Stem cell transplantation for metastatic breast cancer: analysis of tumor contamination

Abstract

The purpose of this study was to determine the efficacy, engraftment kinetics, effect of bone marrow tumor contamination, and safety of high-dose therapy and granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood progenitor cell (PBPC) support for patients with responding metastatic breast cancer. Forty two patients underwent G-CSF (10 microg/kg) stimulated PBPC harvest. PBPC and bone marrow aspirates were analyzed by histologic and immunocytochemical methods for tumor contamination. Thirty-seven patients received high-dose therapy consisting of cyclophosphamide 6 g/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) given as an infusion over 4 d followed by PBPC reinfusion and G-CSF (5 microg/kg) support. No transplant related deaths or grade 4 toxicity was recorded. CD34+ cells/kg infused was predictive of neutrophil and platelet recovery. With a median follow-up of 38 months, three year survival was 44% with relapse-free survival of 19%. Histological bone marrow involvement, found in 10 patients, was a negative prognostic factor and was associated with a median relapse-free survival of 3.5 months. Tumor contamination of PBPC by immunohistochemical staining was present in 22.5% of patients and found not to be correlated with decreased survival. G-CSF stimulated PBPC collection followed by a single course of high dose chemotherapy and stem cell infusion with G-CSF stimulated marrow recovery leads to rapid, reliable engraftment with low toxicity and promising outcome in women with responding metastatic breast cancer.

Occult tumor cell contamination in patients with stage II/III breast cancer receiving sequential high-dose chemotherapy

“…In this setting, detection of breast cancer cells in hematopoietic grafts 5,12 also raises questions about the potential contribution of these cells to relapse after high-dose chemotherapy supported with the reinfusion of autologous cells and progenitors. Gene marking studies have provided limited arguments for the contribution of contaminating tumor cells to relapse in patients with acute myeloid leukemia, neuroblastoma or chronic myeloid leukemia; 13,14 these reports remain unconfirmed in the case of breast cancer 15,16 and the value of purging products for transplantation is unclear, both in breast cancer, [17][18][19] and in other malignancies, such as multiple myeloma. 20 Observation of tumor cell contamination of apheresis products has mostly been carried out in the setting of autologous stem cell transplantation for metastatic breast cancer, where the impact on outcome may be diluted by several important prognostic factors, such as tumor sites or chemoresistance.…”

The Incidence of Tumor Cell Contamination of Peripheral Blood Stem Cells: A Meta-Analysis to Evaluate the Impact of Mobilization Regimens and the Influence on Outcomes in Breast Cancer Patients

“…The percentage of patients evaluated with stage II/III and stage IV disease was not significantly different in the CO versus C+C groups (data not shown). Only 6 out of 17 studies reported the ER/PR/HER2 status of the breast tumor in patients [6,9,20,23,28,36]. Six studies utilized the CO regimen [20,25,26,27,28,36], 4 studies used the C+C regimen [8,10,24,33], and 7 studies compared both CO and C+C regimens [6,9,22,23,29,35,37].…”

“…Only 6 out of 17 studies reported the ER/PR/HER2 status of the breast tumor in patients [6,9,20,23,28,36]. Six studies utilized the CO regimen [20,25,26,27,28,36], 4 studies used the C+C regimen [8,10,24,33], and 7 studies compared both CO and C+C regimens [6,9,22,23,29,35,37]. Eleven studies used immunocytochemistry of cytokeratin [5,8,10,20,22,25,26,27,35,36,37].…”

“…The studies were published between 1995 and 2006 and are summarized in table 1. Most of the studies included stage IV breast cancer patients [5,6,9,10,20,22,23,24,25,26,27,28,29,30,31,32,33,34]; however, some studies also included high-risk stage II and III patients [5,22,25,26,27,29,32,34,35,36,37]. The percentage of patients evaluated with stage II/III and stage IV disease was not significantly different in the CO versus C+C groups (data not shown).…”

Occult tumor cells detected in autologous blood stem cell harvests have no impact on 5 year outcomes for breast cancer patients with 4–9 positive nodes treated with adjuvant high-dose therapy and stem cell transplantation

“…Higher stage breast cancer patients receiving breast tumor-contaminated nonmobilized 7 and mobilized 8 blood stem cell transplants had a poorer outcome in some studies, but not in others. 9,10 Administration of chemotherapy and/or cytokines to mobilize stem cells to the circulation may mobilize tumor cells as well. 11 Although one study of breast cancer patients showed that collections of hematopoietic stem cells mobilized with a combination of cytokine and chemotherapy did not contain mobilized tumor cells, 12 only one apheresis collection was assayed for each patient.…”