A modified prognostic model in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

In the era of immunochemotherapy, the traditional international prognostic index (IPI) has partially lost its predictive value in diffuse large B-cell lymphoma (DLBCL) and the National Comprehensive Cancer Network-IPI (NCCN-IPI) is unable to effectively identify high-risk patients. Thus, the present study aimed to develop a modified prognostic model (M-PM) to identify high-risk patients that require aggressive treatment. The present study included 169 patients with newly diagnosed DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) or RCHOP-like regimens, between 2011–2017. The results demonstrated that the risk discrimination was improved in the NCCN-IPI compared with the IPI, and patients were divided into four risk groups with a 5-year overall survival rate of 93.8, 76.5, 54.3 and 39.4%, respectively. However, the NCCN-IPI failed to identify the high-risk DLBCL population. The newly developed M-PM presented here included four parameters: Age (≥65 years), an elevated lactate dehydrogenase level, Eastern Cooperative Oncology Group score ≥2 and total metabolic tumor volume ≥300 cm³. The M-PM also divided patients into four risk groups that comprised 40.8, 23.1, 26.0 and 10.1% of the patients, and the 5-year survival rates of these groups were 92.4, 70.6, 52.3 and 24.5%, respectively. Taken together, the results of the present study demonstrated that the M-PM was more accurate compared with the IPI and the NCCN-IPI, which served as an effective tool for identifying patients with DLBCL at high risk of an adverse prognosis.     

改良国际预后指数（NCCN-IPI）对R-CHOP方案治疗弥漫大B 细胞淋巴瘤的预后评估（附168 例临床分析）

目的:验证改良国际预后指数（NCCN-IPI）对弥漫大B 细胞淋巴瘤（DLBCL ）患者免疫化疗后的预后评估价值。方法:回顾性分析天津医科大学肿瘤医院2008年1 月至2013年1 月收治的168 例初治DLBCL 患者的临床特征及预后,采用NCCN-IPI和国际预后指数（IPI）进行危险度分层和预后评估。结果:全组患者中位年龄58（24～80）岁,男性92例（54.8%）,AnnArbor分期Ⅲ～Ⅳ期94例（56.0%）,ECOGPS ≥ 2 分19例（11.3%）;发病时LDH 水平升高（> 245 U/L）占71.4% 。中位随访42（15～88）个月,3年和5 年生存率（OS）分别为（75.9 ± 3.4）% 、（65.1 ± 5.2）% 。全组患者根据IPI 评分系统,低危组占30.4% ,中低危27.4% ,中高危25.0% ,高危17.3% ;3 年OS分别为91.8% 、76.7% 、67.9% 和47.1% 。根据NCCN-IPI评分,低危组19.0% ,中低危38.1% ,中高危31.5% ,高危11.3% 。3 年OS分别为94.5% 、85.4% 、61.2% 和38.1% 。与IPI 评分相比,NCCN-IPI评分区分高危和低危患者的能力更强（NCCN-IPI:3 年OS:94.5% vs . 38.1% ;IPI:91.8% vs . 47.1%）。 结论:在利妥昔单抗一线治疗中,与IPI 指数相比,NCCN-IPI更好地整合了年龄和LDH 水平两个变量的预后作用,可作为DLBCL 患者强有力的预后分层工具。      

A diachronic-comparative analysis for the identification of the most powerful prognostic index for localized diffuse large B-cell lymphoma

