Browsing by Author "Jelicic, Jelena (56180044800)"

Objectives: Recent front-line clinical trials used the International Prognostic Index (IPI) to identify trial-eligible patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, many IPI-like variants with improved accuracy have been developed over the years for rituximab-treated patients. Methods: We assessed the impact of International Prognostic Indices on patient enrolment in clinical trials, aiming to exclude low-risk IPI patients based on POLARIX/EPCORE DLBCL-2 trial criteria. Results: We identified 2877 patients in the Danish Lymphoma Registry who would have been eligible for the POLARIX trial if patients with IPI 0–1 scores were included. IPI and NCCN-IPI assigned 33.3% and 11.9% of patients to the low-risk group, respectively. Shorter 5-year overall survival (91.4% vs. 97.5%), higher relapse rate (9.9% vs. 4.4%), and more deaths (16.1% vs. 4.4%) occurred in the low-risk IPI group compared with low-risk NCCN-IPI group. Analyzed models failed to identify true high-risk patients with poor prognosis. Similar results were found in the confirmatory cohort developed based on EPCORE DLBCL-2 trial eligibility criteria. Conclusion: True low-risk patients are more optimal identified by NCCN-IPI and should be excluded from front-line clinical trials due to their excellent prognosis. However, additional high-risk factors besides clinical prognostic models need to be considered when selecting trial-eligible patients. © 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.

The International Prognostic Index (IPI) has been used for risk stratification for a long time in diffuse large B cell lymphoma (DLBCL). Based on new clinical and biological prognostic markers, many new prognostic models have been described. This review aims to present the progress in development and validation of these prognostic models. A comprehensive literature review was performed to identify studies that proposed a new prognostic model in DLBCL. A total of 38 studies met the inclusion criteria. The IPI, revised IPI (R-IPI), and National Comprehensive Cancer Network (NCCN)-IPI were the most studied prognostic indexes, externally validated and commonly used to compare to other models. Despite an increasing number of prognostic models have been proposed lately, most of them lack external validation. Further studies, that combine biological and clinical markers with prognostic significance, are needed to determine the optimal prognostic tool for more personalized treatment approach to DLBCL patients. © 2018 Elsevier B.V.

Purpose: Despite major advances in the treatment of diffuse large B cell lymphoma (DLBCL), approximately one third of the patients progress or die, suggesting the existence of additional oncogenic events. The purpose of this study was to evaluate the prognostic value of the "Hans classifier", and BCL2 and MYC protein expression and gene alterations in DLBCL patients treated with CHOP or R-CHOP chemotherapy over a 5-year period. Furthermore, we tried to correlate these parameters with the International Prognostic Index (IPI). Methods: The immunohistochemical (IHC) expression of CD10, BCL6, MUM1 and BCL2 on paraffin-embedded formalin-fixed tumor samples from 103 centroblastic DLBCLs was analyzed. IHC expression of MYC and fluorescence in situ hybridization (FISH) for MYC and BCL2 gene alterations was performed on 67 samples using the tissue microarray (TMA) method. Results: The Hans algorithm was not predictive of survival in both therapy groups. No significant difference in BCL2 and MYC alterations or MYC protein expression in relation to complete response (CR), event-free survival (EFS) and overall survival (OS) was observed in our study. High IPI correlated significantly with poor outcome and it was identified as independent prognostic factor for OS and EFS (both p=0.000). The 5-year OS was 61% in the R-CHOP compared to 38% in the CHOP group (p=0.007). Rituximab significantly improved the OS in the BCL2 positive (60 vs 29%, p=0.008), and the BCL6 negative (73 vs 25%, p=0.001) cases. Conclusion: IPI is an independent prognosticator for DLBCL patients and the addition of rituximab significantly improved survival. Furthermore, patients with BCL2+ and BCL6- DLBCL benefited from R-CHOP.

