Study of Telomere Length Kinetics and Telomerase Reverse Transcriptase Gene Polymorphism in Children Undergoing Allogeneic Haematopoietic Stem Cell Transplantation.
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Background: Telomere length and telomerase activity are important determinants of haematopoietic cell proliferative capacity and may influence outcomes after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Genetic variation within the telomerase reverse transcriptase (TERT) gene may further contribute to transplantation success and post-transplant complications. Methods: Telomere length was assessed in 98 paediatric allo-HSCT recipients and their donors using quantitative real-time PCR before allo-HSCT and at one and two years post-transplantation. Selected four TERT polymorphisms (rs2736100, rs2853669, rs2735940, and rs10069690) were genotyped in donors and recipients before allo-HSCT. Associations between telomere length, genetic variants, and clinical outcomes were analysed. Results: Telomere length did not differ between recipients and donors before transplantation; however, donors younger than 18 years exhibited significantly longer telomeres. Telomere length increased at one and two years after allo-HSCT compared with pre-transplant values, with the most pronounced changes observed in patients with acute lymphoblastic leukaemia. No direct associations were found between TERT polymorphisms and telomere length. Nevertheless, the recipient rs2735940 T allele was associated with improved survival, the donor rs2736100 G allele with the achievement of complete chimerism, and the recipient rs2853669 C allele with an increased risk of acute graft-versus-host disease (aGvHD). Haplotype analysis identified associations between TERT variants and cytomegalovirus reactivation as well as aGvHD. Conclusions: Paediatric allo-HSCT is associated with dynamic post-transplant changes in telomere length. Although TERT polymorphisms did not directly affect telomere length, several variants were linked with clinically relevant transplantation outcomes, highlighting the potential role of telomere biology in haematopoietic reconstitution and transplant-related complications.