12 results on '"Schönland, Stefan"'
Search Results
2. Multiple myeloma gammopathies : Eight novel loci implicate shared genetic etiology in multiple myeloma, AL amyloidosis, and monoclonal gammopathy of unknown significance
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Chattopadhyay, Subhayan, Thomsen, Hauke, Weinhold, Niels, Meziane, Iman, Huhn, Stefanie, da Silva Filho, Miguel Inacio, Vodicka, Pavel, Vodickova, Ludmila, Hoffmann, Per, Nöthen, Markus M., Jöckel, Karl-Heinz, Schmidt, Börge, Landi, Stefano, Hajek, Roman, Hallmans, Göran, Pettersson-Kymmer, Ulrika, Ohlsson, Claes, Milani, Paolo, Merlini, Giampaolo, Rowcieno, Dorota, Hawkins, Philip, Hegenbart, Ute, Palladini, Giovanni, Wechalekar, Ashutosh, Schönland, Stefan O., Houlston, Richard, Goldschmidt, Hartmut, Hemminki, Kari, and Försti, Asta
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Medizin - Published
- 2020
3. Leitlinie : ICD10: E85.- : Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen
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Schönland, Stefan, Agis, Hermine, Österreichische Gesellschaft Für Hämatologie & Medizinische Onkologie, Schweizerische Gesellschaft Für Hämatologie, Hegenbart, Ute, Schweizerische Gesellschaft Für Medizinische Onkologie, Nogai, Axel, Schwotzer, Rahel Karen, and Deutsche Gesellschaft Für Hämatologie Und Medizinische Onkologie
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Medizin und Gesundheit - Published
- 2020
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4. Challenges in the management of patients with systemic light chain (AL) amyloidosis during the COVID-19 pandemic
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Kastritis, Efstathios Wechalekar, Ashutosh Schönland, Stefan Sanchorawala, Vaishali Merlini, Giampaolo Palladini, Giovanni Minnema, Monique Roussel, Murielle Jaccard, Arnaud Hegenbart, Ute others
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Health Sciences ,Επιστήμες Υγείας - Published
- 2020
5. Shaping of CD56bri Natural Killer Cells in Patients With Steroid-Refractory/Resistant Acute Graft-vs.-Host Disease via Extracorporeal Photopheresis
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Ni, Ming, Wang, Lei, Yang, Mingya, Neuber, Brigitte, Sellner, Leopold, Hückelhoven-Krauss, Angela, Schubert, Maria-Luisa, Luft, Thomas, Hegenbart, Ute, Schönland, Stefan, Wuchter, Patrick, Chen, Bao-an, Eckstein, Volker, Krüger, William, Yerushalmi, Ronit, Beider, Katia, Nagler, Arnon, Müller-Tidow, Carsten, Dreger, Peter, Schmitt, Michael, and Schmitt, Anita
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Immunology ,Immunology and Allergy - Published
- 2019
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6. CD38 as Immunotherapeutic Target in Light Chain Amyloidosis and Multiple Myeloma—Association With Molecular Entities, Risk, Survival, and Mechanisms of Upfront Resistance
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Seckinger, Anja, Hillengass, Jens, Emde, Martina, Beck, Susanne, Kimmich, Christoph, Dittrich, Tobias, Hundemer, Michael, Jauch, Anna, Hegenbart, Ute, Raab, Marc-Steffen, Ho, Anthony D, Schönland, Stefan, Hose, Dirk, Hematology, and Basic (bio-) Medical Sciences
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multiple myeloma ,amyloidosis ,lcsh:Immunologic diseases. Allergy ,alternative splicing ,hematology ,immune system diseases ,hemic and lymphatic diseases ,Immunology ,immunotherapy ,lcsh:RC581-607 ,survival ,CD38 ,Original Research - Abstract
Monoclonal antibodies against the cell surface antigen CD38, e.g., isatuximab, daratumumab, or Mor202, have entered the therapeutic armamentarium in multiple myeloma due to single agent overall response rates of 29 vs. 36 vs. 31%, effectivity in combination regimen, e.g., with lenalidomide or bortezomib plus dexamethasone, and tolerable side effects. Despite clinical use, many questions remain. In this manuscript, we address three of these: first, upfront CD38 target-expression in AL-amyloidosis, monoclonal gammopathy of unknown significance (MGUS), asymptomatic, symptomatic, and relapsed multiple myeloma. Second, relation