Purpose: Despite major advances in the treatment of diffuse large B cell lymphoma (DLBCL), approximately one third of the patients progress or die, suggesting the existence of additional oncogenic events. The purpose of this study was to evaluate the prognostic value of the "Hans classifier", and BCL2 and MYC protein expression and gene alterations in DLBCL patients treated with CHOP or R-CHOP chemotherapy over a 5-year period. Furthermore, we tried to correlate these parameters with the International Prognostic Index (IPI). Methods: The immunohistochemical (IHC) expression of CD10, BCL6, MUM1 and BCL2 on paraffin-embedded formalin-fixed tumor samples from 103 centroblastic DLBCLs was analyzed. IHC expression of MYC and fluorescence in situ hybridization (FISH) for MYC and BCL2 gene alterations was performed on 67 samples using the tissue microarray (TMA) method. Results: The Hans algorithm was not predictive of survival in both therapy groups. No significant difference in BCL2 and MYC alterations or MYC protein expression in relation to complete response (CR), event-free survival (EFS) and overall survival (OS) was observed in our study. High IPI correlated significantly with poor outcome and it was identified as independent prognostic factor for OS and EFS (both p=0.000). The 5-year OS was 61% in the R-CHOP compared to 38% in the CHOP group (p=0.007). Rituximab significantly improved the OS in the BCL2 positive (60 vs 29%, p=0.008), and the BCL6 negative (73 vs 25%, p=0.001) cases. Conclusion: IPI is an independent prognosticator for DLBCL patients and the addition of rituximab significantly improved survival. Furthermore, patients with BCL2+ and BCL6- DLBCL benefited from R-CHOP.

Over the years, a rising incidence of liver cirrhosis and lymphoma has been observed. Therefore, the risk of having cirrhosis as a comorbidity increases, thus challenging treatment approaches as data on the management of these patients is lacking. We performed a systematic review to summarize papers that analyzed patients with liver cirrhosis that occurred before and/or concomitantly to lymphoma. We identified 153 papers (230 patients) through Pubmed and/or Embase search. Publications comprised predominantly of case reports and/or case series. Most patients had HCV-related cirrhosis (62.6%), and aggressive lymphoma histology (59.6%). Data on liver status was available in 55.7% of all patients, with 46.1% having decompensated liver cirrhosis. These patients experienced more often treatment reductions and/or modifications, treatment side effects, and inferior survival than those with compensated cirrhosis (median 18 months vs. median not reached). Dose reductions and/or treatment modifications primarily due to concomitant liver disease were common. Moreover, liver toxicity was observed in 33.6% of patients with provided information on treatment side effects, ranging from mild toxicity to liver failure with fatal outcomes. Again, despite treatment modification/reduction, patients with decompensated liver cirrhosis developed hepatic toxicity more frequently than patients with compensated liver disease. Although patients suffering from cirrhosis and lymphoma can tolerate standard chemoimmunotherapy, a cautious multidisciplinary approach is needed to evaluate the risks and benefits. © 2022

Over the years, a rising incidence of liver cirrhosis and lymphoma has been observed. Therefore, the risk of having cirrhosis as a comorbidity increases, thus challenging treatment approaches as data on the management of these patients is lacking. We performed a systematic review to summarize papers that analyzed patients with liver cirrhosis that occurred before and/or concomitantly to lymphoma. We identified 153 papers (230 patients) through Pubmed and/or Embase search. Publications comprised predominantly of case reports and/or case series. Most patients had HCV-related cirrhosis (62.6%), and aggressive lymphoma histology (59.6%). Data on liver status was available in 55.7% of all patients, with 46.1% having decompensated liver cirrhosis. These patients experienced more often treatment reductions and/or modifications, treatment side effects, and inferior survival than those with compensated cirrhosis (median 18 months vs. median not reached). Dose reductions and/or treatment modifications primarily due to concomitant liver disease were common. Moreover, liver toxicity was observed in 33.6% of patients with provided information on treatment side effects, ranging from mild toxicity to liver failure with fatal outcomes. Again, despite treatment modification/reduction, patients with decompensated liver cirrhosis developed hepatic toxicity more frequently than patients with compensated liver disease. Although patients suffering from cirrhosis and lymphoma can tolerate standard chemoimmunotherapy, a cautious multidisciplinary approach is needed to evaluate the risks and benefits. © 2022

Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) represents a rare and aggressive extranodal non-Hodgkin’s lymphoma (NHL) with some specific features that differ from other NHLs. Formalin fixed, paraffin wax embedded (FFPE) samples of 21 PT-DLBCLs and 30 comparative patients with DLBCL were analysed. All PT-DLBCL patients were treated with rituximab-containing regimens, intrathecal prophylaxis (10 patients), and irradiation of the contralateral testis (9 patients). FFPE samples were additionally analysed by immunohistochemistry (Bcl-2, c-Myc protein expression) and fluorescence in situ hybridisation (FISH) (BCL2 and MYC). The patients with PT-DLBCL (median age 48.5 years), had low frequency of B symptoms (28.6%) and were often diagnosed in I and II Ann Arbor clinical stage (66.0%). The majority of PT-DLBCL (80.9%) had a non-germinal centre B-cell-like immunophenotype. Immunohistochemical staining showed increased c-Myc protein expression in the PT-DLBCL group compared to the control group (p = 0.016). MYC rearrangement was detected in 1 of 14 (7.0%), and MYC amplification in 3 of 14 (21.0%) patients. One of the 14 cases (7.0%) in the PT DLBCL group showed BCL2 rearrangement, and four of 14 (28.05%) cases showed BCL2 amplification. Complete remission (CR) was achieved in 75.0% of PT-DLBCL patients who had superior survival compared to those who did not achieve CR (median 48 vs. 21 months, p = 0.012). Patients with PT-DLBCL express some immunohistochemical, biological, and clinical features that might differentiate them from nodal and extranodal DLBCL patients, indicating the need for a more personalised treatment approach. © 2018, Termedia Publishing House Ltd. All rights reserved.

We present the case of a 69-year-old Caucasian man with a 5-year history of untreated chronic lymphocytic leukemia who presented with Merkel cell carcinoma on the right gluteal region. Six months after surgical treatment of Merkel cell carcinoma, we detected massive lymphadenopathy in the right retroperitoneum descending to the inguinum. A lymph node biopsy confirmed Merkel cell carcinoma relapse, and the patient was unsuccessfully treated with radiotherapy. As patients with chronic lymphocytic leukemia have a risk for developing a secondary malignancy, skin lesions need to be carefully examined and new lymphadenopathy must be pathohistologically evaluated. © 2015, Taiwanese Dermatological Association. Published by Elsevier Taiwan LLC. All rights reserved.

Lymphoma patients are at increased risk of thromboembolic events but thromboprophylaxis in these patients is largely underused. We sought to develop and validate a simple model, based on individual clinical and laboratory patient characteristics that would designate lymphoma patients at risk for thromboembolic event. The study population included 1,820 lymphoma patients who were treated in the Lymphoma Departments at the Clinics of Hematology, Clinical Center of Serbia and Clinical Center Kragujevac. The model was developed using data from a derivation cohort (n = 1,236), and further assessed in the validation cohort (n = 584). Sixty-five patients (5.3%) in the derivation cohort and 34 (5.8%) patients in the validation cohort developed thromboembolic events. The variables independently associated with risk for thromboembolism were: previous venous and/or arterial events, mediastinal involvement, BMI>30 kg/m2, reduced mobility, extranodal localization, development of neutropenia and hemoglobin level < 100g/L. Based on the risk model score, the population was divided into the following risk categories: low (score 0-1), intermediate (score 2-3), and high (score >3). For patients classified at risk (intermediate and high-risk scores), the model produced negative predictive value of 98.5%, positive predictive value of 25.1%, sensitivity of 75.4%, and specificity of 87.5%. A high-risk score had positive predictive value of 65.2%. The diagnostic performance measures retained similar values in the validation cohort. Developed prognostic Thrombosis Lymphoma – ThroLy score is more specific for lymphoma patients than any other available score targeting thrombosis in cancer patients. Am. J. Hematol. 91:1014–1019, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Follicular Lymphoma International Prognostic Index (FLIPI) is widely used in the identification of risk groups among follicular lymphoma (FL) patients. The aim of the present study was to evaluate the prognostic value of FLIPI combined with the Charlson comorbidity index (CCI) and histological grade of lymphoma. 224 newly diagnosed FL patients (median age 56 years) treated with immunochemotherapy were retrospectively analysed. Low FLIPI had 21.0 % of patients, intermediate 28.1 % and high 46.9 %. 50.9 % of patients had no comorbidities. Only 7.1 % of patients had a high CCI score (≥2), while 25.9 % of patients were histological grade 3. Parameters that influenced overall survival were evaluated using Cox regression analysis, in which CCI, FLIPI and histological grade (p < 0.05) retained prognostic significance. By combining these parameters, we have developed the FCG score, which incorporates FLIPI, CCI, and histological grade. This score defines three risk categories (low: 41.5 %; intermediate: 37.5 %; high: 13.4 %), associated with significantly different survival (p < 0.0001); this consequently improves discriminative power by 9.1 % compared to FLIPI. FCG score represents a possible new prognostic index, highlighting the role of the patient’s clinical state and the histological characteristics of disease, as indicated by comorbidity index and histological grade of lymphoma. © 2016, The Japanese Society of Hematology.

