Efficacy and safety of simultaneous immunomagnetic CD34+cell selection andbreast cancer cell purging in peripheral blood progenitor cell samples used for hematopoietic rescue after high-dose therapy
M. Mohr et al., Efficacy and safety of simultaneous immunomagnetic CD34+cell selection andbreast cancer cell purging in peripheral blood progenitor cell samples used for hematopoietic rescue after high-dose therapy, CLIN CANC R, 5(5), 1999, pp. 1035-1040
We have established a new simultaneous positive/negative selection procedur
e using the Baxter Isolex 300i system. We tested its tumor cell (TC) purgin
g efficacy by tumor contamination tests ex vivo and its safety in a group o
f 17 breast cancer (BC) patients by measuring hematopoietic recovery after
high-dose (HD) therapy and autologous stem cell rescue with the selected ce
lls. Tumor contamination tests resulted in a TC depletion of 4.1-6.0 log st
eps. The CD34+ cell yield in this experimental setting was 38.9-91.5%, and
the CD34+ cell purity was 86.0-96.0%, In a group of 17 BC patients (5 high-
risk adjuvant, greater than or equal to 10 lymph nodes positive, and 12 met
astatic), we processed leukapheresis products (LPs) by simultaneous positiv
e/negative selection. In these clinical samples, the mean CD34+ cell yield
was 56.2% (range, 14.0-80.1%), and the CD34+ cell purity was:94.5% (range,
69.0-99.8%). Additionally, we screened samples of the patients' LPs before
and after the purging procedure for contaminating TC by immunocytochemistry
. In 15 of 17 tested cases, TCs were detectable prior to the purging proced
ure. After the procedure, we could not detect residual TCs in 16 of 17 case
s. In one case, we found a highly reduced number of TCs, Furthermore, we ev
aluated the times for hematopoietic reconstitution in a group of five BC pa
tients in the high-risk adjuvant situation who underwent HD chemotherapy an
d hematopoietic rescue with positive/negative selected stem tells and compa
red it with our own data from 10 BC patients who, after identical HD therap
y, received only positively selected CD34+ cells and 14 patients who, after
identical HD therapy, received autografts purged by incubation with toxic
ether lipids (ET-18-OCH3), In all groups, a leukocyte count of >2000 cells/
mu l was reached at day +10, A platelet count of >50,000 cells/mu l was rea
ched at day +12 in the ET-18-OCH3 group and at day +14 in the other two gro
ups. Furthermore, 12 patients with metastatic disease rescued with positive
/negative selected stem cells after HD therapy also showed fast and compara
ble hematopoietic recovery. The new simultaneous immunomagnetic positive/ne
gative selection using a closed system is effective and safe. Processing LP
s leads to a similar CD34+ cell yield, a higher TC depletion compared to st
andard CD34+ cell selection, and no delay in hematopoietic recovery.