Peripheral blood pressure cells 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 frequency for hematopoietic transplants and have more or less replaced autologous bone marrow transplants. First clinical and experimental reports document the feasibility of PBPCs as a source for allogeneic transplants. Few data exist on the optimal procedure and the ideal number of cells for the transplant. We have previously shown in rabbits that PBPCs can be used for transplants even across a major histocompatibility barrier. We used this model to test whether the number of transplanted precursor cells would influence graft outcome. Adult outbred Red Burgundy rabbits were used as donors, New Zealand White rabbits of the opposite sex as recipients. One individual donor was taken for one individual recipient. Conditioning consisted of single-dose total body irradiation of 10 Gy followed by a short course of cyclosporine to enhance engraftment. Donor animals were treated with recombinant human granulocyte-colony-stimulating factor, 10 micrograms/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 pneumonia between days 12 and 55 (median survival of all animals: 34 days). One animal was still alive after 120 days. Transplanted nucleated cells varied from 7.3 to 15.4 x 10(8)/ kg (median 9.2 x 10(8)/kg) and CFU-GM from 12.3 to 176.8 x 10(4)/kg (median 42 x 10(4)/kg). Survival tended to increase with more CFU-GM) r = 0.716, p = 0.0704). These data confirm that allogeneic PBPCs can engraft across a major histocompatibility barrier and suggest that a higher number of CFU-GM might be advantageous.
Gratwohl
A
A
Department of Research, Kantonsspital Basel, Switzerland.
Baldomero
H
H
John
L
L
Tichelli
A
A
Filipowicz
A
A
Nissen
C
C
Speck
B
B
D000818:Animals; D001772:Blood Cell Count; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007958:Leukocyte Count; D008264:Macrophages / Q000166:cytology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D011817:Rabbits; D014184:Transplantation, Homologous
D016179:Granulocyte Colony-Stimulating Factor