Comprehensive Cancer Network-International Prognostic Index Research Articles

A Multi-Institutional Validation of the Prognostic Value of the Neutrophil-to-Lymphocyte Ratio in Patients With Diffuse Large B-Cell Lymphoma: A Study From The Latin American Group of Lymphoproliferative Disorders (GELL)

IntroductionWe aimed at investigating the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) in 2 independent cohorts of Latin American patients with diffuse large B-cell lymphoma (DLBCL) treated with chemoimmunotherapy. Patients and MethodsThe learning cohort was composed of 274 patients and the validation cohort of 323 patients, for a total of 597 patients. An optimal NLR cutoff ≥ 4 was determined using receiver operating characteristic analysis. ResultsIn multivariate models, NLR ≥ 4 was independently associated with lower odds for complete response to chemoimmunotherapy in the learning (odds ratio, 0.46; P = .006) and the validation cohort (odds ratio, 0.49; P = .01), and independently associated with worse survival in the learning (hazard ratio, 1.55; P = .04) and the validation cohort (hazard ratio, 1.80; P = .003). ConclusionsThe adverse prognostic value of NLR ≥ 4 was independent of the International Prognostic Index and the National Comprehensive Cancer Network-International Prognostic Index score. Based on the results of this multi-institutional study, NLR ≥ 4 emerges as an adverse prognostic factor in Latin American patients with DLBCL treated with chemoimmunotherapy.

Hepatitis B Surface Antigen Positivity Is an Independent Unfavorable Prognostic Factor in Diffuse Large B-Cell Lymphoma in the Rituximab Era.

Patients with diffuse large B-cell lymphoma (DLBCL) with concurrent hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection have distinct clinical features. Nevertheless, the prognostic value of HBsAg in DLBCL in the rituximab era remains unclear. We conducted a retrospective cohort study to investigate the clinical relevance of HBsAg in immunocompetent patients with DLBCL treated with homogeneous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone between 2002 and 2016. Among 416 analyzed patients, 98 (23.6%) were HBsAg positive. HBsAg positivity was associated with a younger age and more advanced stage at diagnosis, more frequent hepatic impairment during perichemotherapy, and a trend of higher National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score at diagnosis. Compared with the HBsAg-negative patients, the HBsAg-positive patients had a lower overall response rate (76.5% vs. 85.5%, p = .043), poorer 5-year overall survival (OS) rate (57.2% vs. 73.5%, p < .001), and shorter 5-year progression-free survival (PFS) rate (47.2% vs. 60.7%, p = .013). Multivariate analyses showed that HBsAg positivity was an independent unfavorable prognostic indicator for OS and PFS. A scoring system incorporating HBsAg positivity, the NCCN-IPI score, and serum albumin levels proved to be useful for stratifying prognostically relevant subgroups of patients with DLBCL. This study demonstrated that HBV infection is uniquely relevant to DLBCL. HBsAg might serve as a novel biomarker to improve clinical risk stratification of patients with DLBCL in areas with high prevalence of HBV infection. Further research investigating the etiopathogenesis of HBV infection in DLBCL is imperative. A considerable disparity exists regarding the prognostic relevance of hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection in patients with diffuse large B-cell lymphoma (DLBCL). In this large, retrospective cohort study from an area with high prevalence of HBV infection, the authors demonstrated that HBsAg was an independent unfavorable factor significantly associated with survival, highlighting its potential as a novel prognostic indicator to improve the risk stratification of patients with DLBCL in the rituximab era.

High Red Cell Distribution Width is an Adverse Predictive and Prognostic Factor in Patients With Diffuse Large B-Cell Lymphoma Treated With Chemoimmunotherapy

IntroductionThe red blood cell distribution width (RDW) is an easy-to-obtain laboratory value that has emerged as a potential prognostic factor in solid and hematologic malignancies. Patients and MethodsWe evaluated 121 patients with de novo diffuse large B-cell lymphoma (DLBCL) treated with standard chemoimmunotherapy at our institution between 2010 and 2012. We categorized patients with high RDW (> 14.6%) and normal RDW (11.6%-14.6%). We fitted multivariate regression models for complete response (CR) and overall survival (OS). ResultsPatients with high RDW were less likely to achieve CR to chemoimmunotherapy than patients with normal RDW (48% vs. 83%; P < .001). The 5-year OS rate for patients with high RDW was lower than in patients with normal RDW (51% vs. 79%; P = .001). In multivariate regression models, high RDW was independently associated with lower odds of achieving CR (odds ratio, 0.32; 95% confidence interval [CI], 0.12-0.83; P = .02) and with higher risk of death from any cause (hazard ratio [HR], 2.04; 95% CI, 1.03-4.02; P = .04) than normal RDW in patients with DLBCL treated with chemoimmunotherapy. High RDW remained an independent adverse factor for OS after adjustment for the International Prognostic Index and the National Comprehensive Cancer Network-International Prognostic Index scores with HR 2.20 (95% CI, 1.12-4.31; P = .02) and HR 2.67 (95% CI 1.28-5.59; P = .009), respectively. ConclusionHigh RDW appears to be an adverse predictive and prognostic factor in patients with de novo DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Comparison of clinical scoring systems in aggressive B-cell lymphomas (BCL): An individual patient-level analysis across international trials (SEAL).

