Prognostic analysis of early lymphocyte recovery in patients with advanced breast cancer receiving high-dose chemotherapy with an autologous hematopoietic progenitor cell transplant.

PURPOSE: The purpose of this study was to evaluate the prognostic effect of early posttransplant lymphocyte recovery in patients with advanced breast cancer receiving high-dose chemotherapy with autologous hematopoietic progenitor cell transplantation. EXPERIMENTAL DESIGN: We analyzed the effect of the absolute lymphocyte count on day +15 posttransplant on freedom from relapse and overall survival in patients with high-risk primary breast cancer or metastatic breast cancer, enrolled between 1990 and 2001 in prospective high-dose chemotherapy trials, using a uniform regimen of cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea. RESULTS: Four hundred and seventy-six patients (264 high-risk primary breast cancer and 212 metastatic breast cancer patients) were evaluated at median follow-up of 8 years (range, 1.5-11 years). The disease-free survival and overall survival rates in the high-risk primary breast cancer group were 67% and 70%, respectively. Patients with metastatic breast cancer patients had 21.8% disease-free survival and 31.5% overall survival rates. Day +15 absolute lymphocyte count correlated with freedom from relapse (P = 0.007) and overall survival (P = 0.04) in the metastatic breast cancer group, but not in the high-risk primary breast cancer group (P = 0.5 and 0.8, respectively). The prognostic effect of absolute lymphocyte count in metastatic breast cancer was restricted to those patients receiving unmanipulated peripheral blood progenitor cells (P = 0.04). In contrast, absolute lymphocyte count had no significant effect in those metastatic breast cancer patients receiving bone marrow or a CD34-selected product. In multivariate analyses, the prognostic effect of day +15 absolute lymphocyte count in metastatic breast cancer was independent of other predictors, such as disease status, pre-high-dose chemotherapy treatment, number of tumor sites, or HER2. CONCLUSIONS: Early lymphocyte recovery is an independent outcome predictor in metastatic breast cancer patients receiving high-dose chemotherapy and an autologous peripheral blood progenitor cell transplant. These observations suggest that immune strategies targeting minimal posttransplant residual disease may prove worthwhile.

Prognostic significance of occult tumor cells in the apheresis products of patients with advanced breast cancer receiving high-dose chemotherapy and autologous hematopoietic progenitor cell support.

We prospectively evaluated the prognostic significance of occult tumor cells (OTCs) contaminating the peripheral blood progenitor cell apheresis products of patients with advanced breast cancer receiving high-dose chemotherapy. Immunocytochemistry of peripheral blood progenitor cells was performed in 242 patients with high-risk primary breast cancer (HRPBC) and in 111 patients with metastatic breast cancer (MBC). OTCs were detected in 6.6% of HRPBC patients and in 16.2% of MBC patients (P = .005). In HRPBC, OTCs correlated with worse prognostic scores and larger tumor sizes, but not with axillary nodal status, hormone receptors, or HER2. In the MBC group, OTCs correlated with bone marrow involvement and with disease status at transplantation. The number of apheresis procedures was not associated with the risk of contamination. In HRPBC patients, at a median follow-up of 7 years (range, 1.5-11 years), the presence of OTCs correlated with worse event-free survival (P = .007) and overall survival (P = .002). In the MBC group, OTCs correlated with worse event-free survival (P = .04), but not overall survival (P = .2). In multivariate analyses, the presence of OTCs had an independent adverse effect on outcome in HRPBC, but not MBC. Our observations imply a direct role of OTCs in posttransplantation relapse in HRPBC.