Telomeres are long stretches of DNA associated with protein complexes located at each chromosome end that protect our genetic data. Each time a cell divides the telomeres shorten and when it is too abbreviated the cell stops proliferating. Consequently, telomere length is a marker of cellular replicative capacity, senescence, and aging.
Short telomere length has been associated with more relapse, evolution to MDS or AML (clonal evolutions) and even with a poorer survival in patients with aplastic anemia treated with immunosuppressive therapies, the standard treatment for those who lack a suitable matched related donor or are older.
For young aplastic anemia patients, hematopoietic stem cell transplantation (HSCT) is recommended when a matched sibling donor is available. Unrelated HSCT (from a non-familial donor) does not achieve results that are as good as related HSCT and thus is not indicated as first-line therapy. However, considering that only one-third of aplastic anemia patients have a matched-sibling donor available, it is necessary to identify factors associated with better results in the setting of unrelated HSCT.
Gadalla et al conducted a study published recently in the Journal of the American Medical Association (JAMA) evaluating the association between leukocyte telomere length and outcomes in 330 matched unrelated HSCT for severe aplastic anemia performed in 84 transplant centers around the world. They showed that longer donor leukocyte telomere length was associated with increased survival in patients who received unrelated HSCT for aplastic anemia, independently of donor age. However, recipient leukocyte telomere length was not associated with outcome and there was no association between donor telomere length and bone marrow engraftment or incidence of graft-versus-host disease (GVHD).
In the same issue of this journal, an editorial by Drs. Saad, Mineishi and Innis-Shelton from the Blood and Marrow Transplantation & Cell Therapy Program, Birmingham, Alabama, discussed the applicability of these findings and point that donor telomere length may help in choosing optimal donors for unrelated HSCT in aplastic anemia. However, a reasonable explanation on how telomere length influence the HSCT outcome is still lacking. Bone marrow engraftment failure and GVHD incidence are major factors that impact HSCT survival in aplastic anemia and none of then were associated with donor leukocyte telomere length in the Gadalla study.
In conclusion, the results presented by Gadalla et al are important and warrant further investigation to define the role of leukocyte telomere length in selecting donors and improving outcomes for aplastic anemia patients who receive HSCT. Many questions need to be resolved before this test can be applied at routine donor surveillance.
*Note this research review also includes this second research article.