7544 Background: Great heterogeneity in survival exists for patients (pts) newly diagnosed with aggressive BCL. Three scoring systems based on simple clinical parameters (age, lactate dehydrogenase, number/sites of involvement, stage, performance status) are widely used: the international prognostic index (IPI), revised-IPI (R-IPI), and National Comprehensive Cancer Network IPI (NCCN-IPI). We studied BCL pts treated with R-CHOP to determine which scoring systems best identifies subgroups with poor outcomes that might benefit from new approaches. Methods: Individual pt data from 7 multicenter trials (1998-2009) of pts with BCL (86% DLBCL) treated front-line with R-CHOP (or variant) were analyzed to determine whether IPI, R-IPI, or NCCN-IPI best discriminated overall survival (OS). The concordance index (c-index) from a proportional hazards model, stratifying on trial and induction therapy, quantified predictive accuracy of each scoring system. Results: 2561 pts (median age 63 yrs, 56% male) were classified into IPI, R-IPI, and NCCN-IPI risk groups (Table). With a median follow-up of 5 yrs, NCCN-IPI had the greatest absolute difference in OS estimates between the highest and lowest risk groups at 1, 3, and 5 yrs, and best discriminated OS (c-index = 0.631, Table). Conclusions: In an independent and large cohort of pts, NCCN-IPI performs best in risk-stratifying pts with aggressive BCL, readily distinguishing pts at high and low risk for treatment failure using clinical parameters (5-yr OS between 48 and 92%). Improvement over the simpler IPI appears incremental, and IPI may remain a valuable alternative. Work integrating molecular features of the tumor into the (NCCN-) IPI is in progress to define high risk groups where targeted novel approaches are needed most. [Table: see text]

Serum Albumin Predicts Survival in Indian Adult Diffuse Large B cell Lymphoma Patients in the Rituximab Era

Abstract Objective: The present study was done to evaluate the prognostic impact of the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) and serum albumin levels in the treatment outcome of Indian diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. Patients and Methods: We retrospectively analyzed the data (2013–2016) of 135 newly diagnosed DLBCL cases ≥18 years of age. All patients received Rituximab-Cyclophosphamide, Adriamycin, Vincristine, Prednisone (R-CHOP) chemotherapy. The analysis was carried out to assess the overall survival (OS) and progression-free survival (PFS) and the prognostic factors predicting the outcome. Results: Of the 135 patients in the study, 89 (65.9%) had B-symptoms, 20 (14.8%) had bulky disease, 79 (58.5%) had advanced disease (Stage III and IV), and 29 (21.5%) had primary extranodal involvement. Serum albumin ≤3.5 g% was present in 71 (52.6%) patients. About 74 (54.8%) cases were risk stratified to NCCN-IPI high-intermediate-risk group, while 18 (13.3%) patients were categorized into high-risk group. The median PFS and OS of our study cohort were 19 months (95% confidence interval [CI] = 2.59–35.4) and 38 months (95% CI = 9.02–55.68), respectively. Serum albumin ≤3.5 g/dl was significantly associated with poor OS (hazard ratio [HR] = 3.99, 95% CI = 2.25–7.07, P &lt; 0.001) and PFS (HR = 3.71, 95% CI = 2.20–6.26, P &lt; 0.002). Similarly, low NCCN-IPI (&lt;4) was significantly associated with improved OS (HR = 0.21, 95% CI = 0.09–0.47, P &lt; 0.005) and PFS (HR = 0.19, 95% CI = 0.09–0.41, P &lt; 0.001), respectively. These two factors (serum albumin and NCCN-IPI) retained their prognostic significance with respect to OS and PFS in the multivariate analysis. Conclusion: The NCCN-IPI prognostic model and serum albumin levels have independent prognostic significance in Indian DLBCL patients. Serum albumin is a readily available, easy to standardize, and cheap investigation requiring no specialized expertise and holds promise for being incorporated in future DLBCL prognostic risk models.

Optimizing Outcome Prediction in Diffuse Large B-Cell Lymphoma by Use of Machine Learning and Nationwide Lymphoma Registries: A Nordic Lymphoma Group Study.