of CD38-expression to survival, disease stages, molecular entities, and high-risk definitions. Third, alternative splicing or lack of CD38-expression as potential mechanisms of upfront resistance. We assessed CD138-purified plasma cell samples from 196 AL-amyloidosis, 62 MGUS, 259 asymptomatic, 764 symptomatic, and 90 relapsed myeloma patients, including longitudinal pairs of asymptomatic/symptomatic (n = 34) and symptomatic/relapsed myeloma (n = 57) regarding interphase fluorescence in situ hybridization (n = 1,380), CD38-expression by gene expression profiling (n = 1,371), RNA-sequencing (n = 593), and flow cytometry (n = 800). Samples of normal bone marrow plasma cells (n = 10), memory B-cells (n = 9), polyclonal plasmablastic cells (n = 9), and human myeloma cell lines (n = 54) were used as comparators. CD38 was expressed in all malignant plasma cell samples, but significantly lower compared to normal plasma cells with small but significant downregulation in longitudinal sample pairs. Higher CD38 expression was associated with the presence of t(4;14) and high-risk according to the UAMS70-gene score, lower expression was associated with del17p13 and hyperdiploidy in symptomatic myeloma as well as t(11;14) in asymptomatic myeloma. Higher CD38-expression was associated with slower progression to symptomatic and relapsed myeloma and better overall survival in the latter two entities. CD38 expression, t(4;14), del17p13, and gain of 1q21 are independently prognostic in multivariate analysis. By contrast, high CD38-expression is associated with adverse survival in AL-amyloidosis. Regarding mechanisms of upfront anti-CD38-treatment resistance, lack of CD38-expression and alternative splicing of receptor binding-sites could be excluded. Here, of the two protein coding CD38-transcripts CD38-001 (eight-exon, full length) and CD38-005 (truncated), CD38-001 conveyed >97% of reads spanning the respective CD38 splice junction.
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- 2018
7. Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective analysis from the European Society for Blood and Marrow Transplantation (EBMT)
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Schetelig, Johannes, de Wreede, Liesbeth C., Andersen, Niels S., Moreno, Carol, van Gelder, Michel, Vitek, Antonin, Karas, Michal, Michallet, Mauricette, Machaczka, Maciej, Gramatzki, Martin, Beelen, Dietrich, Finke, Jürgen, Delgado, Julio, Volin, Liisa, Passweg, Jakob, Dreger, Peter, Schaap, Nicolaas, Wagner, Eva, Henseler, Anja, van Biezen, Anja, Bornhäuser, Martin, Iacobelli, Simona, Putter, Hein, Schönland, Stefan O., Kröger, Nicolaus, Esteve, Jordi, Ljungman, Per, de Witte, Theo, Stelljes, Matthias, Sierra, Jorge, Socié, Gerard, Ganser, Arnold, Wulf, Gerhard G., Deconinck, Eric, Faber, Edgar, Feguex, Nathalie, Gedde-Dahl, Tobias, Kolbe, Karin, Chalandon, Yves, Krüger, William, Huynh, Anne, Bourhis, Jean Henri, Schouten, Harry, Ribera Santasusana, Josep M., Interne Geneeskunde, MUMC+: MA Hematologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Chalandon, Yves
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Oncology ,Male ,Transplantation Conditioning ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Chronic lymphocytic leukemia ,Medizin ,QUALITY MANAGEMENT-SYSTEM ,Kaplan-Meier Estimate ,risk factor analysis ,GUIDELINES ,Biochemistry ,allogeneic stem cell transplantation ,centre effects ,chronic lymphocytic leukaemia ,frailties ,Transplantation Conditioning / methods ,0302 clinical medicine ,Recurrence ,Risk Factors ,Leukemia, Lymphocytic, Chronic, B-Cell / mortality ,Registries ,Delivery of Health Care / statistics & numerical data ,IBRUTINIB ,ddc:616 ,0303 health sciences ,ALEMTUZUMAB ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Professional Practice ,Hematology ,Middle Aged ,3. Good health ,Europe ,030220 oncology & carcinogenesis ,ABT-199 ,Cohort ,SURVIVAL ,Alemtuzumab ,Female ,Europe / epidemiology ,medicine.drug ,Adult ,medicine.medical_specialty ,Allogeneic transplantation ,Immunology ,Lower risk ,DIAGNOSIS ,Settore MED/01 - Statistica