CD34+cells obtained from ""good mobilizers"" are more activated and exhibit lower ex vivo expansion efficiency than their counterparts from ""poor mobilizers""

Abstract

BACKGROUND: The classification of patients into good or poor mobilizers is based on CD34+ cell count in their peripheral blood (PB) after granulocyte-colony-stimulating factor (G-CSF) injection. We hypothesized that, apart from their mobilization from marrow to the blood, the response to G-CSF of CD34+ cells also includes activation of proliferation, metabolic activity, and proliferative capacity. STUDY DESIGN AND METHODS: Mobilized PB CD34+ cells purified from samples obtained by cytapheresis of multiple myeloma or non-Hodgkins lymphoma patients of both good (> 50 CD34+ cells/mu L) and poor (< 50 CD34+ cells/mu L) mobilizers were studied. The initial cell cycle state of CD34+ cells after selection and their kinetics of activation (exit from G(0) phase) during ex vivo culture were analyzed. Their proliferative capacity was estimated on the basis of ex vivo generation of total cells, CD34+ cells, and colony-forming cells (CFCs), in a standardized expansion culture. Indirect insight in metabolic activity was obtained on the basis of their survival (viability and apoptosis follow-up) during the 7-day-long conservation in hypothermia (4 degrees C) in the air or in atmosphere containing 3% O-2/6% CO2. RESULTS: CD34+ cells obtained from good mobilizers were in lower proportion in the G(0) phase, their activation in a cytokine-stimulated culture was accelerated, and they exhibited a lower ex vivo expansion efficiency than those from poor mobilizers. The resistance to hypothermia of good immobilizers CD34+ cells is impaired. CONCLUSION: A good response to G-CSF mobilization treatment is associated with a higher degree of proliferative and metabolic activation of mobilized CD34+ cells with a decrease in their expansion capacity.