A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma

Background:

Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear.

Methods:

We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP ‘group 1'' R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX ‘group 2'' dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX ‘group 3''.

Results:

Overall, 217 patients were identified (49, 125 and 43 in groups 1–3, respectively). With median follow-up of 3.4 (range 0.2–18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1–3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5–33.1%), 6.9% (3.5–13.4%) and 2.3% (0.4–15.4%) in groups 1–3, respectively (P=0.009).

Conclusions:

The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.     

Lack of benefit of central nervous system prophylaxis for diffuse large B-cell lymphoma in the rituximab era: findings from a large national database

BACKGROUND:

Little is known about the utility of central nervous system (CNS) prophylaxis for diffuse large B‐cell lymphoma (DLBCL) in the rituximab era. The objective of this study was to characterize patterns of CNS prophylaxis for patients who received combined rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) chemotherapy using the National Comprehensive Cancer Network Non‐Hodgkin Lymphoma Outcomes Database, a prospective cohort study that collects clinical and outcomes data for patients at 7 participating centers.

METHODS:

Patients who were eligible for this analysis presented with newly diagnosed DLBCL between January 2001 and July 2008, had no evidence of baseline CNS disease, and had received R‐CHOP within 180 days of diagnosis. The authors assessed incidence and covariates of prophylaxis, prophylaxis modality, and, using propensity score analysis, outcomes such as overall survival.

RESULTS:

Of 989 eligible patients, 117 received CNS prophylaxis (11.8%), most intrathecally (71.8%). Involvement of bone marrow, other high‐risk site, >1 extranodal site, higher International Prognostic Index score, and higher stage were associated individually with the receipt of prophylaxis (all P < .0001). At a median follow‐up of 2.5 years, there were 20 CNS recurrences (2% [95% confidence interval, 1.1%‐2.9%]) among all patients, and overall survival was not affected by prophylaxis.

CONCLUSIONS:

Given the overall low rate of CNS recurrence and lack of prophylaxis‐associated survival benefit, the current data called into question the practice of CNS prophylaxis in the rituximab era. Cancer 2011. © 2011 American Cancer Society.     

Serum level of CXCL10 is associated with inflammatory prognostic biomarkers in patients with diffuse large B‐cell lymphoma

Inflammatory biomarkers, such as the neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and Glasgow Prognostic Score (GPS) have been proposed to predict prognosis in diffuse large B‐cell lymphoma (DLBCL). C‐X‐C motif ligand 10 (CXCL10) is a chemokine released from inflammatory cells in the tumor microenvironment and is known to promote tumor cell migration and invasion. In this study, we investigated the clinical impact of pretreatment serum level of CXCL10 on the prognostic value of inflammatory biomarkers in 313 patients with DLBCL who were enrolled into a prospective cohort study. Serum level of CXCL10 was measured in archived pretreatment frozen samples. The high CXCL10 (>median value) group was significantly associated with high tumor burden status, including advanced stage (III‐IV), elevated serum lactic dehydrogenase, and a higher risk International Prognostic Index. Progression‐free survival of the high CXCL10 group was significantly worse than that of the low CXCL10 group, and secondary central nervous system involvement was more frequent in the high CXCL10 group. High CXCL10 was associated with high C‐reactive protein level (r  = 0.246), low albumin level (r  = ?0.289), low absolute lymphocyte count (r  = ?0.185), and risk stratification according to NLR, LMR, and GPS. C‐X‐C motif ligand 10 promoted cell migration of patient‐derived cells and several DLBCL cell lines. However, the prognostic value of high CXCL10 was lost in the multivariate analyses. Nevertheless, we suggest serum CXCL10 may have clinical value if it can be more easily assessed because of its contribution to the prognostic value of NLR, LMR, and GPS in DLBCL.     

