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

Mobilized peripheral blood precursor cells (PBPC) are used with increa sing frequency to restore autologous hematopoiesis following high-dose radio-chemotherapy. The success of this method has aroused interest i n 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 histoincompat ible PBPC transplants in rabbits. Adult outbred Red Burgundy rabbits w ere used as donors, histoincompatible New Zealand White rabbits of the opposite sex as recipients. One individual donor was used for one ind ividual recipient. Conditioning consisted of 10 Gy total body irradiat ion (TBI). Donor animals were pre-treated with recombinant human granu locyte colony-stimulating factor (rh G-CSF) given s.c. at 10 mu g/kg d aily. 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 a fter 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 mon th and infused on day 0 followed by 3 fresh donations on days +4, +8 a nd +11. The median amount of blood processed from donor animals was 47 0 ml (312-602) containing about 10 x 10(8) (5-71 x 10(8)) nucleated ce lls. Recipient animals received a median of 2.7 x 10(8) cells/kg equiv alent 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 tran splanted animals died of TBI toxicity, all others engrafted as documen ted 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. Media n 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 t hat G-CSF-mobilized PBPC can engraft across a major histocompatibility barrier. Repetitive infusions of PBPC appear not to intensify GVHD. T hese data support the continuation of the recently initiated trials wi th growth factor mobilized PBPC for allogeneic transplantation in man.