132 results on '"Mario Bargetzi"'
Search Results
52. Nutritional support practices in hematopoietic stem cell transplantation centers: A nationwide comparison
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Annic Baumgartner, Urs Schanz, Panagiotis Samaras, Jakob Passweg, Urs Hess, Claude Pichard, Zeno Stanga, Luciano Wannesson, Thomas Pabst, Mario Bargetzi, Beat Mueller, Annika Bargetzi, Philipp Schuetz, Micheal Medinger, Yves Chalandon, Michel A. Duchosal, Alessandro Luigi Limonta, Noemi Zueger, University of Zurich, and Schuetz, Philipp
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Pediatrics ,medicine.medical_specialty ,Allogeneic transplantation ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,education ,610 Medicine & health ,Hematopoietic stem cell transplantation ,Qualitative survey ,Transplantation, Autologous ,Nutrition Policy ,03 medical and health sciences ,Nutritional Support/methods/standards ,0302 clinical medicine ,Surveys and Questionnaires ,Medicine ,Autologous transplantation ,Humans ,Medical nutrition therapy ,Intensive care medicine ,ddc:616 ,Nutrition and Dietetics ,Nutritional Support ,business.industry ,Malnutrition ,Hematopoietic Stem Cell Transplantation ,medicine.disease ,3. Good health ,Diet ,Transplantation ,2712 Endocrinology, Diabetes and Metabolism ,Parenteral nutrition ,Nutrition Assessment ,Evaluation Studies as Topic ,030220 oncology & carcinogenesis ,10032 Clinic for Oncology and Hematology ,2916 Nutrition and Dietetics ,Patient Compliance ,business ,Malnutrition/diagnosis ,Switzerland ,030215 immunology - Abstract
Objective In 2009, international nutritional societies published practice guidelines on screening and nutritional support for patients undergoing stem cell transplantation. Little is known about how these guidelines are implemented in clinical practice. We performed a nationwide survey with the aim of understanding current practice patterns, differences between clinical practice, and international recommendations as well as barriers to the use of nutritional therapy. Methods We performed a qualitative survey including all centers across Switzerland offering allogeneic (n = 3) or autologous (n = 7) stem cell transplantation. We focused on in-house protocols pertaining to malnutrition screening, indications for nutritional support, types of nutritional therapy available and provided, and recommendations regarding neutropenic diets. Results All centers offering allogeneic, and most of the centers offering autologous transplantation, had a malnutrition screening tool, mainly the nutritional risk score (NRS 2002) method. Only one center does not provide nutritional support. There is wide variation regarding start and stop of nutritional therapy as well as route of delivery, with five centers recommending parenteral nutrition and five centers recommending enteral nutrition as a first step. Although all centers offering allogeneic transplantation, and approximately every other autologous transplant center, used a neutropenic diet, specific recommendations regarding the type of food and food handling showed significant variation. Conclusion This Swiss survey found wide variation in the use of nutritional therapy in patients undergoing stem cell transplantation, with low adherence overall to current practice guidelines. Understanding and reducing barriers to guideline implementation in clinical practice may improve clinical outcomes. Close collaboration of centers will facilitate future research needed to improve current practice and ensure high quality of treatment.
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- 2017
53. The Power of Programming 2016. Developmental Origins of Adiposity and Long-Term Health. October 13-15, 2016, Munich: Abstracts
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Huaizhuang Ye, Mario Bargetzi, Javier Mancilla-Ramírez, Sarah P. Garnett, Michael Medinger, Ping Li, Liansheng Ruan, Mariela Bernabe-García, Virginia Gordillo-Alvarez, Zheping Yuan, Milan Dastych, Christopher T. Cowell, Weiqiao Liu, Yimin Zhu, Yuwen Zhang, Yufeng Zhu, Jorge Maldonado-Hernández, Maricela Rodríguez-Cruz, Chengguo Liu, Petr Wohl, Pavel Kohout, Hong Chang, Annic Baumgartner, Philipp Schuetz, Zeno Stanga, František Novák, Rodolfo Rivas-Ruiz, Michal Šenkyřík, Noemi Zueger, Louise A. Baur, Xuhui Zhang, Zhanhang Sun, Li Zheng, Jan Maňák, Raúl Villegas-Silva, Xuan Wang, Francisco Blanco-Favela, Richard D. Semba, Anne-Louise M Heath, Meilin Zhang, Guowei Huang, Alfredo Salgado-Sosa, Mardia López-Alarcón, Mandy Ho, Jakob Passweg, Samir Samman, Yiping Tian, Lifeng Jin, Druckerei Stückle, Beat Mueller, Annika Bargetzi, Megan L. Gow, Luis Chávez-Sánchez, and Olivia Madrigal-Muñiz
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0301 basic medicine ,030109 nutrition & dietetics ,Nutrition and Dietetics ,Appetite control ,Energy (esotericism) ,digestive, oral, and skin physiology ,Medicine (miscellaneous) ,Social environment ,Context (language use) ,Biology ,Developmental psychology ,03 medical and health sciences ,Food energy ,Energy density ,Food science ,Association (psychology) ,Sensory cue - Abstract
Infants are born equipped to ingest nutrients, but have to learn how, what and how much to eat. This must occur early, because the mode of feeding evolves dramatically, from ‘tube’ feeding in utero to eating table foods with the family. Eating habits established during early years contribute to the development of subsequent eating habits. Therefore, it is fundamental to understand the most important early periods for the development of eating habits and the drivers of this development. Here we will focus on the first three years of postnatal life. Several characteristics of the eating experience contribute to drive infant’s eating and to shape preferences and energy intake control: food sensory properties; food energy density, social context of eating. The learning processes involve repeated exposure (including to a variety of flavours), association with post-absorptive consequences (energy density) and with contextual signals (interaction with family members). Beyond the first flavour discoveries during the prenatal and lactation periods (through the infant’s exposure to flavours from foods of the mother’s diet), the most important phases for learning food preferences and appetite control may be the beginning of complementary feeding. Infants discover the sensory (texture, taste and flavour) and nutritional properties (energy density) of the foods that will ultimately compose their adult diet; parents are still in charge of providing appropriate foods, timing, context for eating. Inter-individual differences in learning, related to temperamental dimensions, to sensitivity to food cues (sensory cues or energy density) are large and also have to be taken into account.
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- 2016
54. Prospective Long-Term Follow-up after First-Line Subcutaneous Cladribine Treatment in Patients with Hairy Cell Leukemia. a Study of the SAKK (Swiss Group for Clinical Cancer Research)
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Willy Nettekoven, Ulrich Mey, Andreas Lohri, Mario Bargetzi, Nathan Cantoni, Sabine Blum, Yves Chalandon, Georg Stussi, Rudolf Benz, Urban Novak, Qiyu Li, Kornelius Arn, Alix O'Meara, Reinhard Zenhäusern, Martin Andres, Daniel Rauch, Thomas Pabst, Felicitas Hitz, and Simona Berardi
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medicine.medical_specialty ,Colorectal cancer ,business.industry ,Immunology ,Purine analogue ,Cell Biology ,Hematology ,medicine.disease ,Single Center ,Biochemistry ,Gastroenterology ,Clinical trial ,Internal medicine ,medicine ,Hairy cell leukemia ,Rituximab ,Skin cancer ,business ,Cladribine ,medicine.drug - Abstract
Introduction : Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with a very indolent clinical course and patients may survive for many decades. First-line treatment with purine analogues such as cladribine (Cld) is considered standard of care since it is very efficient and induces profound remissions. However, patients with HCL often relapse after purine analogues and repeated treatment may increase morbidity and mortality. Despite good clinical evidence of long term control of the disease by several mainly single center studies of patients treated with purine analogues, there is only one study analyzing mainly subcutaneous (sc) treated patients based on registry data. We therefore performed a pooled long-term follow-up analysis of our prospective multicenter studies treating patients with sc Cld focusing on survival, secondary malignancy and retreatment. Materials and Methods : The SAKK included patients treated for HCL in 4 studies between 1993 and 2005. Three studies focused on first-line regimens with sc Cld, whereas the fourth protocol focused on the effect of Rituximab monotherapy in patients pretreated with Cld. Classical morphologic, immunohistochemistry and flow cytometry criteria were used as inclusion criteria and response was assessed by established criteria. Treatment algorithms in the 4 studies were as follows: 1) 5 days of Cld 0.14mg/kg sc followed by max 2 cycles of 7 days of Cld 0.1mg/kg sc in case of minor response or no response (SAKK 32/93); 2) Single shot of Cld 0.25mg/kg sc followed by a maximum of 2 cycles of 0.14mg/kg sc for 5 day in case of minor response, no response or relapse (SAKK 32/95); 3) 5 consecutive days of Cld 0.14mg/kg sc versus the same dose in 5 weekly applications (SAKK 32/98); 4) Rituximab 375 mg/m2iv weekly for 4 weeks in relapsed patients (SAKK 31/98). SAKK 32/93 included 63, SAKK 32/95 74 and SAKK 32/98 100 patients. Of the 26 patients registered in 31/98 20 were already in SAKK 32/93, 32/95 and 32/98. Therefore, we also included the treatment information and follow-up data of these 20 patients. All patients were subject to life-long follow-up within the clinical trials. Further information including secondary malignancies and retreatments were obtained by sending out questionnaires to the treating physicians of the study patients. Of the 237 patients 4 patients were in two of the studies and 10 patients have been excluded because of non-classical HCL phenotype. Therefore, a total of 223 patients were included in the analysis. Overall survival and follow-up time were assessed by Kaplan-Meier and reverse Kaplan-Meier method, respectively. Results : The median age of patients at the time of diagnosis was 55 (range 21 to 96) years, 50 patients were female (22.4%) and 173 (77.6%) male. At the time of data analysis, the median follow-up time was 12.1 (95%-CI 10.0 to 14.0) years. A total of 129 (57.8%) patients had the last follow-up information more than two years prior to the data cut-off in May 2016, however, the available information of all patients was used for the sub-analyses including secondary malignancies or retreatment. By the cut-off date, 49 patients have died, 14 (28.6%) due to secondary malignancies and 7 (14.3%) due to HCL progression. Median overall survival from diagnosis was 31.6 (95%-CI 31.6 to 37.8) years. Retreatment was necessary in 53 (23.7%) patients after a mean of 6 (0.2 to 20.4) years and first retreatment was mainly Cld (64%), rituximab (19%) or Cld and rituximab (13%). 21 patients (9.4%) required more than one retreatment with a mean number of 1.57 (range 1 to 5) treatments. A total of 42 (18.8%) patients developed secondary malignancies with an average time to occurrence of 7.1 (range: 0.1 to 17.7) years. The majority of the secondary malignancies were of non-hematological origin (85.9%), most frequently skin cancer (31.0%), followed by prostate cancer (19.0%) and colorectal cancer (16.7%). Six patients (14.4%) developed hematological secondary malignancies with a predominance of B-lymphoid neoplasms. Conclusion : Long-term overall survival in HCL patients treated with sc Cld was excellent and comparable to studies using iv Cld. Despite the long follow-up, sc Cld had a curative potential and relapses requiring re-treatment were observed only in a minority of patients. Secondary malignancies were predominantly non-hematological. These data indicate that patients need to be followed carefully with a special focus on secondary malignancies. Disclosures Chalandon: Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs.
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- 2018
55. Argx-110 Targeting CD70, in Combination with Azacitidine, Shows Favorable Safety Profile and Promising Anti-Leukemia Activity in Newly Diagnosed AML Patients in an Ongoing Phase 1/2 Clinical Trial
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Yara Banz, Samson Fung, Markus G. Manz, Carsten Riether, Sabine Höpner, Hans de Haard, Tim Delahaye, Anna Hultberg, Thomas Pabst, Adrian F. Ochsenbein, Domenica Gandini, Mahan Moshir, Rouven Müller, Luc Van Rompaey, Ulrike Bacher, Ellen Erzeel, Mario Bargetzi, Magdalena Hinterbrandner, and Nicolas Leupin
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Myeloid ,medicine.medical_treatment ,Immunology ,Azacitidine ,Hematopoietic stem cell transplantation ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,business.industry ,Myeloid leukemia ,Cell Biology ,Hematology ,medicine.disease ,Chemotherapy regimen ,Clinical trial ,Transplantation ,Leukemia ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Outcomes in elderly patients with acute myeloid leukemia (AML) are still adverse, as the majority does not qualify for intensive therapy or allogenic stem cell transplantation (ASCT). DNA hypomethylating agents (HMAs) induce remissions and prolong survival in a fraction of these patients. However, overall prognosis remains dismal and all patients progress due to therapy-resistant leukemia stem cells (LSCs). We recently demonstrated that HMAs upregulate the expression of CD70 on primary human AML LSCs, potentially contributing to HMA resistance and that blocking the cell-autonomous CD70/CD27 signaling inhibits proliferation and myeloid differentiation of LSCs and contributes to HMA resistance. Consequently, combining HMA treatment with a blocking αCD70 monoclonal antibody potently reduced colony formation of AML LSCs in vitro and effectively eliminated human AML LCSs in xenograft experiments. Based on these results, we initiated an open-label, non-controlled, non-randomized Phase 1/2 trial combining the HMA azacitidine (AZA) with ARGX-110, a human monoclonal antibody targeting CD70, in newly diagnosed AML patients unfit for intensive chemotherapy (ARGX-110-1601, NCT03030612). Trial design ARGX-110 with optimized antibody-dependent cell-mediated cytotoxicity (ADCC), is administered intravenously at 1, 3, 10 or 20 mg/kg once every two weeks (Q2W), in combination with a standard dose of AZA (75 mg/m² subcutaneously for 7 days every 28 days). A 2-week lead-in of ARGX-110 enables studying the effect of αCD70 antibody monotherapy. Primary objectives in the Phase 1 include determining the maximum tolerated dose of ARGX-110 in combination with AZA and the recommended phase 2 dose (RP2D). Secondary objectives comprise safety, pharmacokinetics and anti-leukemic activity of ARGX-110 alone or in combination with AZA (including overall response rate (ORR), frequencies of LSCs and minimal/measurable residual disease (MRD)). Results The trial is ongoing and as of 16th July 2018, 12 newly diagnosed AML patients were treated in the dose-escalation part of the trial, the results of which will be further updated in December 2018. The median age over the dose cohorts was 75 years (range 64-84) and included intermediate (N=6) and adverse (N=6) ELN risk groups. WHO subtypes were AML with recurrent genetic abnormalities (N=2), MDS-related changes (N=6), AML-NOS (N=3) and therapy-related myeloid neoplasms (N=1). No dose-limiting toxicity was observed and the combination of ARGX-110 with a standard dose of AZA was well tolerated. Hematological toxicities, in line with expected AZA toxicities, were the most frequently reported adverse events (AEs). At the cut-off, the ORR (complete remission [CR] + incomplete recovery [CRi] + partial remission [PR] + morphologic leukemia-free status [MLFS]) was 92% (11/12 patients); among the 11 evaluable subjects, the best response was CR/CRi for 9 patients (82%), 1 patient (9%) reached MLFS, and 1 (9%) PR, with 7 patients still on the trial (median duration on the trial at cut-off was 6.9 months [range: 2-14.4 months]). Significantly, 1 patient reached CR and was discontinued after 5 months to undergo ASCT. Five evaluable patients (45%) achieved MRD negativity by flow cytometry. Molecular MRD negativity was achieved in 3/8 patients with available results, two correlating with flow-MRD negativity. The mean time to response for the first 9 patients was 2.8 months and 3.4 months to reach best response. The 3 patients in the 20 mg/kg cohort did not all reach response at the time of cut-off. Based on pharmacokinetics, safety, and pharmacodynamic data, the RP2D of 10 mg/kg was established. Translational studies assessing LSC frequencies in bone marrow aspirates by limiting dilution colony assays and xenograft experiments revealed that ARGX-110 monotherapy and in combination with AZA significantly reduced LSC frequencies in AML patients. Conclusions ARGX-110 in combination with AZA is well tolerated and leads to a higher ORR compared to historical data for AZA alone. Clinical activity of the combination is observed in different AML subtypes and risk categories. Preliminary data indicate that ARGX-110 alone, and in combination with AZA, efficiently eliminates LSCs. These observations warrant further accelerated investigation of ARGX-110 in combination with AZA in AML patients unfit for intensive therapy. Disclosures Ochsenbein: argenx: Research Funding. Riether:argenx: Research Funding. Bacher:argenx: Research Funding. Höpner:argenx: Research Funding. Hinterbrandner:argenx: Research Funding. Van Rompaey:argenx: Employment. Moshir:argenx: Employment. Delahaye:argenx: Employment. Gandini:argenx: Employment. Erzeel:argenx: Employment. Hultberg:argenx: Employment. Fung:argenx: Consultancy. De Haard:argenx: Employment. Leupin:argenx: Employment.
