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Testing of mechanisms of action of rituximab and clinical results in high-risk patients with aggressive CD20+ lymphoma
Barbara Jezeršek Novaković, Vladimir Kotnik, Tanja Južnič Šetina, Marjeta Vovk, Srdjan Novaković, 2007, izvirni znanstveni članek

Povzetek: Background. Rituximab has been applied successfully in the treatment of indolent and aggressive CD20 positive B cell lymphomas, yet the exact in vivo mechanisms of its action have not been unambiguously explained. This study wastherefore aimed to confirm the presumed major mechanisms of action of rituximab and concomitantly to assess the effectiveness of first-line chemoimmunotherapy in high-risk patients with aggressive CD20 lymphomas. Patients, materials and methods. The activity of rituximab was tested in vitroon Raji and SU-DHL-4 cells using the cell proliferation assay and flow cytometry. In the clinical part of the study, 20 high-risk patients with aggressive CD 20 lymphomas were treated with R-CHOP. Results. Only complement-mediated cytotoxicity was observed under the in vitro applied experimental conditions. Neither the direct apoptotic effect nor the antibody-dependent cell-mediated cytotoxicity was detected probably due to a too low concentration of rituximab and a too low ratio of cytotoxic lymphocytes to tumor cells. The treatment outcome in patients was excellent since complete remissions were achieved in 90% of poor-risk patients at the end of primary treatment and 80% of patients were disease free at 18.5 months median observation period. Conclusions. According to our results, the complement-dependent cytotoxicity is an important mechanism of rituximab action in vitro. To achieve direct apoptosis, higher concentrations than 20 micro g/ml of rituximab should be used, while for an effective antibody-dependent cell-mediated cytotoxicity, the ratio of cytotoxic lymphocytes to tumor cells should be higher than 1:1. In the high- risk patients with aggressive CD20 lymphomas, the addition of rituximab to CHOP substantially improves the therapeutic results.
Objavljeno v DiRROS: 22.02.2024; Ogledov: 136; Prenosov: 36
.pdf Celotno besedilo (232,23 KB)

Rituximab affects the prognosis of patients with nonHodgkin's lymphomas
Barbara Jezeršek Novaković, Marjeta Vovk, Simona Borštnar, Radka Tomšič, 2004, izvirni znanstveni članek

Povzetek: Backround. Rituximab - the most widely used monoclonal antibody in the B cell lymphoid malignancies has been applied successfully in the treatment of relapsed and refractory indolent CD20 positive B cell lymphomas and more recently, also in the treatment of aggressive lymphomas in combination with standard chemotherapy. Albeit the chemo-immunotherapy has a wide range of potential applications, there are still several issues that have to be resolved: (1) the optimal scheduling of antibody-chemotherapy combinations, (2) the most active of these combinations, as well as (3) the predictors of response to rituximab. Patients and methods. To facilitate addressing the first two questions, we performed an analysis in 25 patients with different histological types of CD20 positive nonHodgkin's lymphomas (10 aggressive and 15 indolent). Seventeen patients were treated with chemo-immunotherapy for a relapse, and just in 8 patients rituximab was added to first line chemotherapy. Most of the responders received the CHOP regimen, but also otherregimens (FC, BVCPP) were effective in combination with rituximab. Results. The overall response rate was 76%, with 68% complete remissions. The median response duration has not been reached yet. The response was markedly better in the group of previously untreated patients, where the overall response rate reached 100%, with 7 patients in complete and 1 patient in partial remission. Most of the treatment failures occurred in heavily pretreated patients with aggressive lymphomas. No serious adverse effects wereobserved. Conclusion The chemo-immunotherapy improves the treatment outcomes in patients with untreated and relapsed CD20 positive nonHodgkin's lymphomas in comparison to chemotherapy alone. The combined treatment is the most effective when used as soon as possible (preferably as the first line treatment). (Abstract truncated at 2000 characters).
Objavljeno v DiRROS: 07.02.2024; Ogledov: 175; Prenosov: 39
.pdf Celotno besedilo (4,61 MB)

Prognostic value of staging laparotomy in supradiaphragmatic clinical stage I and II Hodgkin's disease
Marjeta Vovk, Tatjana Šumi-Križnik, Marija Jenko-Fidler, Gabrijela Petrič-Grabnar, Marinka Kremžar, Janez Novak, Mojca Senčar, Branko Zakotnik, Alenka Vodnik-Cerar, Branimir Jakšić, 1996, izvirni znanstveni članek

Povzetek: In the period 1974-1989, 219 patients with supradiaphragmatic clinical stage I and II Hodgkin's disease were treated at the Institute of Oncology in Ljubljana; of these 95 (43%) patients underwent staging laparotomy. Of laparotomized patients, those with pathological stage III-IV, and of non-laparotomized, those with unfavorable prognostic factors (B-symptoms, bulky mediastinum) received chemotherapy: the remaining patients were treated by irradiation. No statistically significant difference in the survival and disease-free survival between laparotomized and nonlaparotomized patients could be found.
Objavljeno v DiRROS: 16.01.2024; Ogledov: 158; Prenosov: 44
.pdf Celotno besedilo (364,35 KB)

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