FUNCTIONAL AND PHENOTYPIC CHARACTERIZATION OF HUMAN PERIPHERAL-BLOOD STEM-CELL HARVESTS - A COMPARATIVE-ANALYSIS OF CELLS FROM CONSECUTIVE COLLECTIONS

A considerable number of patients with malignancies who are treated wi th high-dose therapy and hematopoietic stem cell transplantation subse quently relapse. Analyses of peripheral blood stem cell (PBSC) harvest s obtained from 49 cancer patients showed that the PBSC harvest contai ned precursors for antitumor effector cells. Ex vivo manipulation of t hese harvests to maximize the antitumor effector cell activity may pro vide a new therapeutic approach to decrease or eliminate any minimal r esidual disease that remains after high-dose therapy. Characterization of PBSC from consecutive collections determined the collections best suited for ex vivo augmentation of antitumor cytotoxic effector cells. We report the results of a functional and phenotypical characterizati on of PBSC obtained from six consecutive collections from 18 cancer pa tients receiving granulocyte-macrophage colony-stimulating factor (GM- CSF) for hematopoietic stem/progenitor cell mobilization. The PBSC wer e evaluated for their cytotoxicity using the Cr-51-release assay. The frequency and subsets of lymphocytes were determined using flow cytome try with appropriate specific marker antibodies and differential cell counts. The content of hematopoietic progenitor cells in each collecti on was determined using a colony-forming unit granulocyte-macrophage ( CFU-GM) culture assay. The frequency of cytotoxic effector cells inclu ding lymphokine-activated killer (LAK) cell precursors and lymphocytes was significantly greater (P < .05) in the early collections, whereas the later collections contained significantly (P < .05) more CFU-GM p rogenitor cells and fewer cytotoxic effector cells. Thus, our results show that PBSC obtained from advanced cancer patients do contain consi derable levels of precursor cells for the generation of LAK cell popul ations. These results suggest that cells from the earlier collections are best suited for ex vivo manipulation to augment the antitumor effe cts. (C) 1995 by The American Society of Hematology.