Occult tumor contamination of hematopoietic stem-cell products does not affect clinical outcome of autologous transplantation in patients with metastatic breast cancer.

Cooper, Brenda; Moss, Thomas J.; Ross, Alan O.; Ybanez, Jane; Lazarus, Hillard M.

doi:10.1200/jco.1998.16.11.3509

Cited by 70 publications

(49 citation statements)

References 23 publications

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“…4,[6][7][8] Specific markers expressed in the mammary gland or epithelial tissue have been used to detect tumor cells by RT-PCR in peripheral blood, bone marrow and sentinel lymph nodes of patients with breast cancer. Sensitivity of method and specificity for breast cancer cells are central issues for the detection of occult carcinoma.…”

mentioning

confidence: 99%

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

Leone

Perissinotto

Viale

et al. 2001

Bone Marrow Transplant

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mentioning

confidence: 99%

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

Leone

Perissinotto

Viale

et al. 2001

Bone Marrow Transplant

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“…This ex vivo purging model system indicates that it is possible to achieve complete purging up to 1% of tumour burden. Frequently, the clinical tumour burden encountered in AP cells is in the order of o0.01%, 54 and falls well within the range of successful purging seen in our experiments.…”

Section: Discussionmentioning

confidence: 58%

Biological purging of breast cancer cell lines using a replication-competent oncolytic virus in human stem cell autografts

Thirukkumaran¹,

Luider

Stewart

et al. 2005

Bone Marrow Transplant

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Summary:Autologous hematological stem cell transplantation (ASCT) is used for the treatment of many hematological and several solid cancers. ASCT, however, has proven disappointing as a therapeutic strategy for breast cancer. Our group and others have previously shown that breast cancer micrometastases found in patients' apheresis products (APs) predict shorter progression-free and overall survival. The implications of this finding are twofold: (i) contaminating tumor cells (CTCs) in AP reflect a higher systemic disease burden and/or (ii) reinfused CTCs contribute to relapse/progressive disease. To date, purging strategies have been disappointing. We have previously demonstrated the oncolytic properties of reovirus in in vitro, in vivo and ex vivo systems. In the present study, we tested the hypothesis that reovirus purges CTCs in a breast cancer cell line purging model. Reovirus-infected human breast cancer cell lines (HTB 133, HTB 132, SKBR3 and MCF7) exhibited cell death within days. Admixtures of AP with cells from breast tumor cell lines, which were then exposed to reovirus, showed complete purging of CTCs (assessed via flow cytometry/tumor cell outgrowth analysis) without deleterious effect on CD34 þ cells. Our results provide preclinical support for the ex vivo use of reovirus as a purging modality for breast cancer during ASCT.

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“…[6][7][8][9][10][11] In the second place, the possibility of disease relapse due to reinfusion of hematological products contaminated by neoplastic cells is another point of concern. It is known that tumor cells may contaminate bone marrow harvests as well as blood stem cell collections from breast cancer patients, although the clinical relevance of this fact is conflicting: some authors have not found an increased risk of relapse when there is tumor contamination of grafts, 29 while others have, at least for some patient subsets. 30,31 Nonetheless, tumor contamination of reinfused hematopoietic products has been correlated with disease relapse in hematological as well as in solid tumors 32,33 and may also have a role in breast cancer.…”

Section: Discussionmentioning

confidence: 94%

High-dose mitoxantrone and cyclophosphamide without stem cell support in high-risk and advanced solid tumors: a phase I trial

Pérez-Gracia

Colomer

Ruiz-Casado

et al. 2001

Bone Marrow Transplant

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Summary:This phase I study was designed to develop a high-dose combination of two cycles of mitoxantrone and cyclophosphamide in patients with solid tumors, as an alternative to single-cycle high-dose regimens that use only alkylating agents. Treatment was delivered with granulocyte colony-stimulating factor (G-CSF), but without stem cell support, in order to avoid potential tumor cell reinfusion. Thirty-one patients with advanced solid tumors received two cycles of high-dose mitoxantrone (20-30 mg/m 2 ) plus high-dose cyclophosphamide (3000-4000 mg/m 2 ). All patients received G-CSF until hematologic recovery. Dose-escalation was performed when less than 50% of cycles per level had dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) achieved was mitoxantrone 25 mg/m 2 and cyclophosphamide 4000 mg/m 2 . Main dose-limiting toxicities (DLTs) were hematological: grade IV neutropenia lasting more than 7 days and thrombopenia below 20 × 10 9 /l requiring more than one platelet transfusion. Non-hematological DLT consisted predominantly of grade III emesis and asthenia. Follow-up after each cycle was performed in an outpatient setting and there were no toxic deaths. In conclusion, the administration of two cycles of high-dose mitoxantrone and cyclophosphamide with G-CSF support is safe and feasible. MTD was mitoxantrone 25 mg/m 2 and cyclophosphamide 4000 mg/m 2 . Evaluation of this regimen is being done in a phase II trial. Bone Marrow Transplantation (2001) 27, 117-123. Keywords: breast cancer; ovarian cancer; colony-stimulating factors; dose intensification High-dose chemotherapy (HDC) has been widely employed during the last years for the treatment of solid tumors, especially breast cancer. 1 Its use was based on preclinical 2,3 and phase II clinical studies. 4,5 However, several randomized trials have not found significant benefits for this strategy either in the adjuvant or in the metastatic setting [6][7][8][9][10][11] and moreover, the author of the trials that more consistently showed a benefit for HDC 12,13 has been recently discredited due to scientific misconduct. 14 Nonetheless, the interpretation of some of the negative reports has raised a number of issues such as the insufficient number of patients and shortness of follow-up preventing detection of significant differences between the compared treatments, as well as the inadequacy of some of the control arms. 15 In addition, HDC has proved its value in other neoplastic diseases such as lymphomas, 16,17 multiple myeloma 18 and possibly germ cell tumors, 19-21 whenever the procedure and the indications have been adequately established. Therefore, while the currently available data does not recommend the use of HDC in common clinical practice, the validation in the context of controlled clinical trials of alternative approaches that may improve its results is clearly warranted. 15,22 Different methods have been suggested in order to improve the efficacy of currently employed HDC regimens, such as using drugs other than just alkylating agents, avo...

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Occult tumor contamination of hematopoietic stem-cell products does not affect clinical outcome of autologous transplantation in patients with metastatic breast cancer.

Cited by 70 publications

References 23 publications

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

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

Biological purging of breast cancer cell lines using a replication-competent oncolytic virus in human stem cell autografts

High-dose mitoxantrone and cyclophosphamide without stem cell support in high-risk and advanced solid tumors: a phase I trial

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