Negative selection of autologous peripheral blood stem cells

The use of chemotherapy and/or haematopoietic growth factor-mobilized perip heral blood stem cells (PBSC) has been shown to induce a more rapid haemato poietic recovery than the reinfusion of bone marrow (BM)-derived haematopoi etic cells, thus reducing the morbidity and mortality of autologous stem ce ll transplantation (ASCT). PBSC collections were initially believed to have a lower incidence of tumour cells involvement than BM harvests. However, r ecent studies have shown that mobilized blood cell products of cancer patie nts eligible for autografting are frequently contaminated with tumour cells . Whereas positive selection of haematopoietic CD34(+) stem cells has been largely used as a means of indirect purging of circulating CD34(-) neoplast ic cells, few groups have addressed the issue of tumour cell removal by dir ect targeting of cancer cells using physical or pharmacological strategies. In this chapter we review the available data concerning the contamination of tumour cells in PBSC collections from cancer patients, the functional an d kinetic characteristics of primed CD34(+) cells which may affect the haem atopoietic toxicity of purging procedures developed to eliminate the minima l residual disease (MRD) from BM samples, and the preclinical and clinical results of the selective killing of residual tumour cells from leukapherese s. The limited amount of data published so far do not allow any firm conclusio n on the clinical usefulness of purging protocols. Nonetheless, the success ful extension of ex vivo purging to PBSC collections may improve the feasib ility of randomized studies aimed at determining the importance of tumour-f ree autografts.