ACCELERATED TELOMERE SHORTENING IN YOUNG RECIPIENTS OF ALLOGENEIC BONE-MARROW TRANSPLANTS

Background The establishment of donor-derived haemopoiesis in the reci pients of allogeneic bone-marrow transplants (BMT) involves extensive proliferation of haemopoietic stem cells. The biological consequences of this replicative stress are ill defined, but any ''ageing'' effect would carry the risk of an increased frequency of clonal disorders dur ing later life. We compared blood-cell mean telomere lengths in donor/ recipient pairs. Methods Mean telomere length was calculated by in-gel hybridisation to leucocyte DNA from 56 normal individuals aged 0-96 y ears, and from 14 consecutive BMT recipients (aged 2-14 years) plus th eir respective donors (aged 2-46 years). Engraftment was confirmed by variable numbers of tandem repeats (VNTR) or gender analysis. Findings On average, blood-cell telomeres of transplant recipients were 0.4 hb (95% CI -0.2 to -0.6) shorter than those of their respective donors. This degree of telomere loss is equivalent to a median of 15 years' (r ange 0-40) ageing in the healthy controls. Interpretation The kinetics of haemopoietic engraftment impose replicative stress on the haemopoi etic stem cells, resulting in a pronounced ageing effect, which may be sufficient to accelerate the onset of clonal haemopoietic disorders u sually associated with later life. Monitoring of haemopoietic status i n BMT recipients as time since BMT increases will be important. Assess ment of transplant protocols under development in terms of their effec ts on telomere shortening is also indicated.