D. Data can be generated concerning the feasibility of using PBSC’s for allografting in the 
future. 
Background. 
A. Evidence that PBSC’s Collected in the Steady State Engraft, 
Cavins et al, in 1964, demonstrated that cryopreserved autologous leukocytes could 
reconstitute the hematopoietic system of lethally irradiated dogs (1). This study was 
repeated in 1968 by Storb et al who also demonstrated that marrow repopulating cells 
from peripheral blood did not recirculate in the thoracic duct (2). Canine and non- 
human primate allografts have also been achieved at this institution with peripheral 
blood cells or by cross circulation (3-5). Quantitative studies in the dog by Appelbaum 
indicated that 6 X 10‘/kg of peripheral blood mononuclear cells were required for 
autologous engraftment as compared to 0.25 X 10 */kg of nucleated marrow cells (6). 
Other investigators have also demonstrated that auto and allografts can be obtained 
using peripheral blood leukocytes in the canine model (7-9). Autologous PBSC’s have 
also been used to successfully engraft dogs with malignant lymphoma treated with TBI 
( 10 ). 
The presence of lineage-restricted hemopoietic progenitor cells in the peripheral blood 
was demonstrated in culture by McCredie et al in 1971 with a frequency of colony 
formation of 1-10% that. of marrow (11).. Such colony-forming units, especially of 
granulocyte-macrophage lineage (CFU-GM), have become a standard method for 
measuring committed and possibly indirectly of uncommitted primitive stem cell 
populations. 
Despite the relatively low concentration of CFU-GM’s in the peripheral blood successful 
autografts have been achieved in many patients (12-22). However, for successful 
autologous transplants multiple apheresis procedures (an average of 9) are necessary to 
obtain sufficient hematopoietic progenitors for consistent engraftment (23). The largest 
experience with autologous transplants using unstimulated PBSC’s alone is from 
Nebraska (13,14,23). They have collected PBSC’s from 89 patients with a variety of 
malignancies (23). A median of 9 (range 6 - 12) apheresis procedures were required for 
each patient Collections contained a median of 0.66 (range, .04 - 29.67) X 10 4 CFU- 
GM /kg. Sixty-seven patients have been transplanted with PBSC’s following high dose 
therapy without post-transplant cytokine administration. The median time to reach .5 X 
10 9 /L granulocytes after transplant was 24 days (range 11 - 80). Median time for 60 
evaluable patients to reach platelet transfusion independence was 23 days (range 9-91). 
B. Enhancement of PBSC Collection Following Chemotherapy. 
Richmond et al, in 1979, reported a rebound of circulating hemopoietic precursors after 
nonmyeloablative chemotherapy (24). This observation has led to z series of studies 
documenting the feasibility of collecting large quantities of CFU-GM following intensive 
chemotherapy, especially with high-dose cyclophosphamide, utilizing fewer collection 
procedures (25-27). PBSC’s collected after remission induction in patients with AML 
have also been used for autologous transplants (28-31). Prompt and sustained 
engraftment occurs in the majority of patients with AML receiving such autologous 
transplants depending on the dose of CFU-GM collected (29,31). However, some 
patients develop late graft failure which is not related to the dose of CFU-GM and may 
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