BackgroundIn the rituximab era, the conventional International Prognostic index (IPI) lost at least in part its predictive power, while the National Comprehensive Cancer Network-IPI (NCCN-IPI) seems to be a new and valid prognosticator. However, it has not yet been evaluated in patients with localized disease and it has not been compared with the modified IPI (mIPI) of the pre-rituximab era. In order to evaluate the different prognosticators and to assess the importance of rituximab and radiotherapy (RT), we carried out the so far largest retrospective analysis of patients with localized diffuse large B-cell lymphoma (DLBCL).Patients and methodsWe retrospectively assessed clinical and therapeutical data of 1405 patients treated in from 1987 to 2012 in 10 cancer centers in Italy and 1 in Austria.ResultsAll patients underwent an anthracycline containing polychemotherapy and 254 additional rituximab. The median follow-up was 5.7 years (range 0.1–23 years). The 5-year overall survival (OS) was 75%, being significantly superior in those who underwent additional rituximab, while RT consolidation did not improve the outcome of those who received immunochemotherapy. Patients with extranodal disease benefited from the addition of rituximab, while RT did not improve OS of the immunochemotherapy subgroup. In the pre-rituximab era, the mIPI showed a better performance than the others. In rituximab-treated patients, the NCCN-IPI had the highest discriminant value and the 5-years OS varied significantly (P < 0.001) between the three risk groups and was 98% in low-risk patients, 82% in those with a low-intermediate risk and 57% among high-intermediate and high-risk cases.ConclusionsThe NCCN-IPI is so far the best prognosticator for patients with localized DLBCL who underwent R-CHOP(-like). The addition of rituximab is indispensable regardless of the risk category and site of involvement, while the addition of RT should be reserved to those cases who are ineligible to rituximab.     

Protein Kinase C Beta II Expression in Diffuse Large B-Cell Lymphoma Predicts for Inferior Outcome of Anthracycline-Based Chemotherapy With And Without Rituximab

Protein kinase C beta II expression in diffuse large B-cell lymphoma has prognostic significance not only for CHOP therapy in low-risk International Prognostic Index disease but also for all patients receiving CHOP plus rituximab.Full AbstractIntroductionProtein kinase C beta II (PKCbII) expression has been reported to indicate inferior prognosis in diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-based chemotherapy.AimTo compare the prognostic significance of immunohistochemically determined PKCbII expression in de novo DLBCL treated with CHOP chemotherapy (cyclophosphamide/doxorubicin/vincristine/prednisone) with and without rituximab.Patients and Methods80 consecutive patients treated at St. Vincent's Hospital with de novo DLBCL, 48 treated with CHOP, and 32 with R-CHOP (rituximab plus CHOP), were studied using immunohistochemistry for PKCbII on diagnostic tissue samples. Staining results were correlated with patient characteristics and clinical outcome. Overall survival (OS) and progression-free survival (PFS) were determined by the Kaplan-Meier method, and comparisons were determined by the log-rank test.ResultsPKCbII expression correlated with inferior OS and PFS in CHOP-treated patients with low-risk International Prognostic Index (IPI) disease (0–2 adverse factors) but not in the overall patient group unstratified by IPI. PKCbII expression significantly correlated with inferior OS and PFS in R-CHOP—treated patients unstratified by IPI status.ConclusionPKCbII expression has prognostic significance not only for CHOP therapy in low-risk IPI disease but also for all patients receiving R-CHOP. Immunohistochemically demonstrated PKCbII expression thus identified patient subgroups in which alternative treatment strategies might confer superior outcome.     

Peripheral Blood Lymphocyte-to-Monocyte Ratio at Relapse Predicts Outcome for Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma in the Rituximab Era

BackgroundPatients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have a poor prognosis, even in the rituximab era. Several studies have reported the clinical importance of the peripheral blood lymphocyte-to-monocyte ratio (LMR) in various malignancies, including lymphoma. However, the prognostic value of the LMR in relapsed/refractory DLBCL has not been well evaluated. The purpose of the present study was to investigate whether the LMR at relapse can predict clinical outcomes for relapsed/refractory DLBCL patients treated with rituximab.Patients and MethodsWe analyzed data on 74 patients with relapsed/refractory DLBCL, who were initially treated with R-CHOP (rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone) or an R–CHOP-like regimen.ResultsThere was a significant association between a low LMR (≤ 2.6) and shorter overall survival (OS; P < .001) and progression-free survival (PFS; P < .001) compared with the high LMR group (> 2.6). Multivariate analysis showed that LMR was an independent prognostic factor for OS (P < .001) and PFS (P < .001), as was the international prognostic index (IPI) at relapse for OS. In addition, the LMR had an incremental value for OS and PFS compared with the IPI at relapse.ConclusionThe LMR predicts OS and PFS outcomes in relapsed/refractory DLBCL patients treated with rituximab, and might facilitate better stratification among patients in low- and intermediate-risk IPI groups.     