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- 2018
56. Präanalytik in der Hämatologie – Fallen und Tücken
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Adriana Mendez, Andreas Huber, Nathan Cantoni, and Mario Bargetzi
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medicine.medical_specialty ,business.industry ,media_common.quotation_subject ,Medicine ,Quality (business) ,Medical physics ,General Medicine ,Blood collection ,business ,Phase (combat) ,Therapeutic strategy ,media_common - Abstract
In the last few decades we have seen a significant decrease in the rates of analytical errors in clinical laboratories. The test performances have improved, new parameters have been introduced, as well as internal and external quality controls have been used for the monitoring of accuracy. Currently available evidence demonstrates that the pre- and post-analytical steps show higher error rates (up to 70 % of all errors) than the analytical phase. Recognition of the weak points of the preanalytical phase and search for appropriate solutions in case of discrepancies will finally help to lead to the correct therapeutic strategy. In order to avoid problems in the preanaytical phase in hematology it is very important to consider some essential issues. The patients must be identified in appropriate form, the blood collection for the requested tests must be made using the appropriate tubes in the specified sequence and the samples must be transported to the lab at the right temperature and on time to be analysed. In case of special tests additional information for the lab is very important for the interpretation of the results. In case of unexpected results the lab should contact the responsible physician in order to look for an adequate explanation for the abnormal findings. With help of several cases of the daily haematology routine we want to point out some preanalytical problems.
- Published
- 2013
57. Higher emotional distress in female partners of cancer patients: prevalence and patient-partner interdependencies in a 3-year cohort
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Michael T. Moser, Hansjörg Znoj, Alfred Künzler, Mario Bargetzi, and Fridtjof W. Nussbeck
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Coping (psychology) ,medicine.medical_specialty ,media_common.quotation_subject ,Psychological intervention ,Experimental and Cognitive Psychology ,Hospital Anxiety and Depression Scale ,Checklist ,Interdependence ,Psychiatry and Mental health ,Distress ,Oncology ,Cohort ,medicine ,Anxiety ,medicine.symptom ,Psychology ,Psychiatry ,Clinical psychology ,media_common - Abstract
ObjectiveAssessment and treatment of psychological distress in cancer patients was recognized as a major challenge. The role of spouses, caregivers, and significant others became of salient importance not only because of their supportive functions but also in respect to their own burden. The purpose of this study was to assess the amount of distress in a mixed sample of cancer patients and their partners and to explore the dyadic interdependence. MethodsAn initial sample of 154 dyads was recruited, and distress questionnaires (Hospital Anxiety and Depression Scale, Symptom Checklist 9-Item Short Version and 12-Item Short Form Health Survey) were assessed over four time points. Linear mixed models and actor-partner interdependence models were applied. ResultsA significant proportion of patients and their partners (up to 40%) reported high levels of anxiety, depression, psychological distress, and low quality of life over the course of the investigation. Mixed model analyses revealed that higher risks for clinical relevant anxiety and depression in couples exist for female patients and especially for female partners. Although psychological strain decreased over time, the risk for elevated distress in female partners remained. Modeling patient-partner interdependence over time stratified by patients' gender revealed specific effects: a moderate correlation between distress in patients and partners, and a transmission of distress from male patients to their female partners. ConclusionsOur findings provide empirical support for gender-specific transmission of distress in dyads coping with cancer. This should be considered as an important starting point for planning systemic psycho-oncological interventions and conceptualizing further research. Copyright (c) 2013 John Wiley & Sons, Ltd.
- Published
- 2013
58. ABVD in Older Patients With Early-Stage Hodgkin Lymphoma Treated Within the German Hodgkin Study Group HD10 and HD11 Trials
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Helen Görgen, Peter Borchmann, Oliver Schmalz, Annette Pluetschow, Bastian von Tresckow, Eckhart Weidmann, Andreas Engert, Richard Greil, Michael Fuchs, Achim Rothe, Volker Diehl, Christian Junghanß, Boris Böll, Mario Bargetzi, Dennis A. Eichenauer, Hans Theodor Eich, and Alexander Scherpe
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Dacarbazine ,Vinblastine ,Bleomycin ,law.invention ,Young Adult ,chemistry.chemical_compound ,Randomized controlled trial ,law ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Young adult ,Survival rate ,Aged ,Neoplasm Staging ,Chemotherapy ,business.industry ,Remission Induction ,Middle Aged ,Prognosis ,Hodgkin Disease ,Surgery ,Survival Rate ,Oncology ,ABVD ,chemistry ,Doxorubicin ,Feasibility Studies ,Female ,business ,Follow-Up Studies ,medicine.drug - Abstract
Purpose Older patients with Hodgkin lymphoma (HL) account for approximately 20% of all HL patients. ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy is regarded as standard of care in these patients. However, little is known on feasibility and efficacy of ABVD in this age group. Patients and Methods We analyzed the feasibility and efficacy of four cycles of ABVD in older patients age 60 to 75 years with early-stage HL who were treated within the German Hodgkin Study Group (GHSG) HD10 and HD11 trials; results were compared with those of younger patients treated within these trials. Results In total, 1,299 patients received four cycles of ABVD, and 117 of those patients were older than age 60 years (median, 65 years). In 14% of older patients, treatment was not administered according to protocol, mainly because of excessive toxicity. The mean delay of treatment was twice as high in the older patients (2.2 v 1.2 weeks). Fifty-nine percent of older patients achieved a relative dose-intensity of at least 80% compared with 85% of younger patients. Major toxicity (WHO grade 3 and 4), including leucopenia, nausea, infection, and others, was documented in 68% of older patients with a treatment-related mortality of 5%. Complete response was achieved in 89% of older patients, 3% had progressive disease, and 11% relapsed. At a median observation time of 92 months, 28% of the patients had died, and the 5-year progression-free survival estimate was 75% (95% CI, 66% to 82%). Conclusion In patients age ≥ 60 years with HL, four cycles of ABVD is associated with substantial dose reduction, treatment delay, toxicity, and treatment-related mortality.
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- 2013
59. Bendamustine, lenalidomide and dexamethasone (BRd) has high activity as 2
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Ulrich J M, Mey, Wolfram, Brugger, Heike, Schwarb, Stefanie, Pederiva, Andreas, Schwarzer, Tobias, Dechow, Paul, Jehner, Jacqueline, Rauh, Christian J, Taverna, Mathias, Schmid, Martin, Schmidt-Hieber, Steffen, Doerfel, Natalie, Fischer, Axel, Ruefer, Carsten, Ziske, Wolfgang, Knauf, Richard, Cathomas, Roger, von Moos, Felicitas, Hitz, Rafael, Sauter, Elke, Hiendlmeyer, Nathan, Cantoni, Mario, Bargetzi, and Christoph, Driessen
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Aged, 80 and over ,Salvage Therapy ,Neutropenia ,Remission Induction ,Middle Aged ,Thrombocytopenia ,Dexamethasone ,Thalidomide ,Treatment Outcome ,Antineoplastic Combined Chemotherapy Protocols ,Bendamustine Hydrochloride ,Humans ,Multiple Myeloma ,Lenalidomide ,Aged - Abstract
The combination of lenalidomide (Revlimid
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- 2016
60. Revisiting nutritional support for allogeneic hematologic stem cell transplantation-a systematic review
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Philipp Schuetz, Beat Mueller, Annika Bargetzi, Mario Bargetzi, Lisa Bounoure, Filomena Gomes, Zeno Stanga, Noemi Zueger, Michael Medinger, and Annic Baumgartner
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medicine.medical_specialty ,Parenteral Nutrition ,medicine.medical_treatment ,MEDLINE ,Hematopoietic stem cell transplantation ,Cochrane Library ,03 medical and health sciences ,0302 clinical medicine ,Enteral Nutrition ,medicine ,Humans ,Intensive care medicine ,610 Medicine & health ,Case report form ,Transplantation ,business.industry ,Nutritional Support ,Malnutrition ,Hematopoietic Stem Cell Transplantation ,Hematology ,medicine.disease ,Parenteral nutrition ,Treatment Outcome ,030220 oncology & carcinogenesis ,Observational study ,business ,030215 immunology - Abstract
In 2009, the American Society of Parenteral and Enteral Nutrition and its European counterpart (Euopean Society for Parenteral and Enteral Nutrition) published guidelines regarding nutritional support of patients with hematologic stem cell transplantation. Our aim was to do an up-to-date literature review regarding benefit of nutritional interventions and treatment recommendations. We searched MEDLINE, EMBASE and Cochrane Library for interventional and observational clinical studies. We extracted data based on a predefined case report form and assessed bias. Out of 459 potential abstracts, 13 studies of mostly moderate quality with a total of 18 167 patients were included. Two very large trials reported negative associations of malnutrition and survival, transplant-related mortality and relapse risk. Some trials found enteral nutrition (EN) to be as effective as parenteral nutrition (PN) with lower complication rates. In addition, EN was associated with better survival, less acute GvHD and faster neutrophil recovery. A neutropenic diet was not superior regarding overall survival, but in contrast resulted in higher infection risk. Current moderate quality studies show negative associations of malnutrition and clinical outcomes, with EN being superior to PN. There was no benefit of neutropenic diets. Large, randomized controlled studies are needed to better understand optimal nutritional support in this patient population.
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- 2016
61. Association of Nutritional Parameters with Clinical Outcomes in Patients with Acute Myeloid Leukemia Undergoing Haematopoietic Stem Cell Transplantation
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Philipp Schuetz, Jakob Passweg, Mario Bargetzi, Zeno Stanga, Annic Baumgartner, Noemi Zueger, Michael Medinger, Beat Mueller, and Annika Bargetzi
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Medicine (miscellaneous) ,Graft vs Host Disease ,610 Medicine & health ,Comorbidity ,Body Mass Index ,Cohort Studies ,Hospitals, University ,03 medical and health sciences ,Postoperative Complications ,Weight loss ,Risk Factors ,Internal medicine ,Weight Loss ,Medicine ,Humans ,Registries ,Retrospective Studies ,030109 nutrition & dietetics ,Nutrition and Dietetics ,Framingham Risk Score ,business.industry ,Malnutrition ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,Bacterial Infections ,Length of Stay ,Middle Aged ,Overweight ,medicine.disease ,Prognosis ,Transplantation ,Leukemia ,Leukemia, Myeloid, Acute ,Mycoses ,Cohort ,Immunology ,Female ,medicine.symptom ,business ,Body mass index ,Switzerland ,Cohort study ,Follow-Up Studies - Abstract
Introduction: In acute myeloid leukemia (AML) patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT), there is uncertainty about the extent of influence nutritional parameters have on clinical outcomes. In this study, we investigated the association between initial body mass index (BMI) and weight loss during HSCT on clinical outcomes in a well-characterised cohort of AML patients. Methods: We analysed data of the Basel stem-cell transplantation registry (‘KMT Kohorte') including all patients with AML undergoing first allogeneic HSCT from January 2003 to January 2014. We used multivariable regression models adjusted for prognostic indicators (European Group for Blood and Marrow Transplantation risk score and cytogenetics). Results: Mortality in the 156 AML patients (46% female, mean age 46 years) over the 10 years of follow-up was 57%. Compared to patients with a baseline BMI (kg/m2) of 20-25, a low BMI 7 vs. Conclusion: In patients with AML, low initial BMI and more pronounced weight loss during HSCT are strong prognostic indicators associated with lower survival and worse disease outcomes. Intervention research is needed to investigate whether nutritional therapy can reverse these associations.
