Isolation and Transplantation of Highly Purified Autologous Peripheral CD34⁺ Progenitor Cells: Purging Efficacy, Hematopoietic Reconstitution Following High dose Chemotherapy in Patients with Breast Cancer: Results of a Feasibility Study in Japan

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Background: High-dose chemotherapy with autologous stem cell support may have some therapeutic impact on certain groups of the patients with advanced breast cancer (BRCA). Since stem cell contamination by tumor cells might contribute to relapse, development of a tumor cell purging technique would improve the clinical outcome. The present study was undertaken to evaluate the purging efficacy of autologous mobilized CD34⁺ peripheral stem cells in patients with breast cancer (BRCA) in an advanced stage or relapse.
Methods: CD34⁺ cells were selected from autologous peripheral blood stem cells (PBSC) using a clinical scale of magnetic-activated cell sorting system (CliniMACS), followed by high-dose chemotherapy with transplantation of CD34⁺ selected cells. Amplification of cytokeratin 19 (CK19) and 20 (CK20) gene in leukapheresis products were measured to evaluate the performance of tumor cell elimination.
Results: Seven patients were entered into this study. After leukopheresis, 1 patient was dropped form this study due to poor mobilization. Among 6 patient, a total of 8 CD34⁺ selection was performed. The median purity and recovery rate of the CD34⁺ cells post selection was 85.1% (range 62.5-98.1%) and 74.2% (range 50.2-90.2%), respectively. After isolation of CD34⁺ cells, the elimination rate in the logarithmic transformation of CK19 was 2.77 log, and that of CK20 were 2.43 log and 2.53 log. In 4 patients, high-dose chemotherapy was performed, followed by the transplantation of the isolated CD34⁺ cells. Rapid neutrophil recovery, as well as platelet recovery was seen with a median time to reach 0.5 × 10⁹/l neutrophils of 9 days (range 8-9), and 20 × 10⁹/l platelets of 12 days (range 10-13). There was no treatment related death and no serious adverse events directly associated with the selection procedure or infusion of selected cells.
Conclusions: The present study demonstrated that the CliniMACS system is a highly effective positive selection method and that a high purging efficacy could be obtained without compromising the hematopoietic reconstitution capacity of the graft in BRCA patients undergoing high-dose chemotherapy.