Heinz W.J.,University of Wuerzburg Medical Center |
Silling G.,University of Munster |
Current Medical Research and Opinion | Year: 2011
Objective: Invasive fungal infections (IFIs) are an important cause of morbidity and mortality, particularly in patients with cancer. The triazole voriconazole, given as oral or intravenous formulation, has a high bioavailability and proven efficacy against invasive aspergillosis, candidiasis and other fungi. We aimed to assess the utilisation, efficacy and safety of voriconazole with emphasis on the route of administration under standard clinical conditions. Methods: Prospective, observational study performed by 17 hospitals and office-based physicians in Germany. Results: A total of 264 patients received oral (53) or intravenous (22) voriconazole or both formulations sequentially (25). Of 228 patients with specified fungal diagnosis, 95 (36.0) had aspergillosis, 73 (27.7) candidiasis. Sixty (22.7) received voriconazole for other fungal indications (OFI). In 195 of 226 patients (86.2), treatment was successful (39.8 cured and 46.5 partial response). In terms of primary diagnoses, favourable responses were noted in 90 for pulmonary aspergillosis, 85 for candidiasis and 87 for OFI. Microbiological success was documented in 138 patients, of whom 105 (76.1) had complete eradication of fungi. Response rates by initial route were similar for oral and intravenous administration (86 and 87). Twenty-six of 264 patients died during the study, 53 patients experienced a serious adverse event (five treatment related), and 10 withdrew due to all-causality adverse events (AEs). Tolerability was assessed as very good in 55, and good in 40 of patients. Conclusions: Voriconazole as oral or intravenous formulation was well tolerated and equally effective in critically ill patients with IFIs. This study in daily care confirms the outcomes of controlled clinical trials. © 2011 Informa UK Ltd All rights reserved.
Schmidt C.,Ludwig Maximilians University of Munich |
Fingerle-Rowson G.,University of Cologne |
Fingerle-Rowson G.,Hoffmann-La Roche |
Fingerle-Rowson G.,Janssen Cilag GmbH |
And 11 more authors.
Leukemia and Lymphoma | Year: 2015
Today's treatment options for indolent lymphoma and chronic lymphocytic leukemia (CLL) range from watch & wait, immunochemotherapy up to allogeneic transplantation. We describe changes in the diagnosis and treatment of indolent lymphoma and CLL in Germany between 2006 and 2009. Two nation-wide surveys in the fourth quarter of 2006 and 2009 included patients with indolent lymphoma and CLL. Data from 576 patients from 46 centers in Q4/2006 were compared with data from 521 patients from 57 centers in Q4/2009. The subpopulation of patients ≥ 70 years of age and the number of patients with comorbidities increased from 39% to 55% and 47% to 55%, respectively. Both in indolent lymphoma and CLL, Rituximab and R-based immunochemotherapy (50.6% vs. 64.4%) as well as bendamustine (4.8 % vs. 24%) were much more frequently applied. In contrast, high dose chemotherapy consolidation was almost abandoned in first line treatment. Supportive care is given more frequently, with exception of erythropoietin and immunoglobulins. Our national survey confirmed that scientific results were rapidly transferred into clinical care of indolent lymphoma. © 2014 Informa UK, Ltd.
Topp M.S.,Universitatsklinikum Wurzburg |
Gokbuget N.,Goethe University Frankfurt |
Zugmaier G.,Amgen |
Klappers P.,Amgen |
And 16 more authors.