71例原发颅内中枢神经系统DLBCL预后分析

目的 探讨原发颅内中枢神经系统弥漫性大B细胞淋巴瘤(DLBCL)的预后因素。 方法 回顾分析1991—2015年间收治的经病理和临床证实的 71例原发颅内中枢神经系统DLBCL临床资料。全组患者均进行了化疗,59例进行了放疗,化疗方案以HD-MTX (HD-MTX,66/71)为主,放疗方案以全脑放疗 ±局部推量为主。Kaplan-Meier法计算生存率,Logrank法检验和单因素预后分析,Cox模型多因素预后分析。 结果 放化疗结束时 58例CR, 10例PR,3例PD。5年生存率为43%;5年无疾病进展率为34%。单因素分析显示年龄、KPS评分、单发与多发、是否放疗、放化疗完成时评价、有无复发是影响OS的因素(P=0.000~0.047),多因素分析显示年龄、KPS评分、有无复发是影响OS的因素(P=0.000~0.022)。单因素分析化疗方案、是否放疗、总放疗剂量、全脑剂量、放化疗完成时评价、有无复发是影响PFS的因素(P=0.000~0.028);多因素分析KPS评分、有无复发是影响PFS的因素(P=0.000~0.011)。 结论 年轻、KPS评分高、无复发患者总生存更好,单发、接受放疗、放化疗后疗效好的患者可能更好;KPS评分高、放化疗后疗效好、无复发患者PFS更好,接受含HD-MTX化疗、接受放疗、总的放疗剂量和全脑剂量越高患者PFS可能更好。化疗达CR后是否还放疗及放疗靶区、剂量需进一步研究。     

Burkitt lymphoma versus diffuse large B‐cell lymphoma: a practical approach

Burkitt Lymphoma (BL) is listed in the World Health Organization (WHO) classification of lymphoid tumours as an “aggressive B‐cell non‐Hodgkin's lymphoma”, characterized by a high degree of proliferation of the malignant cells and deregulation of the c‐MYC gene. The main diagnostic challenge in BL is to distinguish it from diffuse large B‐cell lymphoma (DLBCL). While in children BL and DLBCL types probably do not differ clinically, and the differential diagnosis between BL and DLBCL may theoretically appear clear‐cut, in adults daily practice shows the existence of cases that have morphological features, immunophenotypic and cytogenetics intermediate between DLBCL and BL, and cannot be classified with certainty in these categories. Distinguishing between BL and DLBCL is critical, as the two diseases require different management. This review summarizes the current practical approach, including the use of a large panel of antibodies, and cytogenetic and molecular diagnostic techniques, to distinguish between BL, DLBCL and the provisional category of “B‐cell lymphoma, unclassificable, with features intermediate between diffuse large B‐cell lymphoma and Burkitt lymphoma”, now listed in the updated WHO classification. Copyright © 2009 John Wiley & Sons, Ltd.     

Isolated central nervous system relapses in primary mediastinal large B‐cell lymphoma after CHOP‐like chemotherapy with or without Rituximab

Central nervous system (CNS) involvement in patients with primary mediastinal large B‐cell (PMLBCL) lymphoma is a rare event, occurring in approximately 6% of patients, on the basis of the review of the literature prior to induction of Rituximab. The aim of this retrospective study was to describe the incidence of CNS relapse among 100 consecutive patients with PMLBCL who were treated with R‐CHOP ± RT in comparison to patients treated with CHOP ± RT (n = 45) in 11 hospitals in Greece. Two patients experienced a CNS relapse, representing an overall frequency of 2.0% in R‐CHOP treated patients and a 2‐year actuarial incidence of 2.3%. Both patients had isolated CNS relapses. The incidence of CNS relapse after CHOP without Rituximab was 2/45 (4.4%) for a 2‐year actuarial incidence of 7.5% (p = 0.29). Again, both patients had isolated CNS relapses. Parenchymal‐only localizations accounted for 3/4 cases. Risk factors for CNS involvement could include leukocytosis, poor performance status and higher age‐adjusted International Prognostic Index, although their impact was weakened by competing risk survival analysis. Both patients relapsing after R‐CHOP required CNS radiotherapy to achieve a complete remission and be forwarded to high‐dose therapy and autologous stem cell transplantation: They are both alive and disease‐free 18 and 23 months after CNS relapse. Both cases relapsing after CHOP without Rituximab were salvaged by CNS radiotherapy (one also received intrathecal chemotherapy) entering long‐term remissions. In conclusion, CNS relapses are rare in PMLBCL tending to be isolated in the CNS, probably reflecting the persistence of latent CNS disease than dissemination of resistant disease. The impact of Rituximab in reducing CNS relapses remains unknown. Established risk factors for CNS involvement in aggressive lymphomas may not be helpful in assessing the risk of CNS recurrence in this disease. Routine CNS prophylaxis is not probably required in PMLBCL. Copyright © 2012 John Wiley & Sons, Ltd.     

