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Investigation of TGFB1 −1347C>T variant as a biomarker after allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 55, pages 215–223 (2020)Cite this article

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Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic option for malignant hematopoietic diseases. Cytokines including transforming growth factor β1 (TGFβ1) play a pivotal role in immune reconstruction, and the development of graft versus host disease (GvHD) or infections. The aim of this study was to investigate the role of TGFB1 gene −1347C>T variant in the outcome of HSCT in a cohort of 409 adult recipient-donor pairs. TGFB1 variant was analysed from genomic DNA with LightCycler hybridisation probe method. In case of myeloablative conditioning, donor TGFB1 genotype correlated with overall survival (60-month OS for CC: 62.1 ± 4.8%; CT: 46.8 ± 4.8%; TT: 35.6 ± 9.3%; p = 0.032), which was independent of age, donor type and GvHD prophylaxis in multivariate analysis (HR:2.35, 95%CI:1.35–4.10, p = 0.003). The cumulative incidence of acute GvHD grade III–IV [CC:10%; CT:17%; TT:24%], and non-relapse mortality was higher in TT-carriers (24-month NRM: CC:24%; CT:26%; TT:46%, p = 0.035). We did not find any association between recipient TGFB1 −1347C>T polymorphism and HSCT outcome. Our results suggest that donor TGFB1 −1347C>T may exert an adverse influence on the outcome of myeloablative conditioning transplantation.

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Acknowledgements

The authors wish to thank Csekő Zsófia, Haluska Brigitta and Petro Peterne for their technical assistance. HA and AB were supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (HA: BO/00579/17/5; AB: BO/00809/18/8), through the New National Excellence Program of the Ministry of Human Resources (HA: ÚNKP-18-4-SE-11). This work was supported by grants from NKFIH K104903 and the NVKP_16-1-2016-0005 program from the National Research, Development and Innovation Office.

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Authors and Affiliations

  1. Laboratory of Molecular Genetics, Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases, Budapest, Hungary

    Petra Kövy, Nóra Meggyesi, Lívia Varga, Katalin Balassa, András Bors & Hajnalka Andrikovics

  2. School of PhD Studies, Semmelweis University, Budapest, Hungary

    Petra Kövy & Lívia Varga

  3. Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases, Budapest, Hungary

    László Gopcsa, Melinda Paksi, Árpád Bátai & Péter Reményi

  4. Department of Microbiology, Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases, Budapest, Hungary

    Eszter Vad & János Sinkó

  5. Department of Pathophysiology, Semmelweis University, Budapest, Hungary

    Attila Tordai

  6. 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary

    Tamás Masszi

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Kövy, P., Meggyesi, N., Varga, L. et al. Investigation of TGFB1 −1347C>T variant as a biomarker after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 55, 215–223 (2020). https://doi.org/10.1038/s41409-019-0656-4

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