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Analysis of non- HLA genomic risk factors in HLA-matched unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia
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Dr Kim Pearce
Dr Shelagh Lowerson
Dr Sally Davies
Professor Anne Dickinson
Pearce KF, Lee SJ, Haagenson M, Petersdorf EW, Norden J, Collin MP, Klein JP, Spellman SR, Lowerson SA, Davies S, Dickinson AM
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For Chronic Myeloid Leukemia (CML) patients who do not respond to tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic cell transplantation (HCT) is the main curative therapy for many congenital or acquired disorders of the hematopoietic system. It has been proposed that Non-HLA gene polymorphisms influence outcome after HCT and could be used alongside traditional patient-donor and transplant characteristics to create a patient risk profile associated with allogeneic HCT.
Design and Methods:
A previous study from the European Group for Blood and Marrow Transplantation showed that the absence of patient TNFRSF1B 196R, absence of donor IL10 ATA/ACC, and presence of donor IL1RN allele 2 genotypes were associated with decreased survival and increased non-relapse mortality in adult patients with CML undergoing myeloablative HLA-identical sibling transplantation. To explore these associations in unrelated donor (URD) transplantation, these polymorphisms were genotyped in 383 adult patients with CML who underwent HCT from 10/10 HLA-matched URDs.
None of the polymorphisms were associated with overall survival, non-relapse mortality, relapse, or acute graft-versus-host disease in the URD cohort. Comp
We did not confirm that non-HLA polymorphisms were associated with outcomes in myeloablative URD HCT for CML, possibly due to the strong association between clinical variables and outcome that masked more subtle genetic effects.
Comparison of the URD and HLA-identical sibling cohorts showed differences in survival and clinical characteristics.
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