title: 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: 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 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.
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Elmar S D
authors.initials: ES
authors.lastname: de Pauw
authors.forename: Sigrid A
authors.initials: SA
authors.lastname: Otto
authors.forename: Juul T
authors.initials: JT
authors.lastname: Wijnen
authors.forename: Jaak M
authors.initials: JM
authors.lastname: Vossen
authors.forename: Margreet H
authors.initials: MH
authors.lastname: van Weel
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Tanke
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
authors.forename: Roel
authors.initials: R
authors.lastname: Willemze
authors.forename: Helene
authors.initials: H
authors.lastname: Roelofs
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D005500:Follow-Up Studies; D006098:Granulocytes / Q000648:ultrastructure; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007156:Immunologic Memory; D007938:Leukemia / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy; D007951:Leukemia, Myeloid / Q000276:immunology / Q000628:therapy; D007962:Leukocytes / Q000648:ultrastructure*; D018655:Lymphocyte Count; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy; D016615:Telomere / Q000648:ultrastructure*; D014019:Tissue Donors; D014184:Transplantation, Homologous