A. Gratwohl et al., TRANSPLANTATION OF G-CSF MOBILIZED ALLOGENEIC PERIPHERAL-BLOOD STEM-CELLS IN RABBITS, Bone marrow transplantation, 16(1), 1995, pp. 63-68
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.