DIFFERENTIAL MOBILIZATION OF MYELOMA CELLS AND NORMAL HEMATOPOIETIC STEM-CELLS IN MULTIPLE-MYELOMA AFTER TREATMENT WITH CYCLOPHOSPHAMIDE AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

Peripheral blood stem cells (PBSCs) mobilized with high-dose chemother apy and hematopoietic growth factors are now widely used to support my eloablative therapy of multiple myeloma and effect complete remissions in up to 50% of patients with apparent extension of event-free and ov erall survival. Because tumor cells are present not only in bone marro w, but also in virtually all PBSC harvests, it is conceivable that aut ografted myeloma cells contribute to relapse after autotransplants. In this study, the kinetics of mobilization of normal hematopoietic stem cells were compared with those of myeloma cells present in PBSC harve sts of 12 patients after high-dose cyclophosphamide and granulocyte-ma crophage colony-stimulating factor administration. CD34(+) and CD34(+) Lin(-)Thy(+) stem cell contents were measured by multiparameter flow c ytometry, and myeloma cells were quantitated by immunostaining for the relevant Ig light chain and by a quantitative polymerase chain reacti on for the myeloma-specific CDRIII sequence. Results indicated marked heterogeneity in the percentages of mobilized stem cells among differe nt patients (0.1% to 22.2% for CD34(+) cells and 0.1% to 7.5% for CD34 (+)Lin(-)Thy(+) cells, respectively). The highest proportions of hemat opoietic progenitor cells were observed early during apheresis, with 9 of 12 patients mobilizing adequate amounts of CD34(+) cells for 2 aut otransplants (>4 x 10(6)/kg) within the first 2 days, whereas peak lev els (percent and absolute numbers) of myeloma cells were present on da ys 5 and 6 (0.5% to 22.0%). During the last days of collection, mobili zed tumor cells exhibited more frequently high labeling index values ( 1% to 10%; median, 4.4%) and an immature phenotype (CD19(+)). The diff erential mobilization observed between normal hematopoietic stem cells and myeloma cells can be exploited to reduce tumor cell contamination in PBSC harvests. (C) 1996 by The American Society of Hematology.