18F-FDG PET-CT在弥漫大B细胞淋巴瘤预后判断中的价值

目的 探讨18F-FDG PET-CT在弥漫大B细胞淋巴瘤(DLBCL)预后判断中的价值.方法 回顾性分析2009年6月至2015年5月130例初诊DLBCL患者的临床资料及治疗前18F-FDG PET-CT检查结果.结果130例DLBCL患者18F-FDG PET-CT检查的最大标准摄取值(SUVmax)、病灶代谢体积(MTV)及病灶糖酵解总量(TLG)的中位数分别为19.93、34.45cm3、459.92.单因素分析结果显示:美国东部肿瘤协作组(ECOG)评分、AnnArbor分期、β2微球蛋白水平、乳酸脱氢酶水平、肿瘤直径、骨髓侵犯、改良国际预后指数(NCCN-IPI)评分、MTV、TLG均是患者无进展生存(PFS)率及总生存(OS)率的影响因素(均P<0.05);年龄是患者PFS率的影响因素(P<0.05).由于MTV与TLG高度相关,多因素分析时,二者中仅纳入TLG,结果显示:ECOG评分、Ann Arbor分期、NCCN-IPI评分及TLG是影响患者PFS率的独立因素(均P<0.05);NCCN-IPI评分及TLG是影响患者OS率的独立因素(均P<0.05).根据NCCN-IPI评分和TLG将患者分为低危组、中危组和高危组.低、中、高危组患者3年PFS率分别为66.0%、36.8%、26.1%,3年OS率分别为70.0%、49.1%、39.1%,差异均有统计学意义(均P<0.05).结论18F-FDG PET-CT所测得的TLG是影响DLBCL患者PFS及OS的独立预后因素,对DLBCL患者预后判断具有一定的参考价值.     

CD43 Expression Is an Adverse Prognostic Factor in Diffuse Large B-Cell Lymphoma

BackgroundCD43 is a transmembrane glycoprotein expressed in different hematopoietic cells, including some subsets of B lymphocytes. About a quarter of diffuse large B-cell lymphomas (DLBCLs) express CD43, but its prognostic significance is unknown.Patients and MethodsWe analyzed the prognostic effect of immunohistochemically determined CD43 expression in 119 patients with newly diagnosed DLBCL. All were treated with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone)—like chemotherapy, 57 without and 62 with rituximab.ResultsA total of 31 DLBCL cases (26%) expressed CD43. Patients with CD43+ and CD43— lymphomas did not differ regarding sex, International Prognostic Index (IPI) factors and score, rituximab treatment, presence of bulky disease, or germinal center subtype. Median follow-up was 45 months. Patients with CD43+ DLBCL had significantly lower complete response rates (59% vs. 80%; P = .019), 2-year event-free survival (EFS) rates (34% vs. 64%; P = .003), and overall survival (OS) rates (45% vs. 76%; P = .002). The prognostic significance of CD43 expression was retained in multivariate analysis (relative risk [RR] 2.04; P = .013 for EFS; RR 2.17; P = .016 for OS). In subgroup analysis, the effect of CD43 expression was significant in patients treated with rituximab and those with low IPI, whereas it was not reached in patients treated without rituximab. The effect was not observed in patients with high IPI.ConclusionThese results indicate that CD43 expression is an important independent adverse prognostic factor in DLBCL.     