Prognostic models for diffuse large B-cell lymphoma (DLBCL), such as the International Prognostic Index (IPI) are widely used in clinical practice. The models are typically developed with simplicity in mind and thus do not exploit the full potential of detailed clinical data. This study investigated whether nationwide lymphoma registries containing clinical data and machine learning techniques could prove to be useful for building modern prognostic tools. This study was based on nationwide lymphoma registries from Denmark and Sweden, which include large amounts of clinicopathologic data. Using the Danish DLBCL cohort, a stacking approach was used to build a new prognostic model that leverages the strengths of different survival models. To compare the performance of the stacking approach with established prognostic models, cross-validation was used to estimate the concordance index (C-index), time-varying area under the curve, and integrated Brier score. Finally, the generalizability was tested by applying the new model to the Swedish cohort. In total, 2,759 and 2,414 patients were included from the Danish and Swedish cohorts, respectively. In the Danish cohort, the stacking approach led to the lowest integrated Brier score, indicating that the survival curves obtained from the stacking model fitted the observed survival the best. The C-index and time-varying area under the curve indicated that the stacked model (C-index: Denmark [DK], 0.756; Sweden [SE], 0.744) had good discriminative capabilities compared with the other considered prognostic models (IPI: DK, 0.662; SE, 0.661; and National Comprehensive Cancer Network-IPI: DK, 0.681; SE, 0.681). Furthermore, these results were reproducible in the independent Swedish cohort. A new prognostic model based on machine learning techniques was developed and was shown to significantly outperform established prognostic indices for DLBCL. The model is available at https://lymphomapredictor.org .

Hepatitis B Surface Antigen Positivity Is an Independent Unfavorable Prognostic Factor for Overall Survival in Patients with Diffuse Large B-Cell Lymphoma Treated with Standard Chemoimmunotherapy

IntroductionHepatitis B virus (HBV) is one of the most common viral infections in humans. Global prevalence of chronic HBV infection is heterogeneous, with 2-20% of a given population being infected with HBV. In some parts of Africa, Asia and South America, HBV infection is endemic and remains to be a significant public health issue.Previous studies have shown a positive association between hepatitis B surface antigen (HBsAg)-positive HBV infection and B-cell non-Hodgkin lymphoma (NHL), such as diffuse large B-cell lymphoma (DLBCL), the most common subtype of B-cell NHL. Nevertheless, the clinical characteristics of HBsAg positivity and negativity, as well as their prognostic implications in DLBCL patients treated with frontline standard chemoimmunotherapy remain to be clarified.MethodsWe conducted a single-institution retrospective study in a tertiary referral hospital in Taiwan, an HBV prevalent country in Asia. From January 2001 to December 2015, patients aged ≥20 years with newly diagnosed DLBCL treated with standard rituximab plus combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were selected. Retrospective chart review was performed to collect data on clinical features, laboratory profiles, serum markers for HBV infection such as HBsAg and HBV-DNA loads before chemotherapy, as well as data on treatment response and outcome. The cohort was followed up until the cutoff date of June 30, 2018.ResultsA total of 393 DLBCL patients were analyzed in this study, with a median age of 60.5 years (range, 23.5 years to 90.9 years) and the sex ratio of 1.38 to 1.The 5-year overall survival (OS) rates were 65.2% after a median follow-up time of 68.8 months. In this cohort, 100 patients (25.4%) were found to have HBsAg positivity before treatment.Eighty-two of them had received prophylactic antiviral therapy, including 28 with lamivudine, 44 with entecavir and 10 with others. Besides, forty-five of HBsAg-positive patients had data of serum HBV-DNA loads before treatment, and 44 of them had received prophylactic anti-HBV therapy. Compared to HBsAg-negative patients, HBsAg-positive patients had a younger median onset age (55.9 years vs. 61.4 years, P=0.004), a trend of more advanced stage (stage III/IV: 62% vs. 51.2%, P=0.064), higher serum LDH levels at diagnosis (62% vs. 50.2%, P=0.048), and a trend of higher National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score (high-intermediate/high: 50% vs. 41.6%, P=0.162).Regarding to treatment response and outcome, HBsAg-positive patients, compared to HBsAg-negative patients, had a trend of lower overall response rates (78% vs. 84.3%, P=0.169) and complete remission rates (73% vs. 79.9%, P=0.163). Furthermore, compared to HBsAg-negative patients, HBsAg-positive patientshad a poorer median OS (median OS, not reached vs. 95.8 months, P=0.001, Figure 1) and a shorter median progression-free survival (PFS) (median PFS, not reached vs. 34.3 months, P=0.031), respectively. By multivariate analysis, HBsAg positivity is an independent poor prognostic factor for OS irrespective of NCCN-IPI score, serum albumin levels and B symptoms.No significant difference was found in outcome between patients with high HBV-DNA loads (> 2000 IU/mL, n=21) and those with low HBV-DNA loads (≤2000 IU/mL, n=24). With respect to prophylactic anti-HBV treatment, patients without prophylactic therapy (n=18), compared to those with prophylactic therapy (n=82), had a trend of shorter median OS (27.9 months vs. 96.2 months, P=0.346). Moreover, no significant difference was found in median OS between HBsAg-positive patients when administrated with anti-HBV lamivudine and those when administrated with anti-HBV entecavir.ConclusionsThis study demonstrated that HBsAg positivity has unique clinical relevance to patients with DLBCL, as well as its impact in the efficacy of treatment. HBsAg positivity may serve as a relevant biomarker to predict clinical outcome in DLBCL patients treated with R-CHOP. Prophylactic anti-HBV therapy may be of great importance in HBsAg-positive DLBCL patients. Further studies to explore the etiopathogenesis of HBV infection in DLBCL may help to discovery new treatment targets to improve the outcome of this group of patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The prognostic value of the international prognostic index, the national comprehensive cancer network IPI and the age-adjusted IPI in diffuse large B cell lymphoma

