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

Abstract

Summary. 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 naïve and memory CD4 + T lymphocytes in recipients of allo‐BMT at long‐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 naïve CD4 + T cells. Our data therefore provide no evidence for sustained telomere shortening in leucocytes, and render the possibility of 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 naïve CD4 + T cells in the blood was significantly lower in recipients (0·4 × 10 9 /l) than in donors (0·7 × 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.