recovery from chemotherapy or during hematopoietic growth 
factor administration was found to increase progenitor or 
stem cell yield. 64 ' 67 
A number of small studies have been carried out with 
peripheral blood stem cell support alone or in combination 
with marrow transplantation in multiple myeloma. 68 ' 73 
Investigators became interested in this approach because it 
seemed to shorten neutropenia after transplant and because 
patients ineligible for bone marrow harvest due to prior 
extensive spine or pelvic radiotherapy or extensive pelvic 
tumor burden could be included in protocols employing this 
technique. 74 Also, peripheral blood was felt to be less 
contaminated than marrow by tumor cells. Results are 
conflicting on this issue, but even using relatively 
insensitive techniques, some investigators have detected 
circulating clonal plasmacytoid cells, s. 68 * 70 * 75 ' 77 There are 
animal models of myeloma suggesting that the malignant cells 
may arise outside of the bone marrow, i.e. in the lymph 
nodes or intestinal lymphoid tissue, then migrate via the 
peripheral blood to seed the bone marrow. 8 
Several studies have reported difficulty in collecting 
adequate numbers of nucleated peripheral blood cells or CFU- 
GM from multiple myeloma patients, most commonly after high- 
dose chemotherapy mobilization without growth factor 
augmentation. 6S ’» 7 ^- 73 . 78 These difficulties were more 
pronounced in patients that had received extensive prior 
chemotherapy. Other groups were able to collect adequate 
numbers of cells and to successfully perform transplants 
with peripheral blood stem cells alone, especially with the 
addition of growth factors to the high-dose chemotherapy 
mobilization regimens. 37,68 ' 70 ' 79 ' 80 
3.4 MECHANISM OF RELAPSE AFTER HIGH-DOSE THERAPY WITH AUTOLOGOUS 
STEM CELL SUPPORT 
The possibility of reinfusion of marrow or peripheral blood 
myeloma tumor cells during autologous transplantation has 
been a major theoretical hurdle to the use of this 
technique. The vast majority of myeloma patients receiving 
autologous marrow transplants have had gross contamination 
of ’mafrow with monoclonal plasma cells at the time of 
harvest. Most studies have excluded patients with > 30% 
marrow plasma cells. When a multivariate analysis was done 
of the impact of various pre-transplant characteristics on 
outcome, the marrow plasma cell percentage (below 30%) at 
the time of harvest had no effect on remission rate or 
median survival after transplantation. 44 One small study 
has been carried out using antibodies against a mature 
plasma cell antigen (PCA-1) , a pan-B cell antigen (CD20) , 
and an immature B-cell antigen (CALLA or CD10) to purge the 
[44] 
Recombinant DNA Research, Volume 16 
