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Maschmeyer G.,Oncology and Palliative Care | Carratala J.,University of Barcelona | Buchheidt D.,University of Mannheim | Hamprecht A.,University of Cologne | And 8 more authors.
Annals of Oncology | Year: 2015

Up to 25% of patients with profound neutropenia lasting for > 10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, β-D-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.


Kreher S.,Charité - Medical University of Berlin | Ochsenreither S.,Charité - Medical University of Berlin | Trappe R.U.,Ev. Diakonie Krankenhaus GmbH | Pabinger I.,Vienna University Hospital | And 7 more authors.
Annals of Hematology | Year: 2014

Patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) like polycythemia vera and essential thrombocythemia are at increased risk of arterial and venous thrombosis. Strategies of prevention may consist of platelet aggregation inhibitors and/or cytoreductive agents depending on the underlying disease and the individual risk. Clinical evidence for management of acute venous thromboembolic events in MPN patients is limited. Modality and duration of therapeutic anticoagulation after venous thrombosis has to be evaluated critically with special regard to the increased risk for spontaneous bleeding events associated with the underlying diseases. Both for therapy of the acute event and for secondary prophylaxis, low-molecular-weight heparins should preferentially be used. A prolongation of the therapeutic anticoagulation beyond the usual 3 to 6 months can only be recommended in high-risk settings and after careful evaluation of potential risks and benefits for the individual patient. New direct oral anticoagulants (NOAC) should not preferentially be used due to lack of clinical experience in patients with MPN and potential drug interactions (e.g. with JAK inhibitors). Consequent treatment of the underlying myeloproliferative disease and periodical evaluation of the response to therapy is crucial for optimal secondary prophylaxis of thromboembolic events in those patients. © 2014, Springer-Verlag Berlin Heidelberg.


Neumann S.,University of Gottingen | Krause S.W.,Friedrich - Alexander - University, Erlangen - Nuremberg | Maschmeyer G.,Oncology and Palliative Care | Schiel X.,Harlaching Hospital | And 2 more authors.
Annals of Hematology | Year: 2013

Bacterial infections are the most common cause for treatment-related mortality in patients with neutropenia after chemotherapy. Here, we discuss the use of antibacterial prophylaxis against bacteria and Pneumocystis pneumonia (PCP) in neutropenic cancer patients and offer guidance towards the choice of drug. A literature search was performed to screen all articles published between September 2000 and January 2012 on antibiotic prophylaxis in neutropenic cancer patients. The authors assembled original reports and meta-analysis from the literature and drew conclusions, which were discussed and approved in a consensus conference of the Infectious Disease Working Party of the German Society of Hematology and Oncology (AGIHO). Antibacterial prophylaxis has led to a reduction of febrile events and infections. A significant reduction of overall mortality could only be shown in a meta-analysis. Fluoroquinolones are preferred for antibacterial and trimethoprim-sulfamethoxazole for PCP prophylaxis. Due to serious concerns about an increase of resistant pathogens, only patients at high risk of severe infections should be considered for antibiotic prophylaxis. Risk factors of individual patients and local resistance patterns must be taken into account. Risk factors, choice of drug for antibacterial and PCP prophylaxis and concerns regarding the use of prophylactic antibiotics are discussed in the review. © 2013 The Author(s).


Gokbuget N.,Goethe University Frankfurt | Kneba M.,University of Kiel | Raff T.,University of Kiel | Trautmann H.,University of Kiel | And 13 more authors.
Blood | Year: 2012

Quantification of minimal residual disease (MRD) by real-time PCR directed to TCR and Ig gene rearrangements allows a refined evaluation of response in acute lymphoblastic leukemia (ALL). The German Multicenter Study Group for Adult ALL prospectively evaluated molecular response after induction/consolidation chemotherapy according to standardized methods and terminology in patients with Philadelphia chromosome-negative ALL. The cytologic complete response (CR) rate was 89% after induction phases 1 and 2. At this time point the molecular CR rate was 70% in 580 patients with cytologic CR and evaluable MRD. Patients with molecular CR after consolidation had a significantly higher probability of continuous complete remission (CCR; 74% vs 35%; P < .0001) and of overall survival (80% vs 42%; P < .0001) compared with patients with molecular failure. Patients with molecular failure without stem cell transplantation (SCT) in first CR relapsed after a median time of 7.6 months; CCR and survival at 5 years only reached 12% and 33%, respectively. Quantitative MRD assessment identified patients with molecular failure as a new high-risk group. These patients display resistance to conventional drugs and are candidates for treatment with targeted, experimental drugs and allogeneic SCT. Molecular response was shown to be highly predictive for outcome and therefore constitutes a relevant study end point. The studies are registered at www.clinicaltrials. gov as NCT00199056 and NCT00198991. © 2012 by The American Society of Hematology.


Behringer D.,Oncology AND Palliative Care | Konemann S.,Thoraxzentrum Ruhrgebiet | Hecker E.,University of Duisburg - Essen
Thoracic Surgery Clinics | Year: 2014

A patient identified with tracheal cancer benefits most from evaluation by an experienced center and an extensive effort to assess the possibility of a complete surgical resection as the most efficient treatment option for cure. Localized, nonoperable disease may still be controlled by combined modality using chemotherapy and concurrent radiation. © 2014 Elsevier Inc.


