Dickinson, Anne M. and Pearce, Kim F. and Norden, Jean and O'Brien, Stephen G. and Holler, Ernst and Bickeboeller, Heike and Balavarca, Yesilda and Rocha, Vanderson and Kolb, Hans-Jochem and Hromadnikova, Ilona and Sedlacek, Petr and Niederwieser, Dietger and Brand, Ronald and Ruutu, Tapatti and Apperleyy, Jane and Szydlo, Richard and Goulmy, Els and Siegert, Wolfgang and de Witte, Theo and Gratwohl, Alois (2010) Impact of genomic risk factors on outcome after hematopoietic stem cell transplantation for patients with chronic myeloid leukemia. HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 95 (6). pp. 922-927. ISSN 0390-6078,
Full text not available from this repository. (Request a copy)Abstract
Background Non-HLA gene polymorphisms have been shown to influence outcome after allogeneic hematopoietic stem cell transplantation. Results were derived from heterogeneous, small populations and their value remains a matter of debate. Design and Methods In this study, we assessed the effect of single nucleotide polymorphisms in genes for interleukin 1 receptor antagonist (IL1RAI), interleukin 4 (IL4), interleukin 6 (IL6), interleukin 10 (IL10), interferon (IFNG), tumor necrosis factor (TNF) and the cell surface receptors tumor necrosis factor receptor II (TNFRSFIB), vitamin D receptor (VDR) and estrogen receptor alpha (ESR1) in a homogeneous cohort of 228 HLA identical sibling transplants for chronic myeloid leukemia. Three good predictors of overall survival, identified via statistical methods including Cox regression analysis, were investigated for their effects on transplant-related mortality and relapse. Predictive power was assessed after integration into the established European Group for Blood and Marrow Transplantation (EBMT) risk score. Results Absence of patient TNFRSFIB 196R, absence of donor IL10 ATA/ACC and presence of donor IL1RN allele 2 genotypes were associated with increased transplantation-related mortality and decreased survival. Application of prediction error and concordance index statistics gave evidence that integration improved the EBMT risk score. Conclusions Non-HLA genotypes were associated with survival after allogeneic hematopoietic stem cell transplantation. When three genetic polymorphisms were added into the EBMT risk model they improved the goodness of fit. Non-HLA genotyping could, therefore, be used to improve donor selection algorithms and risk assessment prior to allogeneic hematopoietic stem cell transplantation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; INTERLEUKIN-10 PROMOTER POLYMORPHISM; CHRONIC MYELOGENOUS LEUKEMIA; GENE POLYMORPHISM; ALLOGENEIC TRANSPLANTATION; IL-10 POLYMORPHISMS; FOLLOW-UP; RECEPTOR; SURVIVAL; genetic risk factors; statistical modeling; hematopoietic stem cell transplantation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Jul 2020 06:37 |
| Last Modified: | 29 Jul 2020 06:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24617 |
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