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- W4313351567 abstract "Abstract Allogeneic stem cell transplant (SCT) is a potentially curative option for many hematologic diseases, yet donor availability remains a challenge, and haploidentical SCT is associated with a higher risk of rejection. We successfully translated a model based on total-body irradiation (TBI) with to humans; however, TBI involves toxicities and risk of malignant side-effects, and we hypothesize that busulfan may be a superior alternative in some settings. G-CSF-mobilized F1/J (C57BL/6-BALB/c hybrid) splenocytes were injected into C57BL/6 hosts who had received 10-30mg/kg IP busulfan the previous day. All recipients received 31 days of 3mg/kg IP sirolimus beginning the day before transplant. No GvHD was observed and counts recovered by week 8 in all groups. Mice conditioned with 30mg/kg busulfan displayed remarkably high donor chimerism (>90%), which was significantly higher than 300cGy TBI-conditioned control mice (64-86%) across all timepoints. Mice receiving 30mg/kg or 20mg/kg busulfan maintained stable chimerism for over 18 months. Mice conditioned with 10mg/kg busulfan showed only transient chimerism through 4 weeks. Proliferation of CD4+ cells in response to donor increases with decreasing busulfan, and mice receiving 30mg/kg responded more strongly than mice receiving TBI. A memory effect was observed in mice that received 10mg/kg busulfan and lost their grafts. Notably, a slightly higher incidence of host-derived Tregs in mice was also observed after graft rejection." @default.
- W4313351567 created "2023-01-06" @default.
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- W4313351567 date "2013-05-01" @default.
- W4313351567 modified "2023-09-27" @default.
- W4313351567 title "Nonmyeloablative conditioning employing busulfan and sirolimus permits donor-dominant stable chimerism in a murine model of haploidentical allogeneic stem cell transplantation (P2192)" @default.
- W4313351567 doi "https://doi.org/10.4049/jimmunol.190.supp.69.34" @default.
- W4313351567 hasPublicationYear "2013" @default.
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