头颈部弥漫大B细胞淋巴瘤患者临床特征及预后模型分析研究

背景与目的：头颈部弥漫大B细胞淋巴瘤（head and neck diffuse large B-cell lymphoma,HN-DLBCL）是该解剖部位常见侵袭性非霍奇金淋巴瘤,随着含有利妥昔单抗免疫化疗方案以及局部放疗和细胞免疫治疗的成功应用,HN-DLBCL患者的缓解率和无病生存率较以往有显著提高,然而仍有一部分患者成为复发/难治性病例。前期临床研究发现,基于预后模型分层治疗可以使高危淋巴瘤患者得到早期充分干预而显著降低其复发或成为难治性病例的概率。系统分析HN-DLBCL患者的临床特点与其预后的相关性,并比较不同预后模型的分层能力。方法：回顾性分析2010年1月—2018年12月在上海交通大学医学院附属第九人民医院诊治的134例HN-DLBCL患者的临床资料,应用Kaplan-Meier法计算生存率并绘制生存曲线,log-rank检验和COX回归模型进行单因素及多因素生存预后分析,进一步采用国际预后指数（International Prognostic Index,IPI）、美国国家综合癌症网络-IPI（National Comprehensive Cancer Network-IPI,NCCN-IPI）和西班牙淋巴瘤/自体骨髓移植工作组-IPI（Spanish Lymphoma/Autologous Bone Marrow Transplant Working Group-IPI,GELTAMO-IPI）进行危险度分层,对比各预后分层系统不同危险程度患者3年生存率的差异。结果：单因素分析结果显示,Ann Arbor临床分期、非生发中心B细胞（non-germinal center B-cell,non-GCB）亚型、血清乳酸脱氢酶（lactate dehydrogenase,LDH）和β2微球蛋白水平是HN-DLBCL患者预后的影响因素（P<0.05）,而多因素COX分析发现,LDH水平是影响患者预后的独立危险因素。根据IPI、NCCN-IPI和GELTAMO-IPI评分系统,高危HN-DLBCL患者3年总生存率（overall survival,OS）分别为44.7%、36.8%和32.8%,3年无进展生存率（progression-free survival,PFS）分别是44.3%、20.7%和16.3%,与IPI预后模型相比,NCCN-IPI和GELTAMO-IPI评分系统更能甄别高危HN-DLBCL患者。结论：在免疫化疗治疗时代,血清LDH水平是HN-DLBCL患者预后的独立危险因素,而改良国际预后模型NCCN-IPI和GELTAMO-IPI较IPI评分更能分辨高危患者。     

The Absolute Monocyte and Lymphocyte Prognostic Index for Patients With Diffuse Large B-Cell Lymphoma Who Receive R-CHOP

BackgroundThe baseline absolute monocyte count and absolute lymphocyte count were used to generate a prognostic index (the AMLPI) for survival in diffuse large B-cell lymphoma (DLBCL).MethodsData from 245 patients with DLBCL who were treated with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) were reviewed. By using the values previously reported for the AMLPI, its prognostic value was examined in our population.ResultsAfter a median follow-up of 22 months for censored observations, the 3-year progression-free survival (PFS) rates for the international prognostic index (IPI) 0-2 and 3-5 risk groups were 73% and 58%, respectively (P = .0004); comparable overall survival (OS) rates were 88% and 68%, respectively (P < .0001). For patients with IPI scores of 0-2, 1-year PFS rates for AMLPI low-, intermediate-, and high-risk groups were 92%, 89%, and 80%, respectively (P = .022); comparable 1-year OS rates were 96%, 95%, and 80%, respectively (P = .049). By multivariate analysis, with the adjustment of IPI in the model, AMLPI effects (low- vs. high-risk groups) on PFS and OS rates were significant, with P = .046 (hazard ratio [HR] 0.402 [95% CI, 0.164-0.986] and P = .052 (HR 0.325 [95% CI, 0.104-1.011]), respectively.ConclusionsThe absolute monocyte and lymphocyte counts prognostic index (the AMLPI) may add prognostic value beyond that of the IPI for patients with DLBCL who receive R-CHOP.     

