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Heparanase polymorphisms: influence on incidence of hepatic sinusoidal obstruction syndrome in children undergoing allogeneic hematopoietic stem cell transplantation

  • Original Article - Clinical Oncology
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Abstract

Purpose

Sinusoidal obstruction syndrome (SOS) is a life-threatening early complication after hematopoietic stem cell transplantation (HSCT), and until now, examinations about the influence of genetic risk factors are extremely rare. The purpose of this study was to identify an association between heparanase (HPSE) single nucleotide polymorphisms (SNPs) and SOS in children undergoing allogeneic HSCT.

Methods

We retrospectively analyzed the distribution of the both HPSE SNPs rs4693608 and rs4364254 and the occurrence of SOS after allogeneic HSCT in 160 children with malignant and non-malignant diseases.

Results

Patients with HPSE genotypes GG or AG of rs4693608 (G>A) had a significantly reduced incidence of SOS on day 100 after HSCT compared to patients with genotype AA (4.7 vs. 14.3 %, P = 0.038). In addition, incidence of SOS in patients with genotype CC or CT of rs4364254 (C>T) was significantly decreased in comparison with patients with genotype TT (2.3 vs. 14.7 %, P = 0.004). Interestingly, no patient with genotype CC developed SOS. Because both SNPs co-occur in vivo, we generated subsets: AA–TT, GG–CC, and a group with remaining SNP combinations. We found significant differences between all three patient groups (P = 0.035). Patients with AA–TT showed the highest incidence of SOS (16.7 %), while SOS did not appear in patients with GG–CC (0 %) and residual combinations were numerically in-between (4.9 %). An impact caused by main patient and donor characteristics, established risk factors for SOS, and conditioning regimen could be excluded in multivariate analyses.

Conclusions

HPSE polymorphisms turned out to be significant independent risk factors (P = 0.030) for development of SOS and should be evaluated in further trials.

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Conflict of interest

The authors have to declare no potential conflicts of interest.

Ethical standards

All children and/or their parents gave their informed consent prior to their inclusion in the study. This study was approved by the Institutional Review Board of the Medical Faculty of the University of Jena (4077-05/14).

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Authors and Affiliations

  1. Section for Hematology and Oncology, Department of Pediatrics, Jena University Hospital, Kochstraße 2, 07740, Jena, Germany

    Claudia Seifert, Susan Wittig, Clemens Arndt & Bernd Gruhn

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  1. Claudia Seifert
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  2. Susan Wittig
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  3. Clemens Arndt
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  4. Bernd Gruhn
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Correspondence to Bernd Gruhn.

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Seifert, C., Wittig, S., Arndt, C. et al. Heparanase polymorphisms: influence on incidence of hepatic sinusoidal obstruction syndrome in children undergoing allogeneic hematopoietic stem cell transplantation. J Cancer Res Clin Oncol 141, 877–885 (2015). https://doi.org/10.1007/s00432-014-1857-2

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  • DOI: https://doi.org/10.1007/s00432-014-1857-2

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