目的比较IPI、美国国家综合癌症网络IPI（NCCN-IPI）及年龄调整的IPI（aa-IPI）三种预后分层模型在弥漫大B细胞淋巴瘤（DLBCL）患者中的预后分层能力。方法回顾性分析2003年1月至2012年12月311例初治DLBCL患者资料，根据治疗方案将患者分为CHOP（环磷酰胺、多柔比星、长春新碱、泼尼松）方案及利妥昔单抗（R）-CHOP方案组，分别采用IPI、NCCN-IPI及aa-IPI对DLBCL患者进行危险度分层。采用Harrell's C统计评价不同模型的预后分层能力。结果①311例患者中接受CHOP方案治疗者128例，接受R-CHOP方案治疗者183例。②CHOP方案组患者的5年总生存（OS）率结果显示，aa-IPI（71.0%对25.0%，P<0.001）、NCCN-IPI（59.7%对26.8%，P<0.001）和IPI（47.6%对36.6%，P=0.003）均能区分中低危和中高危组患者，但前两者区分效果似乎更佳；而R-CHOP方案组，NCCN-IPI拥有更好的预后分层能力，其低危、中低危、中高危患者的5年OS率分别为96.0%、83.0%、66.5%（P=0.009）。③Harrell's C分析结果显示，IPI、NCCN-IPI及aa-IPI预测接受CHOP方案者OS的一致性指数（C-index）分别为0.546、0.667、0.698；预测接受R-CHOP方案者OS的C-index分别为0.611、0.654、0.695。④在≤60岁患者中，IPI、NCCN-IPI、aa-IPI预测接受CHOP方案者OS的C-index分别为0.534、0.675、0.698；预测接受R-CHOP方案者OS的C-index分别为0.584、0.648、0.695。结论NCCN-IPI对于接受利妥昔单抗联合化疗的DLBCL患者有较好的预后分层能力，而aa-IPI对于较年轻的DLBCL患者预后分层能力可能更佳。

A risk stratification model for nodal peripheral T-cell lymphomas based on the NCCN-IPI and posttreatment Deauville score.

The aim of this study was to establish a risk-stratification model integrating posttreatment metabolic response using the Deauville score and the pretreatment National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) in nodal PTCLs. We retrospectively analysed 326 patients with newly diagnosed nodal PTCLs between January 2005 and June 2016 and both baseline and posttreatment PET/CT data. The final model was validated using an independent prospective cohort of 79 patients. Posttreatment Deauville score (1/2, 3, and 4/5) and the NCCN-IPI (low, low-intermediate, high-intermediate, and high) were independently associated with progression-free survival: for the Deauville score, the hazard ratios (HRs) were 1.00 vs. 2.16 (95% CI 1.47-3.18) vs. 7.86 (5.66-10.92), P < 0.001; and for the NCCN-IPI, the HRs were 1.00 vs. 2.31 (95% CI 1.20-4.41) vs. 4.42 (2.36-8.26) vs. 7.09 (3.57-14.06), P < 0.001. Based on these results, we developed a simplified three-group risk model comprising a low-risk group (low or low-intermediate NCCN-IPI with a posttreatment Deauville score of 1 or 2, or low NCCN-IPI with a Deauville score of 3), a high-risk group (high or high-intermediate NCCN-IPI with a Deauville score of 1/2 or 3, or low-intermediate NCCN-IPI with a Deauville score of 3), and a treatment failure group (Deauville score 4 or 5). This model was significantly associated with progression-free survival (5-year, 70.3%, 31.4%, and 4.7%; P < 0.001) and overall survival (5-year, 82.1%, 45.5%, and 14.7%; P < 0.001). Similar associations were also observed in the independent validation cohort. The risk-stratification model integrating posttreatment Deauville score and pretreatment NCCN-IPI is a powerful tool for predicting treatment failure in patients with nodal PTCLs.

