Clinic for Hematology

Serbia

Clinic for Hematology

Serbia
SEARCH FILTERS
Time filter
Source Type

Jaeger U.,Medical University of Vienna | Trneny M.,Charles University | Melzer H.,Medical University of Vienna | Praxmarer M.,Arbeitsgemeinschaft Medikamentose Tumortherapie | And 23 more authors.
Haematologica | Year: 2015

We investigated rituximab maintenance therapy in patients with diffuse large B-cell lymphoma (n=662) or follicular lymphoma grade 3b (n=21) in first complete remission. Patients were randomized to rituximab maintenance (n=338) or observation (n=345). At a median follow-up of 45 months, the event-free survival rate (the primary endpoint) at 3 years was 80.1% for rituximab maintenance versus 76.5% for observation. This difference was not statistically significant for the intent-to-treat population (likelihood ratio P=0.0670). The hazard ratio by treatment arm was 0.79 (95% confidence interval 0.57-1.08; P=0.1433). The secondary endpoint, progression-free survival was also not met for the whole statistical model (likelihood ratio P=0.3646). Of note, rituximab maintenance was superior to observation when treatment arms only were compared (hazard ratio: 0.62; 95% confidence interval 0.43-0.90; P=0.0120). Overall survival remained unchanged (92.0 versus 90.3%). In subgroup analysis male patients benefited from rituximab maintenance with regards to both event-free survival (84.1% versus 74.4%) (hazard ratio: 0.58; 95% confidence interval 0.36-0.94; P=0.0267) and progression-free survival (89.0% versus 77.6%) (hazard ratio: 0.45; 95% confidence interval 0.25-0.79; P=0.0058). Women had more grade 3/4 adverse events (P=0.0297) and infections (P=0.0341). Men with a low International Prognostic Index treated with rituximab had the best outcome. In summary, rituximab maintenance in first remission after R-CHOP-like treatment did not prolong eventfree, progression-free or overall survival of patients with aggressive B-non-Hodgkin lymphoma. The significantly better outcome of men warrants further studies prior to the routine use of rituximab maintenance in men with low International Prognostic Index. This trial is registered under EUDRACT #2005-005187-90 and www.clinicaltrials. gov as #NCT00400478. © 2015 Ferrata Storti Foundation.


Kojic M.,Clinic for Infectious and Tropical Diseases | Nozic D.,Clinic for Infectious and Tropical Diseases | Nozic D.,University of Belgrade | Tarabar O.,Clinic for Hematology | And 2 more authors.
Vojnosanitetski Pregled | Year: 2016

Introduction. Extraintestinal manifestations of nontyphoidal salmonellosis are usually seen in patients with cellular immunodeficiency. Pleural empyema caused by nontyphoidal Salmonella is very rare clinical presentation of salmonellosis and there are just a few cases described in a literature. We presented a very rare case of pleural empyema caused by Salmonella enteritidis in a patient with non-Hodgkin limphoma. Case report. A 60-year-old male with low grade B-cell lymphoma, mucosa associated lymphoid tissue (MALT) type in IV clinical degree, manifested with infiltration of stomach, bronchus, pleura and peritoneum was admitted to the hospital. Initially the patient was presented with nonspecific symptoms and signs, suggesting poor general condition. During the hospitalization his pleural fluid became purulent and changes in blood counts were registered with the increase of leukocytes, especially neutrophils. A large number of leukocytes was found by microscopic evaluation of pleural fluid and Salmonella enteritidis was isolated by its culture. There were no pathogenic bacteria in stool culture and hemoculture remained sterile. Toxins A and B of Clostridium difficile were not detected in stool. The patient was treated by ciprofloxacin and cefrtiaxone for 14 days with drainage of the purulent content, what was followed by the resolution and organization of the pleural fluid. After the stabilization of his general condition, chemotherapy with cyclophosphamide, vincristine, prednisone (COP) was introduced, with complete response. Conclusion. Although rare, pleural empyema caused by nontyphoidal Salmonella should be considered in patients with severe immunosuppression, because appropriate antimicrobial therapy with surgical measures are very important for the outcome in these patients. © 2016, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved.


Penack O.,Oncology and Tumourimmunology | Becker C.,RWTH Aachen | Buchheidt D.,University of Mannheim | Christopeit M.,Martin Luther University of Halle Wittenberg | And 8 more authors.
Annals of Hematology | Year: 2014

Sepsis is a major cause of mortality during the neutropenic phase after intensive cytotoxic therapies for malignancies. Improved management of sepsis during neutropenia may reduce the mortality of cancer therapies. Clinical guidelines on sepsis treatment have been published by others. However, optimal management may differ between neutropenic and non-neutropenic patients. Our aim is to give evidence-based recommendations for haematologist, oncologists and intensive care physicians on how to manage adult patients with neutropenia and sepsis. © 2014 The Author(s).