- Published
- 2016
62. Y
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Michèle, Voegeli, Stephanie, Rondeau, Simona, Berardi Vilei, Erika, Lerch, Luciano, Wannesson, Thomas, Pabst, Jochen, Rentschler, Mario, Bargetzi, Lorenz, Jost, Nicolas, Ketterer, Angelika, Bischof Delaloye, and Michele, Ghielmini
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Aged, 80 and over ,Male ,Time Factors ,Transplantation Conditioning ,Lymphoma ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Antibodies, Monoclonal ,Transplantation, Autologous ,Treatment Outcome ,Drug Resistance, Neoplasm ,Recurrence ,Antineoplastic Combined Chemotherapy Protocols ,Retreatment ,Humans ,Female ,Yttrium Radioisotopes ,Neoplasm Grading ,Melphalan ,Aged - Abstract
Standard conditioning regimens for autologous stem cell transplantation (ASCT) are often not tolerated by elderly patients, on one hand. Single high-dose melphalan, on the other hand, has been shown to be safe and active as a pretransplant preparative regimen in elderly patients. Y
- Published
- 2016
63. Autotransplant for Hodgkin lymphoma after failure of upfront BEACOPP escalated (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone)
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Erika Lerch, Dominik Heim, Alessandra Cerutti, Luciano Wannesson, Urs Hess, Mario Bargetzi, Christoph Renner, Panagiotis Samaras, Emanuele Zucca, Anne Cairoli, and Thomas Pabst
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Adult ,Male ,Oncology ,BEACOPP ,Cancer Research ,medicine.medical_specialty ,Vincristine ,Adolescent ,medicine.medical_treatment ,Dacarbazine ,Procarbazine ,Transplantation, Autologous ,Bleomycin ,Young Adult ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Transplantation, Homologous ,Treatment Failure ,Cyclophosphamide ,Etoposide ,Retrospective Studies ,Chemotherapy ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Combined Modality Therapy ,Hodgkin Disease ,Vinblastine ,ABVD ,Doxorubicin ,Immunology ,Prednisone ,Female ,business ,medicine.drug - Abstract
BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) escalated is the preferred upfront Hodgkin lymphoma (HL) treatment in a number of countries. Upon failure, high-dose chemotherapy with autologous stem cell support (HDT/ASCT) is performed, but its effectiveness has not been verified in this setting. We analyzed all Swiss cases of chemosensitive HL autografted after failure of BEACOPP escalated (n = 22) and compared outcomes with 22 cases of HDT/ASCT following frontline ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) failure. Five-year progression-free survival (PFS) was 76% for ABVD and 42% for BEACOPP escalated (p = 0.029). Two- and 5-year overall survival (OS) was 90% and 71% for ABVD and 72% and 65% for BEACOPP escalated, respectively (p = not significant). Three patients in the ABVD and four in the BEACOPP escalated groups underwent allotransplant for relapse after HDT/ASCT. Grade 3-4 toxicities were comparable in both groups. Three cases of therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/t-AML) were recorded in the BEACOPP escalated group. The acceptable PFS and OS of chemosensitive patients with HL autografted after failure of upfront BEACOPP escalated seem to justify this approach.
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- 2012
64. Favorable effect of priming with granulocyte colony-stimulating factor in remission induction of acute myeloid leukemia restricted to dose escalation of cytarabine
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Thomas, Pabst, Edo, Vellenga, Wim, van Putten, Harry C, Schouten, Carlos, Graux, Marie-Christiane, Vekemans, Bart, Biemond, Peter, Sonneveld, Jakob, Passweg, Leo, Verdonck, Marie-Cecile, Legdeur, Matthias, Theobald, Emanuel, Jacky, Mario, Bargetzi, Johan, Maertens, Gert Jan, Ossenkoppele, Bob, Löwenberg, M, Van Marwijk Kooy, Cardiology, Hematology, Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), CCA - Innovative therapy, Interne Geneeskunde, and RS: GROW - School for Oncology and Reproduction
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Adult ,Male ,Oncology ,Antimetabolites, Antineoplastic ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Biochemistry ,Disease-Free Survival ,POOR-PROGNOSIS ,ARA-C ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,FACTOR GM-CSF ,ELDERLY PATIENTS ,medicine ,Humans ,GROWTH-FACTORS ,ADVANCED MYELODYSPLASTIC SYNDROME ,Chemotherapy ,ACUTE MYELOGENOUS LEUKEMIA ,business.industry ,Remission Induction ,Cytarabine ,Induction chemotherapy ,Myeloid leukemia ,Induction Chemotherapy ,Cell Biology ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,INTENSIVE CHEMOTHERAPY ,Chemotherapy regimen ,COOPERATIVE GROUP ,Granulocyte colony-stimulating factor ,Surgery ,Leukemia, Myeloid, Acute ,Regimen ,Leukemia ,Treatment Outcome ,CYTOSINE-ARABINOSIDE ,Female ,business ,medicine.drug - Abstract
The clinical value of chemotherapy sensitization of acute myeloid leukemia (AML) with G-CSF priming has remained controversial. Cytarabine is a key constituent of remission induction chemotherapy. The effect of G-CSF priming has not been investigated in relationship with variable dose levels of cytarabine. We randomized 917 AML patients to receive G-CSF (456 patients) or no G-CSF (461 patients) at the days of chemotherapy. In the initial part of the study, 406 patients were also randomized between 2 cytarabine regimens comparing conventional-dose (199 patients) versus escalated-dose (207 patients) cytarabine in cycles 1 and 2. We found that patients after induction chemotherapy plus G-CSF had similar overall survival (43% vs 40%, P = .88), event-free survival (37% vs 31%, P = .29), and relapse rates (34% vs 36%, P = .77) at 5 years as those not receiving G-CSF. However, patients treated with the escalated-dose cytarabine regimen benefited from G-CSF priming, with improved event-free survival (P = .01) and overall survival (P = .003), compared with patients without G-CSF undergoing escalated-dose cytarabine treatment. A significant survival advantage of sensitizing AML for chemotherapy with G-CSF was not apparent in the entire study group, but it was seen in patients treated with escalated-dose cytarabine during remission induction. The HOVON-42 study is registered under The Netherlands Trial Registry (www.trialregister.nl) as #NTR230.
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- 2012
65. [Monoclonal gammopathy in family practice]
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Mario, Bargetzi
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Antineoplastic Combined Chemotherapy Protocols ,Humans ,Interdisciplinary Communication ,Cooperative Behavior ,Family Practice ,Multiple Myeloma - Published
- 2015
66. Improvement of Relative Survival in Elderly Patients with Acute Myeloid Leukemia Emerging from Population-Based Cancer Registries in Switzerland from 2001-2013
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Jakob Passweg, Georg Stuessi, Urs Hess, Alicia Rovó, Anna Efthymiou, Olivier Spertini, Nicolas Bonadies, Volker Arndt, Yves Chalandon, Markus G. Manz, Mario Bargetzi, Annatina Schnegg-Kaufmann, Anita Feller, Helen Boldomero, and Michael Gregor
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medicine.medical_specialty ,education.field_of_study ,Relative survival ,business.industry ,medicine.medical_treatment ,Mortality rate ,Incidence (epidemiology) ,Immunology ,Population ,Cancer ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Internal medicine ,Health care ,Epidemiology ,medicine ,business ,education - Abstract
Introduction: Acute Myeloid Leukaemia (AML) is a rare disease with increasing frequency in the elderly and an emerging impact on health care resources. Trends of classification, incidence, mortality, and survival of AML patients have not yet been reported for Switzerland. Given the demographic ageing, we were mainly interested to investigate whether elderly patients have benefited on a population-based level from the recent changes in AML management. Methods: We performed a population-based, observational analysis of AML cases reported to Cantonal Cancer Registries in Switzerland. Data was aggregated by the National Institute for Epidemiology and Cancer Registration and stratified for the two time-periods 2001-2007/2008-2013. The Swiss Federal Statistics Office provided canton-specific mid-year estimates of the size of the general population and mortality statistics. Data from transplanted patients was provided from the registry of the Swiss Blood Stem Cell Transplant Group . Results: 2'351 new AML cases were registered within the observation time at a median age of 68/67 yrs (range 0-96 yrs). The extrapolated mean annual frequency increased from 275 to 305 AML cases (+10.8%) in the two time periods. In contrast, the age-standardized incidence and mortality rates remained stable (3.0 [95 CI: 2.8-3.2] and 1.9-2.0 [1.8-2.1] per 100'000 person-years, respectively). Incidence was up to 1.4-fold more frequent in males and increased up to 7 fold in patients >75 yrs of age. The fraction of non-classifiable AML cases decreased over time (54.6%/41.8%), but remained high in elderly patients (75-84 yrs: 54.1%, 85+ yrs: 59.1%). As expected, 5-year relative survival (RS) correlated directly with AML risk classes (favorable: 61.7-68.4%, intermediate: 14.9%-27.3%, adverse: 11.4%-20.4%, non-classifiable: 11.4%-14.7%) and inversely with age ( Conclusions: AML incidence remained stable during the observation period, indicating that the 10.8% raise in annual case-frequency is mainly related to population growth and ageing and not to an increase of age-specific risk. AML classification improved over time, but non-classifiable AML cases remained high in elderly patients, suggesting that diagnostics and reporting is less accurate with increasing age. A trend towards improved RS was found in AML patients aged 65-74 yrs and with intermediate as well as adverse risk. These trends were caused by multiple factors and mainly based on the general changes of treatment management of AML patients ≥65 yrs. Survival of elderly AML patients remains dismal. Nevertheless, recent progress in clinical management of elderly AML patients resulted in an emerging improvement of survival on a population-based level in Switzerland. The demographic trend will further increase AML burden and has to be taken into account for structural as well as financial considerations for future health care systems. Disclosures Gregor: AbbVie: Other: Personal Fees; Celgene: Other: Personal Fees, Non-Financial Support; Gilead: Other: Personal Fees; GlaxoSmithKline: Other: Personal Fees; Janssen: Other: Personal Fees, Non-Financial Support; Mundipharma: Other: Personal Fees; Novartis: Other: Personal Fees, Non-Financial Support; Roche: Other: Personal Fees, Non-Financial Support.
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- 2017
67. Weekly treatment with a combination of bortezomib and bendamustine in relapsed or refractory indolent non-Hodgkin lymphoma
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Nina Kotrubczik, Peter R. Moosmann, Mario Bargetzi, Marc Heizmann, and M. Wernli
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Bendamustine ,Cancer Research ,business.industry ,medicine.drug_class ,Bortezomib ,Treatment outcome ,Hematology ,medicine.disease ,Antimetabolite ,Lymphoma ,Bendamustine hydrochloride ,Oncology ,Refractory ,Indolent Non-Hodgkin Lymphoma ,Cancer research ,Medicine ,business ,medicine.drug - Abstract
Bendamustine was designed as a bifunctional anticancer compound combining an alkylating and an antimetabolite function. It shows unique mechanisms of action and incomplete cross resistance to other...
- Published
- 2009
68. Efficient mobilization of PBSC with vinorelbine/G-CSF in patients with malignant lymphoma
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Mario Bargetzi, M. Wernli, M Zuberbühler, J Burger, P R Moosmann, I A F M Heijnen, A C O'Meara, A Huber, P Fernandez, and M. Heizmann
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Adult ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Pilot Projects ,Hematopoietic stem cell transplantation ,Vinblastine ,Vinorelbine ,Transplantation, Autologous ,Drug Costs ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,medicine ,Humans ,Progenitor cell ,Hematopoietic Stem Cell Mobilization ,Aged ,Transplantation ,Chemotherapy ,business.industry ,Lymphoma, Non-Hodgkin ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Hodgkin Disease ,Surgery ,Granulocyte colony-stimulating factor ,Stem cell ,business ,medicine.drug - Abstract
High-dose chemotherapy (HDT) and hematopoietic SCT are effective in patients with relapsing or refractory malignant lymphoma. Collection of sufficient numbers of stem cells is a prerequisite for such a therapy. In a pilot trial, we evaluated the feasibility of stem cell mobilization with vinorelbine/G-CSF in patients with lymphoma, a regimen allowing precise timing and harvesting of sufficient stem cells in myeloma patients. Forty-five patients with lymphoma received vinorelbine 35 mg/m(2) i.v. on day 1 and G-CSF 10 microg/kg/day s.c., divided in two daily doses from day 4 until collection. Stem cell collection was successfully performed in 43 patients (96%) with a median of 3.6 x 10(6) CD34(+) cells/kg (range: 1.4-16) in the collected product. In 28 patients (62%), the first stem cell apheresis was performed on day 8, and for 28 patients a sufficient stem cell yield was reached with one apheresis only. All 43 patients underwent high-dose chemotherapy with BEAM and auto-SCT with hematological recovery on time and without unexpected toxicity. In conclusion, vinorelbine/G-CSF allows accurate timing and safe harvesting of sufficient stem cells in patients with malignant lymphoma.
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- 2009
69. Randomized trial of dailyversusweekly administration of 2-chlorodeoxyadenosine in patients with hairy cell leukemia: a multicenter phase III trial (SAKK 32/98)
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Mario Bargetzi, Reinhard Zenhäusern, Urs Hess, Leda Leoncini, Sandrine Meyer-Monard, B. Rufener, Dominik Heim, Andreas Tobler, Max Solenthaler, and S.-F. Hsu Schmitz
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Neutropenia ,Randomization ,Antineoplastic Agents ,Gastroenterology ,Disease-Free Survival ,Drug Administration Schedule ,law.invention ,Young Adult ,Leukocytopenia ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Clinical endpoint ,Chlorodeoxyadenosine ,Humans ,Hairy cell leukemia ,Aged ,Aged, 80 and over ,Leukemia, Hairy Cell ,business.industry ,Standard treatment ,Remission Induction ,Hematology ,Middle Aged ,medicine.disease ,Surgery ,Treatment Outcome ,Oncology ,Cladribine ,Female ,business - Abstract
Daily administration of 2-chlorodeoxyadenosine (Cladribine, CDA) is a standard treatment for hairy cell leukemia, but may cause severe neutropenia and neutropenic fever. This trial compared toxicity and efficacy of weekly versus daily CDA administration. One hundred patients were randomized to receive standard (CDA 0.14 mg/kg/day day 1-5 [Arm A]) or experimental treatment (CDA 0.14 mg/kg/day once weekly for 5 weeks [Arm B]). The primary endpoint was average leukocyte count within 6 weeks from randomization. Secondary endpoints included response rates, other acute hematotoxicity, acute infection rate, hospital admission, remission duration, event-free, and overall survival. There was no significant difference in average leukocyte count. Response rate (complete + partial remission) at week 10 was 78% (95% confidence interval (CI) 64-88%) in Arm A and 68% (95% CI 54-80%) in Arm B (p = 0.13). Best response rates during follow-up were identical (86%) in both arms. No significant difference was found in the rate of grade 3+4 leukocytopenia (94%vs. 84%), grade 3+4 neutropenia (90%vs. 80%), acute infection (44%vs. 40%), hospitalization (38%vs. 34%), and erythrocyte support (22%vs. 30%) within 10 weeks. Overall, these findings indicate that there are no apparent advantages in toxicity and efficacy by giving CDA weekly rather than daily.