Evaluation of Ki-67 as a Prognostic Marker in Diffuse Large B-Cell Lymphoma—A Single-Center Retrospective Cohort Study

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and prognostic information is essential in finding the right treatment. This study evaluated the prognostic significance of Ki-67 in patients with DLBCL. Methods: Patients with DLBCL, treated with first-line R-CHOP, were retrospectively analyzed in groups of high (>70%) and low (≤70%) Ki-67. Parameters of interest were the international prognostic index (IPI), treatment response, progression-free survival (PFS) and overall survival (OS). A chi-squared test or Fisher’s exact test was conducted to analyze categorical variables. Kaplan–Meier and log-rank tests were applied for survival analyses. Finally, a multivariate linear regression analysis was performed, including gender, Ki-67 ≤ 70% or >70%, IPI and presence of B symptoms. Results: Overall, 58 patients were included. No significant association was found between Ki-67 status and IPI (p = 0.148) or treatment response (p = 0.373). Survival in patients with high Ki-67 was significantly inferior with respect to OS (p = 0.047) but not PFS (p = 0.138). Multivariate linear regression, however, yielded only IPI as a risk factor for OS. Conclusion: Future studies with larger patient cohorts are needed in order to elucidate the prognostic role of Ki-67 in patients with DLBCL treated with R-CHOP.     

CD5 expression is potentially predictive of poor outcome among biomarkers in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy

BackgroundSeveral biomarkers indicating poor prognosis have been reassessed in patients receiving rituximab combination chemotherapy for diffuse large B-cell lymphoma (DLBCL). However, few studies have investigated outcome in relation to a combination of these biomarkers. In addition, no large-scale studies have reassessed the outcome of patients with CD5-positive DLBCL treated with rituximab.Patients and methodsWe conducted a retrospective study and investigated the predictive value of three biomarkers—BCL2, germinal center (GC) phenotype and CD5—in 121 DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone.ResultsCD5-positive patients showed significantly poorer event-free survival (EFS) and overall survival (OS) than CD5-negative patients (2-year EFS, 18% versus 73%, P < 0.001; 2-year OS, 45% versus 91%, P = 0.001). However, no significant difference in outcome according to BCL2 or GC phenotype was observed. Multivariate analysis revealed that CD5 expression was a significant prognostic factor for EFS [hazard ratio 14.2, 95% confidence interval (CI) 4.7–43.2] and OS (hazard ratio 20.3, 95% CI 3.6–114.4).ConclusionsCD5 expression was the only significant prognostic factor among the biomarkers examined in this study. Further studies with larger numbers are warranted to confirm the prognostic significance of CD5 expression for patients with DLBCL receiving rituximab-containing chemotherapy.     

Clinical behavior and treatment outcome of primary nasal diffuse large B-cell lymphoma

BACKGROUND:

Nasal diffuse large B‐cell lymphoma (DLBCL) is rare. The objective of this study was to evaluate the clinical features and treatment outcomes of patients with nasal DLBCL.

METHODS:

Twenty‐five patients were included in the study. All patients received combination chemotherapy with or without radiotherapy.

RESULTS:

Patients with nasal DLBCL usually were older and were predominantly men with early stage disease, low frequency of B symptoms and elevated lactate dehydrogenase (LDH), good performance status, and a low‐risk international prognostic index (IPI) score. The overall response rate after initial treatment was 76%, the 3‐year overall survival (OS) rate for the whole group was 44%, and the median OS was 35 months. Performance status and IPI were significant prognostic factors for OS. For patients with IPI scores of 0 or 1, the 3‐year OS rate was 54%, and the median OS was 52 months compared with 17% and 11 months, respectively, for patients with IPI scores of 2 or 3 (P = .033). The prognosis for patients who achieved a complete response (CR) was significantly better than that for patients who did not achieve a CR. Extranodal spread was the primary pattern of failure.