Hyperfibrinogenemia is a poor prognostic factor in diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas worldwide. Previous studies indicated that hyperfibrinogenemia was a poor predictor in various tumors. The purpose of our study was to evaluate the prognostic effect of hyperfibrinogenemia in DLBCL. Data of 228 patients, who were diagnosed with DLBCL in our hospital between May 2009 and February 2016, were analyzed retrospectively. The Kaplan-Meier method and Cox regression were performed to find prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curve and the areas under the curve were used to evaluate the predictive accuracy of predictors. Comparison of characters between groups indicated that patients with high National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score (4-8) and advanced stage (III-IV) were more likely to suffer from hyperfibrinogenemia. The Kaplan-Meier method revealed that patients with hyperfibrinogenemia showed inferior PFS (P < 0.001) and OS (P < 0.001) than those without hyperfibrinogenemia. Multivariate analysis showed that hyperfibrinogenemia was an independent prognostic factor associated with poor outcomes (HR = 1.90, 95% CI: 1.15-3.16 for PFS, P = 0.013; HR = 2.65, 95% CI: 1.46-4.79 for OS, P = 0.001). We combined hyperfibrinogenemia and NCCN-IPI to build a new prognostic index (NPI). The NPI was demonstrated to have a superior predictive effect on prognosis (P = 0.0194 for PFS, P = 0.0034 for OS). Hyperfibrinogenemia was demonstrated to be able to predict poor outcome in DLBCL, especially for patients with advanced stage and high NCCN-IPI score. Adding hyperfibrinogenemia to NCCN-IPI could significantly improve the predictive effect of NCCN-IPI.

A new prognostic model using the NCCN-IPI and neutrophil-to-lymphocyte ratio in diffuse large B-cell lymphoma.

The neutrophil-to-lymphocyte ratio (NLR) has been known to predict the prognosis in diffuse large B-cell lymphoma (DLBCL). We planned to design a new prognostic model in DLBCL using well-known prognostic index and NLR. The data of 232 DLBCL patients treated with first-line R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) from 2004 to 2017 were retrospectively reviewed. Patients with NLR ≥6 and <6 were determined as the high and low NLR groups, respectively. Treatment response and survival were compared according to NLR status. Nomograms for predicting 5-year progression-free survival (PFS) and overall survival (OS) rates were constructed using NLR and other prognostic factors based on the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) NCCN-IPI. The high NLR group had a low complete response (CR) rate compared to low NLR group (51.6% vs. 83.5%; p<0.001). The 5-year PFS and OS rates were 27.4% and 30% in the high NLR group and 61.1% and 63.7% in the low NLR group, respectively (both p<0.001). Multivariate analyses confirmed that NLR is one of the independent risk factors for failure to achieve CR and for worse PFS and OS. The nomogram showed superior discrimination ability for predicting 5-year PFS and OS rates compared with NCCN-IPI (c index 0.78 vs. 0.75 and 0.79 vs. 0.75, respectively). High NLR was associated with poor treatment response and worse PFS and OS in DLBCL. The nomogram developed from NCCN-IPI-based variables and NLR may help the clinicians to predict the prognosis individually in DLBCL patients, although it needs to be validated in the independent cohort.

Intralymphatic Spread is a Rare Finding Associated With Poor Prognosis in Diffuse Large B-Cell Lymphoma With Extranodal Involvements.

Intralymphatic spread is common in solid cancers, but has been rarely studied in lymphomas. Review of 635 extranodal specimens from 475 diffuse large B-cell lymphoma (DLBCL) patients revealed intralymphatic spread in 10 surgical resection specimens from 10 patients including 9 de novo DLBCLs and 1 Richter transformation. The prevalence in de novo DLBCL with extranodal involvements was 1.65%. The most common involved site of intralymphatic spread was the gastrointestinal tract, followed by the female genital tract and breasts. Lymphatic vessels, lined by D2-40-positive endothelial cells, were expanded by lymphoma cells, reminiscent of intravascular lymphoma or tumor emboli. None of the involved lymphatic vessels were located in the mucosa. Patients with intralymphatic spread had a trend of lower overall response rate and a trend of higher progressive disease than those without intralymphatic spread. Compared with patients without intralymphatic spread, those patients with intralymphatic spread had a shorter median overall survival (14.3 vs. 96.2 mo; P=0.004) and a shorter median progression-free survival (11.2 vs. 64.2 mo; P=0.01), respectively. Multivariate analyses showed that intralymphatic spread was an independent poor prognostic factor for overall survival (hazard ratio, 3.029; 95% confidence interval, 1.315-6.978; P=0.009), irrespective of the National Comprehensive Cancer Network-International Prognostic Index, B symptoms, and serum albumin levels. Among patients who underwent surgical resection, intralymphatic spread was still an independent prognostic factor. In conclusion, our study demonstrated extranodal intralymphatic spread in DLBCL. Inspiringly, this rare morphologic finding may serve as a new negative prognostic indicator in DLBCL with extranodal involvements.

