1. Correlation of t(14;18) translocation breakpoint site with clinical characteristics in follicular lymphomaMatej Panjan, Lučka Boltežar, Srdjan Novaković, Ira Koković, Barbara Jezeršek Novaković, 2023, izvirni znanstveni članek Povzetek: Background: t(14;18)(q32;q21) translocation is an important genetic feature of follicular lymphoma resulting in antiapoptotic B-cell lymphoma 2 (BCL2) protein overexpression. On chromosome 18 breakpoint-site variation is high but does not affect BCL2. Breakpoint most commonly occurs at major breakpoint region (MBR) but may happen at minor cluster region (mcr) and between MBR and mcr at 3'MBR and 5'mcr. The aim of this study was to analyze the correlation of t(14;18)(q32;q21) breakpoint site with clinical characteristics in follicular lymphoma. Patients and methods: We included patients diagnosed with follicular lymphoma who received at least 1 cycle of systemic treatment and had the t(14;18)(q32;q21) translocation detected by polymerase chain reaction (PCR) at MBR, mcr or 3'MBR prior to first treatment. Among patients with different breakpoints, sex, age, disease grade, stage, B-symptoms, follicular lymphoma international prognostic index (FLIPI), presence of bulky disease, progression free survival and overall survival were compared. Results: Of 84 patients, 63 had breakpoint at MBR, 17 at mcr and 4 at 3'MBR. At diagnosis, the MBR group had a significantly lower disease stage than the mcr group. Although not significant, in the MBR group we found a higher progression-free survival (PFS) and overall survival (OS), lower grade, age, FLIPI, and less B-symptoms. Conclusions: Compared to patients with mcr breakpoint, those with MBR breakpoint seem to be characterised by more favourable clinical characteristics. However, a larger study would be required to support our observation. Ključne besede: clinical characteristics, follicular lymphoma, t(14, 18) translocation Objavljeno v DiRROS: 25.07.2024; Ogledov: 129; Prenosov: 80
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2. 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, izvirni znanstveni članek Povzetek: 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 Ključne besede: diffuse large B-cell lymphoma, immunohistochemistry, lymphomas, CD56 Objavljeno v DiRROS: 25.07.2024; Ogledov: 143; Prenosov: 47
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3. Long-term outcomes of high dose treatment and autologous stem cell transplantation in follicular and mantle cell lymphomas : a single centre experienceLučka Boltežar, Karlo Pintarić, Jože Pretnar, Maja Pohar Perme, Barbara Jezeršek Novaković, 2017, izvirni znanstveni članek Povzetek: Background. Advanced follicular lymphoma (FL) and mantle cell lymphoma (MCL) are incurable diseases with conventional treatment. The high dose treatment (HDT) with autologous stem cell transplantation (ASCT), however, offers a certain proportion of these patients the prospect of a prolonged disease-free and overall survival. The aim of this study was to investigate the event free survival (EFS) and overall survival (OS) in patients with FL and MCL treated with ASCT. Patients and methods. Seventeen patients with FL and 29 patients with MCL were included, 15 of them were trans- planted to consolidate the response to second line treatment and 24 to consolidate their first remission, respectively. All were conditioned with total body irradiation (TBI) and high dose cyclophosphamide between 2006 and 2014 and all were transplanted with peripheral blood stem cells. Results. The estimated 5-year OS for FL was 87.8% (95% confidence interval [CI] 59.5%-96.8%) and for MCL 79.3% (95% CI 56.1%-91.1%), respectively. The estimated 5-year EFS for FL was 76.0% (95% CI 48.0%-90.3%) and for MCL 69.8% (95% CI 45.5%-84.8%), respectively. There were no secondary hematological malignancies observed in either group. Conclusions. Based on above results, the ASCT with TBI is a good treatment option in terms of long-term survival for patients with follicular and mantle cell lymphoma demonstrating a relatively low rate of late toxicities and secondary malignancies. Ključne besede: follicular lymphoma, mantle cell lymphoma, autologous stem cell transplantation Objavljeno v DiRROS: 03.06.2024; Ogledov: 209; Prenosov: 138
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4. Outcome of severe infections in afebrile neutropenic cancer patientsKsenija Strojnik, Ksenija Mahkovic Hergouth, Barbara Jezeršek Novaković, Boštjan Šeruga, 2016, izvirni znanstveni članek Povzetek: In some neutropenic cancer patients fever may be absent despite microbiologically and/or clinically confirmed infection. We hypothesized that afebrile neutropenic cancer patients with severe infections have worse outcome as compared to cancer patients with febrile neutropenia. Patients and methods. We retrospectively analyzed all adult cancer patients with chemotherapy-induced neutropenia and severe infection, who were admitted to the Intensive Care Unit at our cancer center between 2000 and 2011. The outcome of interest was 30-day in-hospital mortality rate. Association between the febrile status and in-hospital mortality rate was evaluated by the Fishers exact test. Results. We identified 69 episodes of severe neutropenic infections in 65 cancer patients. Among these, 9 (13%) episodes were afebrile. Patients with afebrile neutropenic infection presented with hypotension, severe fatigue with inappetence, shaking chills, altered mental state or cough and all of them eventually deteriorated to severe sepsis or septic shock. Overall 30-day in-hospital mortality rate was 55.1%. Patients with afebrile neutropenic infection had% a trend for a higher 30-day in-hospital mortality rate as compared to patients with febrile neutropenic infection (78% vs. 52%, p = 0.17). Ključne besede: afebrile infection, neutropenia, hypothemia, cancer patients Objavljeno v DiRROS: 30.04.2024; Ogledov: 362; Prenosov: 159
