A delay in bone marrow transplantation after partial conditioning improves engraftment.
BACKGROUND
In the present study we examined the effect of the timing of marrow infusion on engraftment in nonmyeloablatively conditioned mice.


METHODS
B10 mice were conditioned with decreasing doses of total body irradiation (TBI) and reconstituted with bone marrow cells (BMCs) from major histocompatibility complex-disparate donor B10.BR mice at 0 or 6 hr, or on days 1, 2, 3, 4, 5, 8, and 12 with respect to TBI.


RESULTS
After undergoing conditioning with 700 cGy TBI and transplantation with 15 x 10(6) BMCs, 100% of recipients engrafted if the marrow was infused between 0 and 4 days after TBI. For lower doses of TBI, a delay in infusion of the marrow after TBI conditioning was associated with a significant increase in engraftment. Significantly less engraftment was achieved in animals conditioned with 600 cGy TBI if the marrow was infused at 0 or 6 hr compared with a 1- to 4-day delay. When the TBI was decreased to 500 cGy, engraftment occurred only when the transplant was performed between days 2 and 8. The highest proportion of recipients engrafted when the marrow was infused on day 4. This enhanced engraftment after a delay in marrow infusion is associated with a significant reduction in host mixed lymphocyte reaction reactivity and is correlated inversely with serum levels of interleukin-6 in the recipient.


CONCLUSIONS
These data demonstrate for the first time that a delay between conditioning and marrow infusion significantly improves allogeneic engraftment in nonmyeloablatively conditioned recipients and reduces the total conditioning required.
Xu
Hong
H
Institute for Cellular Therapeutics, University of Louisville, Kentucky 40202, USA.
Exner
Beate G
BG
Chilton
Paula M
PM
Tanner
Michael K
MK
Mueller
Yvonne M
YM
Rezzoug
Francine
F
Ildstad
Suzanne T
ST
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods / Q000502:physiology*; D006084:Graft Rejection; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000379:methods / Q000502:physiology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000502:physiology; D014916:Whole-Body Irradiation