Influence of baseline telomere length on the results of immunosuppressive therapy in aplastic anemia patients

Abstract

Background. Acquired aplastic anemia (AA) is a non-tumor disease of the blood system and the pathogenesis is based on immune dysregulation directed against own hematopoietic stem cells, which leads to the development of bone marrow aplasia. Some modern research is directed to the study of intrinsic defects of hematopoietic stem cells, and one of which is the change in telomere length. Several large studies have shown the association of telomere shortening in AA patients with decreased overall survival, poor response to immunosuppressive therapy (IST), high rates of relapse and clonal complications.Aim. To study the influence of the initial telomeric DNA regions length in AA patients on the disease course.Materials and methods. 43 adult patients with acquired AA without previous pathogenetic therapy were included in the study. IST was performed according to a standard protocol including the use of hATG and cyclosporine. Flow-FISH was used as the method for measuring relative telomere length, and peripheral blood mononuclear cells were used as the study material.Results. Telomere length determined before IST did not differ between non-severe and severe AA, but there were significant differences depending on disease duration (p = 0.032). Initially short telomeres correlated with a lower rate of achieving hematologic improvement (53 % vs. 80 %; p = 0.059). In addition, significantly worse results were obtained in achieving partial and complete remission in patients with initially short telomeres compared to those with initially long telomeres (37 % vs. 62 % and 5 % vs. 23 %, respectively; p <0.05). There was a tendency to increase the frequency of new chromosomal aberrations in patients with shorter telomere length.Conclusion. The results obtained do not contradict previous studies and show the association of a decrease in baseline telomere length with poor response to IST and a high risk of clonal complications. The determination of telomere length should be used both in differential diagnosis between the acquired disease and congenital bone marrow failure syndromes, and for timely choice of patient management tactics (IST or allogeneic hematopoietic stem cell transplantation).