Epidemiological Analysis of Lymphoma Subtypes in a Reference Center in João Pessoa

A gradual increase in diagnosed cases of lymphoma has led to greater dissemination of relevant information and has simultaneously revealed a need to improve understanding of the pathology. The prevalence of lymphomas involves many factors that vary regionally, with regional differences in prognosis indeed playing a role in therapeutic decisions. This observational study aimed to retrospectively evaluate the prevalence of lymphoma subtypes diagnosed between 2011 and 2015 at the Napoleao Laureano Hospital, the largest hematology facility in Paraiba, northeastern Brazil and a state reference for hematological oncology. Immunohistochemistry findings and associated prognostic variables were analyzed, including calculation of prognostic indexes such as the international prognostic index (IPI), age adjusted IPI, National Comprehensive Cancer Network IPI (NCCN-IPI), mantle cell lymphoma IPI (MIPI) and follicular lymphoma IPI (FLIPI). The most noteworthy findings include the large number of young people diagnosed with aggressive disease, with poor prognostic indexes but low mortality rates, confirming the technical strength of the institution as reflected in the improved prognosis associated with the disease. The prevalence of Hodgkin lymphoma was found to be high, contradicting a considerable part of the international literature but in agreement with some studies conducted with pediatric populations in Brazil. In addition, the most prevalent subtypes of non-Hodgkin lymphoma, already well discussed in the international literature, were also represented in the present sample. All cases of lymphoma registered at this center were catalogued, with their prognoses and anatomopathological and immunohistochemical diagnoses being analyzed, consequently providing a better database for this geographical region of Brazil.

Analysis of prognostic value of complete response by PET-CT and further stratification by clinical and biological markers in DLBCL patients.

Positron emission tomography-computed tomography (PET-CT) is performed as the standard method for response assessment of diffuse large B cell lymphoma (DLBCL) patients. However, a substantial proportion of patients experience relapse even if they have achieved complete response (CR) defined by PET-CT. We validated the prognostic value of CR by PET-CT and applied the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) and cell of origin (COO) to patients with CR by PET-CT to evaluate their additional predictive ability for survival outcomes. We retrospectively analyzed DLBCL patients who were treated with R-CHOP or an R-CHOP-like regimen and who achieved CR by PET-CT or CT only. A total of 185 patients were analyzed: 114 patients achieved CR by PET-CT and 71 patients by CT only. Patients with CR by PET-CT had significantly better overall survival (OS) than those with CR by CT (5-year OS, 87.5 vs. 62.4%, P=0.003). Patients with high risk according to the NCCN-IPI had a dismal outcome despite achieving CR by PET-CT (5-year OS, 61.8%). In contrast, low-, low-intermediate-, and high-intermediate-risk patients had excellent outcomes (5-year OS, 100, 89.7, and 93.5%, respectively). Among patients with CR by PET-CT, patients with germinal center B cell (GCB) DLBCL (n=40) had significantly better survival than those with non-GCB DLBCL (n=57) (5-year OS, 96.9 vs. 75.5%, P=0.039). We demonstrated that CR by PET-CT was a better predictor of survival outcomes than CR by CT only. The NCCN-IPI and COO subtypes could identify a subpopulation of poor-risk patients among those who achieved CR by PET-CT.

Relevance of prognostic index with β2-microglobulin for patients with diffuse large B-cell lymphoma in the rituximab era.

BackgroundThe International Prognostic Index (IPI) has been a useful tool for predicting the prognosis of aggressive non-Hodgkin lymphoma in the last 20 years. Herein, we aimed to develop a new prognostic model for diffuse large B-cell lymphoma (DLBCL) in the rituximab era.MethodsBetween March 2004 and June 2012, patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy regimen were identified in the database of the Asan Medical Center (AMC) Lymphoma Registry. The primary and secondary endpoints were a new prognostic index for DLBCL and validation of the National Comprehensive Cancer Network-International Prognostic Index in our cohort, respectively.ResultsThe AMC cohort comprised 621 patients. The median follow-up duration was 43.3 months (range, 6.2–122.5 mo). Univariate analysis revealed that age (≤60 vs. >60 yr), lactate dehydrogenase (LDH; within normal vs. increased), Eastern Cooperative Oncology Group performance status (ECOG PS; 0 or 1 vs. ≥2), advanced stage (Ann Arbor stage I/II vs. III/IV), extra-nodal involvement (≤1 vs. >1), B symptoms (no vs. yes), and beta-2 microglobulin (β2MG, ≤2.5 vs. >2.5) can be used to predict overall survival (OS). In multivariate analysis, only age, LDH, ECOG performance status, and β2MG were significantly associated with OS, and we developed a new prognostic model with these 4 factors. The new prognostic model showed better discriminative power compared with the classic IPI.ConclusionOur new prognostic index model for DLBCL in the rituximab era has good discriminative power and is convenient to use.

