be due to intrinsic defects of stem cells in patients with AML (31). PBSC’s mobilized 
after chemotherapy increase the tempo of engraftment when given with marrow (27). 
C. Enhancement of PBSC Collections Following Chemotherapy and Growth Factor 
Administration. 
GM-CSF has been given following chemotherapy to further enhance PBSC yields (33,34). 
PBSC’s exposed to GM-CSF following chemotherapy have produced sustained 
engraftment in a small number of patients. However, most of the experience has been 
with marrow plus PBSC’s. Gianni collected PBSC’s following cytotoxic therapy and GM- 
CSF in 2 patients with multiple myeloma. Both received TBI containing regimens and 
GM-CSF stimulated PBSC’s as the sole source of hematopoietic progenitor cells (33). 
Both patients engrafted promptly and had sustained hematopoiesis at 6 and 9 months 
post-transplant. 
D. Enhancement of PBSC Collection Following Growth Factor Administration without 
Chemotherapy. 
Growth factors given without chemotherapy have also been evaluated for their potential 
to increase hematopoietic progenitors in the peripheral blood. Hermann et al 
demonstrated a dose-related elevation of circulating myeloid progenitor cells with a 
mean 8.1 fold increase at a dose level of 1,000 /*g/m 2 /24 hours in patients with advanced 
hematological malignancies (34). Socinski et al reported a median increase of 18 times in 
the number of CFU-GM in peripheral blood after a continuous infusion of GM-CSF 
with escalating doses from 4-64 /zg/ kg/day in patients with solid tumors who had not 
received chemotherapy (35). 
Duhrsen et al monitored peripheral blood and marrow in 30 patients with cancer 
receiving G-CSF in a PHASE I/II clinical trial (36). The absolute number of circulating 
progenitor cells of granulocyte macrophage, erythroid, and megakaryocyte lineages 
showed a dose-related increase up to 100 fold after 4 days of treatment with G-CSF and 
often remained elevated 2 days after cessation of treatment. Progenitor cells in the 
marrow were in general slightly decreased. Similar findings have been observed by others 
(37,38). 
Janakiraman et al gave G-CSF (5 /tg/kg/day) to 6 patients with malignancy and collected 
PBSC’s on days 6, 8 and 9 (39). They were able to collect a total of 25.6 X 10 9 
mononuclear cells or 8.52 X 10 9 per collection. This was more than twice the quantity 
collected following CY in a similar group of patients. The concentration of CFU-GM and 
BFU-E was similar to that in the PBSC’s collected after Cy suggesting an overall 
increase in the number of progenitors collected. 
E. E ngraftment with PBSC’s Collected after Growth Factor Administration without Prior 
Cytotoxic Therapy. 
At the University of Nebraska thirty-four patients with a variety of malignancies had 
PBSC’s collected following GM-CSF given as a 24 hour infusion at 250 jtg/M 2 until the 
peripheral WBC exceeded 10 X 10 9 /L.(23) GM-CSF dosage was decreased by 50% and 
collections were started and GM-CSF was continued until the collections were complete. 
Dosage was decreased for a WBC > 25 X 10 9 /L or for severe bone pain. Six patients 
failed to reach 10 X 10 9 /L WBC prior to the first apheresis but only 1 patient had WBC 
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Recombinant DNA Research, Volume 16 
