Complete response after high-dose chemotherapy and autologous hemopoietic stem cell transplatation in metastatic breast cancer results in survival benefit.

Metastatic breast cancer is an incurable disease even with high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (ASCT). Even though phase III studies have not shown a survival advantage for this group as a whole, it is possible that a small subset of patients may benefit from HDC/ASCT with careful patient selection. A total of 198 patients from three different institutions were treated with HDC/ASCT. After complete staging, patients with central nervous system or bone marrow involvement were excluded. The HDC regimen consisted of: Carboplatin 600 mg/m(2) IV infusion over 48 hours, Thiotepa 300 mg/m(2) IV infusion over 2 hours, and Cytoxan 60 mg/kg IV infusion given over 2 hours x3 days. The median age at the time of transplant was 46 (24-62) years and median follow-up was 20 months. Hormone receptor status was known in 148 patients, of whom 84 had estrogen receptor (ER) and/or progestrone receptor (PgR)-positive tumors. Eighty patients had no evidence of disease at the time of HDC/ASCT (CR1). At the completion of HDC and ASCT, complete responses (CR) were seen in an additional 57 patients (CR2). Using Kaplan-Meier analysis, the median relapse-free survival (RFS) for the entire group was 15 months and overall survival (OS) was 27 months. The patients in CR1 had a median RFS and OS of 20.7 and 50.6 months, respectively. This was very similar to the RFS and OS in patients achieving CR2 after HDC/ASCT (p < 0.001; median: 19 and 40 months, respectively). In contrast, the patients with persistent residual disease had an RFS and OS of 7 and 12 months (p < 0.001). These data show that patients achieving a CR after HDC/ASCT have a better relapse-free and OS, when compared to patients with persistent residual disease after HDC/ASCT. This study suggests that a subset of patients with residual metastatic breast cancer after standard chemotherapy can achieve CR with HDC and ASCT which may result in better long-term outcome.

Extracorporeal photochemotherapy for the treatment of steroid-resistant chronic GVHD.

Chronic graft-versus-host disease (GVHD) is a major limitation of successful allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photochemotherapy (ECP) has been tested extensively in small cohorts of patients with chronic GVHD. In this study, we retrospectively evaluated 71 patients with severe chronic GVHD treated with ECP. Response rate was 61% (n = 43), and 14 patients had complete responses (CRs). The best responses were observed in skin, liver, oral mucosa, and eye. Factors affecting outcomes were assessed in the less heavily pretreated subgroup (n = 63). Thrombocytopenia was associated with a lower response rate (P = .04), and there was a trend toward a higher response rate in de novo chronic GVHD. At 6 months, a total of 27 (69%) of 39 patients who were alive continued to have a sustained response (CR 4 [10%] of 39, and partial response [PR] 23 [59%] of 39). The cumulative incidence of steroid discontinuation at 1 year was 22%. The overall survival since initiation of therapy was 53% at 1 year. Response to ECP and platelet count at initiation of therapy were the strongest predictors of nonrelapse mortality (NRM) on univariate analysis. Objective responses were observed in a substantial number of patients with both skin and visceral chronic GVHD failing corticosteroids and other immunosuppression.