Role of tumor cells contaminating the graft in breast cancer recurrence after high-dose chemotherapy

Abstract

Summary:been caused by the reinfusion of tumor cells contaminating the graft. This hypothesis is supported by both clinical and laboratory evidence. One of the possible drawbacks to autologous stem cell transplantation in breast cancer (BC) patients is the potential for tumor contamination in the transplanted product. We present a patient with advanced disease Case report who received high-dose chemotherapy (HDC) and PBPC support as consolidation therapy after achievingThe patient was 45 when she developed stage IIB breast cancer in October 1992. She underwent a modified left radcomplete remission with standard-dose first-line treatment, and suffered recurrence of the disease 6 months ical mastectomy which revealed a 4 cm lobular carcinoma and metastases to three out of 12 axillary lymph nodes after transplantation. Retrospective analysis revealed the presence of contaminating cells in the leukapheretic examined. After surgery she received conventional adjuvant CY, MTX and fluorouracil for six cycles followed by product, and clinical evidence suggested a role for these cells in the tumor relapse.tamoxifen. She remained free of disease until December 1994, when supraclavicular and mediastinal node metastKeywords: metastatic breast cancer; PBPC transplantation; tumor recurrence ases were documented by biopsy. She received four cycles of a combination of fluorouracil, epirubicin and CY, and achieved CR. Consolidation with HDC was suggested and the patient High-dose chemotherapy (HDC) with autologous stem cell agreed to undergo this additional treatment. CY (4 g/m 2 ) support is increasingly used in the treatment of breast canfollowed by G-CSF (5 g/kg bw s.c.) was given, and cer (BC), both in the adjuvant setting and in stage IV dis-5.2 × 10 6 CD34 + cells were collected at two consecutive ease. 1 Transplant-related morbidity has decreased signifileukaphereses on days +11 and +12. cantly with the use of blood progenitor cells, which areThe myeloablative regimen consisted of thiotepa 600 now the most commonly used form of hematopoietic mg/m 2 and melphalan 180 mg/m 2 ; G-CSF (5 g/kg bw s.c.) rescue.was given starting on day 1 after reinfusion of both One potential limitation to support with autologous stem unpurged leukapheretic products. Complete hematopoietic cells is possible contamination of the graft by residual engraftment (ANC Ͼ1000/ l and platelet transfusion tumor cells. Several studies have in fact shown that women independence) was reached on day 11 after transplantation. with newly diagnosed BC and no histological evidence of In November 1995, 6 months after transplantation, she bone marrow metastasis had tumor cells detected in their developed shortness of breath and cough along with loss of bone marrow by immunohistochemical methods. 2 In the vision in her left eye. She was hypoxyemic, and neoplastic field of stem cell transplantation, the observation that PBPC lymphangitis involving both lung fields was demonstrated collections from BC patients can contain clonogenic tumor by CT scan. MRI scan of the ...

Improvement of tumor cell depletion by combining immunomagnetic positive selection of CD34-positive hematopoietic stem cells and negative selection (purging) of tumor cells

“…Randomized studies dealing with this problem do not exist so far. However, genemarking studies, [20][21][22][23] case reports and the well known fact that even in remission occult tumor cells can be detected in bone marrow and peripheral blood 15,30 argue in favor of the application of purging procedures. Thus, different purging methods have been developed.…”

Breast cancer cell contamination of blood stem cell products in patients with metastatic breast cancer: Predictors and clinical relevance

“…Firm conclusions from our data are limited, however, given the retrospective analysis design of this study. In future trials, definitive assessment of the effect on clinical outcomes of methods aimed to reduce minimal residual disease, including limiting the number of apheresis procedures, using CD34 + blood stem cell selection, and administering tandem cycles of high-dose chemotherapy, will require prospective study [13,29,[40][41][42]. In this setting, the study of nonchemotherapy posttransplantation treatments including targeted immune therapies may be most applicable [43][44][45][46].…”

Detection of breast cancer cell contamination in leukapheresis product by real-time quantitative polymerase chain reaction

“…1,2 Relapse or progression after high-dose chemotherapy with peripheral blood stem cell rescue might be caused either by the persistence of chemoresistant cells (minimal residual disease) 3 or by the infusion of tumor cells during autotransplant. 4,5 Thus, identification of minimal residual disease and tumor cell contamination of leukapheresis products might have clinical and prognostic implications.…”