Maturation of Mobilized Peripheral Blood Progenitor Cells: Preclinical and Phase I Clinical Studies

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Abstract
The use of mobilized peripheral blood progenitor cells (PBPC) after high-dose chemotherapy has markedly decreased the period of severe neutropenia. In an attempt to further decrease the duration of neutropenia, the potential of PBPC to mature during in vitro culture was assessed, with special attention being paid to culture medium, growth factors, and cell concentration. Concentrations of 106 PBPC/mL resulted in better recovery than 107/mL as far as total cells, CFU-GM, and granulocytes were concerned. The combination of IL-3 + GM-CSF + G-CSF appeared to be better than any of these growth factors alone. Simple media, such as Medium 199, gave poorer cell recovery than more complex media, such as IMDM. With 106/mL nonenriched PBPC in IMDM with IL-3/GM-CSF/G-CSF, on day 15 CFU-GM reached 450% of the initial level. At that point, granulocytes had increased 15-fold. A small phase I study was performed to assess the toxicity of infusing 1000-2000 mL of PBPC cultured for 3 days at 3-10 X 106/mL with IL-3/GM-CSF/G-CSF in LifeCell bags. Although no clear decrease in the duration of neutropenia was observed, the infusions were uncomplicated in 5 of the 6 patients and had minor side effects in the sixth patient. These data suggest that in vitro differentiation of nonenriched PBPC is possible. However, to develop a clinically applicable method, several logistical problems will have to be overcome.