Breast Tumor Contamination of Peripheral Blood Stem Cell Harvests: Increased Sensitivity of Detection Using Immunomagnetic Enrichment

Contaminating tumor cells in peripheral blood stem cell (PBSC) grafts infused for hematopoietic rescue after high-dose chemotherapy could potentially contribute to relapse in BrCa patients. To date the prevalence of PBSC contamination in BrCa patients, as determined by standard immunocytochemistry (ICC) assays, has generally been found to be relatively low. However, assay sensitivity may have an important impact on the ability to detect contamination. In this investigation a novel and highly sensitive BrCa cell assay using immunomagnetic enrichment with a panel of antiBrCa monoclonal antibodies (MAbs) and detection by ICC has been characterized. The immunomagnetic enrichment with ICC detection (IE-ICC) assay was directly compared with standard ICC in ability to detect BrCa contamination of PBSC specimens from patients with high-risk stage II/III and metastatic disease. The sensitivity of the IE-ICC assay was approximately 50-fold greater than that of standard ICC. As determined by standard ICC assay, BrCa cells were present in 1/14 patients (7%) and 2/26 (8%) specimens. In contrast, with IE-ICC assay the proportions of positive findings in patients (12/14, 86%) and specimens (19/26, 73%) were significantly higher ( p 5 0.001 and p , 0.0005, respectively). These preliminary findings suggest that the prevalence of PBSC contamination may be substantially higher than previously appreciated. Consequently, measures to reduce tumor contamination in the graft may have the potential to improve patient outcomes. Higher sensitivity assays such as the IE-ICC assay may play an important role in assessing the risks associated with tumor contamination and the effectiveness of tumor-purging approaches such as positive selection of CD34 1 cells and in monitoring patient response to therapy.