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

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 (...

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Published in:Bone marrow transplantation (Basingstoke) 2020-01, Vol.55 (1), p.215-223
Main Authors: Kövy, Petra, Meggyesi, Nóra, Varga, Lívia, Balassa, Katalin, Bors, András, Gopcsa, László, Paksi, Melinda, Bátai, Árpád, Vad, Eszter, Sinkó, János, Tordai, Attila, Masszi, Tamás, Reményi, Péter, Andrikovics, Hajnalka
Format: Article
Language:English
Subjects:
Adult
Biomarkers
Conditioning
Cytokines
Deoxyribonucleic acid
DNA
Gene polymorphism
Genomics
Graft vs Host Disease
Graft-versus-host reaction
Growth factors
Hematopoietic Stem Cell Transplantation
Hematopoietic stem cells
Humans
Hybridization
Multivariate analysis
Neoplasm Recurrence, Local
Polymorphism
Prophylaxis
Stem cell transplantation
Stem cells
Transforming Growth Factor beta1 - genetics
Transforming growth factor-b1
Transplantation
Transplantation Conditioning
Transplantation, Homologous
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Summary: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.
ISSN:0268-3369
1476-5365
DOI:10.1038/s41409-019-0656-4