Burkitt lymphoma versus diffuse large B‐cell lymphoma: a practical approach

Burkitt Lymphoma (BL) is listed in the World Health Organization (WHO) classification of lymphoid tumours as an ‘aggressive B‐cell non‐Hodgkin's lymphoma’, characterized by a high degree of proliferation of the malignant cells and deregulation of the c‐MYC gene. The main diagnostic challenge in BL is to distinguish it from diffuse large B‐cell lymphoma (DLBCL). While in children BL and DLBCL types probably do not differ clinically, and the differential diagnosis between BL and DLBCL may theoretically appear clear‐cut, in adults daily practice shows the existence of cases that have morphological features, immunophenotypic and cytogenetics intermediate between DLBCL and BL, and cannot be classified with certainty in these categories. Distinguishing between BL and DLBCL is critical, as the two diseases require different management. This review summarizes the current practical approach, including the use of a large panel of antibodies, and cytogenetic and molecular diagnostic techniques, to distinguish between BL, DLBCL and the provisional category of ‘B‐cell lymphoma, unclassifiable, with features intermediate between diffuse large B‐cell lymphoma and Burkitt lymphoma’, now listed in the updated WHO classification. Copyright © 2009 John Wiley & Sons, Ltd.     

Mean platelet volume predicts prognosis in patients with diffuse large B‐cell lymphoma

To determine the prognostic value of baseline mean platelet volume (MPV) in diffuse large B‐cell lymphoma (DLBCL) patients. We retrospectively analyzed 161 DLBCL patients who received R‐CHOP chemotherapy. The associations between MPV and clinicopathological factors were assessed. A low MPV (MPV ≤ 9.1 fl, cut‐off was calculated by receiver operating characteristics) was not associated with any other clinicopathological factors. * Patients with MPV ≤ 9.1 fl experienced a shorter progression‐free survival (PFS) (2‐year PFS rate, 60.6% vs 84.0%, P = 0.003) and overall survival (OS) (2‐year OS rate, 70.4% vs 87.9%, P = 0.030), compared with those with MPV > 9.1 fl. The multivariate analysis demonstrated that MPV ≤ 9.1 fl was an independent prognostic factor of OS (Hazard Ratio [HR] = 0.588, P = 0.045) and PFS (HR = 0.456, P = 0.010). Therefore, we demonstrated that low baseline MPV is an independent prognostic marker of poor outcome in patients with DLBCL.     

The impact of hepatitis B virus (HBV) infection on clinical outcomes of patients with diffuse large B‐cell lymphoma

We performed a retrospective study to analyse the characteristics and clinical outcomes of diffuse large B‐cell lymphoma (DLBCL) patients with hepatitis B virus (HBV) infection and compare with those without HBV infection. The occurrence of hepatitis after withdrawal of prophylactic antiviral treatment on completion of chemotherapy was also assessed. The HBsAg‐positive patients were given prophylactic antiviral treatment until 6 months after finishing chemotherapy. A total of 81 patients were recruited with 16 in the HBsAg‐positive group and 65 in the HBsAg‐negative group. The clinical characteristics were similar in both groups of patients. There was no significant difference in complete remission rate between the two groups (63% in HBsAg‐positive group vs. 54% in HBsAg‐negative group, P = 0.59). There was also no statistically significant difference in overall survival between the two groups (P = 0.23). Four of the 16 HBsAg‐positive patients (25%) had hepatitis after cessation of chemotherapy and prophylactic lamivudine. The mean time of onset of hepatitis was 3 months after stopping lamivudine. In conclusion, HBV infection did not appear to affect the prognosis of DLBCL patients given antiviral prophylaxis. It is reasonable to consider prophylactic antiviral therapy to extend to at least one year on completion of chemotherapy.     