Vehreschild J.J.,University of Cologne | Bohme A.,Onkologikum Frankfurt am Museumsufer | Cornely O.A.,University of Cologne | Cornely O.A.,Clinical Trials Center Cologne Cologne | And 9 more authors.
Annals of Oncology | Year: 2014

Background: Current evidence on myelopoietic growth factors is difficult to overview for the practicing haematologist/oncologist. International guidelines are sometimes conflicting, exclude certain patient groups, or cannot directly be applied to the German health system. This guideline by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO) gives evidence-based recommendations for the use of G-CSF, pegylated G-CSF, and biosimilars to prevent infectious complications in cancer patients undergoing chemotherapy, including those with haematological malignancies. Methods: We systematically searched and evaluated current evidence. An expert panel discussed the results and recommendations. We then compared our recommendations to current international guidelines. Results: We summarised the data from eligible studies in evidence tables, developed recommendations for different entities and risk groups. Conclusion: Comprehensive literature search and expert panel consensus confirmed many key recommendations given by international guidelines. Evidence for growth factors during acute myeloid leukaemia induction chemotherapy and pegfilgrastim use in haematological malignancies was rated lower compared with other guidelines. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Dudeck O.,HELIOS Clinic Berlin Buch | Dudeck O.,Otto Von Guericke University of Magdeburg | Zeile M.,HELIOS Clinic Berlin Buch | Zeile M.,Otto Von Guericke University of Magdeburg | And 4 more authors.
Annals of Oncology | Year: 2011

Background: Controversies exist about computed tomography (CT) response evaluation criteria for patients with gastrointestinal stromal tumor (GIST). Patients and methods: Fifty-one patients with advanced GIST treated se cond line with sunitinib were evaluated with contrast-enhanced CT every 3 months. Response was rated according to RECIST and Choi criteria. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier analysis. Results: According to RECIST, patients were categorized as complete response (CR; n = 0; 0%), partial remission (PR; n = 1; 2.0%), stable disease (SD; n = 37; 72.5%), and progressive disease (PD; n = 13; 25.5%) at 3 months. When Choi criteria were applied responses were CR (n = 0; 0%), PR (n = 16; 31.4%), SD (n = 21; 41.1%), and PD (n = 14; 27.5%). Despite these discrepancies, patients rated as SD with RECIST and PR as well as SD according to Choi criteria displayed similar PFS (41.3, 40.7, and 41.3 weeks, respectively) and OS (100.4, 91.6, and 108.0 weeks, respectively). Patients with PD had significantly shorter PFS (10.1 weeks for both criteria) and OS (29.1 weeks for RECIST; 28.9 weeks for Choi) regardless of the response classification applied. Conclusion: In contrast to absence of progression, discrimination of PR from SD with Choi criteria was of no predictive value. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Seven out of ten patients with advanced cancer receive a palliative care consultation at ESMO Designated Centres of Integrated Oncology and Palliative Care, according to survey results.


Maschmeyer G.,Oncology and Palliative Care | Donnelly J.P.,Radboud University Nijmegen
British Journal of Haematology | Year: 2016

Pulmonary complications affect up to 40% of patients with severe neutropenia lasting for more than 10 d. As they are frequently associated with fever and elevation of C-reactive protein or other signs of inflammation, they are mostly handled as pneumonia. However, the differential diagnosis is broad, and a causative microbial agent remains undetected in the majority of cases. Pulmonary side effects from cytotoxic treatment or pulmonary involvement by the underlying malignancy must always be taken into account and may provide grounds for invasive diagnostic procedures in selected patients. Pneumocystis jirovecii (in patients not receiving co-trimoxazole as prophylaxis), multi-resistant gram-negative bacilli, mycobacteria or respiratory viruses may be involved. High-risk patients may be infected by filamentous fungi, such as Aspergillus spp., but these infections are seldom proven when treatment is initiated. Microorganisms isolated from cultures of blood, bronchoalveolar lavage or respiratory secretions need careful interpretation as they may be irrelevant for determining the aetiology of pulmonary infiltrates, particularly when cultures yield coagulase-negative staphylococci, enterococci or Candida species. Non-culture based diagnostics for detecting Aspergillus galactomannan, beta-D-glucan or DNA from blood, bronchoalveolar lavage or tissue samples can facilitate the diagnosis, but must always be interpreted in the context of clinical and imaging findings. Systemic antifungal treatment with mould-active agents, given in combination with broad-spectrum antibiotics, improves clinical outcome when given pre-emptively. Co-trimoxazole remains the first-line treatment for Pneumocystis pneumonia, while cytomegalovirus pneumonia will respond to ganciclovir or foscarnet in most cases. The clinical outcome of acute respiratory failure can also be successful with proper intensive care, when indicated. © 2016 John Wiley & Sons Ltd.


Maschmeyer G.,Oncology and Palliative Care
Current Infectious Disease Reports | Year: 2011

Pulmonary infiltrates develop in up to 25% of febrile neutropenic patients and are frequently refractory to broad-spectrum antibacterial therapy. Etiologically, Aspergillus spp., Pneumocystis jiroveci, multi-resistant Gram-negative rods as well as mycobacteria and respiratory viruses may be involved. Taking into account the predominant role of fungal pathogens, typically without microbiological proof, prompt addition of mold-active systemic antifungal therapy improves clinical outcome, while other microorganisms should typically be targeted based upon microbiological test results only. Microbial isolates from blood cultures, bronchoalveolar lavage or respiratory secretions must be critically interpreted with respect to their etiological relevance for pulmonary infiltrates. Non-culture based diagnostic procedures to detect circulating antigens such as galactomannan or 1,3-beta-D-glucan, or PCR techniques to amplify DNA from blood, bronchoalveolar lavage or tissue specimens, may facilitate the diagnosis. For pre-emptive antifungal treatment, voriconazole or liposomal amphotericin B are preferred. Antifungal treatment should be continued for at least 14 days before non-response and treatment modification are considered. Primary choice for treatment of Pneumocystis pneumonia remains high-dose trimethoprim-sulfamethoxazole, while cytomegalovirus pneumonia is treated with ganciclovir in the majority of patients affected. © 2011 Springer Science+Business Media, LLC.

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