Heigener D.F.,German Center for Lung Research | Schumann C.,Kempten Oberallgaeu Hospitals GmbH | Sebastian M.,University Hospital Frankfurt | Sadjadian P.,Clinic for Hematology | And 5 more authors.
Oncologist | Year: 2015

Background. Afatinib, an irreversible ErbB family blocker, is approved for treatment of patients with previously untreated non-small cell lung cancer (NSCLC) harboring activating epidermal growth factor receptor (EGFR) mutations. Efficacy of afatinib in EGFR tyrosine kinase inhibitor-naïve (TKI-naïve) patients with uncommon EGFR mutations (other than exon 19 deletions or exon 21 point mutations) has been reported; however, efficacy in TKI-pretreated patients with uncommon EGFR mutations is unknown. Materials and Methods. In the afatinib compassionate use program (CUP), patients with advanced or metastatic, histologically confirmed NSCLC progressing after at least one line of chemotherapy and one line of EGFR-TKI treatment were enrolled. Demographic data, mutation type, response rates, time to treatment failure (TTF), and safety in patients harboring uncommon EGFR mutations were reported. Results. In 60 patients (63% female, median age 63 years [range: 30–84 years]), a total of 66 uncommon EGFR mutations including 30 T790M mutations were reported (18.4% and 11%, respectively, of known EGFR mutations within the CUP). Most patients (67%) received afatinib as third- or fourth-line treatment. Median TTF was 3.8 months (range: 0.2 to >24.6 months; p = .244) in patients with uncommon mutations compared with 5.1 months (range: 0.1 to >21.1 months) in patients with common mutations (n = 165). Pronounced activity was observed with E709X mutations (TTF >12 months). No new safety signals were detected. Conclusion. Afatinib is clinically active and well tolerated in many TKI-pretreated NSCLC patients harboring uncommon EGFR mutations. Compared with results reported in TKI-naïve patients, activity was also indicated in patients with T790M and exon 20 insertion mutations. © AlphaMed Press 2015.


PubMed | University of Cologne, Clinic for Hematology, Saarland University, University Hospital Frankfurt and 4 more.
Type: Journal Article | Journal: The oncologist | Year: 2015

Afatinib, an irreversible ErbB family blocker, is approved for treatment of patients with previously untreated non-small cell lung cancer (NSCLC) harboring activating epidermal growth factor receptor (EGFR) mutations. Efficacy of afatinib in EGFR tyrosine kinase inhibitor-nave (TKI-nave) patients with uncommon EGFR mutations (other than exon 19 deletions or exon 21 point mutations) has been reported; however, efficacy in TKI-pretreated patients with uncommon EGFR mutations is unknown.In the afatinib compassionate use program (CUP), patients with advanced or metastatic, histologically confirmed NSCLC progressing after at least one line of chemotherapy and one line of EGFR-TKI treatment were enrolled. Demographic data, mutation type, response rates, time to treatment failure (TTF), and safety in patients harboring uncommon EGFR mutations were reported.In 60 patients (63% female, median age 63 years [range: 30-84 years]), a total of 66 uncommon EGFR mutations including 30 T790M mutations were reported (18.4% and 11%, respectively, of known EGFR mutations within the CUP). Most patients (67%) received afatinib as third- or fourth-line treatment. Median TTF was 3.8 months (range: 0.2 to >24.6 months; p = .244) in patients with uncommon mutations compared with 5.1 months (range: 0.1 to >21.1 months) in patients with common mutations (n = 165). Pronounced activity was observed with E709X mutations (TTF >12 months). No new safety signals were detected.Afatinib is clinically active and well tolerated in many TKI-pretreated NSCLC patients harboring uncommon EGFR mutations. Compared with results reported in TKI-nave patients, activity was also indicated in patients with T790M and exon 20 insertion mutations.


Lekovic D.,Clinic for Hematology | Gotic M.,University of Belgrade | Ljubic A.,University of Belgrade
Srpski Arhiv za Celokupno Lekarstvo | Year: 2015

Introduction The management of pregnancy in young women with essential thrombocythemia is complex and may present a difficult problem. An adverse pregnancy outcome due to thrombosis or bleeding is a common complication. In addition, little is known about fertility in these women prior to the disease. Case Outline We present the first case of a young woman with primary infertility and essential thrombocythemia who had uneventfully delivered a healthy boy in the fortieth week of pregnancy. Her platelet count was normalized during treatment with interferon-alfa. The patient failed to become pregnant in the natural way and after three attempts of programmed intercourse. She conceived only following intrauterine insemination. During pregnancy, the patient was carefully controlled by a hematologist and gynecologist. Conclusion Natural course and prognosis of essential thrombocythemia is not adversely affected by pregnancy. In these women, the pregnancy should be planned only after normalization of platelet count. The interferon-alpha should be administered before the pregnancy to regulate and maintain the platelet count within the normal range. Intrauterine insemination with minimal hormonal stimulation due to the risk of thrombosis could be recommended as the safest treatment option of infertility in women with essential thrombocythemia. © 2015, Serbia Medical Society. All rights reserved.


