Modulation of CD44/CD31 Expression and Apoptotic Status of Mobilized CD34+ Cells during Continuous Intravenous Administration of Granulocyte-Colony Stimulating Factor in Normal Donors / 대한혈액학회지

BACKGROUND: The aim of the present study is to evaluate the modulation of CD44 and CD31 expression and apoptotic status on mobilized CD34+ cells during continuous intravenous (i.v.) administration of granulocyte-colony stimulating factor (G-CSF), elucidating the mechanism of peripheral blood progenitor cells (PBPC) mobilization in normal donors. METHODS: Fifteen healthy donors were enrolled in this study. G-CSF (10 microgram/kg/day) was administered for 4 consecutive days through continuous i.v. infusion. Measurement of CD34+ cell levels and their expression of CD44, CD31 and 7-aminoactinomycin D (7-AAD) was performed. PB sampling was drawn immediately before the administration of G-CSF (steady-state) and after 4, 8, 24, 48, 72, 96 and 120 hours of G- CSF administration. RESULTS: Although there were considerable variations among the healthy donors, the absolute number of CD34+ cells significantly increased at day 3 (51.12+/-24.83x103/mL) and day 4 (46.66+/-24.93x103/mL),compared to the steady-state level (2.03+/-5.69x103/mL). The expression of CD44 on CD34+ cells revealed a significant reduction from the steady-state level (579.59+/-133.69) after day 3 (281.02+/-105.15, P=0.0059) and day 4 (164.76+/-107.44, P=0.0002) of G-CSF administration. The expression of CD31 on CD34+ cells also significantly decreased from the steady-state level (145.86+/-30.52) after day 4 (34.47+/-38.87, P=0.0055) and day 5 (17.33+/-50.68, P=0.0134) of G-CSF administration. The proportions of apoptotic (7-AADdIm) CD34+ cells were also significantly decreased after day 3 of G-CSF administration. CONCLUSION: Down-regulation of CD44 and CD31 on CD34+ cells is likely to be involved in the mobilization of PBPC and G- CSF may acts as a survival factor for mobilized CD34+ cells by the suppression of apoptosis during continuous i.v. administration of G-CSF in normal donors.

Mobilization Kinetics of CD34+ Cells during Continuous Intravenous Administration of G-CSF in Normal Donors / 대한수혈학회지

BACKGROUND: Peripheral blood progenitor cells collected from normal donors after granulocyte- colony stimulating factor (G-CSF) treatment are increasingly used for allogeneic transplantation. Previously, we investigated the mobilization kinetics of CD34+/Thy-1dim progenitor cells during subcutaneous administration of G-CSF in normal donors (Transfusion 1997;37:406-10). Although it is considered to be a relatively safe procedure, there are still uncertainties about the most efficient method of progenitor cell mobilization. Due to the short elimination half-life of G-CSF of about 3-4 hours we considered the subcutaneous administration of G-CSF once or twice daily might be suboptimal. The aim of the present study is to evaluate the mobilization kinetics of CD34+ cells during continuous intravenous (IV) administration of G-CSF in normal donors. METHODS: Fifteen healthy donors were enrolled in this study. The median age was 38 years (range, 20-56). G-CSF (Filgrastim, 10 microgram/kg/day) was administered for 4 consecutive days through continuous IV infusion. Then, we collected PBPC on the day following the 4th dose of G-CSF using a blood cell separator. For measurement of complete blood counts and CD34+ cell levels, peripheral blood sampling was performed immediately before the administration of G-CSF (steady-state) and after 4, 8, 24, 48, 72, 96, 120 hours of continuous IV administration of G-CSF. RESLUTS: After continuous IV administration of G-CSF, the WBC counts increased up to day 5 and reached approximately 8.4-fold above the steady-state level. Changes in the granulocyte count were similar to those in WBC counts. The number of lymphocytes increased up to day 4 (2.7-fold above the steady-state level), but no further increase occurred on day 5. Although there were considerable variations among the healthy donors, the statistical peaks of CD34+ cell levels were consistently observed on day 3 or day 4. Up to the fourth day of G-CSF treatment, the circulating CD34+ cells expanded by 25-fold. The percentage and absolute number of CD34+ cells significantly increased on day 3 (0.55 +/- 0.09%, 51.12 +/- 24.83x103/mL) and day 4 (0.47 +/- 0.09%, 46.66 +/- 24.93x103/mL), compared with steady-state values (0.06 +/- 0.09%, 2.03 +/- 5.69x103/mL). CONCLUSION: Our results showed that continuous IV administration of G-CSF apparently results in more rapid mobilization of CD34+ cells at least 24-48 hours compared with daily subcutaneous administration of G-CSF in normal donors.