Medica ,03 medical and health sciences ,Leukemia, Lymphocytic, Chronic, B-Cell / therapy ,Hematopoietic Stem Cell Transplantation / methods ,Internal medicine ,medicine ,Humans ,Karnofsky Performance Status ,030304 developmental biology ,Aged ,Retrospective Studies ,business.industry ,Proportional hazards model ,CHRONIC LYMPHOCYTIC-LEUKEMIA ,Retrospective cohort study ,STEM-CELL TRANSPLANTATION ,Cell Biology ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Confidence interval ,Surgery ,Professional Practice / statistics & numerical data ,Transplantation ,business ,Delivery of Health Care ,030215 immunology ,RESPONSES - Abstract
Introduction:Even in the era of novel targeted therapies for the treatment of Chronic Lymphocytic Leukemia (CLL) patients, such as BTK, PI3K and BCL2 inhibitors, allogeneic hematopoietic stem cell transplantations (alloHCT) will remain an important treatment option for a subset of patients with very high risk CLL. The current study focused on the impact of center and procedure-related factors on outcomes after alloHCT, taking into account the impact of patient- and disease-related risk factors. Patients and Methods:Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analyzed. Their data were collected as part of the EBMT CLL Data Quality Initiative. Outcomes of interest were Event-Free Survival (EFS) up to 5 years after transplantation and mortality in the first 100 days after alloHCT. Outcomes were analyzed by means of the Kaplan-Meier method and Cox proportional hazards models with a frailty (random effects) component to take into account unexplained center heterogeneity. The following factors describing center characteristics or the transplant procedure were analyzed: experience in alloHCT in general and, for CLL specifically, accreditation by the Joint Accreditation Committee-ISCT & EBMT (JACIE), Gross National Income (GNI)/capita based on purchasing power parity (PPP) (GNI/cap), donor type, donor-patient sex-match, type of conditioning, stem cell source and T-cell depletion (TCD). Results:Five-year EFS of the whole cohort was 37% (95% Confidence Interval, 33%-42%), Day-100 survival was 90% (88%-92%). Experience of the transplant center was measured by the number of all alloHCTs, and alloHCTs for patients with CLL respectively. The median total number of alloHCTs per center per year was 45 (range 0-169) and the median number of CLL alloHCTs was only 2 per center per year (range 0-19). Greater experience with transplantation of patients with CLL (Hazard Ratio (HR) 0.96 per additional transplant, p=0.002), JACIE accreditation (HR 0.7, p=0.045) and a higher GNI/cap (HR 0.4, 95% CI 0.2-0.96, p=0.04) showed a protective impact on 5-year EFS in the Cox model. In vivo TCD with alemtuzumab (HR 1.5 compared to no TCD, p=0.03) and a female donor for a male patient (HR 1.4 compared to a male donor for a male patient, p=0.02) were the only procedure-related factors significantly associated with EFS. Event-Free Survival after in vivo TCD with Anti-Thymocyte-Globulin or after ex vivo TCD was comparable to EFS without TCD (HR 0.9, 0.7-1.3, p=0.6; HR 0.9, 0.5-1.6, p=0.8). Non-myeloablative conditioning did not have a negative impact on 5-year EFS, and exposed patients to a lower risk of non-relapse mortality. Measured and unmeasured center characteristics did not have a significant impact on 100-day mortality. Even when correcting for patient-, procedure- and center-related characteristics, there was still significant variation in center outcome, expressed by center-specific HRs derived from the frailty models, ranging from 0.6 to 1.2. Their impact is illustrated in a model-based plot for EFS (see Figure) which shows outcomes for three reference patients with the same characteristics who would be transplanted in three centers with the same measured characteristics but with the highest, average and lowest HRs in the dataset. These unexplained center effects likely represent a mixture of differences which could apply to the location of the transplant center, unmeasured characteristics of the patient population transplanted