Evaluation of engraftment of ex vivo expanded cord blood cells in humans

Cord blood transplants (CBT) result in high rates of engraftment in patient s transplanted because of inherited diseases even across marked HLA dispari ties, mostly in children, with less severe manifestations of GVHD than BM a nd PBSC transplants, Evaluation of engraftment potential of CBT based on ea rly progenitor content is difficult due to their inaccurate quantification, Instead, post-thaw nucleated cell counts (Pt-NCC) are commonly used for th is purpose, We have analyzed engraftment as a function of pre-freeze nuclea ted cell counts (Pf-NCC) in patients receiving CBT because of inherited dis eases, We have observed median times to engraftment of 26 days or less, sho rtest times ranging 8 to 13 days, late engraftment or graft failures tendin g to be associated with age >15 years and infusions of <3.7 x 10(7)/Pf-NCC/ kg, These data may be appropriate references to evaluate engraftment of CBT performed with previously ex vivo expanded cells, CBT performed with units of which one aliquot has been previously culture-expanded have resulted in times to engraftment similar to the ones observed in the above-mentioned a nalysis. In these trials it is not possible to trace the actual origin of t he early engrafting cells because the pre-cultured cells lack differentiati ng markers, To better evaluate the engraftment dynamics of culture-expanded CB cells in humans, we have used a model of simultaneously transplanting c ells from two different donors to the same patient, preliminary results of patients that have simultaneously received one uncultured CB unit and cultu re-expanded purified CB CD34(+) cells obtained from a second one show no si gnificant contribution of cultured cells to early engraftment, and no prohi bitive unfavorable immunological problems have been observed,