差于EBV阴性弥漫大B细胞淋巴瘤组。结论在以美罗华治疗弥漫大B细胞淋巴瘤的时代,EBV阳性仍是患者的主要不良预后因素。R-CHOP治疗EBV阳性弥漫大B细胞淋巴瘤的疗效欠佳。EBV可能参与了弥漫大B细胞淋巴瘤的发生、发展的全过程。     

Prognostic significance of PRAME expression based on immunohistochemistry for diffuse large B-cell lymphoma patients treated with R-CHOP therapy

The preferentially expressed antigen of melanoma (PRAME), a tumor-associated antigen, is considered a prognostic marker for various human malignancies. The prognostic significance of PRAME expression for diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab-containing chemotherapy has not been evaluated to date, and the ability of immunohistochemistry (IHC) to detect PRAME expression in these patients has not yet been studied, although IHC is simple to perform in clinical practice. We evaluated the prognostic significance of PRAME expression based on IHC analysis in 160 DLBCL patients treated with R-CHOP therapy. There was a significant association between higher PRAME expression and shorter progression-free survival (PFS), and a trend toward shorter overall survival (OS) in patients with higher PRAME expression than that in patients with lower PRAME expression (5-year PFS, 48.1 vs. 61.1 %; 5-year OS, 65.6 vs. 79.1 %). Patients with high PRAME expression tended to have lower chemotherapeutic responses. Thus, IHC is useful for detecting and assessing PRAME expression in DLBCL. Further, we found a positive correlation between IHC and quantitative real-time RT-PCR measurements of PRAME expression. Our findings indicate that IHC results of PRAME expression can be a novel prognostic maker in DLBCL patients treated with R-CHOP therapy.     

Lymphoma cell VEGFR2 expression detected by immunohistochemistry predicts poor overall survival in diffuse large B cell lymphoma treated with immunochemotherapy (R-CHOP)

Diffuse large B cell lymphoma (DLBCL) is clinically and biologically heterogeneous. In most cases of DLBCL, lymphoma cells co-express vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2, suggesting autocrine in addition to angiogenic effects. We enumerated microvessel density and scored lymphoma cell expression of VEGF, VEGFR1, VEGFR2 and phosphorylated VEGFR2 in 162 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone)-like regimens. VEGFR2 expression correlated with shorter overall survival (OS) independent of International Prognostic Index (IPI) ( P  = 0·0028). Phosphorylated VEGFR2 (detected in 13% of cases) correlated with shorter progression-free survival (PFS, P  = 0·044) and trended toward shorter OS on univariate analysis. VEGFR1 was not predictive of survival on univariate analysis, but it did correlate with better OS on multivariate analysis with VEGF, VEGFR2 and IPI ( P  = 0·036); in patients with weak VEGFR2, lack of VEGFR1 coexpression was significantly correlated with poor OS independent of IPI ( P  = 0·01). These results are concordant with our prior finding of an association of VEGFR1 with longer OS in DLBCL treated with chemotherapy alone. We postulate that VEGFR1 may oppose autocrine VEGFR2 signalling in DLBCL by competing for VEGF binding. In contrast to our prior results with chemotherapy alone, microvessel density was not prognostic of PFS or OS with R-CHOP-like therapy.     

Paraffin-based 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by variable clinical outcomes. Outcome prediction at the time of diagnosis is of paramount importance. Previously, we constructed a 6-gene model for outcome prediction of DLBCL patients treated with anthracycline-based chemotherapies. However, the standard therapy has evolved into rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Herein, we evaluated the predictive power of a paraffin-based 6-gene model in R-CHOP–treated DLBCL patients. RNA was successfully extracted from 132 formalin-fixed paraffin-embedded (FFPE) specimens. Expression of the 6 genes comprising the model was measured and the mortality predictor score was calculated for each patient. The mortality predictor score divided patients into low-risk (below median) and high-risk (above median) subgroups with significantly different overall survival (OS; P = .002) and progression-free survival (PFS; P = .038). The model also predicted OS and PFS when the mortality predictor score was considered as a continuous variable (P = .002 and .010, respectively) and was independent of the IPI for prediction of OS (P = .008). These findings demonstrate that the prognostic value of the 6-gene model remains significant in the era of R-CHOP treatment and that the model can be applied to routine FFPE tissue from initial diagnostic biopsies.