Andjelic B.M.,Clinic for Hematology | Mihaljevic B.S.,Clinic for Hematology | Mihaljevic B.S.,University of Belgrade | Jakovic L.R.,Clinic for Hematology
Pathology and Oncology Research | Year: 2012

Advanced age is considered an unfavourable prognostic factor for Hodgkin's lymphoma (HL). The optimal treatment for these patients is not yet defined, especially for the advanced stages. We analysed the outcome and prognostic relevance of patient and disease characteristics in 46 advanced stage HL patients who were older than 45 years, treated with ABVD. Elderly patients (>60 year) had a significantly higher rate of comorbidities (p<0.05). The complete remission rate was significantly lower in elderly patients and in patients with an IPS ≥3 (p<0.05, p<0.05, respectively). Elderly patients had significantly shorter event-free survival (p<0.01) and overall survival (p<0.01) compared to patients of 45.60 year. Extranodal disease, an IPS ≥3, bulky disease, an ESR>50 and the presence of a large mediastinal tumour mass didn't have an influence on survival (p>0.05). The multivariate Cox regression analysis identified the age of >60 year as an independent prognostic factor. The prospective clinical trials seem to be needed for defining the optimal therapeutic approach in elderly patients. © Arányi Lajos Foundation 2012.


Cross M.,University of Leipzig | Bach E.,University of Leipzig | Tran T.,University of Leipzig | Krahl R.,University of Leipzig | And 5 more authors.
OncoTargets and Therapy | Year: 2013

Background: Epigenetic modulations, including changes in DNA cytosine methylation, are implicated in the pathogenesis and progression of acute myeloid leukemia (AML). Azacitidine is a hypomethylating agent that is incorporated into RNA as well as DNA. Thus, there is a rationale to its use in patients with AML. We determined whether baseline and/or early changes in the methylation of long interspersed element (LINE)-1 or CDH13 correlate with bone marrow blast clearance, hematological response, or survival in patients with AML treated with azacitidine. Methods: An open label, phase I/II trial was performed in 40 AML patients (median bone marrow blast count was 42%) unfit for intensive chemotherapy treated with azacitidine 75 mg/m2/day subcutaneously for 5 days every 4 weeks. Bone marrow mononuclear cell samples were taken on day 0 (pretreatment) and day 15 during the first treatment cycle; LINE-1 and CDH13 methylation levels were quantified by methylation-specific, semiquantitative, real-time polymerase chain reaction. Results: Treatment with azacitidine significantly reduced LINE-1 but not CDH13 methylation levels over the first cycle (P, 0.0001). Absolute LINE-1 methylation levels tended to be lower on day 0 (P = 0.06) and day 15 of cycle 1 (P = 0.03) in patients who went on to achieve subsequent complete remission, partial remission or hematological improvement versus patients with stable disease. However, the decrease in LINE-1 methylation over the first treatment cycle did not correlate with subsequent response (P = 0.31). Baseline methylation levels of LINE-1 or CDH13 did not correlate with disease-related prognostic factors, including cytogenetic risk, relapsed/refractory AML, or presence of NPM1 or FLT3 mutations. No correlation was observed between LINE-1 or CDH13 methylation levels and overall survival. Conclusion: Analysis of baseline LINE-1 methylation levels may help identify elderly AML patients who are most likely to respond to azacitidine therapy. © 2013 Cross et al, publisher and licensee Dove Medical Press Ltd.


Reimer P.,Clinic for Hematology
Cancer Management and Research | Year: 2015

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of rare malignancies that with the exception of anaplastic lymphoma kinase expressing anaplastic large cell lymphoma, share a poor outcome after standard (eg, anthracycline-based) chemotherapy. Most patients are either refractory to initial therapy or eventually relapse. Randomized studies for relapsed/refractory PTCL are not available, however, recently published data show that con-ventional chemotherapy has very limited efficacy in the salvage setting. Thus, novel drugs are urgently needed to improve the outcome in this setting. Belinostat, a pan-histone deacetylase inhibitor, has demonstrated meaningful efficacy and a favorable toxicity profile in two single-arm Phase II trials on 153 patients with relapsed/refractory PTCL. The conclusive results led to an accelerated approval by the US Food and Drug Administration. The present review summarizes the clinical data available for belinostat, its current role, and future perspectives. © 2015 Reimer.


PubMed | Clinic for Hematology
Type: | Journal: Cancer management and research | Year: 2015

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of rare malignancies that with the exception of anaplastic lymphoma kinase expressing anaplastic large cell lymphoma, share a poor outcome after standard (eg, anthracycline-based) chemotherapy. Most patients are either refractory to initial therapy or eventually relapse. Randomized studies for relapsed/refractory PTCL are not available, however, recently published data show that conventional chemotherapy has very limited efficacy in the salvage setting. Thus, novel drugs are urgently needed to improve the outcome in this setting. Belinostat, a pan-histone deacetylase inhibitor, has demonstrated meaningful efficacy and a favorable toxicity profile in two single-arm Phase II trials on 153 patients with relapsed/refractory PTCL. The conclusive results led to an accelerated approval by the US Food and Drug Administration. The present review summarizes the clinical data available for belinostat, its current role, and future perspectives.

Loading Clinic for Hematology collaborators
Loading Clinic for Hematology collaborators