Nonmyeloablative conditioning does not prevent telomere shortening after allogeneic stem cell transplantation.
BACKGROUND
Stem cell transplantation (SCT) may be associated with premature aging of the hematopoietic stem cells. Telomere length reflects the proliferative history of a cell. In most studies published so far on telomere dynamics after myeloablative allogeneic SCT, recipients had shorter telomeres than their respective donors, thus reflecting "accelerated aging" of hematopoietic cells. We evaluated telomere dynamics in patients who underwent transplantation with nonmyeloablative protocols, assuming that the decreased intensity of chemotherapy might prevent telomere attrition.


METHODS
Telomere length was measured using FISH-FACS method. Telomeres of recipients were compared to their respective donors. Twenty-three consecutive patients after nonmyeloablative SCT were evaluated. A control group consisted of 10 donor-recipient pairs after conventional myeloablative transplantation.


RESULTS
There was significant telomere shortening in both recipients of nonmyeloablative and myeloablative conditioning (0.487+/-0.65 kb, P=0.003; 0.361+/-0.50 kb, P=0.047 respectively). The extent of telomere shortening in the two groups was not different (P=0.64). There was no correlation between the degree of shortening and parameters such as time interval from transplant, age of donor or recipient, and the number of infused cells.


CONCLUSIONS
This is the first study on telomere dynamics after nonmyeloablative conditioning SCT. The study demonstrates significant shortening of telomeres in recipients in spite of decreased intensity conditioning. Results of this study suggest that the main mechanism following transplantation is the proliferative stress imposed upon the stem cells and not direct damage by cytotoxic drugs. The different kinetics of restoration of hematopoiesis and the probable ongoing process of graft-versus-leukemia in the bone marrow do not prevent the attrition of telomeric ends of chromosomes.
Lahav
Meir
M
Medicine A, Rabin Medical Center, Beilinson Campus, Petah-Tikva. Sackler School of Medicine, Tel-Aviv University, Israel. mlahav@post.tau.ac.il
Uziel
Orit
O
Kestenbaum
Meir
M
Fraser
Abigail
A
Shapiro
Hava
H
Radnay
Judith
J
Szyper-Kravitz
Martine
M
Avihai
Shimoni
S
Hardan
Izhar
I
Shem-Tov
Noga
N
Nagler
Arnon
A
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D016922:Cellular Senescence; D004247:DNA / Q000032:analysis; D005260:Female; D020544:Graft vs Leukemia Effect; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016615:Telomere / Q000378:metabolism*; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D004247:DNA