1. Cerebral toxoplasmosis in a diffuse large B cell lymphoma patientLina Savšek, Tanja Roš-Opaškar, 2016, izvirni znanstveni članek Povzetek: Toxoplasmosis is an opportunistic protozoal infection that has, until now, probably been an underestimated cause of encephalitis in patients with hematological malignancies, independent of stem cell or bone marrow transplant. T and B cell depleting regimens are probably an important risk factor for reactivation of a latent toxoplasma infection in these patients. Case report. We describe a 62-year-old HIV-negative right-handed Caucasian female with systemic diffuse large B cell lymphoma who presented with sudden onset of high fever, headache, altered mental status, ataxia and findings of pancytopenia, a few days after receiving her final, 8th cycle of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisolone (R-CHOP) chemotherapy regimen. A progression of lymphoma to the central nervous system was suspected. MRI of the head revealed multiple on T2 and fluid attenuated inversion recovery (FLAIR) hyperintense parenchymal lesions with mild surrounding edema, located in both cerebral and cerebellar hemispheres that demonstrated moderate gadolinium enhancement. The polymerase chain reaction on cerebrospinal fluid (CSF PCR) was positive for Toxoplasma gondii. The patient was diagnosed with toxoplasmic encephalitis and successfully treated with sulfadiazine, pyrimethamine and folic acid. Due to the need for maintenance therapy with rituximab for lymphoma remission, the patient now continues with secondary prophylaxis of toxoplasmosis. Conclusions. With this case report, we wish to emphasize the need to consider cerebral toxoplasmosis in patients with hematological malignancies on immunosuppressive therapy when presenting with new neurologic deficits. In such patients, there are numerous differential diagnoses for cerebral toxoplasmosis, and the CNS lymphoma is the most difficult among all to distinguish it from. If left untreated, cerebral toxoplasmosis has a high mortality rate; therefore early recognition and treatment are of essential importance.
Ključne besede: toxoplasmosis, cerebral, lymphoma, rituximab
Objavljeno v DiRROS: 30.04.2024; Ogledov: 16; Prenosov: 6
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2. 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: 16; Prenosov: 4
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3. 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: 45; Prenosov: 15
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4. 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: 69; Prenosov: 24
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5. The influence of folate pathway polymorphisms on high-dose methotrexaterelated toxicity and survival in children with non-Hodgkin malignant lymphomaNina Erčulj, Barbara Faganel Kotnik, Maruša Debeljak, Janez Jazbec, Vita Dolžan, 2014, izvirni znanstveni članek Povzetek: Background. We evaluated the influence of folate pathway polymorphisms on high-dose methotrexate (HD-MTX) related toxicity in paediatric patients with T-cell non-Hodgkin lymphoma (NHL). Patients and methods. In total, 30 NHL patients were genotyped for selected folate pathway polymorphisms. Results. Carriers of at least one MTHFR 677T allele had significantly higher MTX area under the time-concentration curve levels at third MTX cycle (P = 0.003). These patients were also at higher odds of leucopoenia (P = 0.006) or thrombocytopenia (P = 0.041) and had higher number of different HD-MTX-related toxicity (P = 0.035) compared to patients with wild-type genotype. Conclusions. Our results suggest an important role of MTHFR 677C>T polymorphism in the development of HD-MTXrelated toxicity in children with NHL.
Ključne besede: childhood, non-Hodgkin lymphoma, polymorphism
Objavljeno v DiRROS: 16.04.2024; Ogledov: 71; Prenosov: 36
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6. The diffuse large B-cell lymphoma - where do we stand now in everyday clinical practiceBrigita Gregorič, Vesna Zadnik, Barbara Jezeršek Novaković, 2012, izvirni znanstveni članek Povzetek: 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.
Ključne besede: diffuse large B-cell lymphoma, R-CHOP, treatment result, routine treatments
Objavljeno v DiRROS: 21.03.2024; Ogledov: 105; Prenosov: 33
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7. Treatment outcomes and relative dose intensity of chemotherapy in patients with advanced Hodgkin lymphomaSamo Rožman, Barbara Jezeršek Novaković, Nina Ružić Gorenjec, Srdjan Novaković, 2022, izvirni znanstveni članek Povzetek: The present retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of patients with advanced stage Hodgkin lymphoma (HL) receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimens (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 patients with HL treated between 2004 and 2013 were enrolled for evaluation. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, and the majority were male and had stage IV disease. A total of 54 patients received ABVD and 60 received BEACOPP chemotherapy with 24 and four deaths, respectively. Patients in the BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) and better performance status in comparison with the ABVD group, making the comparison of groups not possible. In the ABVD group, RDI was not significantly associated with OS (P=0.590) or PFS (P=0.354) in a multivariate model where age was controlled. The low number of events prevented this analysis in the BEACOPP group. The age of patients was strongly associated with both OS and PFS; all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI, performance status) lost their effect in multivariate analyses where age was controlled. Based on these observations, it was concluded that RDI was not associated with OS or PFS after age is controlled, neither in all patients combined nor in the ABVD group.
Ključne besede: Hodgkin lymphoma, chemotherapy, outcome, primary treatment
Objavljeno v DiRROS: 23.09.2022; Ogledov: 526; Prenosov: 162
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