Clearance kinetics of CD34+ cells from peripheral blood: an independent predictor of hematologic recovery after high-dose chemotherapy and hematopoietic stem cell transplantation.

We measured the concentration of CD34+ cells in peripheral blood (PB) (1/2) h prior to and (1/2), 1, 3, 6, and 12 h following hematopoietic stem cell (HSC) infusion in 34 breast cancer patients treated with high-dose chemotherapy (HDC). The decrease in these concentrations over time enabled us to determine the clearance kinetics of CD34+ cells from PB. The absolute number of CD34+ cells in PB generally peaked at (1/2) h after infusion, then rapidly declined from 1 to 3 h post infusion and continued to fall until 12 h post transplant, but more slowly. In univariate analysis, CD34+cells/kg infused, CFU-GM/kg infused, the CD34+ count at (1/2) h, and the 12-h clearance of CD34+ cells from PB were predictors of hematologic recovery, as were each of the two phases of clearance when the slope was divided into rapid and slow phases (from (1/2) to 3 and from 3 to 12 h post transplant, respectively). We then stratified our population by the number of CD34+ cells/kg infused. In group 1, patients received 7.5 x 10(6) CD34+ cells/kg. After adjusting for CD34+ cells injected, age, and purged or unpurged graft in multivariate analysis, the 12 h clearance remained a predictor of hematologic recovery in group 1. In addition, the second phase of clearance (from 3 to 12 h after infusion) was an even better predictor than the 12 h clearance. In group 2, however, no statistically significant correlation was observed, even with the number of HSC injected. Results suggest that rapidity of clearance of CD34+cells from PB is an independent indicator of hematologic recovery in patients receiving lower doses of CD34+ cells. When the cell dose injected is over a threshold, PB clearance correlations with hematologic recovery are masked.

[Efficiency of high-dose FEC chemotherapy for the mobilization of hematopoietic stem cells into peripheral blood]. / Efficacité d'une chimiothérapie FEC à forte dose pour la mobilisation des cellules souches hématopoïétiques dans le sang périphérique.

The best regimen for mobilizing hematopoietic stem cells (HSC) into peripheral blood is not yet defined. The efficiency of FEC chemotherapy in the treatment of breast cancer is well established and the effects of FEC on HSC mobilization have been characterized. We tested the feasibility and the toxicity of a high-dose FEC regimen which may improve the mobilizing capacity of conventional FEC. Twenty patients with poor prognosis breast cancer received high-dose FEC and filgrastim 5 micrograms/kg. Three leukaphereses were performed on each patient for 3 consecutive days. Total numbers of CFU-GM and CD34+ cells were assessed, and a retrospective analysis was made. The numbers of CFU-GM/kg and CD34+ cells/kg collected (mean +/- standard error) were respectively 12.2 x 10(5) (+/- 2.4) and 14.6 x 10(6) (+/- 2.5). Extra-hematologic toxicity was negligible. Hematologic recovery after CTCb high-dose chemotherapy and HSC infusion was rapid. High-dose FEC is efficient for collecting HSC in peripheral blood. Extra-hematologic toxicity is weak and hematologic recovery after autograft is normal. Increased dosage of epirubicin and cyclophosphamide could allow a single leukapheresis collection of sufficient HSC from peripheral blood.

Quantification of CD34+ cells mobilized into the peripheral blood predicts the yield of the leukapheresis product and can replace progenitor assays.

We reviewed 333 concomitant blood and cytapheresis samples from 101 patients with solid malignancies of various histological cell types. All samples were analyzed for CFU-GM, BFU-E and CD34+ determination. We found a good correlation between progenitor assays CFU-GM and CD34+ determination in the blood and cytapheresis (r = 0.77, p < 0.0001 and r = 0.79, p < 0.0001 respectively). The number of CD34+ cells in the peripheral blood was predictive of the CD34+ yield in the cytapheresis (r = 0.86, p < 0.0001), and we determined that a threshold of 26 CD34+/microliter of blood was sufficient to harvest 10(6) CD34+/kg in a single apheresis. Thirty breast cancer patients received injections of peripheral blood stem cells after the same high-dose chemotherapy. For these patients, we found a significant correlation between the quantity of CD34+ cells or CFU-GM collected and both granulocyte and platelet recovery. In conclusion, there is a very good correlation between CFU-GM assays and CD34+ determination and a good correlation between circulating CD34+ cells and the yield obtained by the cytapheresis. The number of CD34+ cells collected is also significantly correlated with hematological recovery. Because CD34+ quantification is an accurate, fast and inexpensive technique, this can lead to the progressive forsaking of progenitor assays in a clinical setting.

Pattern of antigens A and B distribution on the surface of AB group red blood cells--an argument in support of the concept of "genetic oscillation".

Using a mixture of mouse monoclonal antibodies anti red blood cell (RBC) AgA and human antibodies anti RBC AgB coupled to fluorescein isothiocyanate (FITC) conjugated goat antimouse monoclonal antibodies and to phycoerythrin (PE) conjugated goat antihuman monoclonal antibodies, we obtained the distribution of these antigens on the AB RBC surface. The analysis of 30 samples of 30,000-100,000 RBCs each was carried out using flow cytometry and revealed three kinds of AB RBC populations: (1) a population characterized by maximum concentration of AgA and minimum concentration of AgB; (2) a complementary population characterized by minimum concentration of AgA and maximum concentration of AgB; (3) an intermediary equilibrated population with about equal concentrations of the A and B antigens. This pattern corresponds to the pattern of oscillating genetic activity defined as "genetic oscillation", a concept amply discussed in the paper.