BLOOD-DERIVED AUTOGRAFTS COLLECTED DURING GRANULOCYTE-COLONY-STIMULATING FACTOR-ENHANCED RECOVERY ARE ENRICHED WITH EARLY THY-1(+) HEMATOPOIETIC PROGENITOR CELLS

It was the objective of the study to characterize CD34(+) hematopoietic progenitor cells from peripheral blood (PB) and bone marrow (BM) in a group of 24 cancer patients. After cytotoxic chemotherapy, R-metHu granulocyte colony-stimulating factor (R-metHuG-CSF; filgrastim, 300 mu g daily, subcutaneously) was given to shorten the time of neutropenia as well as to increase the rebound of peripheral blood progenitor cells (PBPC) for harvesting. The proportion of CD34(+) cells in the leukapheresis products (LPs) was 1.4-fold greater than in BM samples that were obtained at the same day (LP: median, 1.4% v BM: median, 1.0%, P < .01). Two- and three-color immunofluorescence showed that blood-derived CD34(+) cells comprised a greater proportion of a particular early progenitor cell than CD34(+) cells of bone marrow. Blood-derived progenitor cells tended to have a higher mean fluorescence intensity of CD34 and expressed significantly lower levels of HLA-DR (mean fluorescence intensity of HLA-DR: 442.6 +/- 44.9 [LP] v 661.5 +/- 64.6 [BM], mean +/- SEM, P < .01). Furthermore, the blood-derived CD34(+) cells comprised a 1.7-fold greater proportion of Thy-1(+) cells (LP: median, 24.4% v BM: median, 14.4%, P < .001) and expressed significantly less c-kit (LP: median, 20.5% v BM: median, 31.0%, P < .01). Three-color analysis showed that high levels of Thy-1 expression were restricted to CD34(+)/HLA-DR(dim) Or CD34(+)/HLA(-)DR(-) cells confirming the early developmental stage of this progenitor cell subset. The proportion of CD34(+)/CD45RA(bright) cells representing late colony-forming unit granulocyte-macrophage (CFU-GM) was smaller in LPs compared with BM (P < .05). For an examination of BM CD34(+) cells before the mobilization chemotherapy, samples of 16 patients were available. The mean proportion of c-kit expressing CD34(+) cells in the bone marrow during G-CSF-stimulated reconstitution decreased 1.8-fold compared with baseline values. There was no difference in the proportion of BM-derived CD34(+)/Thy-1(+) cells and CD34(+)/CD45RA(+) cells between steady-state hematopoiesis and G-CSF-supported recovery. Our data suggest that during G-CSF-enhanced recovery, CD34(+) cells in the PB are enriched with more primitive progenitor cells to evenly replenish the BM after the chemotherapy-related cytotoxic damage. (C) 1995 by The American Society of Hematology.