A Review of Allogeneic Hematopoietic Stem Cell Transplantation in Metastatic Breast Cancer
Breast cancer (BC) has a high mortality rate and metastatic BC is almost incurable despite hormonal therapy and chemotherapy. The second and third lines of chemotherapies usually yield transient responses and the median survival is generally as low as 18-24 months. Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) have been extensively investigated in this setting. The presence of immune mediated anti-tumor effects referred to as graft-versus-tumor (GvT) effects after allogeneic HSCT among patients with solid tumors have been clearly defined. The advantages of allogeneic HSCT over autologous HSCT for metastatic BC are i) cancer-free graft and ii) immune-mediated GvT effects mediated by human leukocyte antigen compatible donor T-cells. In conclusion, a GvT effect does exist against metastatic BC and play a key role in tumor response. This review aims to describe the background, rationale, and clinical results of allogeneic HSCT as a potential alternative treatment in metastatic BC.
Siegel RL, Miller KD, Jemal A. Cancer statistics.CA Cancer J Clin.2016; 66(1):7-30
Hortobagyi GN. Treatment of breast cancer. N Engl J Med .1998;339(14):974-84.
Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783-92.
Crown J, DiérasV, Kaufmann M, et al. Chemotherapy for metastatic breast cancer-report of a European expert panel.Lancet Oncol.2002;3(12):719-27.
Hryniuk W, Bush H. The importance of dose intensity in chemotherapy of metastatic breast cancer. J Clin Oncol.1984;2(11):1281-8.
Hryniuk WM, Levine MN, Levin L. Analysis of dose intensity for chemotherapy in early (stage II) and advanced breast cancer. NCI Monogr. 1986(1):87-94.
Kroger N, Damon L, Zander AR, et al. Secondary acute leukemia following mitoxantrone-based high-dose chemotherapy for primary breast cancer patients. Bone Marrow Transplant. 2003;32(12):1153-7.
Pedrazzoli P, Ferrante P, Kulekci A, et al. Autologous hematopoietic stem cell transplantation for breast cancer in Europe: critical evaluation of data from the European Group for Blood and Marrow Transplantation (EBMT) Registry 1990-1999. Bone Marrow Transplant. 2003;32(5):489-94.
Demirer T, Buckner CD, Appelbaum FR, et al. High-dose busulfan and cyclophosphamide followed by autologous transplantation in patients with advanced breast cancer. Bone Marrow Transplant. 1996;17(5):769-74.
Antman KH. New developments in clinical oncology: the interdependence of bench and bedside. Cancer Res. 1991;51(18 Suppl):5060s-5064s.
Fisher B, Anderson S, Wickerham DL, et al. Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22. J Clin Oncol. 1997; 15(5):1858-69.
Fisher B, Anderson S, DeCillis A, et al. Further Evaluation of Intensified and Increased Total Dose of Cyclophosphamide for the Treatment of Primary Breast Cancer: Findings From National Surgical Adjuvant Breast and Bowel Project B-25. J Clin Oncol.1999;17(11):3374-88.
Henderson IC, Berry DA, Demetri GD, et al. Improved Outcomes From Adding Sequential Paclitaxel but Not From Escalating Doxorubicin Dose in an Adjuvant Chemotherapy Regimen for Patients With Node-Positive Primary Breast Cancer.J Clin Oncol.2003;21(6):976-83.
De Giorgi U, Rosti G, Slavin S, et al. Salvage high-dose chemotherapy for children with extragonadal germ-cell tumours. Br J Cancer. 2005;93(4):412-7.
Demirer T, Gooley T, Buckner CD, et al. Influence of total nucleated cell dose from marrow harvests on outcome in patients with acute myelogenous leukemia undergoing autologous transplantation. Bone Marrow Transplant. 1995;15(6):907-13.
Ladenstein R, Potschger U, Hartman O, et al. 28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures. Bone Marrow Transplant. 2008;41 Suppl 2:S118-27.
Gratwohl A, Baldomero H, Demirer T, et al. Hematopoetic stem cell transplantation for solid tumors in Europe. Ann Oncol. 2004;15(4):653-60.
De Giorgi U, Demirer T, Wandt H, et al. Second-line high-dose chemotherapy in patients with mediastinal and retroperitoneal primary non-seminomatous germ cell tumors: the EBMT experience. Ann Oncol. 2005;16(1):146-51.
Brunvand MW, Bensinger WI, Soll E, et al. High-dose fractionated total-body irradiation, etoposide and cyclophosphamide for treatment of malignant lymphoma: comparison of autologous bone marrow and peripheral blood stem cells. Bone Marrow Transplant. 1996;18(1):131-41.
