9 results on '"Scheid, Christof"'
Search Results
2. TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial.
- Author
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Dreger, Peter, Schnaiter, Andrea, Zenz, Thorsten, Böttcher, Sebastian, Rossi, Marianna, Paschka, Peter, Bühler, Andreas, Dietrich, Sascha, Busch, Raymonde, Ritgen, Matthias, Bunjes, Donald, Zeis, Matthias, Stadler, Michael, Uharek, Lutz, Scheid, Christof, Hegenbart, Ute, Hallek, Michael, Kneba, Michael, Schmitz, Norbert, and Döhner, Hartmut
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GENETIC mutation , *LYMPHOCYTIC leukemia , *HEMATOPOIETIC stem cell transplantation , *HOMOGRAFTS , *MULTIVARIATE analysis , *PATIENTS - Abstract
The purpose of this analysis was to provide 6-year follow-up of the CLL3X trial, which studied reduced-intensity allogeneic hematopoietic stem cell transplantation (HSCT) in patients with poor-risk chronic lymphocytic leukemia (CLL), and to investigate the effect of TP53, SF3B1, and NOTCH1 mutations on HSCT outcome. For 90 allografted patients, 6-year overall survival (OS) was 58% and 6-year event-free survival (EFS) was 38%. TP53, SF3B1, and NOTCH1 mutations were found in 30%, 26%, and 14% of the trial population, respectively. By univariate and multivariate analyses, the mutational status of the TP53, SF3B1, and NOTCH1 genes had no significant effect on OS and EFS. Studies of minimal residual disease confirmed durability of CLL eradication in mutated patients. We conclude that HSCT can provide long-term disease control in patients with poor-risk CLL independent of the presence of TP53, SF3B1, and NOTCH1 mutations. The trial has been registered at the US National Cancer Institute as #EU-20554, NCT00281983. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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3. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion l7p.
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Neben, Kai, Lokhorst, Henk M., Jauch, Anna, Bertsch, Uta, Hielscher, Thomas, van der Holt, Bronno, Salwender, Hans, Blau, Igor W., Weisel, Katja, Pfreundschuh, Michael, Scheid, Christof, Dührsen, Ulrich, Lindemann, Walter, Schmidt-Wolf, Ingo G. H., Peter, Norma, Teschendorf, Christian, Martin, Hans, Haenel, Mathias, Derigs, Hans G., and Raab, Marc S.
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AUTOTRANSPLANTATION , *STEM cell transplantation , *MULTIPLE myeloma treatment , *RANDOMIZED controlled trials , *CHROMOSOME abnormalities - Abstract
In patients with multiple myeloma (MM), risk stratification by chromosomal abnormalities may enable a more rational selection of therapeutic approaches. In the present study, we analyzed the prognostic value of 12 chromosomal abnormalities in a series of 354 MM patients treated within the HOVON-65/GMMG-HD4 trial. Because of the 2-arm design of the study, we were able to analyze the effect of a bortezomib-based treatment before and after autologous stem cell transplantation (arm B) compared with standard treatment without bortezomib (arm A). For all analyzed chromosomal aberrations, progression-free survival (PFS) and over- all survival (OS) were at least equal or superior in the bortezomib arm compared with the standard arm. Strikingly, patients with del(17p13) benefited the most from the bortezomib-containing treatment: the median PFS in arm A was 12.0 months and in arm B it was 26.2 months (P = .024); the 3 year-OS for arm A was 17% and for arm B it was 69% (P = .028). After multivariate analysis, del(17p13) was an independent predictor for PFS (P < .0001) and OS (P < .0001) in arm A, whereas no statistically significant effect on PFS(P = .28)or OS(P = .12) was seen in arm B. In conclusion, the adverse impact of del(17p13) on PFS and OS could be significantly reduced by bortezomib-based treatment, suggesting that long-term administration of bortezomib should be recommended for patients carrying del(17p13). This trial is registered at the International Standard Randomised Controlled Trial Number Register as ISRCTN64455289. (Blood. 2012;119(4): 940-948) [ABSTRACT FROM AUTHOR]
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- 2012
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4. Unrelated donor transplantation with post-transplant cyclophosphamide versus ATG for myelodysplastic neoplasms.
