Should telomere length be tested before a stem cell transplant?

Stem cell transplants save lives; but should doctors be considering donor telomere length ahead of a transplant, and if so, why?

What is a stem cell transplant and why are they needed?

Stem cell transplants (SCTs) involve collecting cells from the blood stream or bone marrow and delivering them to the recipient’s blood by transfusion. Once transfused, stem cells migrate to the recipient’s bone marrow and will go on to engraft and produce healthy blood cells. Hematopoietic stem cells produce red blood cells (erythrocytes), white blood cells (leukocytes), and platelets.

SCTs are one of the available treatments for bone marrow failure, aplastic anemia and primary immune deficiencies; as well as being used to treat some cancers, including leukemia, lymphoma and myeloma.

Stem cells can come from a sibling, a parent or an unrelated donor (allogeneic). In the case of cancer, stem cells can even come from the recipient themselves – donated prior to their chemo- or radiotherapy. A lot of work goes into making sure a donor is a good match for the recipient to enable the most successful outcomes.

Telomeres and stem cell transplants

Telomeres are the protective structures located at the ends of chromosomes. When telomeres are extremely short, cells can no longer divide effectively and may be subjected to genomic instability. You can learn more about telomere structure and function here.

In cells that have high levels of proliferation over a lifetime, such as bone marrow stem cells, telomere length (TL) is a key indicator of proliferative reserve. This may be even more important following a SCT, with evidence showing accelerated telomere shortening in the first-year post-transplant due to heightened cell production.

Despite this shortening of telomeres in the initial phase following transplantation, studies do indicate a strong relationship between donor pre-transplant TL and recipient post-transplant TL. This provides support for the testing of TL when selecting a stem cell donor, particularly when considering a related donor for a transplant to treat a telomere biology disorder or another heritable disease.

Furthermore, multiple studies have found an association between longer donor TL and improved survival after hematopoietic SCT in severe aplastic anemia. While donor age itself is also a factor in transplant outcome success, the association with longer TL is still observed when controlling for age. This indicates that TL remains an important independent factor in the success of a SCT for aplastic anemia.

Conversely, a study investigating TL in relation to outcomes following SCT for acute leukemia did not find a significant association.

In summary, there is a growing body of evidence to support the consideration of donor TL prior to a SCT, alongside other critical factors such as HLA matching, to ensure the optimal outcome of a successful transplant. More research will help to indicate how this TL information can be applied in different SCT circumstances.

RepeatDx is the leading laboratory offering comprehensive telomere length testing, providing reliable results in an efficient turn around time, and even the option of an expedited service. You can find out more information, and order a telomere length analysis here.

Sources

Aliénor, X. et al. Clinical profile, biological markers, and comorbidity index as predictors of transplant-related mortality after allo-HSCT. Blood Advances. vol. 1,18 1409-1413. 2 Aug. 2017, doi:10.1182/bloodadvances.2017008094.

Ruella, M. et al. Comparative assessment of telomere length before and after hematopoietic SCT: role of grafted cells in determining post-transplant telomere status. Bone Marrow Transplant. 2010 Mar;45(3):505-12. doi: 10.1038/bmt.2009.297.

Shahinaz, G,M. et al. Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia. JAMA. vol. 313,6 (2015): 594-602. doi:10.1001/jama.2015.7.

Shahinaz, G,M. et al. Donor telomere length and causes of death after unrelated hematopoietic cell transplantation in patients with marrow failure. Blood. vol. 131,21 (2018): 2393-2398. doi:10.1182/blood-2017-10-812735.

Shahinaz, G,M. et al. No association between donor telomere length and outcomes after allogeneic unrelated hematopoietic cell transplant in patients with acute leukemia. Bone Marrow Transplantation. vol. 53,4 (2018): 383-391. doi:10.1038/s41409-017-0029-9.