Journal of Clinical Oncology | Year: 2014
Purpose: Patients with relapsed or refractory acute lymphoblastic leukemia (ALL) have a dismal prognosis. CD19 is homogenously expressed in B-precursor ALL and can be targeted by the investigational bispecific T cell-engager antibody blinatumomab. A phase II trial was performed to determine clinical activity in this patient cohort. Patients and Methods: Thirty-six patients with relapsed or refractory B-precursor ALL were treated with blinatumomab in cycles of 4-week continuous infusion followed by a 2-week treatment-free interval in a single-arm study with a dose-finding stage and an extension stage. The primary end point was complete remission (CR) or CR with partial hematologic recovery (CRh). Major secondary end points included minimal residual disease (MRD) response, rate of allogeneic hematopoietic stem-cell transplantation (HSCT) realization, relapse-free survival (RFS), overall survival (OS), and incidence of adverse events (AEs). Results: Median age was 32 years (range, 18 to 77 years). Twenty-five patients (69%) achieved a CR or CRh, with 88% of the responders achieving an MRD response. Median OS was 9.8 months (95% CI, 8.5 to 14.9), and median RFS was 7.6 months (95% CI, 4.5 to 9.5). Thirteen responders (52%) underwent HSCT after achieving a CR or CRh. The most frequent AE during treatment was pyrexia (grade 1 or 2, 75%; grade 3, 6%). In six patients with nervous system or psychiatric disorder AEs and in two patients with cytokine release syndrome, treatment had to be interrupted or discontinued. These medical events were resolved clinically. Conclusion: The data support further investigation of blinatumomab for the treatment of adult patients with relapsed or refractory ALL in a larger confirmatory study. © 2014 by American Society of Clinical Oncology.
Hoelzer D.,ONKOLOGIKUM |
Gokbuget N.,Goethe University Frankfurt
Blood Reviews | Year: 2012
ALL blast cells express a variety of specific antigens e.g. CD19, CD20, CD22, CD33, and CD52, which serve as targets for Monoclonal Antibodies (MoAbs). So far, the most experience is available for anti-CD20 (rituximab), which has been combined with chemotherapy for treatment of mature B-ALL/Burkitt's lymphoma. Studies with rituximab have also been completed in B-precursor ALL. Another antigen, CD19, is of great interest due to a very high rate of expression in ALL. It can be targeted by a bispecific monoclonal antibody, Blinatumomab, directed against CD19 and CD3. Smaller studies or case reports are also available for the anti CD52 antibody (Alemtuzumab), for anti CD22 (Epratuzumab) or anti CD33 (Gemtuzumab). Available data demonstrate that MoAb therapy in ALL is a highly promising targeted treatment. However, several details for an optimal treatment approach e.g. the required level of antigen expression, timing, schedule, dosage and stage of disease still need to be defined. © 2012.
Topp M.S.,University of Würzburg |
Gokbuget N.,Goethe University Frankfurt |
Zugmaier G.,Amgen |
Degenhard E.,Amgen |
And 21 more authors.
Blood | Year: 2012
Persistence or recurrence of minimal residual disease (MRD) after chemotherapy results in clinical relapse in patients with acute lymphoblastic leukemia (ALL). In a phase 2 trial of B-lineage ALL patients with persistent or relapsed MRD, a T cell-engaging bispecific Ab construct induced an 80% MRD response rate. In the present study, we show that after a median follow-up of 33 months, the hematologic relapse-free survival of the entire evaluable study cohort of 20 patients was 61% (Kaplan-Meier estimate). The hematologic relapse-free survival rate of a sub-group of 9 patients who received allogeneic hematopoietic stem cell transplantation after blinatumomab treatment was 65% (Kaplan-Meier estimate). Of the sub-group of 6 Philadelphia chromosome-negative MRD responders with no further therapy after blinatumomab, 4 are in ongoing hematologic and molecular remission. We conclude that blinatumomab can induce long-lasting complete remission in B-lineage ALL patients with persistent or recurrent MRD. © 2012 by The American Society of Hematology.