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- 2009
70. Efficacious and save use of biosimilar filgrastim for hematopoietic progenitor cell chemo-mobilization with vinorelbine in multiple myeloma patients
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Julia-Tatjana, Maul, Frank, Stenner-Liewen, Burkhardt, Seifert, Sarah, Pfrommer, Ulf, Petrausch, Michael K, Kiessling, Urs, Schanz, Gayathri, Nair, Axel, Mischo, Christian, Taverna, Adrian, Schmidt, Mario, Bargetzi, Roger, Stupp, Christoph, Renner, and Panagiotis, Samaras
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Clinical Protocols ,Dose-Response Relationship, Drug ,Filgrastim ,Humans ,Cell Count ,Drug Therapy, Combination ,Vinorelbine ,Hematopoietic Stem Cells ,Multiple Myeloma ,Vinblastine ,Biosimilar Pharmaceuticals ,Hematopoietic Stem Cell Mobilization ,Retrospective Studies - Abstract
Biosimilars are increasingly being licensed as equipotent drugs, although efficacy and safety data are not available for all clinical indications. Accordingly, the efficacy of the biosimilar filgrastim Zarzio® combined with vinorelbine for chemo-mobilization of CD34+ hematopoietic progenitor cells (HPC) in patients with multiple myeloma has not been evaluated yet. We compared the efficacy of vinorelbine combined with this biosimilar filgrastim for HPC mobilization to vinorelbine plus original filgrastim (Neupogen®). Overall, 105 multiple myeloma patients received vinorelbine 35 mg/m
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- 2015
71. Current status and updated recommendations for diagnosis and treatment of plasma cell myeloma in Switzerland
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Urs Hess, Nicolas Ketterer, Panagiotis Samaras, Dominik Heim, Daniel Betticher, Christoph Renner, Erika Lerch, Thomas Matthes, Mario Bargetzi, Michel A. Duchosal, Ulrich Mey, Thilo Zander, Thomas Pabst, Christian Taverna, University of Zurich, and Renner, Christoph
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medicine.medical_specialty ,610 Medicine & health ,2700 General Medicine ,Monoclonal Gammopathy of Undetermined Significance ,Maintenance Chemotherapy ,Quality of life ,Recurrence ,hemic and lymphatic diseases ,Plasma Cell Myeloma ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Intensive care medicine ,Multiple myeloma ,Lenalidomide ,Neoplasm Staging ,ddc:616 ,business.industry ,Bortezomib ,Antineoplastic Combined Chemotherapy Protocols/therapeutic use ,Monoclonal Gammopathy of Undetermined Significance/pathology ,Multiple Myeloma/diagnosis ,Multiple Myeloma/therapy ,Hematopoietic Stem Cell Transplantation ,General Medicine ,medicine.disease ,Thalidomide ,Consolidation Chemotherapy ,10032 Clinic for Oncology and Hematology ,Relapsed refractory ,Practice Guidelines as Topic ,Retreatment ,business ,Multiple Myeloma ,Median survival ,Switzerland ,medicine.drug - Abstract
The availability of drugs such as thalidomide, bortezomib and lenalidomide changed the landscape in myeloma treatment and has extended the median survival up to 10 years with a substantial improvement in quality of life. This development prompted a Swiss expert panel to re-evaluate the current status and formulate updated clinical recommendations for the diagnosis and treatment of plasma cell myeloma. These recommendations should help clinicians in their decision making to achieve the best outcome based on currently available data.
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- 2015
72. Procalcitonin Improves the Glasgow Prognostic Score for Outcome Prediction in Emergency Patients with Cancer: A Cohort Study
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Antoinette Conca, Susan Felder, Anna Christina Rast, Sebastian Haubitz, Andreas Huber, Ulrich Buergi, Svenja Laukemann, Lukas Faessler, Alexander Kutz, Deborah Steiner, Mario Bargetzi, Beat Mueller, Philipp Schuetz, and Barbara Reutlinger
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Calcitonin ,Male ,medicine.medical_specialty ,Article Subject ,Calcitonin Gene-Related Peptide ,education ,Clinical Biochemistry ,Glasgow Outcome Scale ,Procalcitonin ,Cohort Studies ,Predictive Value of Tests ,Internal medicine ,Neoplasms ,Genetics ,Biomarkers, Tumor ,Medicine ,Humans ,Urea ,Protein Precursors ,Vitamin D ,Molecular Biology ,Serum Albumin ,Aged ,lcsh:R5-920 ,biology ,business.industry ,Biochemistry (medical) ,C-reactive protein ,Cancer ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Surgery ,C-Reactive Protein ,Predictive value of tests ,biology.protein ,Calcium ,Female ,business ,lcsh:Medicine (General) ,Cohort study ,Research Article - Abstract
The Glasgow Prognostic Score (GPS) is useful for predicting long-term mortality in cancer patients. Our aim was to validate the GPS in ED patients with different cancer-related urgency and investigate whether biomarkers would improve its accuracy. We followed consecutive medical patients presenting with a cancer-related medical urgency to a tertiary care hospital in Switzerland. Upon admission, we measured procalcitonin (PCT), white blood cell count, urea, 25-hydroxyvitamin D, corrected calcium, C-reactive protein, and albumin and calculated the GPS. Of 341 included patients (median age 68 years, 61% males), 81 (23.8%) died within 30 days after admission. The GPS showed moderate prognostic accuracy (AUC 0.67) for mortality. Among the different biomarkers, PCT provided the highest prognostic accuracy (odds ratio 1.6 (95% confidence interval 1.3 to 1.9),P<0.001, AUC 0.69) and significantly improved the GPS to a combined AUC of 0.74 (P=0.007). Considering all investigated biomarkers, the AUC increased to 0.76 (P<0.001). The GPS performance was significantly improved by the addition of PCT and other biomarkers for risk stratification in ED cancer patients. The benefit of early risk stratification by the GPS in combination with biomarkers from different pathways should be investigated in further interventional trials.
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- 2015
73. Efficacy of vinorelbine plus granulocyte colony-stimulation factor for CD34+ hematopoietic progenitor cell mobilization in patients with multiple myeloma
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Urs Schanz, Mario Bargetzi, Christoph Renner, Adrian Schmidt, Gayathri Nair, Roger Stupp, Burkhardt Seifert, Panagiotis Samaras, Christian Taverna, Frank Stenner-Liewen, Axel Mischo, Sarah Pfrommer, and Ulf Petrausch
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Adult ,Male ,Abdominal pain ,medicine.medical_specialty ,Constipation ,Filgrastim ,CD34 ,Gene Expression ,Antigens, CD34 ,Cell Count ,Vinorelbine ,Vinblastine ,Transplantation, Autologous ,Chemo-mobilization ,Risk Factors ,Granulocyte Colony-Stimulating Factor ,medicine ,Humans ,Leukapheresis ,Lenalidomide ,Multiple myeloma ,Aged ,Retrospective Studies ,Transplantation ,business.industry ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Hematopoietic Stem Cells ,Antineoplastic Agents, Phytogenic ,Hematopoietic Stem Cell Mobilization ,Recombinant Proteins ,Surgery ,Thalidomide ,Hematopoietic progenitor cell mobilization ,Treatment Outcome ,Anesthesia ,Drug Therapy, Combination ,Female ,medicine.symptom ,business ,Multiple Myeloma ,medicine.drug - Abstract
We aimed to assess the efficacy of vinorelbine plus granulocyte colony-stimulating factor (G-CSF) for chemo-mobilization of CD34(+) hematopoietic progenitor cells (HPC) in patients with multiple myeloma and to identify adverse risk factors for successful mobilization. Vinorelbine 35 mg/m(2) was administered intravenously on day 1 in an outpatient setting. Filgrastim 5 μg/kg body weight (BW) was given twice daily subcutaneously from day 4 until the end of the collection procedure. Leukapheresis was scheduled to start on day 8 and be performed for a maximum of 3 consecutive days until at least 4 × 10(6) CD34(+) cells per kg BW were collected. Overall, 223 patients were mobilized and 221 (99%) patients proceeded to leukapheresis. Three (1.5%) patients required an unscheduled hospitalization after chemo-mobilization because of neutropenic fever and renal failure (n = 1), severe bone pain (n = 1), and abdominal pain with constipation (n = 1). In 211 (95%) patients, the leukaphereses were started as planned at day 8, whereas in 8 (3%) patients the procedure was postponed to day 9 and in 2 (1%) patients to day 10. In the great majority of patients (77%), the predefined amount of HPC could be collected with 1 leukapheresis. Forty-four (20%) patients needed a second leukapheresis, whereas only 6 (3%) patients required a third leukapheresis procedure. The median number of CD34(+) cells collected was 6.56 × 10(6) (range, .18 to 25.9 × 10(6)) per kg BW at the first day of leukapheresis and 7.65 × 10(6) (range, .18 to 25.9 × 10(6)) per kg BW in total. HPC collection was successful in 212 (95%) patients after a maximum of 3 leukaphereses. Patient age (P = .02) and prior exposition to lenalidomide (P.001) were independent risk factors for a lower HPC amount collected in multiple regression analysis. Vinorelbine plus G-CSF enables a very reliable prediction of the timing of leukapheresis and results in successful HPC collection in 95% of the patients.
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- 2015
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74. A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis
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Heiko, Witt, Miklos Sahin Toth, Olfert, Landt, Jian Min Chen, Thilo, Kahne, Drenth, Joost P. H., Zoltan, Kukor, Edit, Szepessy, Walter, Halangk, Stefan, Dahm, Klaus, Rohde, Hans Ulrich Schulz, Cedric Le Marechal, Nejat, Akar, Ammann, Rudolf W., Kaspar, Truninger, Mario, Bargetzi, Eesh, Bhatia, Carlo, Castellani, Giulia Martina Cavestro, Milos, Cerny, DESTRO-BISOL, Giovanni, Spedini, Gabriella, Hans, Eiberg, Jansen, Jan B. M. J., Monika, Koudova, Eva, Rausova, Milan, Macek, Macek Jr, M., Nuria, Malats, Real, Francisco X., Hans Jurgen Menzel, Pedro, Moral, Roberta, Galavotti, Pier Franco Pignatti, Olga, Rickards, Julius, Spicak, Narcis Octavian Zarnescu, Wolfgang, Bock, Gress, Thomas M., Helmut, Friess, Johann, Ockenga, Hartmut, Schmidt, Roland, Pfutzer, Matthias, Lohr, Peter, Simon, Frank Ulrich Weiss, Lerch, Markus M., Niels, Teich, Volker, Keim, Thomas, Berg, Bertram, Wiedenmann, Werner, Luck, David Alexander Groneberg, Michael, Becker, Thomas, Keil, Andreas, Kage, Jana, Bernardova, Markus, Braun, Claudia, Guldner, Juliane, Halangk, Jonas, Rosendahl, Ulrike, Witt, Matthias, Treiber, Renate, Nickel, Claude, Ferec, Witt, H, SAHIN TOTH, M, Landt, O, Chen, Jm, Kahne, T, Drenth, Jp, Kukor, Z, Szepessy, E, Halangk, W, Dahm, S, Rohde, K, Schulz, Hu, LE MARECHAL, C, Akar, N, Ammann, Rw, Truninger, K, Bargetzi, M, Bhatia, E, Castellani, C, Cavestro, GIULIA MARTINA, Cerny, M, DESTRO BISOL, G, Spedini, G, Eiberg, H, Jansen, Jb, Koudova, M, Rausova, E, MACEK M., Jr, Malats, N, Real, Fx, Menzel, Hj, Moral, P, Galavotti, R, Pignatti, Pf, Rickards, O, Spicak, J, Zarnescu, No, Bock, W, Gress, Tm, Friess, H, Ockenga, J, Schmidt, H, Pfutzer, R, Lohr, M, Simon, P, Weiss, Fu, Lerch, Mm, Teich, N, Keim, V, Berg, T, Wiedenmann, B, Luck, W, Groneberg, Da, Becker, M, Keil, T, Kage, A, Bernardova, J, Braun, M, Guldner, C, Halangk, J, Rosendahl, J, Witt, U, Treiber, M, Nickel, R, and Ferec, C.
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trypsin inhibitor ,Models, Molecular ,Enteropeptidase ,Pancreatic disease ,Membrane transport and intracellular motility [NCMLS 5] ,arginine ,genetic risk ,chemistry.chemical_compound ,Models ,proteinosis ,Trypsin ,Pancreatic Secretory Trypsin Inhibitor ,PRSS1 gene ,enteropeptidase ,medicine.diagnostic_test ,adult ,Hydrolysis ,cationic trypsinogen ,protection ,unclassified drug ,enzyme activity ,female ,priority journal ,risk factor ,CHRONIC PANCREATITIS ,protein degradation ,Trypsinogen ,medicine.drug ,medicine.medical_specialty ,anionic trypsinogen ,Proteolysis ,Biology ,Article ,male ,Internal medicine ,Genetics ,medicine ,Matrix-Assisted Laser Desorption-Ionization ,Humans ,PRSS2 ,controlled study ,human ,Molecular gastro-enterology and hepatology [IGMD 2] ,gene ,DNA Primers ,Genetic polymorphism ,catalysis ,Base Sequence ,Spectrometry ,disease predisposition ,Molecular ,cationic trypsinogen prss1 ,glycine ,pancreatic secretory trypsin inhibitor spink1 ,trypsin ,trypsinogen ,article ,chronic pancreatitis ,codon ,genetic susceptibility ,major clinical study ,nucleotide sequence ,Chronic Disease ,Haplotypes ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Mass ,medicine.disease ,Tripsinogen ,Tripsina ,Settore BIO/18 - Genetica ,Endocrinology ,Genetic defects of metabolism [UMCN 5.1] ,Pancreatitis ,chemistry ,Genètica - Abstract
Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis. The initial experiments were supported by the DFG (Wi 2036/1-1). This work was supported by the Sonnenfeld-Stiftung, Berlin, Germany (to H.W.), the US National Institutes of Health (NIH) (grant DK058088 to M.S.-T.), INSERM (Institut National de la Santé et de la Recherche Médicale) and the Programme Hospitalier de Recherche Clinique (grant PHRC R 08-04 to C.F.)
- Published
- 2006
75. Effect of Single-Agent Rituximab Given at the Standard Schedule or As Prolonged Treatment in Patients With Mantle Cell Lymphoma: A Study of the Swiss Group for Clinical Cancer Research (SAKK)
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Sergio Cogliatti, Rolf A. Stahel, Michele Ghielmini, Hubert Schefer, Ursula Waltzer, Shu-Fang Hsu Schmitz, Nicolas Ketterer, Thomas Cerny, Mario Bargetzi, Francesco Bertoni, Martin F. Fey, Gabriella Pichert, and Daniel Betticher
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Anemia ,Antineoplastic Agents ,Lymphoma, Mantle-Cell ,Gastroenterology ,Drug Administration Schedule ,law.invention ,Antibodies, Monoclonal, Murine-Derived ,Randomized controlled trial ,Refractory ,law ,Internal medicine ,medicine ,Humans ,Aged ,Aged, 80 and over ,business.industry ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Surgery ,Lymphoma ,Clinical trial ,medicine.anatomical_structure ,Oncology ,Female ,Mantle cell lymphoma ,Rituximab ,Bone marrow ,business ,medicine.drug - Abstract
Purpose To evaluate the effect of single-agent rituximab given at the standard or a prolonged schedule in patients with newly diagnosed, or refractory or relapsed mantle cell lymphoma (MCL). Patients and Methods After induction treatment with the standard schedule (375 mg/m2 weekly × 4), patients who were responding or who had stable disease at week 12 from the start of treatment were randomly assigned to no further treatment (arm A) or prolonged rituximab administration (375 mg/m2) every 8 weeks for four times (arm B). Results The trial enrolled 104 patients. After induction, clinical response was 27% with 2% complete responses. Among patients with detectable t(11;14)-positive cells in blood and bone marrow at baseline, four of 20, and one of 14, respectively, became polymerase chain-reaction–negative after induction. Anemia was the only adverse predictor of response in the multivariate analysis. After a median follow-up of 29 months, response rate and duration of response were not significantly different between the two schedules in 61 randomly assigned patients. Median event-free survival (EFS) was 6 months in arm A versus 12 months in arm B; the difference was not significant (P = .1). Prolonged treatment seemed to improve EFS in the subgroup of pretreated patients (5 months in arm A v 11 months in arm B; P = .04). Thirteen percent of patients in arm A and 9% in arm B presented with grade 3 to 4 hematologic toxicity. Conclusion Single-agent rituximab is active in MCL, but the addition of four single doses at 8-week intervals does not seem to significantly improve response rate, duration of response, or EFS after treatment with the standard schedule.