The prognostic value of the International Prognostic Index (IPI) has been re-evaluated in the rituximab-treated diffuse large B cell lymphoma (DLBCL) patients. Accordingly, National Comprehensive Cancer Network-IPI (NCCN-IPI) has been introduced to estimate prognosis of DLBCL patients. However, comorbidities that frequently affect elderly DLBCL patients were not analyzed. The aim of this study was to evaluate the prognostic significance of comorbidities using Charlson Comorbidity Index (CCI) in 962 DLBCL patients. According to CCI, majority of patients (73.6%) did not have any comorbidity, while high CCI (≥ 2) was observed in 71/962 (7.4%) patients, and in 55/426 (12.9%) of the elderly patients aged ≥ 60 years. When the CCI was analyzed in a multivariate model along with the NCCN-IPI parameters, it stood out as a threefold independent risk factor of a lethal outcome. Also, we have developed a novel comorbidity-NCCN-IPI (cNCCN-IPI) by adding additional 3 points if the patient had a CCI ≥ 2. Four risk groups emerged with the following patient distribution in low, low-intermediate, high-intermediate, and high group: 3.4, 34.3, 49.4, and 12.5%, respectively. The prognostic value of the new cNCCN-IPI was 2.1% improved compared to that of the IPI, and 1.3% improved compared to that of the NCCN-IPI (p < 0.05). This difference was more pronounced in elderly patients, in whom the cNCCN-IPI showed a 5.1% better discriminative power compared to that of the IPI, and 3.6% better compared to the NCCN-IPI. The NCCN-IPI enhanced by the CCI and combined with redistributed risk groups is better for differentiating risk categories in unselected DLBCL patients, especially in the elderly. © 2017, Springer-Verlag GmbH Germany, part of Springer Nature.

Background Consideration of comorbidity, disability, and frailty represents a significant part of the treatment of elderly multiple myeloma (MM) patients. The aim of study was to analyze the effect of the Charlson Comorbidity Index (CCI) and scale of Instrumental Activities of Daily Living (IADL) on the course of disease. Patients and Methods The study included 110 newly diagnosed MM patients older than 65 years of age. According to the CCI most patients had at least 1 comorbidity (CCI score of 1) and most of them (51 of 110 patients; 46.4%) had an age-adjusted CCI (aaCCI) score of 5 to 6. Most of our patients were capable of performing routine daily activities (IADL ≥ 6). Patients were treated with thalidomide- and bortezomib- based combinations, or with conventional chemotherapy. Results International Staging System (ISS) score 3 correlated with high scores of CCI or aaCCI (R = 0.314, P <.003; R =.317, P <.002, respectively), and lower IADL (R = 0.259, P <.007). The probability of adverse events was 70% greater for CCI score ≥ 2 (odds ratio [OR], 1.72); 28% for aaCCI ≥ 5 (OR, 1.28) and 22% higher for IADL < 3 (OR, 2.25). The patients with a CCI score of 0 to 1 had significantly longer overall survival (OS; log rank, 6.538; P <.011). The patients with aaCCI ≥ 5 had significantly shorter OS (log rank, 4.209; P <.040), and the patients with IADL > 3 had significantly longer OS (log rank, 6.62; P <.001). In the proposed model, aaCCI ≥ 5 and IADL > 3 scores had a major effect on the OS (χ2, 8.46; P =.037). Conclusion CCI, aaCCI, and IADL scale are clinical parameters of prognostic significance. A proposed model for a personalized treatment approach is based on variables such as scores for aaCCI ≥ 5 and IADL > 3. © 2015 Elsevier Inc. All rights reserved.