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Chalandon Y, Eikema DJ, Moiseev IS, Ciceri F, Koster L, Vydra J, Passweg JR, Rovira M, Ozcelik T, Gedde-Dahl T, Kröger N, Potter V, Yakoub-Agha I, Rambaldi A, Itälä-Remes M, Tanase AD, Onida F, Gurnari C, Scheid C, Drozd-Sokolowska J, Raj K, McLornan DP, and Robin M
- Abstract
Prospective randomized trials have reported a benefit for anti-thymocyte globulin (ATG)-based graft-versus-host disease (GvHD) prophylaxis in the setting of allogeneic hematopoietic stem cell transplantation (Allo-HSCT) with unrelated donors (UD). However, the optimal GvHD prophylaxis strategy has been recently challenged by the increasing use of post-transplant cyclophosphamide (PTCY). We report from the EBMT registry the outcomes of 960 patients with myelodysplastic neoplasms (MDS) undergoing allo-HSCT from UD with PTCY or ATG as GvHD prophylaxis. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Disease characteristics were similar in both groups. Day 28 neutrophil engraftment was significantly better with ATG (93% vs 85%, p<0.001). With a median follow-up of 4.4 years (95% confidence interval [CI] 4.2 - 4.8), 5-year OS was 58% (95% CI 50-65) with PTCY and 49% (95% CI 46-53%) in the ATG group, p=0.07. 5-year PFS was higher for PTCY with 53% (95% CI 45-60) vs 44% (95% CI 40-48) for ATG, p=0.043. Grade II-IV aGvHD incidence was lower using PTCY (23% [95% CI 17-29%] vs 30% [95% CI 27-33%]), p=0.044 while there was no difference in incidence of cGvHD at 5 years. Multivariable analyses confirmed better OS and PFS with PTCY, with a HR for ATG of 1.32 (1 - 1.74), p=0.05, and a better PFS for PTCY with a HR for ATG of 1.33 (1.03 - 1.73), p=0.03. This study suggests that GvHD prophylaxis using PTCY instead of ATG in this setting remains a valid option. Further prospective randomized studies would be essential to confirm these results., (Copyright © 2024 American Society of Hematology.)
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- 2024
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5. PTCy versus CNI-based GVHD prophylaxis in HLA-matched transplants for Hodgkin Lymphoma: a study of the LWP of the EBMT.
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Montoro J, Ngoya M, Kulagin A, Giebel S, Broers AEC, Bramanti S, Halahleh K, Perez-Simon JA, Solano C, Ozcelik T, Blaise D, Sanz J, Henriques M, Peffault de Latour R, Martino R, Scheid C, Fox L, Gromek T, Jurado M, Sakellari I, van Gorkom G, Matteucci P, Nagler A, Koc Y, and Glass B
- Abstract
Studies comparing the efficacy of post-transplant cyclophosphamide (PTCy) to conventional calcineurin inhibitor (CNI)-based GVHD prophylaxis regimens in Hodgkin lymphoma (HL) patients are scarce. This study aimed to compare the outcomes of HL patients undergoing hematopoietic stem cell transplantation from HLA-matched donors who received GVHD prophylaxis with either PTCy or conventional CNI-based regimens, using data reported to the EBMT database between January 2015 and December 2022. Among the cohort, 270 recipients received conventional CNI-based prophylaxis and 176 received PTCy prophylaxis. Notably, PTCy prophylaxis was associated with delayed hematopoietic recovery, but also with a lower risk of chronic (25% versus 43%, p<0.001) and extensive chronic GVHD (13% versus 28% p=0.003) compared to the CNI-based cohort. The 2-year cumulative incidence of non-relapse mortality and relapse were 11% versus 17% (p=0.12), and 17% versus 30% (p=0.007) for PTCy and CNI-based, respectively. Moreover, the 2-year overall survival, progression-free survival and GVHD-free, relapse-free survival were all significantly better in the PTCy group compared with the CNI-based group: 85% versus 72% (p=0.005), 72% versus 53% (p<0.001), and 59% versus 31% (p<0.001), respectively. In multivariable analysis, PTCy was associated with a lower risk of chronic and extensive chronic GVHD, reduced relapse, and better OS, PFS, and GRFS compared to the CNI-based platform. Our findings suggest that PTCy as GVHD prophylaxis offers more favorable outcomes compared to conventional CNI-based prophylaxis in adult patients with HL undergoing HSCT from HLA-matched donors., (Copyright © 2024 American Society of Hematology.)