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- 2005
76. Reconstitution of dendritic and natural killer–cell subsets after allogeneic stem cell transplantation: effects of endogenous flt3 ligand
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Alois Gratwohl, Elena Chklovskaia, Aleksandra Wodnar-Filipowicz, Catherine Nissen, Mario Bargetzi, and Pegah Nowbakht
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Adult ,Cytotoxicity, Immunologic ,Adolescent ,Immunology ,Graft vs Host Disease ,Stem cell factor ,Biology ,Biochemistry ,Immunophenotyping ,Natural killer cell ,Interleukin 21 ,medicine ,Humans ,Regeneration ,Transplantation, Homologous ,Cell Lineage ,Lymphokine-activated killer cell ,Graft Survival ,Hematopoietic Stem Cell Transplantation ,Membrane Proteins ,Dendritic Cells ,Cell Biology ,Hematology ,Middle Aged ,Killer Cells, Natural ,Transplantation ,Kinetics ,medicine.anatomical_structure ,Interleukin 15 ,Hematologic Neoplasms ,Cyclosporine ,Myeloid-derived Suppressor Cell ,Cytokines ,Stem cell - Abstract
Recovery of dendritic cells (DCs) and natural killer (NK) cells after allogeneic stem cell transplantation (SCT) is important for allograft responses and antitumor immunity and thus for treatment outcome. Regulation of this regenerative process is not well understood. We investigated the influence of endogenous cytokines on the recovery and diversification of DC and NK cell subsets up to 6 months after SCT. Reconstitution of circulating DCs and NK cells was rapid but accompanied by prolonged skewing of cell subsets. The speed of recovery of CD11c+CD123low DC1 exceeded that of CD11c– CD123+ DC2, and correlated with plasma levels of flt3 ligand (FL), but not with granulocyte or granulocyte-macrophage colony-stimulating factors and stem cell factor. There was a 5-fold increase in interferon-γ–producing CD56highCD16–/low NK cells and a corresponding reduction in the CD56lowCD16high subset, accompanied by strongly reduced NK cell cytotoxicity. In vitro data implicate an inhibitory effect of cyclosporin A on NK cell differentiation and cytotoxicity. NK cell numbers did not correlate with plasma levels of FL or interleukin 15. Our results demonstrate that endogenous FL has distinct effects on the kinetics of reconstitution of DCs and NK cells and have potential implications for the modulation of immune responses after allogeneic SCT.
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- 2004
77. Mutant NPM1 MRD and FLT3-ITD Status are Independent Prognostic Factors for the Risk of Relapse in AML Patients
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François G. Kavelaars, Thomas Pabst, Tim Grob, Rosa Meijer, Markus G. Manz, Marie-Christiane Vekemans, Peter J. M. Valk, Mario Bargetzi, Gert J. Ossenkoppele, Carlos Graux, Bob Löwenberg, Mojca Jongen-Lavrencic, and Jakob Passweg
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Oncology ,Cancer Research ,medicine.medical_specialty ,NPM1 ,business.industry ,Internal medicine ,Mutant ,medicine ,Hematology ,Relapse risk ,business ,Flt3 itd - Published
- 2016
78. Immune thrombocytopenia and anticoagulation: the role of romiplostim in the early treatment
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Mario Bargetzi, Nathan Cantoni, and Marc Heizmann
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Romiplostim ,business.industry ,Treatment outcome ,Immunology ,medicine ,Platelet ,Hematology ,business ,Immune thrombocytopenia ,medicine.drug - Published
- 2012
79. Effects of the Sympathicomimetic Agonist Mirabegron on Disease Course, Mutant Allele Burden, Marrow Fibrosis, and Nestin Positive Stem Cell Niche in Patients with JAK2-Mutated Myeloproliferative Neoplasms. a Prospective Multicenter Phase II Trial SAKK 33/14
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Pontus Lundberg, Alexandre Theocharides, Christine Biaggi, Radek C. Skoda, Geneviève Favre, Martin Bigler, Alexandar Tzankov, Mario Bargetzi, Andrea Fuhrer, Nathan Cantoni, Beatrice Drexler, Markus G. Manz, Simón Méndez-Ferrer, Peter Keller, Georg Stuessi, Axel Rüfer, Jakob Passweg, and Rudolf Benz
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0301 basic medicine ,medicine.medical_specialty ,Myeloid ,medicine.diagnostic_test ,business.industry ,Surrogate endpoint ,Immunology ,CD34 ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,03 medical and health sciences ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,Internal medicine ,Biopsy ,medicine ,Bone marrow ,Progenitor cell ,business ,Myelofibrosis - Abstract
Myeloproliferative neoplasms (MPN) are clonal hematopoietic disorders characterized by aberrant proliferation of erythroid, megakaryocytic and myeloid lineages. They are associated with decreased survival, thromboembolic complications, hemorrhage and leukemic transformation. MPN can be subdivided into polycythemiavera(PV), essentialthrombocythemia(ET) and primary myelofibrosis (PMF). The JAK2-V617F mutation is present in 70-80% of all MPN patients. MPN is initiated and maintained by mutated hematopoietic stem and progenitor cells (HSPC). Bone marrow mesenchymal stem cells expressing the intermediate filament proteinnestin(nestin+ MSCs) that are innervated by sympathetic nerve fibers constitute an important component of the stem cell niche and regulate normal HSCs. Thesenestin+ MSCs are strongly reduced in bone marrow of JAK2-V617F positive MPN patients and in mice expressing JAK2-V617F due to damage of the sympathetic nerve fibers triggered by cytokines from the mutant cells. In a JAK2-V617F mouse model of MPN, treatment with a beta-3sympathicomimeticagonist corrected the damage inflicted by the MPN clones on their niches and ameliorated the MPN phenotype. To test the potentially beneficial effect on disease-control by modulating bone marrow niche cells in patients with MPN, we performed a phase II trial with the beta-3sympathicomimeticagonistmirabegron. Patients and Methods: The trial consisted ofmirabegrontreatment with 25 mg daily during the first week, followed by 50 mg daily for at least 24 weeks. Patients with acytohistologicallyconfirmed diagnosis of MPN and a JAK2-V617F allele burden >20% in granulocytes at study entry were eligible, if not treated with JAK2 inhibitors or interferon. Reduction of the JAK2-V617F mutant allele burden ³50% in granulocytes was defined as the primary end point. Secondary end points included changes in blood counts or MPN related symptoms. As a side study, bone marrow biopsies were quantified fornestin+ MSCs, fibrosis and CD34+ HSPCs. N=39 patients have been accrued in 10 institutions in Switzerland. Eight (21%) had ET, 22 (56%) PV, and 9 (23%) PMF. N=27 (69%) were male, the median age was 62 (Q1-Q3 53-72) years. Median mutated allele burden at study onset was 52% (Q1-Q3 33-73%). All patients had prior treatment, N=28 (72%) patients hadcytoreductivetreatment, the remaining patients hadantiaggregation, anticoagulation or phlebotomy. Results: No patient reached the primary endpoint of 50% reduction in allele burden, one patient achieved a 25% reduction by 24 weeks of treatment. Adverse events were mostly grade I or II on the CTCAE scale. Three patients had grade III events: two were considered to be at least possibly related to study medication. In the side study, 24 patients agreed to bone marrow biopsy prior to and at the end ofmirabegrontreatment and for 20 patients both measurements are available. In these patients an increase in thenestin+ MSCs cells from a median of 1.09 (Q1-Q3 0.38-3.27)/mm2 to 3.95 (Q1-Q3 1.98-8.79)/mm2 (p Conclusion: In this prospective phase II clinical trial treatment with the beta-3-sympathicomimetic agonistmirabegronfor 24 weeks failed to achieve the primary endpoint to reduce the JAK2-V617F mutant allele burden >50% in patients with MPN. However, an increase in thenestin+ MSCs in bone marrow and a slight decrease of myelofibrosis were found, which will be further investigated. Figure 1 Bone marrow histology of a patient before (week 0) and at the end ofmirabegron treatment (week 24). Upper panel,reticulin fibers are stained black by silver impregnation (Gomori). Lower panel, immunohistochemistry staining with antibodies against humannestin protein (brown staining). Note decrease inreticulin fibrosis and increase innestin+ cells after 24 weeks of treatment. Magnification: 200x. Figure 1. Bone marrow histology of a patient before (week 0) and at the end ofmirabegron treatment (week 24). Upper panel,reticulin fibers are stained black by silver impregnation (Gomori). Lower panel, immunohistochemistry staining with antibodies against humannestin protein (brown staining). Note decrease inreticulin fibrosis and increase innestin+ cells after 24 weeks of treatment. Magnification: 200x. Disclosures Theocharides: Novartis: Consultancy, Honoraria. Rüfer:Novartis: Consultancy, Speakers Bureau. Benz:Celgene: Consultancy. Tzankov:Novartis: Speakers Bureau; Abbott: Speakers Bureau. Skoda:Novartis: Consultancy, Speakers Bureau; Baxalta: Speakers Bureau; Shire: Consultancy, Speakers Bureau.
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- 2016
80. Diagnosis and treatment of mantle cell lymphoma
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Sergio Cogliatti, Andreas Lohri, Mario Bargetzi, Felicitas Hitz, Christian Taverna, Christoph Renner, and Ulrich Mey
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Salvage therapy ,Lymphoma, Mantle-Cell ,Disease ,Transplantation, Autologous ,Maintenance Chemotherapy ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Chemotherapy ,business.industry ,Remission Induction ,Age Factors ,Consolidation Chemotherapy ,Chemoradiotherapy ,General Medicine ,medicine.disease ,Lymphoma ,Surgery ,Transplantation ,Rituximab ,Mantle cell lymphoma ,Immunotherapy ,Neoplasm Recurrence, Local ,business ,Stem Cell Transplantation ,medicine.drug - Abstract
Mantle cell lymphoma (MCL) is a relatively rare lymphoma entity accounting for an estimated 3%-6% of all non-Hodgkin's lymphoma cases. Characterised by both the incurability of indolent lymphomas and the rapid growth of aggressive lymphomas, MCL has a median overall survival of only 4-5 years. Although the disease often shows an encouraging response to first-line treatment, its clinical course is usually marked by recurrent relapses, resulting in a dismal long-term outcome. The choice of therapy for managing the disease is a complex problem that still requires evidence-based guidance. Owing to the rarity of MCL, the bulk of data comes from phase II trials in small numbers of patients. Nevertheless, therapeutic strategies for MCL have evolved in an effort to adapt treatment according to the individual patient's risk profile, and the overall survival has nearly doubled in the last 30 years. The use of effective immunochemotherapy regimens in first-line therapy, advances in stem cell transplantation, and the development of more active salvage therapy regimens have improved the outcome. This review will summarise the key factors that drive clinical practice with respect to the management of MCL.
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- 2013
81. Repeated treatment with horse antilymphocyte globulin for severe aplastic anaemia
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T Hoffmann, Bruno Speck, Aleksandra Wodnar-Filipowicz, Catherine Nissen, Signer E, Jakob Passweg, André Tichelli, Alois Gratwohl, and Mario Bargetzi
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medicine.medical_specialty ,business.industry ,Anemia ,Incidence (epidemiology) ,Horse ,Hematology ,medicine.disease ,Gastroenterology ,Surgery ,Internal medicine ,Toxicity ,Serum sickness ,Medicine ,Aplastic anemia ,business ,Complication ,Survival analysis - Abstract
In a single-centre study the feasibility and efficacy of repeated antilymphocyte globulin (ALG) for patients with severe aplastic anaemia (SAA) not responding to an initial ALG treatment or relapsing after initial response to ALG was evaluated. 139 consecutive patients with newly diagnosed SAA were treated with ALG between 1976 and 1995. 89 patients responded to a first course; 50 patients did not become transfusion independent. Of the 89 responders, 66 remained in remission, 23 relapsed. 43 patients received a second or subsequent course of ALG for failure to respond (n = 25) or relapse (n = 18) and were given a total of 53 courses. Acute reactions in the multiply exposed patients occurred during the first ALG treatment in 11 (26%) and during subsequent exposures in 16/53 courses (30%; P > 0.2). Incidence of serum sickness was 63% (27/43) after the initial course compared to 57% (30/53) after subsequent courses (P > 0.2), but clinical signs of serum sickness occurred earlier after repeated (median 6 d) as compared to initial exposure (13d; P = 0.008). Transfusion-independent haemopoiesis was achieved in 27/43 (63%) and survival probabilities for the 43 patients receiving multiple courses of ALG was 52 +/- 8% at 10 years. The probability of developing a late clonal disorder was 53 +/- 10% after multiple, as compared to 34 +/- 7% after single exposure (P = 0.15). No difference in results was observed between patients retreated for failure to first ALG or for relapse. ALG of the same species can be repeated without increased risks of side-effects in patients with SAA. A second or subsequent course of ALG from the same source can be effective when the first course has failed.
