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Sökning: WFRF:(Nagler A)

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  • 2019
  • Tidskriftsartikel (refereegranskat)
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  • Crawley, C, et al. (författare)
  • Outcomes of reduced-intensity transplantation for chronic myeloid leukemia : an analysis of prognóstic factors from the Chronic Leukemia Working Party of the EBMT
  • 2005
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 106:9, s. 2969-2976
  • Tidskriftsartikel (refereegranskat)abstract
    • This study reports outcomes of allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC) in 186 patients with chronic myeloid leukemia (CML) from the European Group for Blood and Marrow Transplantation (EBMT). The median age was 50 years, and 64% were in first chronic phase (CP1), CP2 13%, accelerated phase 17%, and blast crises 6%. The median EBMT transplant score was 3. The day 100 transplantation-related mortality (TRM) was 6.1% (confidence interval [CI], 3.4%-11%) but rose to 23.3% (CI, 14%-27%) at 2 years. Fludarabine, busulfan, and antithymocyte globulin (Fd/Bu/ATG) was associated with the lowest TRM of 11.6% (CI, 4.7%-11%) at 1 year. Acute graft-versus-host disease (GvHD) grade II to IV occurred in 32% and chronic GvHD in 43% (extensive in 24%). ATG was associated with a lower incidence of chronic GvHD (cGvHD). The overall survival (OS) and progression-free survival (PFS) at 3 years were 58% (CI, 50%-66%) and 37% (CI, 30%-45%), respectively. Adverse OS was associated with advanced disease (relative risk [RR], 3.4). PFS was inferior in advanced disease (RR, 2.7) and a trend to improved outcomes with Fd/Bu/ATG (RR, 0.58). RIC allografts are feasible in CML in first or second CP. Since no other RIC regimen demonstrated superiority, Fd/Bu/ATG should be considered as baseline in future prospective trials.
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  • Crawley, C, et al. (författare)
  • Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT
  • 2005
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 105:11, s. 4532-4539
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the outcome of 229 patients who received an allograft for myeloma with reduced-intensity conditioning (RIC) regimens from 33 centers within the European Group for Blood and Marrow Transplantation (EBMT). The median age was 52 years and 64% were male. Conditioning regimens were heterogeneous, but most were fludarabine based and T cell depleted with antithymocyte globulin or alemtuzumab. Transplantation-related mortality (TRIM) at 1 year was 22%. The 3-year overall survival (OS) and progression-free survival (PFS) were 41% and 21 %, respectively. Adverse OS was associated with chemoresistant disease (relative risk [RR], 2.9), more than 1 prior transplantation (RR, 2.0), and male patients with female donors (FIR, 1.45). Adverse PFS was associated with chemoresistance (RR, 2.4) and alemtuzumab (RR, 1.8). TRM was increased with female-to-male donation (RR, 2.5) and transplantation more than 1 year from diagnosis (RR, 2.3). Grades II to IV acute graft-versus-host disease (aGvHD) occurred in 31%. Chronic GvHD was associated with better OS and PFS and were 84% and 46% for limited, 58% and 30% for extensive, and 29% and 12% in its absence suggesting that a graft-versus-myeloma effect is important. While RIC is feasible, heavily pretreated patients and patients with progressive disease do not benefit.
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  • Kawakatsu, Taiji, et al. (författare)
  • Epigenomic Diversity in a Global Collection of Arabidopsis thaliana Accessions
  • 2016
  • Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 492-505
  • Tidskriftsartikel (refereegranskat)abstract
    • The epigenome orchestrates genome accessibility, functionality, and three-dimensional structure. Because epigenetic variation can impact transcription and thus phenotypes, it may contribute to adaptation. Here, we report 1,107 high-quality single-base resolution methylomes and 1,203 transcriptomes from the 1001 Genomes collection of Arabidopsis thaliana. Although the genetic basis of methylation variation is highly complex, geographic origin is a major predictor of genome-wide DNA methylation levels and of altered gene expression caused by epialleles. Comparison to cistrome and epicistrome datasets identifies associations between transcription factor binding sites, methylation, nucleotide variation, and co-expression modules. Physical maps for nine of the most diverse genomes reveal how transposons and other structural variants shape the epigenome, with dramatic effects on immunity genes. The 1001 Epigenomes Project provides a comprehensive resource for understanding how variation in DNA methylation contributes to molecular and non-molecular phenotypes in natural populations of the most studied model plant.
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  • Alonso-Blanco, Carlos, et al. (författare)
  • 1,135 Genomes Reveal the Global Pattern of Polymorphism in Arabidopsis thaliana
  • 2016
  • Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 481-491
  • Tidskriftsartikel (refereegranskat)abstract
    • Arabidopsis thaliana serves as a model organism for the study of fundamental physiological, cellular, and molecular processes. It has also greatly advanced our understanding of intraspecific genome variation. We present a detailed map of variation in 1,135 high-quality re-sequenced natural inbred lines representing the native Eurasian and North African range and recently colonized North America. We identify relict populations that continue to inhabit ancestral habitats, primarily in the Iberian Peninsula. They have mixed with a lineage that has spread to northern latitudes from an unknown glacial refugium and is now found in a much broader spectrum of habitats. Insights into the history of the species and the fine-scale distribution of genetic diversity provide the basis for full exploitation of A. thaliana natural variation through integration of genomes and epigenomes with molecular and non-molecular phenotypes.
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  • Mohty, M., et al. (författare)
  • Reduced intensity conditioning allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia : A retrospective study from the European Group for Blood and Marrow Transplantation
  • 2008
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 93:2, s. 303-306
  • Tidskriftsartikel (refereegranskat)abstract
    • This retrospective study reported the outcome of 97 adult acute lymphoblastic leukemia patients who received a reduced-intensity conditioning allogeneic stem cell transplantation. With a median follow-up of 2.8 years, two year overall-survival, leukemia-free survival and non-relapse mortality were significantly better in patients transplanted in first complete remission (CR1, 52±9%, 42±10%, and 18±7% respectively) compared with those transplanted in more advanced phase (p=0.003, p=0.002 and p=0.01 respectively). In multivariate analysis, disease status (CR1 vs. advanced, p=0.001) and chronic graft-vs-host disease (p=0.01) were associated with an improved overall-survival, suggesting that reduced-intensity conditioning allogeneic stem cell transplantation is feasible in patients with high risk lymphoblastic leukemia in remission at transplantation. ©2008 Ferrata Storti Foundation.
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