r 
Day 
ANC 
>100 
Day 
ANC > 
500 
Day 
ANC> 
1000 
Day pit 
indep 
(20,000/mm 3 
# pit 
units 
# rbc 
units 
Max 
creat. 
Day dis- 
charge 
GM- 
CSF 
(n=22) 
11 
15 
19 
21 
66 
6 
1.0 
25 
Placebo 
(n=19) 
11 
17 
27 
30 
104 
11 
1.6 
33 
p value 
038 
0.78 
0.03 
0.002 
0.027 
0.029 
0.039 
.006 
Patients who received rhGM-CSF had significantly earlier neutrophil recoveries which were associated 
with fewer infections and earlier discharge. Patients who received rhGM-CSF required less parenteral 
j nutrition (p= 0.004), antibiotics (p=0.01), and amphotericin (p=0.03). These results have also been 
duplicated in the initial 24 patients at Dana Farber using the same protocol (17). However, despite 
significant improvement in treatment related morbidity after administration of rhGM-CSF, a significant 
period of severe myelosuppression and associated complications remains. The number of days in which 
a patient’s ANC remains less than 100/mm 3 and 500/mm 3 after BMT was not shortened in patients 
who receive rhGM-CSF (6-8). 
Gianni, et al. have shown a significant reduction in the number of days without detectable 
jrculating leukocytes (p = 0.002) by supplementing autologous bone marrow cells with peripheral blood 
nucleated cells collected after prior myelosuppressive chemotherapy. In addition, the days in which the 
ANC reached 100, 500 and 1,000 cells/mm 3 (p= 0.003), the day of platelet independence (p = 0.001), the 
number of RBC transfusions (p = 0.017), the number of significant infections and the day of discharge 
(p= 0.045) were all significantly reduced compared to historical controls (18). Preliminary data from 
one study using 3 days of G-CSF primed PBMC, added to marrow and posttransplant G-CSF have 
shown modest improvement in the recovery of neutrophils but a large difference in time to platelet 
independence (Sheridan, W. personal communication). These results have been duplicated and further 
improved with the use of rhGM-CSF stimulated peripheral blood cells (19,20,21,22) and with the 
administration of rhGM-CSF after bone marrow infusions supplemented with peripheral blood 
(19,20,21,22). However, one investigator who has had experience with both GM-CSF and G-CSF 
primed peripheral blood cells added to marrow has claimed little difference in time to recovery of 
peripheral counts with either cytokine (Peters, personal communication). Most studies with G-CSF 
have utilized a 7 day administration schedule with peripheral blood collections on days 5-7. Peak 
concentrations of CFU-GM begin to appear in the blood on day 4-5 after G-CSF and last through days 
7 - 8 . 
When autologous peripheral blood transplants are performed without supplementation of bone 
marrow cells following myelosuppressive chemo-radiotherapy the majority of patients achieve rapid and 
sustained granulocyte recovery reaching ANC’s of 500/mm 3 within 10-15 days (23-29). However, in 
some studies platelet engraftment has been delayed (30,31) and subsequent falls in peripheral blood cell 
counts followed by marrow hypoplasia has been observed (31,32). Marrow hypoplasia after initial 
engraftment of peripheral blood cell transplants may be related to a reduced number of pluripotent 
stem cells. Since the episodes of secondary thrombocytopenia and neutropenia are observed mostly in 
Recombinant DNA Research, Volume 16 
[343] 
