1. Are there clinically relevant prognostic factors in diffuse large B-cell lymphoma beyond International Prognostic IndexMilica Miljković, Vita Šetrajčič Dragoš, Gorana Gašljević, Srdjan Novaković, Lučka Boltežar, Barbara Jezeršek Novaković, 2025, original scientific article Abstract: Diffuse large B-cell lymphoma (DLBCL) has variable prognosis, with only 50 to 60% of patients cured by standard first line treatment. Identifying patients unlikely to benefit from standard first line therapy is therefore crucial. Schmitz’s study identified four molecular subtypes of DLBCL with differing prognoses: MCD, BN2, N1, and EZB, with BN2 and EZB showing more favorable outcomes. This study aimed to evaluate the effectiveness of the Archer FusionPlex Lymphoma Assay in identifying the newly defined genetic subtypes of DLBCL, while also exploring the association between immunohistochemical (IHC) and next-generation sequencing (NGS) methods for classifying the cell of origin (COO) and assessing their predictive value for patient survival. Materials and methods. We classified 131 DLBCL patients using Hans algorithm into GCB (germinal center B-celllike) and ABC (activated B-cell-like) subtypes, and with NGS applying Archer FusionPlex lymphoma assay into ABC, GCB, unclassified, and into Schmitz’s novel genetic subtypes. A mutational analysis of just 7 genes (MYD88L265P, CD79B, EZH2, NOTCH1, NOTCH2, BCL2, and BCL6) was used for genetic classification. Various statistical models were applied to assess survival differences between subtypes. Finally, STRATOS analysis was conducted to validate our preliminary statistical findings. Results. 35.9% of patients were successfully classified into new genetic subtypes, with acceptable consistency between IHC and NGS method for COO determination. However, the new genetic subtype classification by NGS did not correlate with overall survival, nor did the COO classifications by IHC or NGS. The inclusion of these classifications also did not improve the predictive value of models compared to the basic model based on the International Prognostic Index (IPI) only. Conclusions. The Archer FusionPlex Lymphoma assay showed a somewhat lower detection rate of novel genetic subtypes compared to reports based on exome sequencing, yet identified novel genetic subtypes in over one-third of patients. However, an in-depth STRATOS statistical analysis did not confirm its predictive value for DLBCL prognosis, likely due to factors like patient selection and sample size limitations.
Keywords: diffuse large B-cell lymphoma, new genetic types, prognostic factors
Published in DiRROS: 26.11.2025; Views: 242; Downloads: 66
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2. Prognostic Value of Multiple Manual Segmentation Methods for Diffuse Large B-Cell Lymphoma with 18F-FDG PET/CTAndrej Doma, Andrej Studen, Barbara Jezeršek Novaković, 2025, original scientific article Abstract: Abstract: Quantitative 18F-FDG PET/CT-derived metabolic metrics are strongly associated with patient outcomes in diffuse large B-cell lymphoma (DLBCL), but the lack of consensus on optimal segmentation thresholds limits standardization. This study evaluated the prognostic value of various metabolic tumor volume (MTV) segmentation approaches in 140 stage II–IV DLBCL patients treated with standard immunochemotherapy. MTV was derived using fixed SUV (≥2.5, ≥4.0), relative (>41% SUVmax), and adaptive (liver-tobackground) thresholds. Baseline MTV metrics significantly correlated with 3-year overall survival (OS3) in univariate analysis in overall cohort, with MTV41 showing the strongest association (HR: 1.27; p = 0.003). MTV25 and MTV41 remained significant in the stage 4 patient subgroup. However, in multivariate analysis, no MTV metric independently predicted OS3 when adjusted for the International Prognostic Index (IPI), which remained the dominant predictor (HR: 1.95; p < 0.0001). ROC analysis confirmed superior AUC for IPI (0.76) over PET-based metrics (0.64–0.69). Predictive models integrating IPI with PET metrics were robust but failed to improve prognostic accuracy beyond IPI alone. Although PET-derived MTV metrics provide prognostic value in univariate analysis, threshold selection has minimal impact, and their added value is limited when combined with IPI, reinforcing its role as the most reliable survival predictor in DLBCL.
Keywords: diffuse large B-cell lymphoma, 18F-FDG, overall survival, PET/CT
Published in DiRROS: 21.11.2025; Views: 200; Downloads: 58
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3. The impact of bone marrow involvement on prognosis in diffuse large B-cell lymphoma : an 18F-FDG PET/CT volumetric segmentation studyAndrej Doma, Andrej Studen, Barbara Jezeršek Novaković, 2024, original scientific article Abstract: Background: This study assessed the prognostic value of tumor burden in bone marrow (BM) and total disease (TD), as depicted on 18F-FDG PET/CT in 140 DLBCL patients, for complete remission after first-line systemic treatment (iCR) and 3- and 5-year overall survival (OS3 and OS5). Methods: Baseline 18F-FDG PET/CT scans of 140 DLBCL patients were segmented to quantify metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUVmax in BMI, findings elsewhere (XL), and TD. Results: Bone marrow involvement (BMI) presented in 35 (25%) patients. Median follow-up time was 47 months; 79 patients (56%) achieved iCR. iCR was significantly associated with TD MTV, XL MTV, BM PET positivity, and International Prognostic Index (IPI). OS3 was significantly worse with TD MTV, XL MTV, IPI, and age. OS5 was significantly associated with IPI, but not with MTVs and TLGs. Univariate factors predicting OS3 were XL MTV (hazard ratio [HR] = 1.29), BMI SUVmax (HR = 0.56), and IPI (HR = 1.92). By multivariate analysis, higher IPI (HR = 2.26) and BMI SUVmax (HR = 0.91) were significant independent predictors for OS3. BMI SUVmax resulted in a negative coefficient and hence indicated a protective effect. Conclusions: Baseline 18F-FDG PET/CT MTV is significantly associated with survival. BMI identified on 18F-FDG PET/CT allows appropriate treatment that may improve survival.