Primary diffuse large B‐cell lymphoma of the tonsil

BACKGROUND: The purpose was to evaluate the prognostic factors and treatment outcome of Indian patients with primary diffuse large B-cell lymphoma (DLBCL) of the tonsil treated at a single institution. METHODS: In all, 121 patients with DLBCL of the tonsil, treated at the Tata Memorial Hospital, Mumbai, India, from January 1990 to December 2002, were included. The median age was 45 years and the majority of patients (68%) were males. Systemic symptoms were present in 12% of patients; 28% presented with stage I and 67% had stage II disease. Treatment consisted of a combination of chemotherapy (CTh) and radiotherapy (RT) for the majority of patients (69.4%). Among those receiving RT, 64% received an RT dose of > or =45 Gy. RESULTS: After a median follow-up of 62 months, disease-free survival (DFS) and overall survival (OS) were 66.4% and 81.6%, respectively. Significant prognostic factors included: WHO performance score > or =2 (OS: 72.1% vs 95.6%, P = .016), bulky tumors (OS: 68.5% vs 86.9%, P = .001), presence of B-symptoms (OS: 36.7% vs 79.6%, P < .001), and Ann Arbor stage. On multivariate analysis; WHO performance score > or =2 (hazard ratio [HR], 4.27; 95% confidence interval [CI], 1.20-15.12), and B symptoms (HR, 6.27; 95% CI, 2.38-16.48), retained statistical significance. CTh + RT resulted in a significantly better outcome than those treated with CTh alone (OS: 85.7% vs 70.7%, P = .008). The complete response (P = .053), DFS (P = .039), and OS (P = .014) rates were significantly better for patients receiving an RT dose > or =45 Gy. CONCLUSIONS: Tumor bulk, WHO performance score, the presence of B symptoms, and Ann Arbor stage significantly influence outcome. A combined modality treatment, consisting of CTh and RT (with an RT dose of > or =45 Gy), results in a satisfactory outcome in patients with this uncommon neoplasm.     

Relapse in stage I(E) diffuse large B‐cell lymphoma

Despite a general favourable outcome in limited stage diffuse large B‐cell lymphoma (DLBCL), relapses occur in about 10 to 20% of patients. Prognostic models only partially identify patients at risk for relapse. Moreover, it is not known whether the outcome after such a relapse is similar to the outcome after relapse in advanced stages. From January 2004 through December 2012, all newly diagnosed patients with stage I(E) DLBCL were retrospectively analysed from 2 clinical databases to investigate the relapse pattern and outcome in relation to initial treatment and clinical characteristics. In 126 patients (median age 64 years), histologically confirmed stage I(E) DLBCL was diagnosed. With a median follow‐up of 53 months (range 5‐132 months), 1 progressive disease and 18 relapses occurred. The 5‐year time to tumour progression and disease‐specific survival were 85% (95% CI 79‐91%) and 92% (95% CI 87%‐97%), respectively. We observed no significant difference in relapse localization, time to tumour progression, and disease‐specific survival between patients treated with abbreviated R‐CHOP plus involved field radiotherapy or with 6 to 8 cycles of R‐CHOP. Analysis of relapses showed relapse >5 years after initial treatment (late relapse) in 5 of 19 patients (26%). Six of 19 patients (32%) had central nervous system relapse. Three of 11 relapsed cases available for analysis (28%) showed an MYC translocation, suggesting an overrepresentation in the relapse group. Outcome of patients with a relapse was poor with a median survival after relapse of 8 months. Only 1 patient (5%) underwent successful autologous stem cell transplantation. To improve outcome in these patients, early identification of new biological factors such as a MYC translocation or a high risk for CNS dissemination might be helpful. Moreover, treatment of any relapse after stage I disease should be taken seriously. Salvage treatment should be similar to relapses after advanced DLBCL.     

PD‐L1 expression is low in large B‐cell lymphoma with MYC or double‐hit translocation

In large B‐cell lymphoma (LBCL), MYC translocation and MYC/BCL2 or MYC/BCL6 double hit (DH) are associated with poor prognosis, and there is an unmet need for novel treatment targets in this patient group. Treatments targeting the PD‐L1/PD‐1 pathway are still poorly elucidated in LBCL. PD‐L1 expression might predict response to treatment targeting the PD‐L1/PD‐1 pathway. We therefore investigated the relationship between PD‐L1 protein and mRNA expression levels and MYC and DH translocation in LBCL. We detected MYC, BCL2, and BCL6 translocation by fluorescent in situ hybridization in tissue samples from 130 patients randomly selected from two cohorts of patients with LBCL: 49 patients with MYC translocation of whom 36 had DH and 81 without MYC translocation. PD‐L1 protein expression was detected by immunohistochemistry (IHC) in tissue samples from 77 patients and PD‐L1 mRNA expression by next‐generation RNA sequencing (NGS) in another 77 patients. Twenty‐four patients overlapped, ie, were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences. PD‐L1 protein expression level was significantly lower in patients with MYC (n = 42, median = 3.3%, interquartile range [IQR] 0.0‐10.8) or DH translocations (n = 31, median = 3.3%, IQR 0.0‐10.0) compared with patients with no MYC (n = 35, median = 16.7%, IQR 3.3‐30.0) or no DH translocations (n = 46, 13.3%, IQR 2.5‐30.0), P = .004 and P ≤ .001, respectively. PD‐L1 mRNA expression was also significantly lower in patients with MYC or DH translocations, P = .001 and P = .006, respectively. Higher PD‐L1 protein and mRNA expression levels were associated with non–germinal centre (GC) type compared with germinal centre B‐cell (GCB)‐type diffuse LBCL (DLBCL), P = .004 and P = .002, respectively. In conclusion, we report an association between low PD‐L1 expression and MYC and DH translocation in patients with LBCL. Our findings may indicate that patients with MYC or DH translocation may benefit less from treatment with PD‐L1/PD‐1‐inhibitors compared with patients without these translocations. This should be evaluated in larger, prospective, consecutive trials.     