Background Consideration of comorbidity, disability, and frailty represents a significant part of the treatment of elderly multiple myeloma (MM) patients. The aim of study was to analyze the effect of the Charlson Comorbidity Index (CCI) and scale of Instrumental Activities of Daily Living (IADL) on the course of disease. Patients and Methods The study included 110 newly diagnosed MM patients older than 65 years of age. According to the CCI most patients had at least 1 comorbidity (CCI score of 1) and most of them (51 of 110 patients; 46.4%) had an age-adjusted CCI (aaCCI) score of 5 to 6. Most of our patients were capable of performing routine daily activities (IADL ≥ 6). Patients were treated with thalidomide- and bortezomib- based combinations, or with conventional chemotherapy. Results International Staging System (ISS) score 3 correlated with high scores of CCI or aaCCI (R = 0.314, P <.003; R =.317, P <.002, respectively), and lower IADL (R = 0.259, P <.007). The probability of adverse events was 70% greater for CCI score ≥ 2 (odds ratio [OR], 1.72); 28% for aaCCI ≥ 5 (OR, 1.28) and 22% higher for IADL < 3 (OR, 2.25). The patients with a CCI score of 0 to 1 had significantly longer overall survival (OS; log rank, 6.538; P <.011). The patients with aaCCI ≥ 5 had significantly shorter OS (log rank, 4.209; P <.040), and the patients with IADL > 3 had significantly longer OS (log rank, 6.62; P <.001). In the proposed model, aaCCI ≥ 5 and IADL > 3 scores had a major effect on the OS (χ2, 8.46; P =.037). Conclusion CCI, aaCCI, and IADL scale are clinical parameters of prognostic significance. A proposed model for a personalized treatment approach is based on variables such as scores for aaCCI ≥ 5 and IADL > 3. © 2015 Elsevier Inc. All rights reserved.

Currently, the International Prognostic Index (IPI) is the most used and reported model for prognostication in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). IPI-like variations have been proposed, but only a few have been validated in different populations (e.g., revised IPI (R-IPI), National Comprehensive Cancer Network IPI (NCCN-IPI)). We aimed to validate and compare different IPI-like variations to identify the model with the highest predictive accuracy for survival in newly diagnosed DLBCL patients. We included 5126 DLBCL patients treated with immunochemotherapy with available data required by 13 different prognostic models. All models could predict survival, but NCCN-IPI consistently provided high levels of accuracy. Moreover, we found similar 5-year overall survivals in the high-risk group (33.4%) compared to the original validation study of NCCN-IPI. Additionally, only one model incorporating albumin performed similarly well but did not outperform NCCN-IPI regarding discrimination (c-index 0.693). Poor fit, discrimination, and calibration were observed in models with only three risk groups and without age as a risk factor. In this extensive retrospective registry-based study comparing 13 prognostic models, we suggest that NCCN-IPI should be reported as the reference model along with IPI in newly diagnosed DLBCL patients until more accurate validated prognostic models for DLBCL become available. [Figure not available: see fulltext.] © 2023, Springer Nature Limited.

Over the last decade, several prognostic models have been proposed for primary central nervous system lymphoma (PCNSL), but consensus on the optimal model for these patients is absent or lacking. This study aims to review available prognostic models for PCNSL and discuss their prognostic features. A comprehensive literature search performed in Pubmed/Embase identified ten studies with a variable number of analysed patients (range 32–3453), which proposed 12 prognostic models. Age and performance status were the most important prognostic factors in PCNSL and an integral part of the majority of the proposed models. However, there is no universally accepted prognostic model for PCNSL owning to a number of limitations such as a small number of patients, limited samples obtained for genetic analysis, retrospective nature of studies, single centre studies, and lack of validation. Future multicentre studies are necessary to determine the optimal prognostic model for PCNSL by combining different prognostic markers of significance. © 2021 Elsevier B.V.

