Long-term follow-up of recipients of allogeneic bone marrow grafts reveals no progressive telomere shortening and provides no evidence for haematopoietic stem cell exhaustion

Accelerated telomere shortening has been proposed as a possible long-term risk of allogeneic bone marrow transplantation (allo-BMT). In this study we monitored telomere length in white blood cells (WBC), granulocytes, and naive and memory CD4(+) T lymphocytes in recipients of allo-BMT at tong-term follow-up. Peripheral blood was collected from 10 allo-BMT recipients and donors at a median interval of 18 years after allo-BMT. Telomere length was determined using Southern blot analysis, Similar to results previously reported at short-term follow-up, a small difference in telomere length (0.1-0.3 kb) between recipients and donors was detected in WBC, granulocytes and naive CD4(+) T cells. Our data therefore provide no evidence for sustained telomere shortening in leucocytes, and render the possibility long-term haematopoietic graft failure unlikely. In addition, we observed two phenomena that may be related to involution of the thymus. First, the number of naive CD4(+) T cells in the blood was significantly lower in recipients (0.4 x 10(9)/l) than in donors (0.7 x 10(9)/l) (P < 0.05). Second, telomeres in memory CD4(+) T cells from recipients were on average 0.6 kb shorter than those from donors (P = 0.01). The latter may be related to the reported rapid peripheral expansion of memory T cells immediately after transplantation.