CONCLUSIONS:

The current results indicated that primary nasal DLBCL appears to have distinct clinical features; its poor outcome and propensity for extranodal failure illustrate the need for innovative therapies. Cancer 2011;. © 2011 American Cancer Society.     

Immunophenotype as prognostic factor for diffuse large B-cell lymphoma in patients undergoing clinical risk-adapted therapy.

BACKGROUND: For patients with diffuse large B-cell lymphoma (DLBCL), the International Prognostic Index (IPI) predicts the likelihood for cure with chemotherapy. Biological parameters, including expression of Bcl-6, Bcl-2, CD10, major histocompatibility complex class II, and categorization as germinal center (GC) type have been described as IPI-independent prognostic factors. PATIENTS AND METHODS: Biological parameters were evaluated retrospectively by immunohistochemistry in 60 consecutive DLBCL patients of the prerituximab era. Forty-one of 60 patients underwent a risk-adapted treatment strategy including autologous stem-cell transplantation for high-risk patients (age-adjusted IPI = 2-3; slow response to chemotherapy). RESULTS: Bcl-6 expression was associated with superior overall survival (OS) independently of the IPI. Inferior progression-free survival (PFS) was independently correlated with high expression of Bcl-2 and low positivity for HLA-DR and CD10. Distinction into GC and non-GC DLBCL on the basis of Bcl-6, CD10, and IRF-4 expression had no independent prognostic value. Within the risk-adapted treatment strategy, only HLA-DR retained a prognostic impact on OS (P = 0.0058) and PFS (P = 0.0002). CONCLUSIONS: In 60 patients with DLBCL treated with risk-adapted therapy, immunohistochemical subcategorization of DLBCL into GC and non-GC type has little clinical value. The IPI-associated risk appears to be mitigated by intensified upfront therapy. Low HLA-DR expression is associated with poor outcome after intensified upfront therapy. Therefore, additional treatment modalities appear to be required.     

High expression of cell division cycle 7 protein correlates with poor prognosis in patients with diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma. According to the clinical risk factors and biological heterogeneity, clinical outcome of DLBCL is extremely various, with 5-year survival rates between 30 and 80?%. Although the International Prognostic Index (IPI) remains the primary clinical tool used to predict outcome for patients with DLBCL, notable variability in outcome is still observed within the same IPI score. The cell division cycle 7 (CDC7) is a serine?Cthreonine kinase, which is required to initiate DNA replication. Study showed that high expression of CDC7 was correlated with poor prognosis in patients with DLBCL. Whether CDC7 is an independent prognostic factor for DLBCL remains debatable. We studied the expression of CDC7 protein in 60 Chinese DLBCL patients with immunohistochemical analysis, 34 patients (56.7?%) categorized as low CDC7 expression and 26 patients (43.3?%) as high CDC7 expression. The median survival time of patients with low CDC7 expression was not achieved and that of high expression was 9?months (P?=?0.027). A multivariate analysis showed that IPI score and Ann Arbor stage were independent prognostic factors in relation to patients?? OS (P?<?0.05). Pearson correlation analysis showed that CDC7 expression level was positively correlated with IPI score and Ann Arbor stage (P?<?0.001). The results suggest that CDC7 expression level in combination with IPI score and Ann Arbor stage can be specific prognostic factors for DLBCL patients. CDC7 could also be a potential therapeutic target in DLBCL, especially for ABC-DLBCL.     