at this center, selection criteria which were not reported and factors determining the success of the transplant procedure which might differ between centers. Conclusion: We have confirmed that both center- and procedure-related factors have a significant impact on the EFS of patients with CLL undergoing alloHCT. Our results may help to interpret outcomes of single or multicenter studies better. Since non-myeloablative conditioning did not have a negative impact on EFS and exposed patients to a lower risk of non-relapse mortality, this approach should be favored for future alloHCT for CLL. Probability of Event-Free Survival up to Five Years Post-HCT for three Reference Patients Contribution: J.S. designed the research and wrote the paper. L.C.d.W conducted the statistical analysis and produced the figure. Figure Figure. Disclosures Schetelig: Sanofi: Honoraria. Gramatzki:Janssen: Other: Travel/Accommodation/Expenses, Research Funding. Dreger:Gilead: Consultancy; Gilead: Speakers Bureau; Janssen: Consultancy; Novartis: Speakers Bureau; Novartis: Consultancy; Roche: Consultancy.
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- 2017
8. Leitlinie : ICD10: E85.- : Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen
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Schönland, Stefan, Hegenbart, Ute, and Deutsche Gesellschaft Für Hämatologie Und Medizinische Onkologie
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Medizin und Gesundheit - Published
- 2017
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9. Reply to S. Girnius et al
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Palladini, Giovanni Dispenzieri, Angela Gertz, Morie Kumar, Shaji Wechalekar, Ashutosh Hawkins, Philip N Schönland, Stefan Hegenbart, Ute Comenzo, Raymond Kastritis, Efstathios others
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Health Sciences ,Επιστήμες Υγείας - Published
- 2013
10. Hereditary Apolipoprotein AI-Associated Amyloidosis in Surgical Pathology Specimens: Identification of Three Novel Mutations in the APOA1 Gene
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Eriksson, Magdalena, Schönland, Stefan, Yumlu, Saniye, Hegenbart, Ute, von Hutten, Hanna, Gioeva, Zarina, Lohse, Peter, Büttner, Janine, Schmidt, Hartmut, and Röcken, Christoph
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Adult ,Male ,Apolipoprotein A-I ,Biopsy ,Sequence Analysis, DNA ,Middle Aged ,Immunohistochemistry ,Protein Structure, Secondary ,Consultations in Molecular Diagnostics ,Mutation ,Humans ,Female ,Amyloidosis, Familial ,Aged - Abstract
Apolipoprotein AI-derived (AApoAI) amyloidosis may present either as a non-hereditary form with wild-type protein deposits in atherosclerotic plaques or as a hereditary form due to germline mutations in the APOA1 gene. Currently, more than 50 apoAI variants are known, and 13 are associated with amyloidosis. We describe six patients with AApoAI amyloidosis due to APOA1 germline mutations that affect the larynx, small intestine, large intestine, heart, liver, kidney, uterus, ovary, or pelvic lymph nodes. In each patient, the amyloid showed a characteristic apple green birefringence when viewed under polarized light after Congo red staining and was immunoreactive with antibodies against apoAI. Sequence analyses revealed one known (p.Leu75Pro) and three novel APOA1 mutations that included gene variations leading to two different frameshifts (p.Asn74fs and p.Ala154fs) and one amino acid exchange (p.Leu170Pro). These three novel mutations extend our knowledge about both the location of the mutations and the organ distribution in hereditary AApoAI amyloidosis. Thirteen of the now sixteen amyloidogenic mutations are localized in two hot-spot regions that span residues 50 to 93 and 170 to 178. The organ distribution and clinical presentation of AApoAI amyloidosis seems to depend on the position of the mutation. Patients with alterations in codons 1 to 75 mostly develop hepatic and renal amyloidosis, while carriers of mutations in residues 173 to 178 mainly suffer from cardiac, laryngeal, and cutaneous amyloidosis.