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- 1998
82. A european perspective on haematopoietic growth factors in haemato-oncology : report of an expert meeting of the EORTC
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Heinz Ludwig, H. Zwierzina, A.J. Croockewit, T. de Witte, W. Lange, Roland Mertelsmann, Mario Bargetzi, Matti Aapro, J. Crown, R. Willemze, M.H. Bronchud, Giovanni Martinelli, A. Gratwohl, V. Nuessler, and Zittoun R
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Cancer Research ,medicine.medical_specialty ,Neutropenia ,Dose-Response Relationship, Immunologic ,Hematopoietic Cell Growth Factors ,Granulocyte Colony-Stimulating Factor ,Medicine ,Humans ,Tumor pathology ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Erythropoietin ,Leukemia ,Hematopoietic cell ,business.industry ,Hematopoietic Stem Cell Transplantation ,Granulocyte-Macrophage Colony-Stimulating Factor ,Anemia ,Tumor pathologie ,Surgery ,Anemia, Sideroblastic ,Oncology ,The influence of hematopoietic growth factors on growth and cell kinetics of circulating hematopoietic stem cells in patients with lymphoproliferative malignancies ,Family medicine ,Myelodysplastic Syndromes ,business ,De invloed van hematopoietische groeifactoren op groeipotentie en celkinetiek van circulerende hemato-poietische voorlopercellen - Abstract
Contains fulltext : 25507___.PDF (Publisher’s version ) (Open Access)
- Published
- 1997
83. [Pitfalls and challenges of the preanalytical phase in hematology]
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Adriana, Méndez, Mario, Bargetzi, Andreas, Huber, and Nathan, Cantoni
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Blood Specimen Collection ,Hematologic Tests ,Humans ,Hematology ,Artifacts - Abstract
In the last few decades we have seen a significant decrease in the rates of analytical errors in clinical laboratories. The test performances have improved, new parameters have been introduced, as well as internal and external quality controls have been used for the monitoring of accuracy. Currently available evidence demonstrates that the pre- and post-analytical steps show higher error rates (up to 70 % of all errors) than the analytical phase. Recognition of the weak points of the preanalytical phase and search for appropriate solutions in case of discrepancies will finally help to lead to the correct therapeutic strategy. In order to avoid problems in the preanaytical phase in hematology it is very important to consider some essential issues. The patients must be identified in appropriate form, the blood collection for the requested tests must be made using the appropriate tubes in the specified sequence and the samples must be transported to the lab at the right temperature and on time to be analysed. In case of special tests additional information for the lab is very important for the interpretation of the results. In case of unexpected results the lab should contact the responsible physician in order to look for an adequate explanation for the abnormal findings. With help of several cases of the daily haematology routine we want to point out some preanalytical problems.Um präanalytische Fehler zu vermeiden, sind bereits vor der Blutentnahme einige Punkte zu beachten. Eine korrekte Identifikation des Patienten, bereitstellen der für die gewünschte Analyse richtigen Entnahmeröhrchen, die dann korrekt beschriftet und in der richtigen Reihenfolge abgenommen werden, sowie das Einhalten der entsprechenden Entnahme- und Transporttemperaturen sind Grundvoraussetzung für die nachfolgenden Untersuchungen im Labor. Ebenfalls, insbesondere bei Spezialanalysen, ist die Weitergabe von Zusatzinformationen über den Patienten für die Interpretation der erhobenen Resultate entscheidend. Das Labor wiederum sollte bei unklaren Laborbefunden den Kontakt mit dem Kliniker suchen, um eine Erklärung der unerwarteten Resultate anzustreben.
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- 2013
84. Optimizing triage and hospitalization in adult general medical emergency patients: the triage project
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Sebastian Haubitz, Alexander Kutz, Mario Bargetzi, Pierre Hausfater, Zeljka Caldara, Pasqualina Perrig-Chiello, Andreas R. Huber, Devendra Amin, Eva Grolimund, Barbara Reutlinger, Philipp Schuetz, Stefanie von Felten, Petra Schäfer-Keller, Ursula Schild, Katharina Regez, Lukas Fässler, Krassen Nedeltchev, Sabina De Geest, Timo Kahles, Ulrich Buergi, Beat Mueller, Antoinette Conca, Gabrielle Sauvin, and Andriy Zhydkov
- Subjects
Adult ,Post-acute care needs ,medicine.medical_specialty ,Vital signs ,610 Medicine & health ,000 Computer science, knowledge & systems ,Manchester triage system ,law.invention ,Study Protocol ,Quality of life (healthcare) ,law ,Surveys and Questionnaires ,Health care ,Humans ,Medicine ,Prospective Studies ,Early discharge ,business.industry ,Medical record ,Biomarker ,Emergency department ,medicine.disease ,Triage ,Intensive care unit ,Hospitalization ,Observational Studies as Topic ,Emergency medicine ,Emergency Medicine ,Medical emergency ,Emergency Service, Hospital ,150 Psychology ,business ,Algorithms ,Switzerland - Abstract
Background Patients presenting to the emergency department (ED) currently face inacceptable delays in initial treatment, and long, costly hospital stays due to suboptimal initial triage and site-of-care decisions. Accurate ED triage should focus not only on initial treatment priority, but also on prediction of medical risk and nursing needs to improve site-of-care decisions and to simplify early discharge management. Different triage scores have been proposed, such as the Manchester triage system (MTS). Yet, these scores focus only on treatment priority, have suboptimal performance and lack validation in the Swiss health care system. Because the MTS will be introduced into clinical routine at the Kantonsspital Aarau, we propose a large prospective cohort study to optimize initial patient triage. Specifically, the aim of this trial is to derive a three-part triage algorithm to better predict (a) treatment priority; (b) medical risk and thus need for in-hospital treatment; (c) post-acute care needs of patients at the most proximal time point of ED admission. Methods/design Prospective, observational, multicenter, multi-national cohort study. We will include all consecutive medical patients seeking ED care into this observational registry. There will be no exclusions except for non-adult and non-medical patients. Vital signs will be recorded and left over blood samples will be stored for later batch analysis of blood markers. Upon ED admission, the post-acute care discharge score (PACD) will be recorded. Attending ED physicians will adjudicate triage priority based on all available results at the time of ED discharge to the medical ward. Patients will be reassessed daily during the hospital course for medical stability and readiness for discharge from the nurses and if involved social workers perspective. To assess outcomes, data from electronic medical records will be used and all patients will be contacted 30 days after hospital admission to assess vital and functional status, re-hospitalization, satisfaction with care and quality of life measures. We aim to include between 5000 and 7000 patients over one year of recruitment to derive the three-part triage algorithm. The respective main endpoints were defined as (a) initial triage priority (high vs. low priority) adjudicated by the attending ED physician at ED discharge, (b) adverse 30 day outcome (death or intensive care unit admission) within 30 days following ED admission to assess patients risk and thus need for in-hospital treatment and (c) post acute care needs after hospital discharge, defined as transfer of patients to a post-acute care institution, for early recognition and planning of post-acute care needs. Other outcomes are time to first physician contact, time to initiation of adequate medical therapy, time to social worker involvement, length of hospital stay, reasons for discharge delays, patient’s satisfaction with care, overall hospital costs and patients care needs after returning home. Discussion Using a reliable initial triage system for estimating initial treatment priority, need for in-hospital treatment and post-acute care needs is an innovative and persuasive approach for a more targeted and efficient management of medical patients in the ED. The proposed interdisciplinary , multi-national project has unprecedented potential to improve initial triage decisions and optimize resource allocation to the sickest patients from admission to discharge. The algorithms derived in this study will be compared in a later randomized controlled trial against a usual care control group in terms of resource use, length of hospital stay, overall costs and patient’s outcomes in terms of mortality, re-hospitalization, quality of life and satisfaction with care. Trial registration ClinicalTrials.gov Identifier, NCT01768494
- Published
- 2013
85. Haematopoietic stem cell transplantation: activity in Switzerland compared with surrounding European countries
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Thomas Pabst, Yves Chalandon, Kurt Leibundgut, Michel A. Duchosal, Mario Bargetzi, Christoph Bucher, Grazia Nicoloso de Faveri, Alois Gratwohl, Urs Schanz, Sbst, Urs Hess, Martin Stern, Christoph Renner, Georg Stussi, Jakob Passweg, Tayfun Güngör, Hulya Ozsahin, Helen Baldomero, SBST (Swiss Blood Stem Cell Transplantation Group), University of Zurich, and Passweg, J R
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Blood stem cell ,Lymphoma ,Hemoglobinuria, Paroxysmal ,Hemoglobinuria, Paroxysmal/surgery ,2700 General Medicine ,0302 clinical medicine ,Registries ,Bone Marrow Diseases ,ddc:616 ,education.field_of_study ,ddc:618 ,Leukemia ,Population size ,Hematopoietic Stem Cell Transplantation ,Anemia, Aplastic ,General Medicine ,Tissue Donors ,Tissue Donors/statistics & numerical data ,3. Good health ,Europe ,Haematopoiesis ,surgical procedures, operative ,030220 oncology & carcinogenesis ,Cord blood ,Stem cell ,Switzerland ,medicine.medical_specialty ,Population ,610 Medicine & health ,Autoimmune Diseases/surgery ,Autoimmune Diseases ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,education ,Health Care Surveys ,Hematopoietic Stem Cell Transplantation/methods ,Hematopoietic Stem Cell Transplantation/statistics & numerical data ,Leukemia/surgery ,Lymphoma/surgery ,business.industry ,Bone Marrow Failure Disorders ,Surgery ,Transplantation ,Institutional repository ,Hematopoietic Stem Cell Transplantation/methods/statistics & numerical data/utilization ,10036 Medical Clinic ,10032 Clinic for Oncology and Hematology ,business ,030215 immunology - Abstract
Haematopoietic stem cell transplantation (HSCT) is a highly specialised procedure used to treat malignancies of the lymphohaematopoietic system as well as some acquired and inherited disorders of the blood. This analysis by the Swiss Blood Stem Cell Transplantation Group, based on data from 2008-2011, describes, treatment rates in Switzerland for specific indications and compares this with data from Germany, France, Italy and the Netherlands, corrected for the size of the population. Differences in transplant rates, in rates for particular indications, and in the use of specific transplant technologies such as use of unrelated donors, use of cord blood or mismatched family donors are described. These data are put in correlation with donor availability from international registries and with number of transplant teams and number of procedures per team all corrected for population size.
- Published
- 2013
86. Deregulated Expression of EVI1 Defines a Poor Prognostic Subset of MLL-Rearranged Acute Myeloid Leukemias: A Study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group
- Author
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Michael Lübbert, Karina Eiwen, Gerrit Jan Schuurhuis, Brigitte Schlegelberger, Claudia Erpelinck, Jan Engelmann, Arnold Ganser, Veronika Rockova, Hartmut Döhner, Mario Bargetzi, Ulrich Germing, H. Berna Beverloo, Ruud Delwel, Peter Vandenberghe, Peter J. M. Valk, Veronica Teleanu, Stefan Gröschel, Ingo G.H. Schmidt-Wolf, Richard F. Schlenk, Jürgen Krauter, Bob Löwenberg, Marije Havermans, Edo Vellenga, Leo F. Verdonck, Thomas Pabst, Gert J. Ossenkoppele, Gregor Verhoef, Michael W.M. Kühn, Konstanze Döhner, Hematology laboratory, Hematology, CCA - Disease profiling, Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), Epidemiology, and Clinical Genetics
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Oncology ,Male ,Cancer Research ,Myeloid ,Translocation, Genetic ,0302 clinical medicine ,hemic and lymphatic diseases ,Medicine ,ADULT PATIENTS ,Prospective Studies ,Acute myeloid leukemias ,Gene Rearrangement ,0303 health sciences ,ABNORMALITIES ,Remission Induction ,Myeloid leukemia ,Middle Aged ,Prognosis ,3. Good health ,DNA-Binding Proteins ,Survival Rate ,MLL gene rearrangements ,Leukemia ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,TRIAL ,Female ,Viral integration ,Chromosomes, Human, Pair 9 ,Myeloid-Lymphoid Leukemia Protein ,Adult ,medicine.medical_specialty ,Adolescent ,MLL-AF9 ,03 medical and health sciences ,Young Adult ,Internal medicine ,Proto-Oncogenes ,Cooperative group ,Humans ,60 YEARS OLD ,TRANSLOCATIONS ,neoplasms ,030304 developmental biology ,Aged ,Neoplasm Staging ,Chromosome Aberrations ,TET2 ,MUTATIONS ,business.industry ,Chromosomes, Human, Pair 11 ,Gene rearrangement ,Histone-Lysine N-Methyltransferase ,medicine.disease ,GENE ,TRANSFORMATION ,MDS1 and EVI1 Complex Locus Protein ,Karyotyping ,Immunology ,business ,Follow-Up Studies ,Transcription Factors - Abstract
Purpose To evaluate the prognostic value of ecotropic viral integration 1 gene (EVI1) overexpression in acute myeloid leukemia (AML) with MLL gene rearrangements. Patients and Methods We identified 286 patients with AML with t(11q23) enrolled onto German-Austrian Acute Myeloid Leukemia Study Group and Dutch-Belgian-Swiss Hemato-Oncology Cooperative Group prospective treatment trials. Material was available from 177 AML patients for EVI1 expression analysis. Results We divided 286 MLL-rearranged AMLs into three subgroups: t(9;11)(p22;q23) (44.8%), t(6;11)(q27;q23) (14.7%), and t(v;11q23) (40.5%). EVI1 overexpression (EVI1+) was found in 45.8% of all patients with t(11q23), with t(6;11) showing the highest frequency (83.9%), followed by t(9;11) at 40.0%, and t(v;11q23) at 34.8%. Concurrent gene mutations were rare or absent in all three subgroups. Within all t(11q23) AMLs, EVI1+ was the sole prognostic factor, predicting for inferior overall survival (OS; hazard ratio [HR], 2.06; P = .003), relapse-free survival (HR, 2.28; P = .002), and event-free survival (HR, 1.79; P = .009). EVI1+ AMLs with t(11q23) in first complete remission (CR) had a significantly better outcome after allogeneic transplantation compared with other consolidation therapies (5-year OS, 54.7% v 0%; Mantel-Byar, P = .0006). EVI1− t(9;11) AMLs had lower WBC counts, more commonly FAB M5 morphology, and frequently had additional trisomy 8 (39.6%; P < .001). Among t(9;11) AMLs, EVI1+ again was the sole independent adverse prognostic factor for survival. Conclusion Deregulated EVI1 expression defines poor prognostic subsets among AML with t(11q23) and AML with t(9;11)(p22;q23). Patients with EVI1+ MLL-rearranged AML seem to benefit from allogeneic transplantation in first CR.