Within a personalized treatment approach in multiple myeloma (MM), the prognostic significance of cereblon (CRBN) expression was analyzed in 92 newly diagnosed patients. In patients treated with thalidomide-based combinations, CRBN expression significantly affected the treatment response (P = .028) and progression-free survival (P = .017). With implications for the treatment outcome, measurement of CRBN expression might represent an additional prognostic tool in a personalized treatment approach. Background To personalize the treatment approach for patients with multiple myeloma (MM), molecular markers such as cereblon (CRBN) are currently the focus of investigation. The aim of the present study was to test the prognostic significance of CRBN expression in MM patients ineligible for autologous stem cell transplantation (ASCT). Patients and Methods The data from 92 previously untreated patients were analyzed. The distribution according to the International Staging System score was 26.1%, 30.4%, and 43.5% with a score of 1, 2, and 3, respectively. Thalidomide- and bortezomib-based combinations were used in 83.7% and 16.3% of the patients, respectively. Results A treatment response (complete remission, very good partial remission, partial remission) was achieved in 83.7% of the patients and correlated with high CRBN expression (P = .006), mainly in the patients treated with thalidomide (P = .028). Low CRBN expression affected progression-free survival (PFS; P = .017) but not overall survival (OS) in patients treated with thalidomide and had no influence on OS in the bortezomib group. In the Cox regression model, low CRBN expression was the most important prognostic parameter that influenced PFS in the thalidomide-treated patients (P = .012). Conclusion CRBN expression is of prognostic value in MM patients ineligible for ASCT treated with thalidomide as an immunomodulatory drug. With low expression indicating a possible suboptimal treatment outcome, measurement of CRBN expression might serve as additional prognostic tool in the personalized treatment approach. © 2016 Elsevier Inc.

Within a personalized treatment approach in multiple myeloma (MM), the prognostic significance of cereblon (CRBN) expression was analyzed in 92 newly diagnosed patients. In patients treated with thalidomide-based combinations, CRBN expression significantly affected the treatment response (P = .028) and progression-free survival (P = .017). With implications for the treatment outcome, measurement of CRBN expression might represent an additional prognostic tool in a personalized treatment approach. Background To personalize the treatment approach for patients with multiple myeloma (MM), molecular markers such as cereblon (CRBN) are currently the focus of investigation. The aim of the present study was to test the prognostic significance of CRBN expression in MM patients ineligible for autologous stem cell transplantation (ASCT). Patients and Methods The data from 92 previously untreated patients were analyzed. The distribution according to the International Staging System score was 26.1%, 30.4%, and 43.5% with a score of 1, 2, and 3, respectively. Thalidomide- and bortezomib-based combinations were used in 83.7% and 16.3% of the patients, respectively. Results A treatment response (complete remission, very good partial remission, partial remission) was achieved in 83.7% of the patients and correlated with high CRBN expression (P = .006), mainly in the patients treated with thalidomide (P = .028). Low CRBN expression affected progression-free survival (PFS; P = .017) but not overall survival (OS) in patients treated with thalidomide and had no influence on OS in the bortezomib group. In the Cox regression model, low CRBN expression was the most important prognostic parameter that influenced PFS in the thalidomide-treated patients (P = .012). Conclusion CRBN expression is of prognostic value in MM patients ineligible for ASCT treated with thalidomide as an immunomodulatory drug. With low expression indicating a possible suboptimal treatment outcome, measurement of CRBN expression might serve as additional prognostic tool in the personalized treatment approach. © 2016 Elsevier Inc.

