Cellular senescence of white blood cells in very long-term survivors after allogeneic hematopoietic stem cell transplantation: the role of chronic graft-versus-host disease and female donor sex.
In this single-center, cross-sectional study, we evaluated 44 very long-term survivors with a median follow-up of 17.5 years (range, 11-26 years) after hematopoietic stem cell transplantation. We assessed the telomere length difference in human leukocyte antigen-identical donor and recipient sibling pairs and searched for its relationship with clinical factors. The telomere length (in kb, mean +/- SD) was significantly shorter in all recipient blood cells compared with their donors' blood cells (P < .01): granulocytes (6.5 +/- 0.9 vs 7.1 +/- 0.9), naive/memory T cells (5.7 +/- 1.2 vs 6.6 +/- 1.2; 5.2 +/- 1.0 vs 5.7 +/- 0.9), B cells (7.1 +/- 1.1 vs 7.8 +/- 1.1), and natural killer/natural killer T cells (4.8 +/- 1.0 vs 5.6 +/- 1.3). Chronic graft-versus-host disease (P < .04) and a female donor (P < .04) were associated with a greater difference in telomere length between donor and recipient. Critically short telomeres have been described in degenerative diseases and secondary malignancies. If this hypothesis can be confirmed, identification of recipients at risk for cellular senescence could become part of monitoring long-term survivors after hematopoietic stem cell transplantation.
Department of Hematology, University Hospital, University of Bern, Bern, Switzerland. Gabriela.Baerlocher@insel.ch
Gabriela M
GM
Baerlocher
Alicia
A
Rovó
Astrid
A
Müller
Sybille
S
Matthey
Martin
M
Stern
Jörg
J
Halter
Dominik
D
Heim
Johannes
J
Rischewski
Alois
A
Gratwohl
André
A
Tichelli
D000293:Adolescent; D000328:Adult; D016922:Cellular Senescence; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007962:Leukocytes / Q000145:classification / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D035781:Siblings; D016615:Telomere / Q000473:pathology; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous; D055815:Young Adult