Highly sensitized patients are forced to stay on transplant waiting lists f
or many years and ultimately may never find a donor. Peripheral blood stem
cell (PBSC) transplantation may provide a strategy to decrease host allorea
ctivity through the production of a chimeric state. We investigated allorea
ctivity and chimerism. in a highly sensitized 40-year-old patient with sick
le cell disease who underwent a nonradiation based conditioning regimen con
sisting of fludarabine, ATG, and high dose melphalan, for allogeneic stem c
ell transplant. Host monocytes and lymphocytes became donor in origin by da
y 14. PRA, initially 100% pretransplant, fell to 0 by day 263. Anti-red blo
od cells antibody became undetectable by day 152. The use of a new nonradia
tion-based conditioning regimen enabled successful engraftment of allogenei
c donor PBSCs and the elimination of alloantibody. As new less toxic condit
ioning regimens are developed, PBSC transplantation might provide a new sol
ution to allosensitization.