PERIPHERAL-BLOOD PRECURSOR CELL TRANSPLANTS ACROSS A MAJOR HISTOCOMPATIBILITY BARRIER IN RABBITS - POSITIVE EFFECTS OF A HIGHER NUMBER OF PRECURSOR CELLS
A. Gratwohl et al., PERIPHERAL-BLOOD PRECURSOR CELL TRANSPLANTS ACROSS A MAJOR HISTOCOMPATIBILITY BARRIER IN RABBITS - POSITIVE EFFECTS OF A HIGHER NUMBER OF PRECURSOR CELLS, Acta haematologica, 95(3-4), 1996, pp. 176-180
Peripheral blood precursor cells (PBPCs) are used with increasing freq
uency for hematopoietic transplants and have more or less replaced aut
ologous bone marrow transplants. First clinical and experimental repor
ts document the feasibility of PBPCs as a source for allogeneic transp
lants. Few data exist on the optimal procedure and the ideal number of
cells for the transplant. We have previously shown in rabbits that PB
PCs can be used for transplants even across a major histocompatibility
barrier. We used this model to test whether the number of transplante
d precursor cells would influence graft outcome. Adult outbred Red Bur
gundy rabbits were used as donors, New Zealand White rabbits of the op
posite sex as recipients. One individual donor was taken for one indiv
idual recipient. Conditioning consisted of single-dose total body irra
diation of 10 Gy followed by a short course of cyclosporine to enhance
engraftment. Donor animals were treated with recombinant human granul
ocyte-colony-stimulating factor, 10 mu g/kg subcutaneously daily from
day -2 until day +9. PBPCs were obtained from the artery of the donor
animal by repetitive centrifugation of 2 x 40 ml heparinized blood on
each day of donation, i.e. days 0, +2, +3, +6, +8, and +10 and infused
without further manipulation. Eight animals underwent transplantation
. Seven took the grafts, six died of graft-versus-host disease and pne
umonia between days 12 and 55 (median survival of all animals: 34 days
). One animal was still alive after 120 days. Transplanted nucleated c
ells varied from 7.3 to 15.4 x 10(8)/kg (median 9.2 x 10(8)/kg) and CF
U-GM from 12.3 to 176.8 x 10(4)/kg (median 42 x 10(4)/kg). Survival te
nded to increase with more CFU-GM) r = 0.716, p = 0.0704). These data
confirm that allogeneic PBPCs can engraft across a major histocompatib
ility barrier and suggest that a higher number of CFU-GM might be adva
ntageous.