13 research outputs found

    The assessment of angiogenesis in chronic lymfocytic leukemia

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    Academic Department of Internal MedicineKatedra interních oborůLékařská fakulta v Hradci KrálovéFaculty of Medicine in Hradec Králov

    The assessment of angiogenesis in chronic lymfocytic leukemia

    No full text
    Academic Department of Internal MedicineKatedra interních oborůLékařská fakulta v Hradci KrálovéFaculty of Medicine in Hradec Králov

    How I Treat Elderly or Comorbid Patients with Chronic Lymphocytic Leukemia

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    Treatment of chronic lymphocytic leukemia (CLL) has recently undergone several major changes. Most importantly, large randomized trials (CLL-8 in first line and REACH in relapse) clearly demonstrated superiority of chemoimmunotherapy consisting of fludarabine, cyclophosphamide and rituximab (FCR) over fludarabine and cyclophosphamide (FC) alone, thus establishing FCR regimen as the new gold standard in younger and physically fit patients. However, management of elderly and/or comorbid patients is still a challenging task because they cannot be treated with agressive approaches due to high risk of unacceptable toxicity. To date, no randomized trials in this patient population have improved therapeutic results over chlorambucil; therefore, this agent remains the backbone of treatment against which the new protocols should be tested. When deciding about the intensity of treatment, performance status, biological age and number as well as severity of comorbidities should be taken into account. Emerging treatment concepts for elderly/comorbid patients include combination of chlorambucil with monoclonal antibodies (rituximab, ofatumumab, GA-101), fludarabine-based regimens in reduced doses or protocols based on bendamustine and lenalidomide. Combination of highdose steroids with rituximab represent a promising option in relapsed/refractory CLL; however, infectious toxicity remains a serious issue. Finally, ofatumumab monotherapy appears to be a safe and effective therapy for heavily pretreated patients with CLL. This article reviews the current and future possibilities in the treatment of elderly and comorbid patients with CLL

    Biological Prognostic Markers in Chronic Lymphocytic Leukemia

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    Chronic lymphocytic leukemia (CLL) is the most frequent leukemic disease of adults in the Western world. It is remarkable by an extraordinary heterogeneity of clinical course with overall survival ranging from several months to more than 15 years. Classical staging sytems by Rai and Binet, while readily available and useful for initial assessment of prognosis, are not able to determine individual patient’s ongoing clinical course of CLL at the time of diagnosis, especially in early stages. Therefore, newer biological prognostic parameters are currently being clinically evaluated. Mutational status of variable region of immunoglobulin heavy chain genes (IgVH), cytogenetic aberrations, and both intracellular ZAP- 70 and surface CD38 expression are recognized as parameters with established prognostic value. Molecules regulating the process of angiogenesis are also considered as promising markers. The purpose of this review is to summarize in detail the specific role of these prognostic factors in chronic lymphocytic leukemia

    Addition of Rituximab Significantly Improves Outcomes in Patients with Diffuse Large B-cell Lymphoma – a Single-center, Retrospective Study

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    CHOP chemotherapy has been used as a standard first-line treatment for diffuse large B-cell lymphoma since the 1970s. Phase III trials have shown that the addition of rituximab (R) to CHOP chemotherapy leads to significant improvements in response rate, progression-free survival and overall survival. This single-center, retrospective study was performed to evaluate the role of the addition of R to chemotherapy (CHT) in a real-world clinical setting. Outcomes were assessed in 85 patients with newly diagnosed DLBCL treated with CHT alone (n=38) and R-CHT (n=47). Complete response (CR) rates were significantly higher after R-CHT than CHT (93 % vs. 73 %; p=0.02). The relapse rate was significantly higher after CHT compared with R-CHT (38 % versus 12 %; p=0.01). Progression-free survival was significantly extended by the addition of R (median not reached versus 26.1 months; p=0.04). These data bring further support for rituximab- based immunochemotherapy as a standard first-line therapy for patients with DLBCL

    Ofatumumab maintenance versus observation in relapsed chronic lymphocytic leukaemia (PROLONG): an open-label, multicentre, randomised phase 3 study

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    Background: Ofatumumab is a human anti-CD20 monoclonal antibody that has proven efficacy as monotherapy in refractory chronic lymphocytic leukaemia. We assessed the efficacy and safety of ofatumumab maintenance treatment versus observation for patients in remission after re-induction treatment for relapsed chronic lymphocytic leukaemia. Methods: This open-label, multicentre, randomised phase 3 study enrolled patients aged 18 years or older from 130 centres in 24 countries who had chronic lymphocytic leukaemia in complete or partial remission after second-line or third-line treatment. Eligible patients had a WHO performance status of 0-2, had a response assessment within the previous 3 months, did not have refractory disease, autoimmune haemolytic anaemia requiring treatment, chronic or active infection requiring treatment, and had not previously received maintenance treatment or autologous or allogeneic stem-cell transplant. Using a randomisation list generated by a central computerised system and an interactive voice recognition system, we randomly assigned (1: 1) patients to receive ofatumumab (300 mg followed by 1000 mg 1 week later and every 8 weeks for up to 2 years) or undergo observation. Randomisation was stratified by number and type of previous treatment and remission status after induction treatment (block size of four). Treatment assignment was open label. The primary endpoint was investigator-assessed progression-free survival in the intentionto-treat population. We report the results of a prespecified interim analysis after two-thirds of the planned study events (disease progression or death) had happened. This trial is closed to accrual but follow-up is ongoing. This trial is registered with ClinicalTrials.gov, number NCT00802737. Findings: Between May 6, 2010, and June 19, 2014, we enrolled 474 patients: 238 patients were randomly assigned to receive ofatumumab maintenance treatment and 236 to undergo observation. One (<1%) patient in the ofatumumab group did not receive the allocated intervention (withdrawal of consent). The median follow-up was 19.1 months (IQR 10.3-28.8). Progression-free survival was improved in patients assigned to the ofatumumab group (29.4 months, 95% CI 26.2-34.2) compared with those assigned to observation (15.2 months, 11,8-18.8; hazard ratio 0.50, 95% CI 0.38-0.66; p<0.0001). The most common grade 3 or higher adverse events up to 60 days after last treatment were neutropenia (56 [24%] of 237 patients in the ofatumumab group vs 23 [10%] of 237 in the observation group) and infections (31 [13%] vs 20 [8%]). 20 (8%) of 237 patients in the ofatumumab group and three (1%) of 237 patients in the observation group had adverse events that led to permanent discontinuation of treatment. Up to 60 days after last treatment, two deaths related to adverse events occurred in the ofatumumab treatment group and five deaths related to adverse events occurred in the observation group; no deaths were attributed to the study drug. Interpretation: These data are important for the development of optimum maintenance strategies in patients with relapsed chronic lymphocytic leukaemia, notably in the present era of targeted drugs, many of which are to be used until progression
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