PERIPHERAL-BLOOD PRECURSOR CELL TRANSPLANTS ACROSS A MAJOR HISTOCOMPATIBILITY BARRIER IN RABBITS - POSITIVE EFFECTS OF A HIGHER NUMBER OF PRECURSOR CELLS

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.