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- 2009
11. A Randomized Phase III Trial of Melphalan and Dexamethasone (MDex) Versus Bortezomib, Melphalan and Dexamethasone (BMDex) for Untreated Patients with AL Amyloidosis
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Efstathios Kastritis, Xavier Leleu, Bertrand Arnulf, Elena Zamagi, Peter Mollee, Teresa Cibeira, M., Schönland, Stefan O., Philippe Moreau, Roman Hajek, Arnaud Jaccard, Emanuelle Nicolas-Virelizier, Ribin Filshie, Bradley Augustson, María-Victoria Mateos, Paolo Milani, Dimopoulos, Meletios A., Eric Hachulla, Jean-Paul Fermand, Andrea Foli, Antonio Palumbo, Pieter Sonneveld, Hans Erik Johnsen, Giampaolo Merlini, and Giovanni Palladini
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Abstract
Background. The combination of melphalan and dexamethasone (MDex) is considered standard treatment for patients with AL amyloidosis who are not eligible for autologous stem cell transplant at most referral centers. When full-dose (40 mg) dexamethasone can be combined with melphalan, hematologic response is achieved in three fourths of patients, with complete remissions (CRs) in 30% of cases and prolonged survival (median >7 years). Several studies showed that bortezomib is highly effective in AL amyloidosis with response rates as high as 80-90%, with 50-60% CRs, when used in combinations with alkylating agents and dexamethasone, suggesting that these regimens could replace current standard of care in AL amyloidosis. A recent case-control study indicated that the addition of bortezomib to MDex (BMDex) does not overcome the poor prognosis of patients with advanced cardiac involvement. Here we report the first interim analysis of a multicenter randomized phase III trial comparing MDex and MDex with the addition of bortezomib (BMDex) in newly-diagnosed AL amyloidosis ongoing in Europe and Australia (EMN-03 study, NCT01277016). Patients and Methods. Main eligibility criteria included measurable disease (M-protein >10 g/L or dFLC >50 mg/L), estimated glomerular filtration rate (eGFR) ³30 mL/min, and adequate liver function. Previously treated patients, those who had >30% bone marrow plasma cell or lytic bone lesions, NYHA class >II heart failure, grade 3 sensory or grade 1 painful peripheral neuropathy, or ECOG performance status >2 were excluded. In January 2013 the protocol was amended to include Mayo stage III patients, provided their NT-proBNP was Results. Heart and renal involvement were present in 26 (74%) and 22 (63%) patients in the MDex arm, and in 25 (71%) and 24 (69%) in the BMDex arm, respectively. Five patients in each arm were stage III. In the MDex arm 15 patients (43%) experienced grade 3-4 adverse events [cytopenia (6), fluid retention (4), fatigue (2), need for a coronary stent (1), diarrhea (1), and renal failure (1)]. In the BMDex arm grade 3-4 adverse events were reported in 21 patients (63%, P=0.151 compared to MDex): cytopenia (12, febrile in 1 case), fluid retention (3), insomnia (2), transient troponin increase (1), peripheral neuropathy (1), renal failure (1), and injection site reaction (1). Three patients died in the first three months, 1 was treated with MDex and 2 with BMDex. Response was evaluated by intent to treat. Fifty-one patients, 26 treated with MDex and 25 who received BMDex, completed cycle 3 or died before completion and are evaluable for response. Overall, 15 patients (58%) responded in the MDex arm, and 19 (76%) in the BMDex arm (P=0.166). After cycle 3, nine patients (35%) in the MDex group and 16 (65%) in the BMDex group achieved at least very good partial response (P=0.036). Renal response was achieved in 2 of 8 evaluable patients in the MDex group and in 2 out of 10 subjects in the BMDex arm. Cardiac response was reached in 4 of 15 evaluable patients in the MDex arm and in 2 out of 12 in the BMDex arm. After a median follow-up of 14 months, 9 patients (13%) died, 4 in the MDex arm and 5 in the BMDex