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- 2024
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6. Allogeneic hematopoietic cell transplantation for VEXAS syndrome: results of a multicenter study of the EBMT.
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Gurnari C, Koster L, Baaij L, Heiblig M, Yakoub-Agha I, Collin M, Passweg J, Bulabois CE, Khan A, Loschi M, Carnevale-Schianca F, Crisà E, Caravelli D, Kuball J, Saraceni F, Olivieri A, Rambaldi A, Kulasekararaj AG, Hayden PJ, Badoglio M, Onida F, Scheid C, Franceschini F, Mekinian A, Savic S, Voso MT, Drozd-Sokolowska J, Snowden JA, Raj K, Alexander T, Robin M, Greco R, and McLornan DP
- Subjects
- Transplantation, Homologous, Humans, Hematopoietic Stem Cell Transplantation methods, Myelodysplastic Syndromes, Skin Diseases, Genetic
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- 2024
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7. MCT1 is a predictive marker for lenalidomide maintenance therapy in multiple myeloma.
- Author
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Stroh J, Seckinger A, Heider M, Rudelius M, Eichner R, Schick M, Slawska J, Emde-Rajaratnam M, Salwender H, Bertsch U, Goldschmidt H, Weisel K, Scheid C, Keller U, Hose D, and Bassermann F
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- Biomarkers, Bortezomib pharmacology, Bortezomib therapeutic use, Humans, Lenalidomide therapeutic use, Thalidomide pharmacology, Thalidomide therapeutic use, Multiple Myeloma therapy
- Abstract
Biomarkers that predict response to lenalidomide maintenance therapy in patients with multiple myeloma (MM) have remained elusive. We have shown that immunomodulatory drugs (IMiDs) exert anti-MM activity via destabilization of MCT1 and CD147. In this study, cell samples of 654 patients with MM who received lenalidomide (n = 455), thalidomide (n = 98), or bortezomib (n = 101) maintenance were assessed by gene expression profiling and RNA sequencing, followed by correlation of MCT1 and CD147 expression with data for progression-free survival (PFS) and overall survival (OS). Patients with high expression levels of MCT1 showed significantly reduced PFS (31.9 months vs 48.2 months in MCT1high vs MCT1low; P = .03) and OS (75.9 months vs not reached [NR] in MCT1high vs MCT1low; P = .001) in cases with lenalidomide maintenance, whereas MCT1 expression had no significant impact on PFS or OS in cases with bortezomib maintenance. We validated the predictive role of MCT1 for IMiD-based maintenance in an independent cohort of patients who received thalidomide (OS, 83.6 months vs NR in MCT1high vs MCT1low; P = .03). Functional validation showed that MCT1 overexpression in human MM cell lines significantly reduced the efficacy of lenalidomide, whereas no change was observed with bortezomib treatment, either in vitro or in a MM xenograft model. Our findings have established MCT1 expression as a predictive marker for response to lenalidomide-based maintenance in patients with MM., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2022
- Full Text
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8. Randomized controlled study of ECP with methoxsalen as first-line treatment of patients with moderate to severe cGVHD.
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Jagasia M, Scheid C, Socié G, Ayuk FA, Tischer J, Donato ML, Bátai Á, Chen H, Chen SC, Chin T, Boodée H, Mitri G, and Greinix HT
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- Adult, Aged, Female, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Male, Methoxsalen pharmacology, Middle Aged, Quality of Life, Severity of Illness Index, Treatment Outcome, Young Adult, Graft vs Host Disease diagnosis, Graft vs Host Disease therapy, Methoxsalen administration & dosage, Photopheresis methods
- Abstract
The investigation of extracorporeal photopheresis (ECP) plus standard of care (SoC) (SoC+ECP) in chronic graft-versus-host disease (cGVHD) within prospective, randomized clinical studies is limited, despite its frequent clinical use. This phase 1/pilot study was the first randomized, prospective study to investigate ECP use as first-line therapy in cGVHD, based on the 2015 National Institutes of Health (NIH) consensus criteria for diagnosis and response assessment. Adult patients with new-onset (≤3 years of hematopoietic stem cell transplantation) moderate or severe cGVHD were randomized 1:1 to 26 weeks of SoC+ECP vs SoC (corticosteroids and cyclosporine A/tacrolimus) between 2011 and 2015. The primary endpoint was overall response rate (ORR), defined as complete or partial response, at week 28 in the intention-to-treat population (ITT). Other outcomes included quality of life (QoL) measures and safety. Sixty patients were randomized; ITT included 53 patients (SoC+ECP: 29; SoC: 24). Week 28 ORR was 74.1% (SoC+ECP) and 60.9% (SoC). Investigator-assessed ORR was 56.0% (SoC+ECP) and 66.7% (SoC). Patients treated with SoC experienced a decline in QoL over the 28-week study period; QoL remained unchanged in SoC+ECP patients. Most frequent treatment-emergent adverse events (TEAEs) in SoC+ECP patients were hypertension (31.0%), cough (20.7%), dyspnea (17.2%), and fatigue (17.2%). Seventeen patients (SoC+ECP: 8; SoC: 9) experienced 35 serious adverse events (SAEs). No TEAEs or SAEs were considered related to the ECP instrument or methoxsalen. The encouraging short-term results of this study could inform the design of subsequent studies. This trial was registered at www.clinicaltrials.gov as #NCT01380535., (© 2019 by The American Society of Hematology.)
