Mobilized CD34+ cells as a biomarker candidate for the efficacy of combined maximal tolerance dose and continuous infusional chemotherapy and G-CSF surge in gastric cancer

Abstract

We investigated whether the level of bone marrow-derived progenitor cells and mature endothelial cells could be used as predictors of clinical outcome in patients receiving taxotere-based chemotherapy for advanced gastric cancer. Peripheral blood mononuclear cells were obtained from 49 gastric cancer patients who received taxotere combined with 5-FU and leucovorin and prophylactic G-CSF treatment. To categorize the cells, the cell markers CD34, vWF, P1H12, and CD31 were stained. Changes in these cells were examined before and after chemotherapy, and the clinical significance of these changes to response prediction and prognosis were investigated. Before the second cycle of chemotherapy, the number of CD34+/vWF+ and CD34+ cells was higher in non-responders as compared to the responders. Patients with > or =6.2 CD34+/vWF+ cells/ml had a shorter progression free survival (3.7 months) as against patients with <6.2 CD34+/vWF+/ml (6.0 months, p = 0.076). Patients with > or =5.8 CD34+ cells/ml had shorter progression free survival (4.0 months) than patients with <5.8 CD34+ cells/ml (6.1 months, p = 0.046). In an ex vivo pharmacokinetic study, the maximum inhibition (I(max)) for HUVEC and YCC3 cells was 13.0 +/- 6.6% and 74.0 +/- 2.0%, respectively. The time to reach I(max) (T(max)) was 72 h in all HUVEC cells and 0.5 hours in YCC3 cells. We suggested that CD34+/vWF+ and CD34+ cells can be used as a biomarker for prediction and CD34+ cells for prognosis.