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Research ArticleClinical Studies

Pharmacogenetic Analysis of Liver Toxicity after Busulfan/Cyclophosphamide-based Allogeneic Hematopoietic Stem Cell Transplantation

ERAY GOEKKURT, JAN STOEHLMACHER, CHRISTIAN STUEBER, CHRISTINE WOLSCHKE, THOMAS EIERMANN, SIMONA IACOBELLI, AXEL R. ZANDER, GERHARD EHNINGER and NICOLAUS KRÖGER
Anticancer Research November 2007, 27 (6C) 4377-4380;
ERAY GOEKKURT
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  • For correspondence: eray.goekkurt@uniklinikum-dresden.de
JAN STOEHLMACHER
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CHRISTIAN STUEBER
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CHRISTINE WOLSCHKE
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THOMAS EIERMANN
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SIMONA IACOBELLI
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AXEL R. ZANDER
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GERHARD EHNINGER
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NICOLAUS KRÖGER
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Abstract

The aim of this study was to evaluate the impact of genomic polymorphisms of methylene-tetrahydrofolate-reductase (MTHFR-C677T, MTHFR-A1298C) and various glutathione S-transferases (GSTP1-Ile105Val, GSTA1*a/b, GSTM1, GSTT1) on the occurrence of liver toxicity in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Patients and Methods: Eighty-four adult patients were enrolled in this retrospective study. All patients were treated with busulfan/cyclophosphamide as a conditioning regimen and received cyclosporine and short-course MTX for GvHD prophylaxis. Genotyping was performed using PCR based restriction-fragment-length-polymorphism (RFLP) techniques. Results: Multivariate analysis identified the MTHFR-A1298C polymorphism as an independent predictor for maximum levels of bilirubin (p=0.0025) and duration of hyperbilirubinaemia (p=0.013). Furthermore, there was an association between this polymorphism and the occurrence of the sinusoidal obstruction syndrome (SOS) (p=0.048). No significant associations between the MTHFR-C677T or the various GST polymorphisms and liver toxicity were observed. Conclusion: The MTHFR-A1298C polymorphism might be associated with liver toxicity in patients receiving allogeneic HSCT.

  • Allogeneic hematopoietic stem cell transplantation
  • glutathione S-tranferases
  • methylene-tetrahydrofolate-reductase
  • sinusoidal obstruction syndrome

Footnotes

  • ↵* Both authors contributed equally to this work.

  • Received June 5, 2007.
  • Revision received August 22, 2007.
  • Accepted October 8, 2007.
  • Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 27 (6C)
Anticancer Research
Vol. 27, Issue 6C
November-December 2007
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Pharmacogenetic Analysis of Liver Toxicity after Busulfan/Cyclophosphamide-based Allogeneic Hematopoietic Stem Cell Transplantation
ERAY GOEKKURT, JAN STOEHLMACHER, CHRISTIAN STUEBER, CHRISTINE WOLSCHKE, THOMAS EIERMANN, SIMONA IACOBELLI, AXEL R. ZANDER, GERHARD EHNINGER, NICOLAUS KRÖGER
Anticancer Research Nov 2007, 27 (6C) 4377-4380;

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Pharmacogenetic Analysis of Liver Toxicity after Busulfan/Cyclophosphamide-based Allogeneic Hematopoietic Stem Cell Transplantation
ERAY GOEKKURT, JAN STOEHLMACHER, CHRISTIAN STUEBER, CHRISTINE WOLSCHKE, THOMAS EIERMANN, SIMONA IACOBELLI, AXEL R. ZANDER, GERHARD EHNINGER, NICOLAUS KRÖGER
Anticancer Research Nov 2007, 27 (6C) 4377-4380;
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