Prognostic Value of NCCN-IPI and Interim PET/CT Based on Visual Assessment in the Treatment of Peripheral T Cell Lymphomas

BackgroundIt has been well known that peripheral T cell lymphoma (PTCL) has undergone poor prognosis compared with other non-Hodgkin lymphomas (NHL). Although the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) has been proposed to determining prognosis for patients with diffuse large B-cell lymphoma (DLBCL) at 2014, there is no study examines whether NCCN-IPI could apply to the T-cell NHLs. In addition, a few studies suggest prognostic utility of interim PET/CT in PTCL, but the role of interim PET/CT is not clear.PurposeWe evaluate the predictive efficacy of the NCCN-IPI and interim PET/CT based on visual assessment in patients with newly diagnosed PTCLs.MethodsThis study included 153 patients with de novo peripheral PTCLs, diagnosed from January 2010 to August 2015. The NCCN-IPI was calculated as following the original references. Survival outcomes were compared with a matched result of IPI and/or Prognostic Index for peripheral T cell lymphoma, unspecified (PIT). Visual assessment of interim PET/CT based on Deauville five point scales was performed at the time of diagnosis, mid-treatment and completion of CHOP/CHOP-like or other non-anthracycline chemotherapy.ResultsThe subtypes of PTCLs included PTCL, not otherwise specified (PTCL-NOS) (26%), angioimmunoblastic T cell lymphoma (20%), anaplastic large cell lymphoma (13%), extranodal NK/T cell lymphoma, nasal type (35%), and the others (6%). The NCCN-IPI showed better risk-based prognostic discrimination than IPI and PIT, especially between high-intermediate and high risk subgroups (3-year overall survival 40% vs. 27% vs. 26% among the high-intermediate risk group, respectively; 3-year overall survival 15% vs. 33% vs. 32% among the high risk group, respectively) with a median follow-up of 25.1 months (Figure 1). The absolute difference of survival rates between the low and high risk groups was 75% based on the NCCN-IPI stratification compared with 45% on the IPI stratification or 54% on the PIT stratification, respectively. When divided into two histologic subgroups (nodal vs. extra-nodal type), the NCCN-IPI showed considerable discriminatory capacity in both histologic groups. However, the IPI or PIT classification could not have discrimination in extra-nodal PTCLs. The interim PET-CT was significantly predicting for progression free survival in all PTCL patients, however, it also showed no predictive value in the patients with extranodal PTCLs, especially NK/T cell lymphoma.ConclusionsThe NCCN-IPI is a powerful prognostic model in PTCLs predicting overall survival among high-intermediate and high risk patients. Also, interim PET/CT response based on visual assessment could be a valuable prediction tool in nodal PTCLs, however, it should be carefully interpreted in the treatment of extranodal subtypes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Highly elevated serum lactate dehydrogenase is associated with central nervous system relapse in patients with diffuse large B-cell lymphoma: Results of a multicenter prospective cohort study.

Central nervous system involvement remains a challenging issue in the treatment of patients with diffuse large B-cell lymphoma. We conducted a prospective cohort study with newly diagnosed diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone to identify incidence and risk factors for central nervous system involvement. Among 595 patients, 279 patients received pre-treatment central nervous system evaluation, and 14 patients had central nervous system involvement at diagnosis (2.3% out of entire patients and 5.0% out of the 279 patients). For those patients, median follow-up duration was 38.2 months and some of them achieved long-term survival. Out of 581 patients who did not have central nervous system involvement at diagnosis, 26 patients underwent secondary central nervous system relapse with a median follow-up of 35 months, and the median time to central nervous system involvement was 10.4 months (range: 3.4–29.2). Serum lactate dehydrogenase > ×3 upper limit of normal range, the Eastern Cooperative Oncology Group performance status ≥ 2, and involvement of sinonasal tract or testis, were independent risk factors for central nervous system relapse in multivariate analysis. Our study suggests that enhanced stratification of serum lactate dehydrogenase according to the National Comprehensive Cancer Network-International Prognostic Index may contribute to better prediction for central nervous system relapse in patients with diffuse large B-cell lymphoma. This trial was registered at clinicaltrials.gov identifier: 01202448.

Beta-2 microglobulin as a significant prognostic factor and a new risk model for patients with diffuse large B-cell lymphoma.

Previous reports have evaluated the prognostic value of serum beta-2 microglobulin (B2MG) level in patients with non-Hodgkin lymphoma. However, its role in predicting clinical outcome of patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been extensively investigated. Here, we evaluated the prognostic value of B2MG and proposed a new prognostic model including B2MG for patients with DLBCL. A total of 274 patients with newly diagnosed de novo DLBCL were retrospectively analyzed. We defined the best cutoff value as 3.2 mg/L by using a receiver operating characteristic curve. Patients with a B2MG level ≥3.2 mg/L had significantly lower overall survival (OS) and progression-free survival than those with a B2MG level <3.2 mg/L (3-year OS, 50.9% vs. 89.4%, p < 0.001; 3-year progression-free survival, 45.3% vs. 79.7%, p < 0.001). Multivariate analysis showed that B2MG, age, performance status, and Ann Arbor stage were independent prognostic factors for OS. We developed a new prognostic model consisting of these four significant factors. We stratified patients into four-risk groups: low (L, 0 factor), low-intermediate (LI, 1-2 factors), high-intermediate (HI, 3 factors), high (H, 4 factors). This new prognostic model showed better risk discrimination compared with the National Comprehensive Cancer Network-International Prognostic Index (5-year OS: 100% and 23.4% vs. 100% and 27.1%, in L and H risk groups, respectively). Our study suggested that B2MG level is a significant prognostic factor in patients with DLBCL. A new prognostic index composed of age, performance status, stage, and B2MG could stratify the outcomes of patients with DLBCL effectively and appears to be a valuable risk model for these patients. Copyright © 2016 John Wiley & Sons, Ltd.