Anemia as a useful biomarker in patients with diffuse large B‐cell lymphoma treated with R‐CHOP immunochemotherapy

The aim of the current study is to evaluate the prognostic value of anemia, an easily estimable parameter in patients with diffuse large B‐cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R‐CHOP) immunochemotherapy. A total of 157 patients with newly diagnosed diffuse large B‐cell lymphoma treated with ≥1 cycle of R‐CHOP were included. Hemoglobin level without red cell transfusion within 7 days of initiation of treatment was chosen as a parameter of baseline cancer‐induced anemia. To investigate the clinical significance of chemotherapy‐induced anemia and its recovery after completion of treatment, 87 patients in complete remission for ≥6 months from the time of the last cycle of R‐CHOP were grouped and analyzed separately. Patients with a cancer‐induced anemia of hemoglobin <10 g/dL showed inferior event‐free and disease‐free survival compared to those with hemoglobin ≥10 g/dL. This finding was observed irrespective of the status of pre‐treatment bone marrow involvement. In multivariate analysis, hemoglobin <10 g/dL was found to be an international prognostic index‐independent prognostic factor. Risk of relapse was significantly higher for patients who were still anemic at 6 months after R‐CHOP, compared to those who achieved complete recovery from chemotherapy‐induced anemia within 6 months.     

原发性中枢神经系统弥漫大B细胞淋巴瘤临床病理学观察

目的：观察原发性中枢系统弥漫大B细胞淋巴瘤（PCNS-DLBCL）临床病理学、影像学特点,探讨其免疫组化、基因重排检测及microRNA表达特征。方法：收集确诊的PCNS -DLBCL 25例,观察并分析影像学、病理组织学、免疫组化标记特点,并进行重链和轻链基因重排检测。对其中10例典型PCNS-DLBCL、10例颅外生发中心来源的弥漫大B细胞淋巴瘤（GC-DLBCL）和10例颅外非生发中心来源的弥漫大B细胞淋巴瘤（NGC-DLBCL）的石蜡包埋组织块微切割提取microRNA,进行芯片杂交,对三者间的差异性进行比较。结果：PCNS-DLBCL多累及两个或两个以上脑叶（10/25例）,其中额叶受累最为常见（6/25例）。所有病例均可见中心母细胞样的大淋巴细胞围绕血管呈靶环样生长。免疫组化染色结果显示,25/25例均弥漫强阳性表达CD20、CD79a,不表达CD3、CD5、CD23、CyclinD1,Ki-67阳性率在50％-90％（平均80％）,仅有3例表达CD10（占12％）,19例表达Bcl-6（占76％）,22例表达Mum-1（88％）。基因重排检测显示24/25例呈B细胞单克隆性（96％）。microRNA芯片杂交显示,与NGC-DLBCL比较,升高2倍及以上者788个microRNA或片段,下降0．5倍以下者401个microRNA或片段;与GC-DLBCL比较,升高2倍及以上者611个microR-NA或片段,下降0．5倍以下者229个microRNA或片段。结论：PCNS-DLBCL以老年男性好发,常累及多个部位,免疫组化显示大部分为活化B细胞来源,基因重排检测B细胞单克隆性高,microRNA芯片杂交显示, PCNS-DLBCL microRNA表达明显不同于颅外NGC-DLBCL和GC-DLBCL,可能存在microRNA诊断性标志物。从microRNA表达差异的数量看,PCNS-DLBCL与颅外GC-DLBCL差异较小,此与二者的预后接近相关。     

Refractory diffuse large B‐cell lymphoma after first‐line immuno‐CT: Treatment options and outcomes

