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: 81
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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. 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. 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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8. Ali visoko maligni B-celični limfomi, dvojni ekspresorji, res potrebujejo intenzivnejšo kemoterapijoLučka Boltežar, Samo Rožman, Gorana Gašljević, Biljana Grčar-Kuzmanov, Barbara Jezeršek Novaković, 2023, objavljeni znanstveni prispevek na konferenci Povzetek: Velikocelični B limfomi z BCL2 in BCL6 preureditvijo so imenovani "double-hit" oziroma "triplehit" limfomi, z imunohistokemično ekspresijo pa dvojni ekspresorji (DE) in vsi imajo slabšo prognozo od klasičnih velikoceličnih limfomov B. Opravljena je bila študija vseh bolnikov z visoko malignimi B limfomi in difuznim velikoceličnim limfomom B, zdravljenih na Onkološkem inštitutu Ljubljana med leti 2017 in 2021. Večina izmed 154 vključenih bolnikov je bila zdravljenih z R-CHOP terapijo (rituksimab, ciklofosfamid, doksorubicin, vinkristin in prednizon), mediani čas spremljanja bolnikov je bil 22 mesecev. 110 bolnikov (71,4 %) ni imelo ponovitve bolezni v opazovanem obdobju. V primerjavi štirih uporabljenih terapevtskih protokolov v skupini DE nismo našli razlik v preživetju (p < 0,712). Preživetje bolnikov z "double-hit" in "triple-hit" limfomi je bilo, pričakovano, slabo. Naši podatki kažejo, da je velik del bolnikov z DE, zdravljen z R-CHOP in standardno CŽS profilakso, tudi uspešno ozdravljen. Za potrditev naših izsledkov so potrebne večje randomizirane raziskave. Ključne besede: limfomi, kemoterapija, onkološko zdravljenje Objavljeno v DiRROS: 16.06.2023; Ogledov: 571; Prenosov: 235
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9. Priporočila za obravnavo bolnikov z malignimi limfomiBarbara Jezeršek Novaković, Lučka Boltežar, Andreja Eberl, Gorana Gašljević, Biljana Grčar-Kuzmanov, Monika Jagodic, Tanja Južnič Šetina, Veronika Kloboves-Prevodnik, Gregor Kos, Aleš Christian Mihelač, Milica Miljković, Urška Rugelj, Marija Skoblar Vidmar, Uroš Smrdel, Danijela Štrbac, Miha Toplak, Lorna Zadravec-Zaletel, 2023, strokovna monografija Ključne besede: maligni limfomi, smernice, novotvorbe Objavljeno v DiRROS: 24.01.2023; Ogledov: 940; Prenosov: 397
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