HLA-DR protein status predicts survival in patients with diffuse large B-cell lymphoma treated on the MACOP-B chemotherapy regimen

Loss of major histocompatibility class II (MHC class II) molecules on diffuse large B-cell lymphoma (DLBCL) has been associated with poor survival; however, none of these reports analysed a uniformly treated patient cohort. This study was designed to validate one MHC class II antigen, HLA-DR, as a prognostic marker in patients uniformly treated with the MACOP-B regimen. Immunostaining results were correlated with the international prognostic index (IPI) score and overall survival (OS). Of the 97 cases, 82 had interpretable staining. Of these, 52 expressed HLA-DR (median OS, 16.2 years) while 30 were negative (median OS, 4.2 years, P = 0.037). The IPI was also predictive of OS in the study group (P = 0.023). A Cox multivariate model established both IPI (P = 0.031) and HLA-DR (P = 0.04) as independent predictors of OS. This is the first demonstration of the prognostic relevance of HLA-DR in a uniformly treated DLBCL patient group.     

Prognostic value of BCL2 and TP53 genetic alterations for diffuse large B-cell lymphoma patients treated with R-CHOP

Objective:Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) are available. This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients, and examine correlation of BCL2, TP53 and other genetic alterations with outcomes in patients treated with R-CHOP.Methods:Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL. MYC, BCL2, and BCL6 protein expressions were detected by immunohistochemistry.Results:The presence of BCL2 alterations significantly correlated with poor progression-free survival (PFS) (5-year PFS: 13.7% vs. 40.8%; P = 0.003) and overall survival (OS) (5-year OS: 34.0% vs. 70.9%; P = 0.036). Importantly, patients who harbored BCL2 gain/amplifications (BCL2^GA/AMP) also had a remarkably inferior 5-year PFS (11.1% vs. 38.3%; P < 0.001) and OS (22.1% vs. 69.6%; P = 0.009). In contrast, neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival. Multivariable analyses showed that the presence of BCL2 alterations, especially BCL2^GA/AMP, TP53 mutations, and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models for OS were constructed based on 3 risk factors, including BCL2 alterations (Model 1) or BCL2^GA/AMP (Model 2), TP53 mutations, and IPI, to stratify patients into 4 risk groups with different survival outcomes.Conclusions:This study showed that DLBCL patients treated with R-CHOP, BCL2 alterations, especially BCL2^GA/AMP and TP53 mutations were significantly associated with inferior outcomes, which were independent of the IPI. The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP, but further validation of the prognostic models is still warranted.     

Clinical impact of controlling nutritional status score on the prognosis of patients with diffuse large B-cell lymphoma

The controlling nutritional status (CONUT) score is a nutritional index calculated from serum albumin and total cholesterol levels and lymphocyte counts. Its role in predicting clinical outcomes of diffuse large B-cell lymphoma (DLBCL) has not been evaluated. In this retrospective study, data from 476 patients with DLBCL were analyzed. The cutoff value of the CONUT score was set as 4. CONUT score significantly stratified the overall survival (OS) and the progression-free-survival (PFS) (5-year OS, 49.0% vs 83.2%, P < .001; 5-year PFS, 46.1% vs 73.1%, P < .001) of the patients. Among patients at high-intermediate or high risk, as per the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), 5-year OS was lower in patients with high CONUT scores than in those with low CONUT scores (high-intermediate risk, 51.2% vs 75.5%, P < .001; high risk, 29.9% vs 63.3%, P = .007). Additionally, in patients with high CONUT scores, maintenance of relative dose intensity (RDI) of chemotherapy did not affect the 5-year OS (RDI > 80% vs RDI ≤ 80%: 59.8% vs 50.9%, P = .73). In the present study, we have demonstrated that the CONUT score is an independent prognostic factor in patients with DLBCL.     

