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Graft-Versus-Tumor Effects

CT60 single-nucleotide polymorphism as a surrogate marker for donor lymphocyte infusion outcome after allogeneic cell transplantation for acute leukemia

Bone Marrow Transplantation volume 47, pages 411–415 (2012)Cite this article

Abstract

The benefit of survival at the expense of new GVHD after DLI for acute leukemia following human allogeneic hematopoietic cell transplantation (allo-HCT) remains a matter of controversy. The detection of biological markers predicting this outcome would be an enormous breakthrough. The purpose of this study was the analysis of CT60 single-nucleotide polymorphism (SNP) of the CTLA-4 T-regulatory gene as a surrogate marker for DLI outcome in this difficult setting. Using Pyrosequencing, we genotyped the alleles of the CT60 SNP of 79 DLI donors and correlated them with the post-DLI outcome of their matching recipients. The presence of a donor ‘AA’ or ‘AG’ CT60 genotype vs a ‘GG’ genotype was an independent factor for remaining in complete chimerism/remission post-DLI (odds ratio (OR) 2.61 vs 0.42, respectively, P=0.05). Further, in cases with evident post-DLI allo-reactivity the importance of an ‘AA’ or ‘AG’ vs a ‘GG’ genotype gained significance for ongoing complete chimerism (OR 4.35 vs 0.32, P=0.03). Neither alterations in cumulative DLI dose nor any other clinical parameter significantly weakened the importance of CT60 SNP. Our results provide evidence for the necessity of genotyping CT60 SNP prior to DLI administration in patients with acute leukemia.

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Author notes

  1. Y Metaxas and H Bertz: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology/Oncology, University of Freiburg, Freiburg, Germany

    Y Metaxas, H Bertz & J Finke

  2. Division of Hematology, Department of Internal Medicine, University of Patras, Rio/Patras, Greece

    A Spyridonidis

  3. Department of Immunology, ‘Alexandra’ General Hospital, Athens, Greece

    M Spyroupoulou-Vlachou

  4. Institute of Medical Biometry and Medical Informatics, University Medical Center Freiburg, Freiburg, Germany

    C Porzelius

Authors
  1. Y Metaxas
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  2. H Bertz
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  4. M Spyroupoulou-Vlachou
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  5. C Porzelius
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  6. J Finke
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Correspondence to Y Metaxas.

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Metaxas, Y., Bertz, H., Spyridonidis, A. et al. CT60 single-nucleotide polymorphism as a surrogate marker for donor lymphocyte infusion outcome after allogeneic cell transplantation for acute leukemia. Bone Marrow Transplant 47, 411–415 (2012). https://doi.org/10.1038/bmt.2011.101

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