In the rituximab era, one‐third of diffuse large B‐cell lymphoma patients experience relapse/refractory disease after first‐line anthracycline‐based immunochemotherapy. Optimal management remains an unmet medical need. The aim of this study was to report the outcomes of a cohort of refractory patients according to their patterns of refractoriness and the type of salvage option. We performed a retrospective analysis, which included 104 diffuse large B‐cell lymphoma patients treated at Lyon Sud University Hospital (2002‐2017) who presented with refractory disease. Refractoriness was defined as progressive/stable disease during first‐line treatment (primary refractory, N = 47), a partial response after the end of first‐line treatment that required subsequent treatment (residual disease, N = 19), or relapse within 1 year of diagnosis after an initial complete response (CR) (early relapse, N = 38). The 2‐year overall survival (OS) rates for primary refractory, early relapse, and residual disease patients were 27%, 25%, and 52%, respectively, while the event‐free survival rates for those groups were 13%, 13%, and 42%, respectively. In a univariate analysis, lactate dehydrogenase level, Ann Arbor stage, poor performance status, high age‐adjusted International Prognostic Index score, and age > 65 years were associated with shorter OS. The use of rituximab and platinum‐based chemo during the first salvage treatment was associated with prolonged OS. In a multivariate analysis, age (HR:2.06) and rituximab use (HR:0.54) were associated with OS. Among patients <65 years who achieved a CR, autologous stem‐cell transplant was associated with higher 2‐year OS (90% vs 74%, P = 0.10). Patients who were treated with a targeted therapy in the context of a clinical trial after second‐line treatment had a higher 2‐year OS (34% vs 19%, P = 0.06). In conclusion, patients with primary refractory disease or early relapse have very poor outcomes but may benefit from rituximab retreatment during the first salvage treatment.     

Frontline treatment of diffuse large B‐cell lymphoma: Beyond R‐CHOP

Although the majority of patients with diffuse large B‐cell lymphoma (DLBCL) can be cured with the standard immunochemotherapy R‐CHOP, one‐third of them relapses with a dismal outcome in most cases. In the recent years, remarkable advances have been achieved based on the discovery of molecular genetics in DLBCL. In addition to the major cell‐of‐origin designations of germinal center B‐cell and activated B‐cell subtypes, next‐generation sequencing has unveiled the remarkable complexity of DLBCL and identified potential molecular targets for tailored therapies. Despite these findings, the current standard of care for DLBCL patients is still R‐CHOP, and optimization of frontline therapy remains an important goal. In this review, we summarize recent updates on the evolution of frontline therapies for DLBCL.     

Diffuse large B‐cell lymphoma

BACKGROUND:

The objective of this study was to compare the clinical features and prognosis of patients with diffuse large B‐cell lymphoma (DLBCL) of Waldeyer ring (WR‐DLBCL) and patients with lymph node DLBCL (N‐DLBCL).

METHODS:

One hundred eighty‐one patients with WR‐DLBCL and N‐DLBCL were reviewed. There were 57 patients with stage I disease, 83 patients with stage II disease, 26 patients with stage III disease, and 15 patients with stage IV disease. Among them, 101 patients had primary N‐DLBCL, and 80 patients had primary WR‐DLBCL.

RESULTS:

Patients with WR‐DLBCL and N‐DLBCL usually presented at an older age and had localized disease, a low frequency of B symptoms, a good performance status, and a low‐risk International Prognostic Index (IPI) score. Compared with patients who had N‐DLBCL, patients who had WR‐DLBCL presented with more stage II disease and lower tumor burdens. The overall response rate after treatment was similar in both groups. The 5‐year overall survival (OS) and progression‐free survival (PFS) rates were 76% and 61% in patients with WR‐DLBCL, respectively, and 56% and 50% in patients with N‐DLBCL, respectively (P = .119 for OS; P = .052 for PFS). IPI scores and elevated β2‐microglobulin and LDH levels were associated with a poor prognosis for patients who had WR‐DLBCL; whereas bulky tumor, elevated β2‐microglobulin levels, and IPI scores were associated with poor OS for patients who had N‐DLBCL.

CONCLUSIONS:

The current results supported the continued inclusion of WR‐DLBCL as a lymph node group in the staging of DLBCL. Patients with WR‐DLBCL had clinical features and prognosis similar to those of patients with N‐DLBCL. Cancer 2009. © 2009 American Cancer Society.