Keywords: bone marrow, diffuse large B-cell lymphoma, survival
Published in DiRROS: 09.01.2025; Views: 819; Downloads: 494
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4. CD56-positive diffuse large B-cell lymphoma : comprehensive analysis of clinical, pathological, and molecular characteristics with literature reviewGorana Gašljević, Lučka Boltežar, Srdjan Novaković, Vita Šetrajčič Dragoš, Barbara Jezeršek Novaković, Veronika Kloboves-Prevodnik, 2023, original scientific article Abstract: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. The expression of CD56 in DLBCL is highly unusual. Little is known about its incidence and clinical importance. So far, no genetic profiling was performed in CD56 positive DLBCL.Patients and methods. Tissue microarrays have been constructed, sectioned, and stained by H&E and immuno-histochemistry for 229 patients with DLBCL diagnosed 2008–2017. For CD56 positive cases, clinical data was collected including age at diagnosis, stage of the disease, International Prognostic Index (IPI) score, treatment scheme and number of chemotherapy cycles, radiation therapy, treatment outcome, and possible relapse of the disease. Overall survival (OS) and progression-free survival (PFS) were calculated. For four patients, RNA was extracted and targeted RNA (cDNA) sequencing of 125 genes was performed with the Archer FusionPlex Lymphoma kit.Results. CD56 expression was found in 7 cases (3%). The intensity of expression varied from weak to moderate focal, to very intensive and diffuse. All patients had de novo DLBCL. The median age at the time of diagnosis was 54.5 years. Five of them were women and 2 males. According to the Hans algorithm, 6 patients had the germinal centre B cells (GBC) type and one non-GBC (activated B-cell [ABC]) type, double expressor. Genetic profiling of four patients ac-cording to Schmitz’s classification showed that 1 case was of the BN2 subtype, 1 of EZB subtype, 2 were unclassified. The six treated patients reached a complete response and did not experience progression of the disease during the median follow-up period of 80.5 months.Conclusions. We report on one of the largest series of CD56+DLBCL with detailed clinicopathological data and for the first time described genetical findings in a limited number of patients. Our results show that CD56 expression is rare, but seems to be present in prognostic favourable subtypes of DLBCL not otherwise specified (NOS) as tested by immunohistochemical or genetic profiling
Keywords: diffuse large B-cell lymphoma, immunohistochemistry, lymphomas, CD56
Published in DiRROS: 25.07.2024; Views: 1005; Downloads: 363
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5. The diffuse large B-cell lymphoma - where do we stand now in everyday clinical practiceBrigita Gregorič, Vesna Zadnik, Barbara Jezeršek Novaković, 2012, original scientific article Abstract: Background. Due to superior results observed with the addition of rituximab into treatment of patients with the diffuse large B-cell lymphoma (DLBCL),the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen and its variants became the standard initial treatment of these patients. However, the treatment recommendations are based on resultsof clinical studies while the conditions of routine treatment are far different from the ones in clinical studies. The aim of this retrospective study was therefore to compare the treatment results of routinelz treated patients with the DLBCL to results reported by some larger studies. Patients and methods. Two hundred and ninety five patients with the DLBCL were treated between 2004 and 2008 according to the then protocol with R-CHOP or R-CHOP-like regimens at the Institute of Oncology Ljubljana. Treatment response was evaluated according to Chesonʼs criteria and the disease-free andoverall survival by means of Kaplan Meier survival curves. Results. Response to treatment in our evaluation diverged from the reported one predominately in the low risk group (international prognostic index [IPI] categorisation) and in the very good prognosis group (revised international prognostic index (R-IPI) categorisation). The determined complete response (CR) rates in other IPI and R-IPI groups were generally within expectations. Also in the disease-free survival the largest discrepancy occurred in the low-risk patient group (3 year disease-free survival rate of 75%) and in the very good prognosis group (4 year disease-free survival rate of 59%). In all other IPI risk groups, the disease-free survival at 3 zears (low intermediate risk 76%, high intermediate risk group 57%, and high risk group 53%) agreed verz well with the quoted ones. Slightly worse was the compliance of the 4 year disease-free survival rates (72% in the good prognosis and 51% in the poor prognosis group) with the results from the literature. The 3 year overall survival rates (low risk patients 87%, high intermediate risk 61% and high risk patients 51%) were somewhat worse than the reported ones in all IPI subgroups except in the low intermediate risk group (82%). On the other hand, the 4 year overall survival rates of the R-IPI categories (94% in the very good prognosis group, 80% in the good prognosis group, 56% in the poor prognosis group) were much better correlated with the data from the literature. Conclusions. In total, the treatment outcomes of routinely treatedpatient with the DLBCL at our institute are quite encouraging when compared to results of some larger studies. There are probably no dilemmas about how to treat young good prognosis patients and patients aged over 60 years at present. However, the 5 year overall survival rate of 76% for the young poor prognosis group is unsatisfying and needs to be improved. At present, quite a few studies are underway to clarify which of the regimens will perform best in this population.
Keywords: diffuse large B-cell lymphoma, R-CHOP, treatment result, routine treatments
Published in DiRROS: 21.03.2024; Views: 1254; Downloads: 339
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