ENHANCED LEVELS AND ENHANCED CLONOGENIC CAPACITY OF BLOOD PROGENITOR CELLS FOLLOWING ADMINISTRATION OF STEM-CELL FACTOR PLUS GRANULOCYTE-COLONY-STIMULATING FACTOR TO HUMANS

Administration of hematopoietic growth factors is being used increasin gly to obtain populations of blood progenitor/stem cells (PBPC) for cl inical transplantation. Here we examined the effect of combining stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) ve rsus G-CSF alone in a randomized clinical study involving 62 women wit h early-stage breast cancer. In the first patient cohorts, escalating doses of SCF were administered far 7 days with concurrent G-CSF admini stration. At baseline, levels of progenitor cells in the bone marrow o r blood were comparable in the different patient groups. As with admin istration of G-CSF alone, the combination of SCF plus G-CSF did not al ter the wide variation in levels of PBPC observed between individuals and did not alter the selective nature of PBPC release, with preferent ial release of day-14 granulocyte-macrophage colony-stimulating factor (GM-CFC) versus day-7 GM-CFC. However, SCF acted to sustain the level s of PBPC after cessation of growth factor treatment; levels of PBPC w ere elevated 100-fold at later timepoints compared with G-CSF alone. I n addition, the maximum levels of PBPC observed were increased approxi mately fivefold at day 5 of growth-factor administration. The increase d levels of PBPC resulted in significantly increased levels oi PBPC ob tained by leukapheresis. In a subsequent patient cohort, 3-days pretre atment with SCF was introduced and followed by 7 days concurrent SCF p lus G-CSF. The 3-days pretreatment with SCF resulted in an earlier wav e of PBPC release in response to commencement of G-CSF. In addition, m aximum PBPC levels in blood and PBPC yield in leukapheresis products w ere further increased. Unexpectedly however, SCF pretreatment resulted in progenitor cells with enhanced self-generation potential. Reclonin g assays documented the ability of approximately 30% of primary granul ocyte-macrophage (GM) colonies from control cell populations to genera te secondary GM colonies (n = 1,106 primary colonies examined). In con trast approximately 90% of GM colonies from PBPC after SCF pretreatmen t generated secondary clones and 65% generated secondary colonies. The action of SCF was not explicable in terms of altered SCF, GM-CSF, or G-CSF responsiveness, but SCF pretreatment was associated with maximum serum SGF levels at the time G-CSF was commenced. These results show that PBPC populations mobilized by different growth factor regimens ca n differ in their functional properties and caution against solely con sidering number of harvested progenitor cells without regard to their function. (C) 1997 by The American Society of Hematology.