Low serum cholesterol levels predict inferior prognosis and improve NCCN‐IPI scoring in diffuse large B cell lymphoma

Low circulating cholesterol concentration is associated with elevated cancer incidence and mortality. However, the association between cholesterol levels and diffuse large B cell lymphoma (DLBCL) remains unknown. The aim of our study was to evaluate the prognostic value of serum lipid profile in DLBCL. Five hundred and fifty enrolled subjects with detailed serum lipid levels at diagnosis of DLBCL were randomly divided into a training set (n = 367) and a validation set (n = 183) (ratio, 2:1). Multivariate Cox regression analyses screened the prognostic factors associated with progression‐free survival (PFS) and overall survival (OS). Performances of models were compared using C‐index and area under the curve in internal and external validation. The results showed that decreased levels of total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C) and low‐density lipoprotein cholesterol (LDL‐C) were associated with unfavorable PFS and OS in the rituximab era, and concurrently low HDL‐C together with low LDL‐C was an independent prognostic indicator for both PFS and OS. Patients achieving complete remission or partial remission after 6–8 circles of chemotherapies had significantly increased cholesterol levels compared to the levels at DLBCL diagnosis, and HDL‐C or LDL‐C elevations were correlated with better survival. Furthermore, the predictive and discriminatory capacity of the National Comprehensive Cancer Network (NCCN)‐International Prognostic Index (IPI) together with low cholesterol levels was superior to NCCN‐IPI alone both in the training and validation set. In conclusion, serum cholesterol levels are simple and routinely tested parameters, which may be good candidates for predicting prognosis in the future clinical practice of DLBCL.     

Low lymphocyte-to-monocyte ratio predicts unfavorable prognosis in non-germinal center type diffuse large B-cell lymphoma

The peripheral blood lymphocyte to monocyte ratio (LMR) at diagnosis has been used to predict survival in diffuse large B-cell lymphoma (DLBCL) patients, but its prognostic significance with respect to different cell-of-origin (COO) subtypes remains unknown. We retrospectively analyzed 168 de novo DLBCL patients in this study and found that a low LMR (≤2.6) correlates with B symptoms, elevated LDH, advanced Ann Arbor stage and higher international prognostic index (IPI) score (p < 0.05). The low LMR is a negative prognostic parameter for overall survival (OS) and event-free survival (EFS) in non-germinal center (GC) type DLBCL patients, as compared with the high LMR, especially in those treated with R-CHOP. However, the LMR has less correlation with the OS and EFS in GC type DLBCL patients (p = 0.545 and 0.547, respectively). Multivariate analysis adjusting for IPI revealed that the low LMR indicates a shorter survival retain both OS and EFS in non-GC subtypes (p = 0.023 and 0.005, respectively). In the non-GC DLBCL patients treated with R-CHOP a low LMR still showed a trend to predict poor EFS (p = 0.052). In conclusion, these data suggest that a low LMR at diagnosis may imply a poor prognosis in non-GC subtype DLBCL patients, especially in those treated with R-CHOP, but not in those GC subtype DLBCL patients.     

Prognostic models for diffuse large B-cell lymphoma in the rituximab era: a never-ending story

BackgroundImproved treatment have modified survival outcome in patients with diffuse large B-cell lymphoma (DLBCL) and altered the importance of previously recognized prognostic markers.Design and methodsTo evaluate International Prognostic Index (IPI) score before and after rituximab introduction and to validate the absolute lymphocyte count (ALC)/revised International Prognostic Index (R-IPI) model, we carried out a retrospective analysis on a total of 831 patients with DLBCL.ResultsOur results show that IPI lost its discriminating power with the introduction of rituximab. The analysis of our second set allowed us to validate the ALC/R-IPI model. The R-IPI and ALC/R-IPI could still be used for designing clinical trials, but both have difficulty recognizing a high percentage of poor prognosis patients, though it remains an important goal of a good prognostic model considering the modest impact of salvage treatments on survival.ConclusionsA new model on the basis of significant variables in the rituximab era and built on a large database of patients treated with rituximab is urgently needed. As prognostic models are changing with the efficacy and mechanisms of action of treatment utilized, looking for a new prognostic score is a never-ending story in which researchers are trying to hit a continuously moving target.