TRANSPLANTATION OF G-CSF MOBILIZED ALLOGENEIC PERIPHERAL-BLOOD STEM-CELLS IN RABBITS

Mobilized peripheral blood precursor cells (PBPC) are used with increasing frequency to restore autologous hematopoiesis following high-dose radio-chemotherapy. The success of this method has aroused interest in the use of mobilized PBPC for allogeneic transplants. This approach would eliminate the need for marrow aspiration and general anesthesia. In this project we tested the feasibility of allogeneic histoincompatible PBPC transplants in rabbits. Adult outbred Red Burgundy rabbits were used as donors, histoincompatible New Zealand White rabbits of the opposite sex as recipients. One individual donor was used for one individual recipient. Conditioning consisted of 10 Gy total body irradiation (TBI). Donor animals were pre-treated with recombinant human granulocyte colony-stimulating factor (rh G-CSF) given s.c. at 10 mu g/kg daily. Three schedules of PBPC collection and reinfusion were tested in 3 groups of animals, each consisting of 5 donor recipient pairs: (A) PBPC were collected either on days -2, -1 and 0, and infused at once after TBI on day 0; (B) collected and infused on days 0, +2, +4, +7, +9 and +11; (C) collected on 3 consecutive days, cryopreserved for 1 month and infused on day 0 followed by 3 fresh donations on days +4, +8 and +11. The median amount of blood processed from donor animals was 470 ml (312-602) containing about 10 x 10(8) (5-71 x 10(8)) nucleated cells. Recipient animals received a median of 2.7 x 10(8) cells/kg equivalent to 9.6 x 10(4) colony-forming units granulocyte-macrophages (CFU-GM)/kg (data derived from Group C of the animals). Two of the 15 transplanted animals died of TBI toxicity, all others engrafted as documented by histology or chromosomal analysis. Two animals (one in Group B and one in Group C) became long-term complete chimeras. Three rabbits died of bleeding or infection (one in each group) and 8 of GVHD. Median survival was 17 days (1-23) in Group A, 39 days (12 to >180 days) in Group B and 18 days (0 to >180 days) in Group C. These results show that G-CSF-mobilized PBPC can engraft across a major histocompatibility barrier. Repetitive infusions of PBPC appear not to intensify GVHD. These data support the continuation of the recently initiated trials with growth factor mobilized PBPC for allogeneic transplantation in man.