Evaluation of engraftment of ex vivo expanded cord blood cells in humans.
Cord blood transplants (CBT) result in high rates of engraftment in patients transplanted because of inherited diseases even across marked HLA disparities, mostly in children, with less severe manifestations of GVHD than BM and PBSC transplants. Evaluation of engraftment potential of CBT based on early progenitor content is difficult due to their inaccurate quantification. Instead, post-thaw nucleated cell counts (Pt-NCC) are commonly used for this purpose. We have analyzed engraftment as a function of pre-freeze nucleated cell counts (Pf-NCC) in patients receiving CBT because of inherited diseases. We have observed median times to engraftment of 26 days or less, shortest times ranging 8 to 13 days, late engraftment or graft failures tending 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 analysis. In these trials it is not possible to trace the actual origin of the early engrafting cells because the pre-cultured cells lack differentiating markers. To better evaluate the engraftment dynamics of culture-expanded CB cells in humans, we have used a model of simultaneously transplanting cells from two different donors to the same patient. Preliminary results of patients that have simultaneously received one uncultured CB unit and culture-expanded purified CB CD34+ cells obtained from a second one show no significant contribution of cultured cells to early engraftment, and no prohibitive unfavorable immunological problems have been observed.
Clínica Puerta de Hierro, Universidad Autónoma de Madrid, Spain.
M N
MN
Fernández
A
A
Grañena
I
I
Millán
C
C
Regidor
R
R
Cabrera
S
S
Querol
J
J
García
D000293:Adolescent; D000328:Adult; D001782:Blood Donors; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D005312:Fetal Blood / Q000166:cytology*; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D012189:Retrospective Studies; D013997:Time Factors