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5. Granulomatosis after autologous stem cell transplantation in nonHodgkin lymphoma : experience of single institution and a review of literatureLučka Boltežar, Ivana Žagar, Barbara Jezeršek Novaković, 2016, pregledni znanstveni članek Povzetek: Sarcoidosis before and after treatment of malignancy is an important differential diagnosis that has to be distinguished from lymphoma. Patients and methods. Hodgkin lymphoma, diffuse large B-cell lymphoma and aggressive follicular lymphoma are being staged and treatment effect is evaluated with PET-CT. We report three cases of aggressive lymphoma after high dose therapy and autologous stem cell transplantation with positive lymph nodes on PET-CT, which were histologically diagnosed as sarcoidosis/granulomatosis. In the literature, we found that false positive lymph nodes were more common after allogeneic than after autologous transplantation. Conclusions. Post-treatment PET-CT positive lymph nodes should always be examined histologically prior to any further treatment decision to avoid unnecessary toxic procedures. Ključne besede: granulomatosis, nonHodgin lymphoma, PET-CT, differential diagnosis Objavljeno v DiRROS: 30.04.2024; Ogledov: 304; Prenosov: 94
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6. Immunotoxin - a new treatment option in patients with relapsed and refractory Hodgkin lymphomaBarbara Jezeršek Novaković, 2015, pregledni znanstveni članek Povzetek: Background. Even though Hodgkin lymphoma is a highly curable disease, some of the patients have either a refractory disease or experience a relapse following a successful primary therapy. Durable responses and remissions in patients with relapsed or refractory disease may be achieved in approximately one-half with salvage chemotherapy followed by high dose chemotherapy (HDT) and autologous hematopoietic cell rescue (SCT). On the other hand, patients who relapse after HDT and autologous SCT or those who have failed at least two prior multi-agent chemotherapy regimens and are not candidates for HDT have limited treatment options. Conclusions. A new treatment option in this population is an immunotoxin Brentuximab vedotin composed of a CD30 directed antibody linked to the antitubulin agent monomethyl auristatin E. It has demonstrated a substantial effectiveness and an acceptable toxicity. In the pivotal study, the overall response rate was 75% with 34% of complete remissions. The median durations of response were 20.5 and 6.7 months for those with complete remission and all responding patients, respectively. The median overall survival was 40.5 months (3-years overall survival 54%) and the median progression-free survival 9.3 months. The most common non-hematologic toxicities were peripheral sensory neuropathy, nausea, and fatigue while the most common severe side effects were neutropenia, thrombocytopenia, anemia, and peripheral sensory neuropathy. Ključne besede: immunotoxin, Hodgkin lymphoma, toxicity, new treatment option Objavljeno v DiRROS: 22.04.2024; Ogledov: 609; Prenosov: 435
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8. Do double-expressor high-grade B-cell lymphomas really need intensified treatment : a report from the real-life series of high-grade B-cell lymphomas treated with different therapeutic protocols at the Institute of Oncology LjubljanaLučka Boltežar, Samo Rožman, Gorana Gašljević, Biljana Grčar-Kuzmanov, Barbara Jezeršek Novaković, 2024, izvirni znanstveni članek Povzetek: High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are known for their aggressive clinical course and so are the ones with MYC and BCL2 protein overexpression. The optimal therapy for these lymphomas remains to be elucidated. A retrospective analysis of all diffuse large B-cell lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements diagnosed between 2017 and 2021 at the Institute of Oncology Ljubljana, Slovenia, has been performed. Only patients with double-expressor lymphoma (DEL), double-hit lymphoma (DHL), or triple-hit lymphoma (THL) were included. Demographic and clinical parameters were assessed, as well as progression-free survival (PFS) and overall survival (OS). In total, 161 cases out of 309 (161/309; 52,1%) were classified as DEL. Sixteen patients had DHL, MYC/BCL2 rearrangement was observed in eleven patients, and MYC/BCL6 rearrangement was observed in