Fe. Davies et al., Positive and negative selection to reduce tumour contamination in peripheral blood stem cell harvests, HEMATOL ONC, 18(3), 2000, pp. 111-120
Peripheral blood progenitor cells used during high dose treatments for mali
gnancy may be contaminated with tumour cells that could later contribute to
recurrence. CD34 + selected harvests still contain tumour cells and an add
itional negative selection may be capable of reducing this contamination. W
e have assessed a two-stage technique in which a CD34 + selection is follow
ed by a tumour specific depletion stage using a B cell or breast cancer spe
cific antibody panel. Initial small-scale selections on 11 patients with NH
L and breast cancer showed that cell loss was greatest following the CD34 selection with a median yield of 38.8 per cent (range 17.2-56.4 per cent).
The addition of the depletion stage resulted in a minimal loss of CD34 + c
ells with a yield for this step of 94.2 per cent (range 77.5-99.3 per cent)
. Clinical scale selections were performed on seven patients with CLL and a
median of 2.8x10(6)/kg CD34 + cells (range 1.5-6.1 x 10(6)/kg) were collec
ted. Cell recovery was 53.3 per cent following CD34 + selection and 76.9 pe
r cent following the tumour specific depletion stage, resulting in a final
product containing a median of 1.0 x 10(6)/kg CD34 + cells (range 0.55-2.0
x 10(6)/kg). All unmanipulated harvests were heavily contaminated with tumo
ur cells (median contamination 10.2 per cent, range 2.0-83.1 per cent) as m
easured by flow cytometry and a median 4.7 log (range 3-5 log) tumour cell
purge was produced following two-stage selection. Six of the patients have
received cells manipulated in this way with median engraftment times of neu
trophils > 0.5 x 10(9)/l = 16 days (range 13-20 days) and platelets > 20 x
10(9)/l = 16.5 days (range 11-42 days). At a median follow-up of 25 months,
these transplanted patients remain well and in molecular complete remissio
n. Copyright (C) 2000 John Wiley & Sons, Ltd.