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- 2013
87. High Prognostic Impact of Flow Cytometric Minimal Residual Disease Detection in Acute Myeloid Leukemia: Data From the HOVON/SAKK AML 42A Study
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Johan Maertens, Leo F. Verdonck, Georgine E. de Greef, Wim L.J. van Putten, Okke de Weerdt, Bob Löwenberg, Rik A. Brooimans, Alexander N Snel, Nancy Boeckx, Marie-Christiane Vekemans, Peter C. Huijgens, Urs Schanz, Thomas Pabst, Angèle Kelder, Vincent H.J. van der Velden, Bart J. Biemond, Gert J. Ossenkoppele, Yvonne J M Oussoren, Yves Chalandon, Marie-Cecile Legdeur, Urs Hess, Mario Bargetzi, J. Slomp, Peter J. M. Valk, P. W. Wijermans, Michel van Gelder, Frank Preijers, Gerrit Jan Schuurhuis, Monique Terwijn, Jan W. Gratama, Mojca Jongen-Lavrecic, Angelika M. Dräger, Willemijn J Scholten, Jürgen Kuball, Carlos Graux, Jakob Passweg, Hematology, Immunology, Medical Oncology, University of Zurich, Schuurhuis, G J, AII - Amsterdam institute for Infection and Immunity, CCA -Cancer Center Amsterdam, Clinical Haematology, Interne Geneeskunde, MUMC+: MA Hematologie (9), RS: GROW - School for Oncology and Reproduction, Hematology laboratory, and CCA - Innovative therapy
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Oncology ,Male ,Cancer Research ,Neoplasm, Residual ,Myeloid ,0302 clinical medicine ,hemic and lymphatic diseases ,Granulocyte Colony-Stimulating Factor ,1306 Cancer Research ,Granulocyte Colony-Stimulating Factor/administration & dosage ,ddc:616 ,Remission Induction ,Myeloid leukemia ,Induction Chemotherapy ,Middle Aged ,Flow Cytometry ,Prognosis ,3. Good health ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,2730 Oncology ,Sample collection ,Adult ,medicine.medical_specialty ,Adolescent ,Context (language use) ,610 Medicine & health ,Neoplasm Recurrence, Local/diagnosis ,03 medical and health sciences ,Induction Chemotherapy/methods ,Young Adult ,SDG 3 - Good Health and Well-being ,Translational research [ONCOL 3] ,Internal medicine ,medicine ,Consolidation Chemotherapy/methods ,Humans ,Proportional Hazards Models ,Leukemia, Myeloid, Acute/diagnosis/drug therapy ,business.industry ,Induction chemotherapy ,Neoplasm, Residual/diagnosis ,medicine.disease ,Minimal residual disease ,Flow Cytometry/methods ,Consolidation Chemotherapy ,Clinical trial ,body regions ,Immunology ,10032 Clinic for Oncology and Hematology ,Neoplasm Recurrence, Local ,business ,030215 immunology - Abstract
Purpose Half the patients with acute myeloid leukemia (AML) who achieve complete remission (CR), ultimately relapse. Residual treatment-surviving leukemia is considered responsible for the outgrowth of AML. In many retrospective studies, detection of minimal residual disease (MRD) has been shown to enable identification of these poor-outcome patients by showing its independent prognostic impact. Most studies focus on molecular markers or analyze data in retrospect. This study establishes the value of immunophenotypically assessed MRD in the context of a multicenter clinical trial in adult AML with sample collection and analysis performed in a few specialized centers. Patients and Methods In adults (younger than age 60 years) with AML enrolled onto the Dutch-Belgian Hemato-Oncology Cooperative Group/Swiss Group for Clinical Cancer Research Acute Myeloid Leukemia 42A study, MRD was evaluated in bone marrow samples in CR (164 after induction cycle 1, 183 after cycle 2, 124 after consolidation therapy). Results After all courses of therapy, low MRD values distinguished patients with relatively favorable outcome from those with high relapse rate and adverse relapse-free and overall survival. In the whole patient group and in the subgroup with intermediate-risk cytogenetics, MRD was an independent prognostic factor. Multivariate analysis after cycle 2, when decisions about consolidation treatment have to be made, confirmed that high MRD values (> 0.1% of WBC) were associated with a higher risk of relapse after adjustment for consolidation treatment time-dependent covariate risk score and early or later CR. Conclusion In future treatment studies, risk stratification should be based not only on risk estimation assessed at diagnosis but also on MRD as a therapy-dependent prognostic factor.
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- 2013
88. Quantitative Monitoring of BCR – ABL Transcript – Suggestion of a Simplified Approach Considering Inaccuracy of Measurement and Calibration
- Author
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Christian Stricker, Benno Röthlisberger, Mario Bargetzi, Martin Hergersberg, Roberto Herklotz, and Andreas R. Huber
- Subjects
Cancer Research ,Serial dilution ,Reverse Transcriptase Polymerase Chain Reaction ,Calibration curve ,Sample (material) ,Total rna ,Fusion Proteins, bcr-abl ,Routine laboratory ,Hematology ,Reference Standards ,Biology ,Bioinformatics ,Sensitivity and Specificity ,Peripheral blood ,Standard curve ,Oncology ,Research Design ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Calibration ,Humans ,RNA, Neoplasm ,Algorithm - Abstract
According to standard-protocols, real time quantitative RT – PCR (RQ – PCR) for quantification of BCR – ABL fusion transcripts in CML patients is performed with the construction of a standard curve for each run, each sample is analyzed at least in duplicate and 10 – 40 ml peripheral blood are processed. This approach is appropriate for a research laboratory, but is not suitable for a routine laboratory setting. We show that the calibration curve based on the common 5 dilution standards (between 10 and 10 6 copies) is strongly influenced by the large variability of the measurements below 100 copies of the gene. In other words, including a standard with 10 copies is a source of error, which cannot be reduced through the construction of a standard curve with each run. Adding additional dilutions between 10 and 100 copies to the standard curve, the variance of the obtained curve is much reduced. As a conclusion, it is unnecessary to construct a calibration curve with each run since only negligible inaccuracy of calibration is added to the inaccuracy of measurement. Running of the samples in duplicate seems unnecessary since the inaccuracy of the method can be correctly estimated. Finally, we propose a standardized collection and isolation of total RNA from only 2.5 ml blood using an integrated system, which allows RNA stabilization for up to 5 days and provides snapshots of BCR – ABL fusion transcripts with higher accuracy than with non-stabilized blood samples.
- Published
- 2004
89. Recombinant human interleukin-3 in refractory severe aplastic anaemia: a phase I/II trial
- Author
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Agnès Devergie, Bruno Speck, André Tichelli, Mario Bargetzi, Catherine Nissen, Alois Gratwohl, A. Wodnar-Filipowicz, Eliane Gldckman, Helene Esperou, and Janusz Kabata
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Microgram ,medicine.medical_treatment ,Hemorrhage ,Infections ,Gastroenterology ,Antibodies ,Leukocyte Count ,Refractory ,Internal medicine ,Humans ,Medicine ,Platelet ,Prospective Studies ,Aplastic anemia ,Adverse effect ,Platelet Count ,business.industry ,Anemia, Aplastic ,Hematology ,medicine.disease ,Recombinant Proteins ,Surgery ,Cytokine ,Tolerability ,Female ,Interleukin-3 ,business ,Dyskeratosis congenita - Abstract
In a prospective open-labelled phase I/II trial we tested efficacy and tolerability of recombinant human interleukin-3 (rhIL-3) alone in patients with refractory severe aplastic anaemia (SAA). 15 patients with idiopathic (12 patients) or secondary (one post-hepatitic, one drug induced, one dyskeratosis congenita) SAA, refractory or relapsing after one to three courses of antilymphocyte globulin were included. 14 patients were transfusion dependent (RBC 14, platelet 12). RhIL-3 was planned for three patients each at five escalating dose levels of 1, 2, 4, 8 and 16 micrograms/kg, given daily as 24 h continuous infusion for 21 d. RhIL-3 was prematurely withdrawn at days 10 and 11 for adverse events in two patients. 9/15 patients showed an increase in WBC; 2/6 at the 1-2 micrograms/kg and 7/9 at the 4-16 micrograms/kg level, but no sustained effects were seen. No patient showed a response in platelet counts. Additionally, platelet and RBC transfusion requirements were unchanged pre and post study. All patients experienced one or more adverse event, mainly fever (15 patients), bleeding (nine patients), and headache (six patients). Occurrence of adverse events was dose related and the maximum tolerated dose was reached with 8 micrograms/kg. Five patients suffered serious adverse events. RhIL-3 as single growth factor and used alone is of minimal benefit in severe aplastic anaemia.
- Published
- 1995
90. Therapieleitfaden maligne Lymphome
- Author
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Mario Bargetzi and Mario Bargetzi
- Abstract
Die Therapie maligner Lymphome unterliegt einem ständigen Wandel. Die Frage nach den optimalen Therapie-Schemata und der geeigneten Kombinationstherapie wird jedoch noch diskutiert. Das vorliegende Buch gibt einen Überblick über die Pathologie, Diagnostik und Einteilung von Lymphomerkrankungen. Es fasst die aktuellen Strategien zur Behandlung der einzelnen Lymphomentitäten zusammen und gibt einen Ausblick auf zukünftige Therapieansätze.
- Published
- 2011
91. A multicenter phase II trial (SAKK 36/06) of single-agent Everolimus(RAD001) in patients with relapsed or refractory mantle cell lymphoma
- Author
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Christoph Renner, Emmanuel Gyan, Pier Luigi Zinzani, Pierre-Yves Dietrich, Remy Gressin, Krimo Bouabdallah, Peter Brauchli, Walter Mingrone, Andreas Lohri, Mario Bargetzi, Felicitas Hitz, Nicolas Ketterer, Dirk Klingbiel, Andreas Trojan, Giovanni Martinelli, Sergio Cogliatti, Francesco Bertoni, Michele Ghielmini, Christine Biaggi, Renner C, Zinzani P.L., Gressin R, Klingbiel D, Dietrich PY, Hitz F, Bargetzi M, Mingrone W, Martinelli G, Trojan A, Bouabdallah K, Lohri A, Gyan E, Biaggi C, Cogliatti S, Bertoni F, Ghielmini M, Brauchli P, Ketterer N., Swiss SAKK, French GOELAMS group from European Mantle Cell Lymphoma Network, University of Zurich, and Renner, C
- Subjects
Male ,medicine.medical_treatment ,2720 Hematology ,Lymphoma, Mantle-Cell ,Gastroenterology ,Recurrence ,Clinical endpoint ,Prospective Studies ,ddc:616 ,Aged, 80 and over ,TOR Serine-Threonine Kinases/antagonists & inhibitors ,TOR Serine-Threonine Kinases ,Remission Induction ,Hematology ,Middle Aged ,Neoplasm Proteins ,Refractory Mantle Cell Lymphoma ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Neoplasm Proteins/antagonists & inhibitors ,mantle cell lymphoma ,610 Medicine & health ,Lymphoma, Mantle-Cell/drug therapy/mortality ,Neutropenia ,Disease-Free Survival ,Drug Administration Schedule ,Multicenter trial ,Internal medicine ,Protein Kinase Inhibitors/administration & dosage/adverse effects ,medicine ,Humans ,Protein Kinase Inhibitors ,RAD001 ,Aged ,Neoplasm Staging ,Sirolimus ,Chemotherapy ,Everolimus ,business.industry ,medicine.disease ,everolimus ,Sirolimus/administration & dosage/adverse effects/analogs & derivatives ,Surgery ,relapsed ,refractory ,10032 Clinic for Oncology and Hematology ,Mantle cell lymphoma ,Original Articles and Brief Reports ,business - Abstract
Background Mantle cell lymphoma accounts for 6% of all B-cell lymphomas and is generally incurable. It is characterized by the translocation t(11;14) leading to cyclin D1 over-expression. Cyclin D1 is downstream of the mammalian target of rapamycin threonine kinase and can be effectively blocked by mammalian target of rapamycin inhibitors. We set out to examine the single agent activity of the orally available mammalian target of rapamycin inhibitor everolimus in a prospective, multicenter trial in patients with relapsed or refractory mantle cell lymphoma ([NCT00516412][1]). Design and Methods Eligible patients who had received a maximum of three prior lines of chemotherapy were given everolimus 10 mg for 28 days (one cycle) for a total of six cycles or until disease progression. The primary endpoint was the best objective response. Adverse reactions, progression-free survival and molecular response were secondary endpoints. Results Thirty-six patients (35 evaluable) were enrolled and treatment was generally well tolerated with Common Terminology Criteria grade ≥3 adverse events (>5%) including anemia (11%), thrombocytopenia (11%) and neutropenia (8%). The overall response rate was 20% (95% CI: 8–37%) with two complete remissions and five partial responses; 49% of the patients had stable disease. At a median follow-up of 6 months, the median progression-free survival was 5.5 months (95% CI: 2.8–8.2) overall and 17.0 (6.4–23.3) months for 18 patients who received six or more cycles of treatment. Three patients achieved a lasting complete molecular response, as assessed by polymerase chain reaction analysis of peripheral blood. Conclusions Everolimus as a single agent is well tolerated and has anti-lymphoma activity in relapsed or refractory mantle cell lymphoma. Further studies of everolimus in combination with chemotherapy or as a single agent for maintenance treatment are warranted. ([Clinicaltrials.gov][2] identifier: [NCT00516412][1]) [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00516412&atom=%2Fhaematol%2F97%2F7%2F1085.atom [2]: http://Clinicaltrials.gov
- Published
- 2012
92. Monoklonale Gammopathie in der hausärztlichen Praxis
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Mario Bargetzi
- Subjects
Oncology ,medicine.medical_specialty ,Monoclonal gammopathy ,business.industry ,Internal medicine ,medicine ,Interdisciplinary communication ,General Medicine ,Cooperative behavior ,medicine.symptom ,medicine.disease ,business ,Multiple myeloma - Published
- 2015
93. Recommandations pour le diagnostic et le traitement de la leucémie lymphoïde chronique en Suisse. 1re partie
- Author
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Michel A. Duchosal, M Gregor, Jeroen S. Goede, W Korte, Mario Bargetzi, Dominik Heim, C Helg, Max Solenthaler, R Zenhäsern, and Leda Leoncini
- Published
- 2011
94. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia
- Author
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Edo, Vellenga, Wim, van Putten, Gert J, Ossenkoppele, Leo F, Verdonck, Matthias, Theobald, Jan J, Cornelissen, Peter C, Huijgens, Johan, Maertens, Alois, Gratwohl, Ron, Schaafsma, Urs, Schanz, Carlos, Graux, Harry C, Schouten, Augustin, Ferrant, Mario, Bargetzi, Martin F, Fey, Bob, Löwenberg, M, Van Marwijk Kooy, Hematology, CCA - Innovative therapy, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), Cardiology, Interne Geneeskunde, RS: GROW - School for Oncology and Reproduction, Amsterdam institute for Infection and Immunity, Cancer Center Amsterdam, Clinical Haematology, University of Zurich, and Vellenga, E
- Subjects
Oncology ,1303 Biochemistry ,medicine.medical_treatment ,2720 Hematology ,Hematopoietic stem cell transplantation ,Biochemistry ,1307 Cell Biology ,Antineoplastic Combined Chemotherapy Protocols ,Prospective Studies ,Etoposide ,ACUTE MYELOGENOUS LEUKEMIA ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Hematology ,1ST COMPLETE REMISSION ,Middle Aged ,COLONY-STIMULATING FACTOR ,Prognosis ,Combined Modality Therapy ,Chemotherapy regimen ,HIGH-DOSE CYTARABINE ,Leukemia, Myeloid, Acute ,Treatment Outcome ,medicine.drug ,POSTREMISSION THERAPY ,Adult ,medicine.medical_specialty ,Adolescent ,Cyclophosphamide ,Immunology ,610 Medicine & health ,Antineoplastic Agents ,Transplantation, Autologous ,Young Adult ,DAUNORUBICIN ,Internal medicine ,medicine ,Humans ,Antineoplastic Agents, Alkylating ,Busulfan ,2403 Immunology ,Chemotherapy ,business.industry ,MUTATIONS ,Consolidation Chemotherapy ,Cell Biology ,ADULTS ,Antineoplastic Agents, Phytogenic ,BONE-MARROW-TRANSPLANTATION ,INTENSIVE CHEMOTHERAPY ,Surgery ,Transplantation ,10032 Clinic for Oncology and Hematology ,Mitoxantrone ,business - Abstract
We report the results of a prospective, randomized phase 3 trial evaluating autologous peripheral blood stem cell transplantation (ASCT) versus intensive consolidation chemotherapy in newly diagnosed AML patients in complete remission (CR1). Patients with AML (16-60 years) in CR1 after 2 cycles of intensive chemotherapy and not eligible for allogeneic SCT were randomized between intensive chemotherapy with etoposide and mitoxantrone or ASCT ater high-dose cyclophosphamide and busulfan. Of patients randomized (chemotherapy, n = 259; ASCT, n = 258), more than 90% received their assigned treatment. The 2 groups were comparable with regard to prognostic factors. The ASCT group showed a markedly reduced relapse rate (58% vs 70%, P = .02) and better relapse-free survival at 5 years (38% vs 29%, P = .065, hazard ratio = 0.82; 95% confidence interval, 0.66-1.1) with nonrelapse mortality of 4% versus 1% in the chemotherapy arm (P = .02). Overall survival was similar (44% vs 41% at 5 years, P = .86) because of more opportunities for salvage with second-line chemotherapy and stem cell transplantation in patients relapsing on the chemotherapy arm. This large study shows a relapse advantage for ASCT as postremission therapy but similar survival because more relapsing patients on the chemotherapy arm were salvaged with a late transplantation for relapse. This trial is registered at www.trialregister.nl as #NTR230 and #NTR291.