five patients. Five patients were diagnosed with THL. Out of 154 patients (according to inclusion/exclusion criteria) included in further evaluation, one-hundred and thirty-five patients had double-expressor lymphoma (DEL), sixteen patients had DHL, and three patients had THL. In total, 169 patients were treated with R-CHOP, 10 with R-CHOP and intermediate-dose methotrexate, 19 with R-DA-EPOCH, and 16 with other regimens. The median follow-up was 22 months. The 5-year OS for the whole DEL group was 57.1% (95% CI 45.9–68.3%) and the 5-year PFS was 76.5% (95% CI 72.6–80.4%). The log-rank test disclosed no differences in survival between treatment groups (p = 0.712) while the high-risk international prognostic index (IPI) carried a significantly higher risk of death (HR 7.68, 95% CI 2.32–25.49, p = 0.001). The 5-year OS for DHL patients was 32.4% (95% CI 16.6–48.2%) while all three TH patients were deceased or lost to follow-up. Our analyses of real-life data disclose that the R-CHOP protocol with CNS prophylaxis is a successful and curative treatment for a substantial proportion of DEL patients. Ključne besede: lymphoma, double-expressor lymphoma, oncology Objavljeno v DiRROS: 18.04.2024; Ogledov: 306; Prenosov: 174
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9. Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in breast cancer : correlation with traditional prognostic factorsMaja Lampelj, Darja Arko, Nina Čas-Sikošek, Rajko Kavalar, Maja Ravnik, Barbara Jezeršek Novaković, Sarah Dobnik, Nina Fokter Dovnik, Iztok Takač, 2015, izvirni znanstveni članek Povzetek: Background. Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients. Patients and methods. 606 primary breast cancer patients were enrolled in the prospective study in the Department of gynaecological oncology and breast oncology at the University Medical Centre Maribor between the years 2004 and 2010. We evaluated the traditional prognostic factors (age, menopausal status, tumour size, pathohistological type, histologic grade, lymph node status, lymphovascular invasion and hormone receptor status), together with uPA and PAI-1. We used Spearman%s rank correlation, Mann Whitney U test and X2 test for statistical analysis. Results. Our findings indicate a positive correlation between uPA and tumour size (p < 0.001), grade (p < 0.001), histological type (p < 0.001), lymphovascular invasion (p = 0.01) and a negative correlation between uPA and hormone receptor status (p < 0.001). They also indicate a positive correlation between PAI-1 and tumour size (p = 0.004), grade (p < 0.001), pathohistological type (p < 0.001) and negative correlation between PAI-1 and hormone receptor status (p = 0.002). Conclusions. Our study showed a relationship between uPA and PAI-1 and traditional prognostic factors. Their role as prognostic and predictive factors remains to be further evaluated. Ključne besede: urokinase plasminogen activator, plasminogen activator inhibitor, breast cancer Objavljeno v DiRROS: 17.04.2024; Ogledov: 318; Prenosov: 171
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10. Clonality analysis of lymphoid proliferations using the BIOMED-2 clonality assays : a single institution experienceIra Koković, Barbara Jezeršek Novaković, Petra Škerl, Srdjan Novaković, 2014, izvirni znanstveni članek Povzetek: Background. Clonality determination in patients with lymphoproliferative disorders can improve the final diagnosis.The aim of our study was to evaluate the applicative value of standardized BIOMED-2 gene clonality assay protocolsfor the analysis of clonality of lymphocytes in a group of different lymphoid proliferations.Materials and methods. With this purpose, 121 specimens from 91 patients with suspected lymphoproliferationssubmitted for routine diagnostics from January to December 2011 were retrospectively analyzed. According to thefinal diagnosis, our series comprised 32 cases of B-cell lymphomas, 38 cases of non-Hodgkins T-cell lymphomas and51 cases of reactive lymphoid proliferations. Clonality testing was performed using the BIOMED-2 clonality assays.Results. The determined sensitivity of the TCR assay was 91.9%, while the sensitivity of the IGH assay was 74.2%. Thedetermined specificity of the IGH assay was 73.3% in the group of lymphomas and 87.2% in the group of reactivelesions. The determined specificity of the TCR assay was 62.5% in the group of lymphomas and 54.3% in the group ofreactive lesions.Conclusions. In the present study, we confirmed the utility of standardized BIOMED-2 clonality assays for the detectionof clonality in a routine diagnostical setting of non-Hodgkins lymphomas. Reactions for the detection of thecomplete IGH rearrangements and reactions for the detection of the TCR rearrangements are a good choice forclonality testing of a wide range of lymphoid proliferations and specimen types while the reactions for the detectionof incomplete IGH rearrangements have not shown any additional diagnostic value. Ključne besede: Biomed-2, clonality analysis, lymphomas, IGH rearrangement, TCR rearrangement Objavljeno v DiRROS: 11.04.2024; Ogledov: 336; Prenosov: 97
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