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.
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.
Authors: Hong Xu; Yiming Huang; Paula M Chilton; Lala-Rukh Hussain; Michael K Tanner; Jun Yan; Suzanne T Ildstad Journal: J Immunol Date: 2008-11-01 Impact factor: 5.422
Authors: Yunchuan Ding; Marcello Rotta; Scott S Graves; Barry E Storer; Laura J Peterson; George E Sale; Reza Forough; Eustacia Zellmer; George E Georges; Brenda M Sandmaier; Christian S Kuhr; Rainer Storb Journal: Biol Blood Marrow Transplant Date: 2009-08-03 Impact factor: 5.742