Background: Several clinical prognostic models for diffuse large B-cell lymphoma (DLBCL) have been proposed, including the most commonly used International Prognostic Index (IPI), the National Comprehensive Cancer Network IPI (NCCN-IPI), and models incorporating beta-2 microglobulin (β2M). However, the role of β2M in DLBCL patients is not fully understood. Methods: We identified 6075 patients with newly diagnosed DLBCL treated with immunochemotherapy registered in the Danish Lymphoma Registry. Results: A total of 3232 patients had data available to calculate risk scores from each of the nine considered risk models for DLBCL, including a model developed from our population. Three of four models with β2M and NCCN-IPI performed better than the International Prognostic Indexes (IPI, age-adjusted IPI, and revised IPI). Five-year overall survival for high- and low-risk patients were 43.6% and 86.4% for IPI and 34.9% and 96.2% for NCCN-IPI. In univariate analysis, higher levels of β2M were associated with inferior survival, higher tumor burden (advanced clinical stage and bulky disease), previous malignancy and increased age, and creatinine levels. Furthermore, we developed a model (β2M-NCCN-IPI) by adding β2M to NCCN-IPI (c-index 0.708) with improved discriminatory ability compared to NCCN-IPI (c-index 0.698, p < 0.05) and 5-year OS of 33.1%, 56.2%, 82.4%, and 96.4% in the high, high-intermediate, low-intermediate and low-risk group, respectively. Conclusion: International Prognostic Indices, except for NCCN-IPI, fail to accurately discriminate risk groups in the rituximab era. β2M, a readily available marker, could improve the discriminatory performance of NCCN-IPI and should be re-evaluated in the development setting of future models for DLBCL. © 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

Background: Several clinical prognostic models for diffuse large B-cell lymphoma (DLBCL) have been proposed, including the most commonly used International Prognostic Index (IPI), the National Comprehensive Cancer Network IPI (NCCN-IPI), and models incorporating beta-2 microglobulin (β2M). However, the role of β2M in DLBCL patients is not fully understood. Methods: We identified 6075 patients with newly diagnosed DLBCL treated with immunochemotherapy registered in the Danish Lymphoma Registry. Results: A total of 3232 patients had data available to calculate risk scores from each of the nine considered risk models for DLBCL, including a model developed from our population. Three of four models with β2M and NCCN-IPI performed better than the International Prognostic Indexes (IPI, age-adjusted IPI, and revised IPI). Five-year overall survival for high- and low-risk patients were 43.6% and 86.4% for IPI and 34.9% and 96.2% for NCCN-IPI. In univariate analysis, higher levels of β2M were associated with inferior survival, higher tumor burden (advanced clinical stage and bulky disease), previous malignancy and increased age, and creatinine levels. Furthermore, we developed a model (β2M-NCCN-IPI) by adding β2M to NCCN-IPI (c-index 0.708) with improved discriminatory ability compared to NCCN-IPI (c-index 0.698, p < 0.05) and 5-year OS of 33.1%, 56.2%, 82.4%, and 96.4% in the high, high-intermediate, low-intermediate and low-risk group, respectively. Conclusion: International Prognostic Indices, except for NCCN-IPI, fail to accurately discriminate risk groups in the rituximab era. β2M, a readily available marker, could improve the discriminatory performance of NCCN-IPI and should be re-evaluated in the development setting of future models for DLBCL. © 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

Background: Primary testicular lymphoma (PTL) is a rare and highly aggressive extranodal non-Hodgkin's lymphoma. Patients and Methods: We evaluated the clinical and histopathological features and outcomes of 10 PTL patients treated in the period of 2003-2013 with multimodal therapy (rituximab, CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), intrathecal prophylaxis, irradiation of the contralateral testis) following orchiectomy. Results: Complete remission was achieved in 8 patients after first-line therapy while 2 patients had disease progression. The median follow-up duration was 30 months (range 6-110 months). Relapse occurred in 3 patients. 1 patient relapsed in the contralateral testis, while the other 2 patients relapsed to the skin and the central nervous system (CNS), respectively. The time to relapse was 2, 8, and 9 months. Patients with disease progression and relapse received ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) as salvage treatment, except for 1 patient who was treated with palliative radiotherapy. After second-line therapy, only 1 patient had a short partial remission of 2 months. The median overall survival was 48 months, and the mean progression-free survival was 36 months (the median was not reached). Conclusions: We evaluated 10 patients with PTL treated with rituximab plus CHOP, prophylactic intrathecal chemotherapy, and prophylactic irradiation of the contralateral testis, resulting in good outcome and low incidence of relapse in the contralateral testis; however, the benefit of intrathecal chemotherapy is not yet confirmed. © 2014 S. Karger GmbH, Freiburg.