The clinical significance of fibrinogen plasma levels in patients with diffuse large B cell lymphoma

BackgroundFibrinogen plays a crucial role in the pathophysiology of tumour cell growth, invasion and metastasis. The aim of this study was to evaluate the prognostic significance of pretreatment plasma fibrinogen...

Addition of Etoposide to CHOP Is Associated with Improved Outcome in Adult Anaplastic Large Cell Lymphoma Patients: A Nordic Lymphoma Group Study

INTRODUCTIONAnaplastic Large Cell Lymphomas (ALCL) are rare T-cell neoplasms grouped according to whether they express the fusion protein anaplastic lymphoma kinase (ALK+) or not (ALK-). ALK+ ALCL has consistently been found to have a favorable outcome compared to ALK- ALCL, but ALK+ ALCL is also associated with young age and other low risk features and not all studies have found ALK-expression to be an independent prognostic factor. In this population-based study, we aimed at analyzing the outcome and risk factors for survival in a bi-national cohort of patients with systemic ALCL.METHODSAll adult (>18 years) patients with systemic ALCL in the Swedish and Danish Lymphoma Registries diagnosed between 2000 and 2010 were included in the study. Primary cutaneous ALCL cases were excluded. The diagnosis of ALCL was established in routine care and no study-specific pathology review was performed.RESULTSA total of 371 patients (ALK+ ALCL n=122) were identified, representing 1.3% of all lymphomas, through both national registries. ALK-status was missing in 33 patients (ALK u ALCL). The median follow-up was 7.2 years. ALK+ patients were younger than ALK- patients (median age 40 versus 66 years, p<0.001).In all, 209 patients died (ALK+ n=32, ALK- n=151, ALK u n=26) and among the 328 patients with available relapse data, 118 patients experienced relapse or progression (ALK+ n=20, ALK- n= 83, ALK u n=15). The 5-year overall and progression-free survival (OS and PFS, respectively) were 78% and 64% in ALK+ ALCL, 37% and 32% in ALK- ALCL and 27% and 25% in ALK u ALCL.Data on primary treatment was available in 341 out of 371 patients (92%). The majority of patients (n=278, 82%) was treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or CHOP plus etoposide (CHOEP). Up-front autologous stem cell transplantation (ASCT) was performed in 38 patients with ALK- ALCL and in 6 patients with ALK+ ALCL. Most ALK- ALCL patients undergoing up-front ASCT consolidation received CHOEP as induction treatment.Age had a profound impact on survival and based on the Kaplan-Meier estimates the age cut-offs described for the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) were used. All features, including treatment with CHOP compared to CHOEP, that were associated with survival at the level of p<0.1 in univariable analysis were tested in a multivariable model. The only independent risk factors in the multivariable analysis were treatment with CHOEP, which was associated with better OS (HR 0.48 95% CI 0.32-0.74, p=0.001), and increasing NCCN-IPI score (HR [for each increment] 1.6 95% CI 1.5-1.8, p<0.001), which was associated with inferior OS.A separate multivariable risk factor analysis for OS was performed in patients treated with CHOEP (N=108). In this analysis, age (HR 2.9 95% CI 1.5-5.3, p=0.001), ALK-negativity (HR 2.6 95% CI 1.2-6.0, p=0.020) and elevated LDH (HR 2.1 95% CI 1.0-4.3, p=0.047) were independently associated to worse OS. Assigning 0,1 and 2 points for age <40, 40-60 and 60-75 respectively, ALK negativity 1 point and elevated LDH 1 point, we created a score that identified 4 groups with significantly different OS. Patients with a score of 3 or 4 had a similar OS, and were thus combined.DISCUSSIONThis population-based study based on two national registries reports the outcome of the largest cohort of adult ALCL patients published so far. Our study confirms the favourable outcome of ALK+ ALCL patients and the association with low-risk features. The addition of etoposide to CHOP was independently associated with a superior OS, and when adjusting for this treatment modification, the impact of ALK-expression on OS was mitigated.We also performed a separate risk factor analysis in the group of patients receiving CHOEP treatment. Age, ALK-negativity and elevated LDH were independent risk factors for OS in this group and were assembled in a proposed novel score, which could represent a useful tool in future management strategies in ALCL.Our data supports that the addition of etoposide to CHOP, if tolerated, is an important component in the treatment of ALCL and that the impact of ALK-expression on outcome is affected by treatment. Based on multivariable risk factor analysis in CHOEP treated patients, we propose a novel ALCL-specific score for future validation in independent cohorts. DisclosuresRelander:Respiratorius: Patents & Royalties: valproate for DLBCL.