Heimpel H.,University of Ulm |
Diem H.,Wurmtal Labor |
Medizinische Klinik | Year: 2010
In clinical practice, the reticulocyte count is the most useful method to estimate red cell life span and red cell production. However, experience of hematologists as well as surveys have shown that counting of reticulocytes is often neglected in the diagnostic work-up of unclassified anemias, and many physicians have difficulties in interpreting the results. Formerly, this was partly due to the low precision of manual counts. Today, this method is largely replaced by flow cytometry, available in almost all larger systems for automated blood count analysis, at low costs and sufficient analytic precision. Interpretation is supported by calculated parameters such as the Reticulocyte Production Index. Here, the authors discuss the limits of the analytic methods and the problems of interpretation in the context of the laboratory profile and the clinical setting. © 2010 Urban & Vogel.
Mousset S.,Interdisziplinares Zentrum fur Palliativmedizin |
Buchheidt D.,Universitatsmedizin Mannheim |
Heinz W.,Universitatsklinikum Wurzburg |
Ruhnke M.,Charité - Medical University of Berlin |
And 16 more authors.
Annals of Hematology | Year: 2014
The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new antifungal agents have been licensed, and agents already approved have been studied in new indications. The choice of the most appropriate antifungal treatment depends on the fungal species suspected or identified, the patient's risk factors (e.g., length and depth of neutropenia), and the expected side effects. This guideline reviews the clinical studies that served as a basis for the following recommendations. All recommendations including the levels of evidence are summarized in tables to give the reader rapid access to the information. © 2013 The Author(s).
Bruggemann M.,University of Kiel |
Schrauder A.,University of Kiel |
Raff T.,University of Kiel |
Pfeifer H.,Goethe University Frankfurt |
And 28 more authors.
Leukemia | Year: 2010
Assessment of minimal residual disease (MRD) has acquired a prominent position in European treatment protocols for patients with acute lymphoblastic leukemia (ALL), on the basis of its high prognostic value for predicting outcome and the possibilities for implementation of MRD diagnostics in treatment stratification. Therefore, there is an increasing need for standardization of methodologies and harmonization of terminology. For this purpose, a panel of representatives of all major European study groups on childhood and adult ALL and of international experts on PCR-and flow cytometry-based MRD assessment was built in the context of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008. The panel summarized the current state of MRD diagnostics in ALL and developed recommendations on the minimal technical requirements that should be fulfilled before implementation of MRD diagnostics into clinical trials. Finally, a common terminology for a standard description of MRD response and monitoring was established defining the terms complete MRD response, MRD persistence and MRD reappearance. The proposed MRD terminology may allow a refined and standardized assessment of response to treatment in adult and childhood ALL, and provides a sound basis for the comparison of MRD results between different treatment protocols. © 2010 Macmillan Publishers Limited All rights reserved.
Cancer | Year: 2013
Inotuzumab ozogamicin achieves high response and molecular remission rates in patients with relapsed/refractory acute lymphoblastic leukemia with tolerable toxicity. It warrants further studies of inotuzumab in combination with chemotherapy or other targeted therapy. © 2013 American Cancer Society.
PubMed | ONKOLOGIKUM
Type: Journal Article | Journal: Blood reviews | Year: 2011
ALL blast cells express a variety of specific antigens e.g. CD19, CD20, CD22, CD33, and CD52, which serve as targets for Monoclonal Antibodies (MoAbs). So far, the most experience is available for anti-CD20 (rituximab), which has been combined with chemotherapy for treatment of mature B-ALL/Burkitts lymphoma. Studies with rituximab have also been completed in B-precursor ALL. Another antigen, CD19, is of great interest due to a very high rate of expression in ALL. It can be targeted by a bispecific monoclonal antibody, Blinatumomab, directed against CD19 and CD3. Smaller studies or case reports are also available for the anti CD52 antibody (Alemtuzumab), for anti CD22 (Epratuzumab) or anti CD33 (Gemtuzumab). Available data demonstrate that MoAb therapy in ALL is a highly promising targeted treatment. However, several details for an optimal treatment approach e.g. the required level of antigen expression, timing, schedule, dosage and stage of disease still need to be defined.