arm (Figure 1). Conclusion. This is the first prospective randomized trial of novel agents in AL amyloidosis. The present interim analysis indicates that the addition of bortezomib to MDex grants more profound hematologic responses that should be balanced with relative increase in toxicity. Longer follow-up is required to demonstrate a benefit in terms of organ improvement and of overall survival. Updated data will be presented at the meeting. We would like to acknowledge the European Myeloma Network and the Leukaemia Foundation of Australia for their ongoing support, and Janssen-Cilag for partially funding the trial and providing the study drug. Figure 1 Patients’ survival Figure 1. Patients’ survival Disclosures Leleu: Janssen, Celgene, leopharma, Takeda, Amgen, Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zamagni:Janssen and Celgene: Honoraria. Cibeira:Janssen and Celgene: Honoraria. Schönland:Janssen: Honoraria. Moreau:Millenium and Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hajek:Merck and Celgene: Consultancy, Honoraria; Janssen: Honoraria. Mateos:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dimopoulos:Celgene and Orthobiotech: Honoraria. Sonneveld:Celgene, Janssen, Onyx, Millennium: Research Funding; Celgene, Janssen, Onyx, Millennium: Membership on an entity's Board of Directors or advisory committees. Merlini:Millennium Takeda: Honoraria. Off Label Use: Bortezomib in AL amyloidosis.
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- 2014
12. Improved outcome of patients with graft-versus-host disease after allogeneic hematopoietic cell transplantation for hematologic malignancies over time: an EBMT mega-file study
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Ibrahim Yakoub-Agha, Dirk-Jan Eikema, Silvia Montoto, Hildegard Greinix, Arnon Nagler, Mohamad Mohty, Marie Robin, Yves Chalandon, Stephen D. Robinson, Christian Chabannon, Nicolaus Kröger, Liesbeth C. de Wreede, Francesco Lanza, Stefan Schönland, Malgorzata Mikulska, Zinaida Peric, Olaf Penack, Linda Koster, Annalisa Ruggeri, Grzegorz W. Basak, Jan Styczyński, Greinix, Hildegard T, Eikema, Dirk-Jan, Koster, Linda, Penack, Olaf, Yakoub-Agha, Ibrahim, Montoto, Silvia, Chabannon, Christian, Styczynski, Jan, Nagler, Arnon, Robin, Marie, Robinson, Stephen, Chalandon, Yve, Mikulska, Malgorzata, Schönland, Stefan, Peric, Zinaida, Ruggeri, Annalisa, Lanza, Francesco, De Wreede, Liesbeth C, Mohty, Mohamad, Basak, Grzegorz W, and Kröger, Nicolaus
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Male ,medicine.medical_specialty ,Graft vs Host Disease ,Disease ,survival ,Graft vs Host Disease* / prevention & control ,prevention ,Unrelated Donor ,Internal medicine ,medicine ,Humans ,Sibling ,Alemtuzumab ,ddc:616 ,Hematopoietic Stem Cell Transplantation* / adverse effects ,Hematopoietic cell ,business.industry ,Incidence (epidemiology) ,Hematologic Neoplasms* / complications ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,mortality ,Graft vs Host Disease* / etiology ,Transplantation ,stem cell ,diagnosi ,Graft-versus-host disease ,surgical procedures, operative ,haploidentical bone marrow ,Hematologic Neoplasms ,Female ,business ,Unrelated Donors ,Calendar time - Abstract
Acute graft-versus-host disease (aGvHD) remains a major threat to successful outcome following allogeneic hematopoietic cell transplantation though advances in prophylaxis and supportive care have been made. The aim of this study is to test whether the incidence and mortality of aGvHD have decreased over time. 102,557 patients with a median age of 47.6 years and with malignancies after first allogeneic sibling or unrelated donor (URD) transplant were studied in the following periods: 1990-1995, 1996-2000, 2001-2005, 2006-2010 and 2011-2015. Findings: 100-day incidences of aGvHD grades II-IV decreased from 40% to 38%, 32%, 29% and 28%, respectively, over calendar time (P
- Published
- 2020
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