- Published
- 2011
95. Diagnose und Behandlung der primären Immun-Thrombozytopenie
- Author
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A Schmidt, P Keller, A Rüfer, J Goede, P Imbach, Ulrich Mey, U Hess, A AngelilloScherrer, T Kühne, Mario Bargetzi, and S MachPascual
- Published
- 2010
96. Diagnostic et prise en charge de la Thrombocytopénie immune primaire
- Author
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A Schmidt, S MachPascual, P Keller, Ulrich Mey, Jeroen S. Goede, Thomas Kühne, Urs Hess, Mario Bargetzi, A AngelilloScherrer, A Rüfer, and P Imbach
- Abstract
La thrombocytopenie immune primaire (ITP) est une affection auto-immune acquise avec diminution de la survie des plaquettes et perturbation de la production plaquettaire. Il n'existe aucun test clinique simple permettant de prouver la nature auto-immune de l'affection. Pour cette raison, il s'agit presque toujours d'un diagnostic par exclusion d'autres causes. Bien que les plaquettes soient souvent inferieures a 10 x 109/l lors de la presentation initiale, la tendance hemorragique est etonnamment moderee chez la majorite des patients. Le traitement initial fait toujours appel aux corticosteroides, combines a des immunoglobulines intraveineuses et a des transfusions de plaquettes dans les formes compliquees avec hemorragies significatives. Chez l'enfant, la maladie est souvent induite par des infections virales et son evolution est benigne et spontanement regressive dans la majorite des cas. Chez l'adulte, la maladie est plus souvent persistante ou chroniquement recidivante, et le taux de plaquettes se situe souvent a un taux suffisant pour prevenir des hemorragies spontanees. Seule une faible proportion de patients souffre d'une thrombocytopenie severe prolongee accompagnee de saignements reguliers avec risque d'hemorragies potentiellement fatales. C'est probablement ce groupe de patients restreint qui tirera surtout profit des nouvelles options therapeutiques telles que les agonistes du recepteur de la thrombopoietine. A la lumiere de ces nouvelles possibilites, un groupe d'hematologues suisses s'est reuni pour elaborer des directives concernant la prise en charge de l'ITP conformement aux besoins et aux habitudes de notre pays.
- Published
- 2010
97. Integrating novel agents into multiple myeloma treatment - current status in Switzerland and treatment recommendations
- Author
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Ulrich Mey, Urs Hess, Michael Gregor, Thomas Pabst, Thomas Matthes, Dominik Heim, Mario Bargetzi, J. Gmur, Nicolas Ketterer, Christian Taverna, Erika Lerch, Daniel Betticher, and Christoph Renner
- Subjects
medicine.medical_specialty ,Plasma Cells ,Antineoplastic Agents ,Drug Administration Schedule ,Bortezomib ,Bone Marrow ,medicine ,Humans ,Combined Modality Therapy ,Intensive care medicine ,Lenalidomide ,Multiple myeloma ,Aged ,Bone Marrow Transplantation ,Evidence-Based Medicine ,Dose-Response Relationship, Drug ,business.industry ,Biopsy, Needle ,Treatment options ,General Medicine ,Evidence-based medicine ,Middle Aged ,medicine.disease ,Boronic Acids ,Thalidomide ,Surgery ,Drug Resistance, Neoplasm ,Novel agents ,Pyrazines ,Retreatment ,Neoplasm Recurrence, Local ,Multiple Myeloma ,business ,Switzerland ,medicine.drug - Abstract
The treatment of multiple myeloma has undergone significant changes in the recent past. The arrival of novel agents, especially thalidomide, bortezomib and lenalidomide, has expanded treatment options and patient outcomes are improving significantly. This article summarises the discussions of an expert meeting which was held to debate current treatment practices for multiple myeloma in Switzerland concerning the role of the novel agents and to provide recommendations for their use in different treatment stages based on currently available clinical data. Novel agent combinations for the treatment of newly diagnosed, as well as relapsed multiple myeloma are examined. In addition, the role of novel agents in patients with cytogenetic abnormalities and renal impairment, as well as the management of the most frequent side effects of the novel agents are discussed. The aim of this article is to assist in treatment decisions in daily clinical practice to achieve the best possible outcome for patients with multiple myeloma.
- Published
- 2010
98. Efficacy of rituximab and cladribine in patients with chronic lymphocytic leukemia and feasibility of stem cell mobilization: a prospective multicenter phase II trial (protocol SAKK 34/02)
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Kurt Beretta, Mario Bargetzi, Alicia Rovó, Andreas Himmelmann, Max Solenthaler, Dominik Heim, Peter Brauchli, Reinhard Zenhäusern, Silvia Hanselmann, Jan C. Schuller, Michael Gregor, and Nicolas Leupin
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Transplantation Conditioning ,Cyclophosphamide ,Chronic lymphocytic leukemia ,Nodular Partial Remission ,Neutropenia ,Gastroenterology ,Drug Administration Schedule ,Antibodies, Monoclonal, Murine-Derived ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,medicine ,Humans ,Cladribine ,Aged ,Dose-Response Relationship, Drug ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Antibodies, Monoclonal ,Hematology ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Leukemia, Lymphocytic, Chronic, B-Cell ,Hematopoietic Stem Cell Mobilization ,Surgery ,Leukemia ,Treatment Outcome ,Oncology ,Feasibility Studies ,Rituximab ,Female ,Lymphocytopenia ,business ,medicine.drug - Abstract
This phase II trial investigated rituximab and cladribine in chronic lymphocytic leukemia. Four induction cycles, comprising cladribine (0.1 mg/kg/day days 1-5, cycles 1-4) and rituximab (375 mg/m(2) day 1, cycles 2-4), were given every 28 days. Stem cell mobilization (rituximab 375 mg/m(2) days 1 and 8; cyclophosphamide 4 g/m(2) day 2; and granulocyte colony-stimulating factor 10 microg/kg/day, from day 4) was performed in responders. Of 42 patients, nine achieved complete remission (CR), 15 very good partial remission, and two nodular partial remission (overall response rate 62%). Stem cell mobilization and harvesting (> or = 2 x 10(6) stem cells/kg body weight) were successful in 12 of 20 patients. Rituximab infusion-related adverse events were moderate. The main grade 3/4 adverse events during induction were neutropenia and lymphocytopenia. Rituximab plus cladribine was effective; however, the CR rate was modest and stem cell harvest was impaired in a large number of responding patients.
- Published
- 2010
99. Toll-like receptor 4 gene polymorphism modulates phenotypic expression in patients with hereditary hemochromatosis
- Author
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Beat Müllhaupt, Mario Bargetzi, Martin Hersberger, Pierre-Alexandre Krayenbuehl, Friedrich E. Maly, Georg Schulthess, Kaspar Truninger, and University of Zurich
- Subjects
Adult ,Liver Cirrhosis ,Male ,Heterozygote ,medicine.medical_specialty ,Nod2 Signaling Adaptor Protein ,Penetrance ,610 Medicine & health ,Metacarpophalangeal Joint ,Liver disease ,Internal medicine ,NOD2 ,Humans ,Medicine ,Genetic Predisposition to Disease ,2715 Gastroenterology ,Hemochromatosis Protein ,Receptor ,Genetic Association Studies ,Hemochromatosis ,Retrospective Studies ,Polymorphism, Genetic ,Hepatology ,medicine.diagnostic_test ,business.industry ,Histocompatibility Antigens Class I ,Gastroenterology ,Membrane Proteins ,Middle Aged ,medicine.disease ,Toll-Like Receptor 4 ,Phenotype ,10219 Clinic for Gastroenterology and Hepatology ,Endocrinology ,10036 Medical Clinic ,Toll-Like Receptor 9 ,Hereditary hemochromatosis ,Liver biopsy ,Mutation ,Immunology ,Female ,2721 Hepatology ,Gene polymorphism ,Arthropathy, Neurogenic ,10029 Clinic and Policlinic for Internal Medicine ,business - Abstract
BACKGROUND: Clinical penetrance of hereditary hemochromatosis is highly variable. We hypothesized that it might be modified by factors involved in the cellular immune response, such as toll-like receptors (TLRs) or nucleotide oligomerization domain proteins (NODs). METHODS: Clinical expression of hemochromatosis was assessed as a function of TLR4, TLR9, and NOD2 polymorphisms in 99 homozygous carriers of the HFE C282Y mutation with mild-to-severe iron overload. RESULTS: Thirteen (13%) of the 99 hemochromatosis patients were heterozygous for a TLR4 Asp299Gly polymorphism and 86 (87%) were TLR4 wild-type-only carriers. Clinical expression of hemochromatosis was observed more frequently in carriers of the TLR4 polymorphism (100%) than in TLR4 wild-type carriers (56%, P = 0.002). This was based on higher prevalences of liver disease (92 vs. 45%, P = 0.002) and arthropathy of metacarpophalangeal joints (69 vs. 35%, P = 0.018) in TLR4 polymorphism carriers. The finding was strengthened by the strong association of TLR4 polymorphism with liver fibrosis in the subgroup of 52 patients who underwent a liver biopsy (P = 0.011). The TLR4 polymorphism did, however, not correlate with body iron overload. The study results remained significant in multiple regression analyses after excluding possible confounding effects, such as age, sex, alcohol, or meat intake, and in the subgroup of 84 patients presenting as the first members of their families. CONCLUSION: TLR4 Asp299Gly polymorphism modulates clinical expression in patients with hereditary hemochromatosis. The polymorphism does not correlate with iron overload suggesting that TLR4 plays a role in an inflammatory process arising from toxic effects of iron accumulation.
- Published
- 2010
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100. DV-ICE, intensive induction and early transplantation for adult patients with acute lymphoblastic leukemia: a phase II study
- Author
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Alois Gratwohl, Jakob Passweg, M. Wernli, André Tichelli, Mario Bargetzi, and Christine Dudler
- Subjects
Male ,Hydrocortisone ,medicine.medical_treatment ,Phases of clinical research ,Pilot Projects ,Hematopoietic stem cell transplantation ,Kaplan-Meier Estimate ,Gastroenterology ,Dexamethasone ,Antineoplastic Combined Chemotherapy Protocols ,Prospective Studies ,Treatment Failure ,Prospective cohort study ,Cytarabine/administration & dosage/adverse effects ,Etoposide ,ddc:616 ,Standard treatment ,Cytarabine ,Hematopoietic Stem Cell Transplantation ,Hematology ,General Medicine ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Middle Aged ,Combined Modality Therapy ,Vincristine ,Idarubicin/administration & dosage/adverse effects ,Early Termination of Clinical Trials ,Female ,Methotrexate/administration & dosage/adverse effects ,Vincristine/administration & dosage/adverse effects ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/surgery/*therapy ,Disease-Free Survival ,Young Adult ,Hydrocortisone/administration & dosage/adverse effects ,Internal medicine ,Dexamethasone/administration & dosage/adverse effects ,medicine ,Idarubicin ,Humans ,Aged ,Hematopoietic Stem Cell Transplantation/adverse effects ,business.industry ,Surgery ,Transplantation ,Methotrexate ,Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ,Etoposide/administration & dosage/adverse effects ,business ,Follow-Up Studies - Abstract
OBJECTIVES: Eighty percent of adult patients with acute lymphoblastic leukemia (ALL) achieve a complete remission (CR) but only 30-40% are long term survivors. Best treatment strategies remain to be defined. The role of induction intensity, first remission hematopoietic stem cell transplantation (HSCT) and maintenance chemotherapy continues to be discussed. We tested a strategy of high intensity treatment of short duration followed by HSCT. PATIENTS AND METHODS: This prospective phase II study used induction with DV-ICE followed by immediate allogeneic or autologous HSCT (depending on donor availability) without additional consolidation or maintenance treatment. DV-ICE consisted of dexamethasone, vincristine, idarubicin, etoposide, and conventional dose cytosine arabinoside; HSCT was planned immediately if CR was achieved or after an additional course of intermediate high dose cytosine arabinoside and etoposide for patients with induction failure. A total of 42 consecutive patients between 17 and 67 yr of age (median 43 yr) were enrolled. Of the 42 patients, 57% were male, 76% had B-lineage ALL, 19% T-lineage ALL and two patients biphenotypic ALL. 29% were Ph+; 7% had 11q23 and 45% had a normal karyotype. CNS involvement was found in three patients. RESULTS: Thirty-three patients (79%) achieved a CR, 24 patients after induction I or II and nine patients after rescue HSCT. 31 patients received a HSCT (seven autologous and 24 allogeneic). 11 patients did not receive a HSCT because of early death in nine (treatment toxicity in five, refractory disease in four), one patient refused transplantation, one patient was not suitable. Disease-free survival (DFS) of the entire cohort was 46% (95% CI +/-16%) at 1 yr and 16% (+/-13%) at 5 yr. Overall survival (OS) was 63% (+/-15%) at 1 yr and 23% (+/-15%) at 5 yr, with a median follow-up of surviving patients of 55 (4-136) months. Neither disease subtype, cytogenetic abnormalities nor patient age or gender was significantly associated with survival. CONCLUSIONS: Intensive induction using DV-ICE followed by early transplantation without treatment beyond 4 months failed to improve outcome compared with standard treatment.
- Published
- 2009
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