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- 2019
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9. Prognostic significance of cytogenetic heterogeneity in patients with newly diagnosed multiple myeloma.
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Merz M, Jauch A, Hielscher T, Bochtler T, Schönland SO, Seckinger A, Hose D, Bertsch U, Neben K, Raab MS, Hillengass J, Salwender H, Blau IW, Lindemann HW, Schmidt-Wolf IGH, Scheid C, Haenel M, Weisel KC, and Goldschmidt H
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- Adolescent, Adult, Bortezomib therapeutic use, Humans, In Situ Hybridization, Fluorescence, Middle Aged, Multiple Myeloma genetics, Netherlands, Prognosis, Transplantation, Autologous, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chromosome Aberrations, Multiple Myeloma diagnosis
- Abstract
We investigated subclonal cytogenetic aberrations (CA) detected by interphase fluorescence in situ hybridization (iFISH) in patients with newly diagnosed multiple myeloma (MM) enrolled in the Haemato Oncology Foundation for Adults in the Netherlands (HOVON)-65/German-Speaking MM Group (GMMG)-HD4 phase 3 trial. Patients were either treated with 3 cycles of vincristine, Adriamycin, and dexamethasone or bortezomib, Adriamycin, and dexamethasone and then thalidomide or bortezomib maintenance after tandem autologous transplantation. Subclones were defined either by presence of different copy numbers of the same chromosome loci and/or CA present in at least 30% less and maximally 2/3 of cells compared with the main clone CA. Patients with subclones harbored more frequently high risk (31.0%) or hyperdiploid main clone aberrations (24.8%) than patients with t(11;14) in the main clone (10.1%). Gains and deletions of c-MYC were the only CA that occurred more frequently as subclone (8.1%/20.5%) than main clone (6.2%/3.9%, respectively). Treatment with bortezomib completely overcame the negative prognosis of high-risk CA in patients without subclones, but not in patients with additional subclonal CA. High-risk patients treated without bortezomib showed dismal outcome whether subclones were present or not. Cytogenetic heterogeneity defined by subclonal CA is of major prognostic significance in newly diagnosed MM patients treated with bortezomib within the HOVON-65/GMMG-HD4 trial., Competing Interests: Conflict-of-interest disclosure: M.M. received travel grants from Celgene, Abbvie, Amgen, and Janssen and acts on advisory boards for Amgen. D.H. received research funding from Sanofi and EngMab, as well as personal fees outside this work from Celgene. H.S. received speakers honoraria and travel grants from Celgene, Amgen, and Sanofi. I.G.H.S.-W. received research funding from Janssen and Novartis. C.S. received funding outside this work from Novartis, Celgene, and Janssen. K.C.W. received consultancy honoraria from Amgen, Takeda, and BMS, as well as honoraria from Novartis, research funding from Janssen and Celgene, and consultancy honoraria from Onyx. H.G. received consultancy honoraria and research funding from Janssen, Celgene, and Novartis, as well as consultancy honoraria from Onyx and Millenium and fees outside this work from BMS. J.H. received speakers honoraria from Celgene, acts on advisory boards for Janssen, BMS, and Amgen, and received consultancy honoraria from Janssen, Novartis, and Amgen as well as research funding from Sanofi. The remaining authors declare no competing financial interests.
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- 2017
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