Holmberg LA, Demirer T, Rowley S, et al. High-dose busulfan, melphalan and thiotepa followed by autologous peripheral blood stem cell (PBSC) rescue in patients with advanced stage III/IV ovarian cancer. Bone Marrow Transplant. 1998;22(7):651-9.
Demirer T, Petersen FB, Bensinger WI, et al. Autologous transplantation with peripheral blood stem cells collected after granulocyte colony-stimulating factor in patients with acute myelogenous leukemia. Bone Marrow Transplant. 1996;18(1):29-34.
Demirer T, Buckner CD, Appelbaum FR, et al. Busulfan, cyclophosphamide and fractionated total body irradiation for autologous or syngeneic marrow transplantation for acute and chronic myelogenous leukemia: phase I dose escalation of busulfan based on targeted plasma levels. Bone Marrow Transplant. 1996;17(4):491-5.
Demirer T, Buckner CD, Appelbaum FR, et al. Busulfan, cyclophosphamide and fractionated total body irradiation for allogeneic marrow transplantation in advanced acute and chronic myelogenous leukemia: phase I dose escalation of busulfan based on targeted plasma levels. Bone Marrow Transplant. 1996;17(3):341-6.
Demirer T, Celebi H, Arat M, et al. Autoimmune thrombocytopenia in a patient with small cell lung cancer developing after chemotherapy and resolving following autologous peripheral blood stem cell transplantation. Bone Marrow Transplant. 1999;24(3):335-7.
Bensinger WI, Demirer T, Buckner CD, et al. Syngeneic marrow transplantation in patients with multiple myeloma. Bone Marrow Transplant. 1996;18(3):527-31.
Berry DA, Ueno NT, Johnson MM, et al. High-dose chemotherapy with autologous stem-cell support as adjuvant therapy in breast cancer: overview of 15 randomized trials. J Clin Oncol. 2011;29(24):3214-23.
de la Rochefordiere A, Asselain B, Campana F, et al. Age as prognostic factor in premenopausal breast carcinoma. Lancet. 1993;341(8852):1039-43.
Fisher B, Redmond CK, Wickerham DL, et al. Relation of estrogen and/or progesterone receptor content of breast cancer to patient outcome following adjuvant chemotherapy. Breast Cancer Res Treat. 1983;3(4):355-64.
Taylor SGt, Knuiman MW, Sleeper LA, , et al. Six-year results of the Eastern Cooperative Oncology Group trial of observation versus CMFP versus CMFPT in postmenopausal patients with node-positive breast cancer. J Clin Oncol. 1989;7(7):879-89.
Neville AM, Bettelheim R, Gelber RD, et al. Factors predicting treatment responsiveness and prognosis in node-negative breast cancer. The International (Ludwig) Breast Cancer Study Group. J Clin Oncol. 1992;10(5):696-705.
Davis BW, Gelber RD, Goldhirsch A, et al. Prognostic significance of tumor grade in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis. Cancer. 1986;58(12):2662-70.
Bonadonna G, Valagussa P, Rossi A, et al. Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat. 1985;5(2):95-115.
Ueno NT, Rizzo JD, Demirer T, et al. Allogeneic hematopoietic cell transplantation for metastatic breast cancer. Bone Marrow Transplant 2008;41(6):537-45.
Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006;354(17):1813-26.
Dazzi F, Goldman J. Donor lymphocyte infusions. Curr Opin Hematol. 1999;6(6):394-9.
Demirer T, Barkholt L, Blaise D, et al. Transplantation of allogeneic hematopoietic stem cells: an emerging treatment modality for solid tumors. Nat Clin Pract Oncol. 2008;5(5):256-67.
McSweeney PA, Niederwieser D, Shizuru JA, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood. 2001;97(11):3390-400.
Slavin S, Nagler A, Naparstek E, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998;91(3):756-63.
Berry DA, Ueno NT, Johnson MM, et al. High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in metastatic breast cancer: overview of six randomized trials. J Clin Oncol. 2011;29(24):3224-31.
Pedrazzoli P, Ledermann JA, Lotz JP, , et al. High dose chemotherapy with autologous hematopoietic stem cell support for solid tumors other than breast cancer in adults. Ann Oncol. 2006;17(10):1479-88.
Eibl B, Schwaighofer H, Nachbaur D, et al. Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer. Blood. 1996;88(4):1501-8.
Secondino S, Carrabba MG, Pedrazzoli P, et al. Reduced intensity stem cell transplantation for advanced soft tissue sarcomas in adults: a retrospective analysis of the European Group for Blood and Marrow Transplantation. Haematologica. 2007;92(3):418-20.
Aglietta M, Barkholt L, Schianca FC, et al. Reduced-intensity allogeneic hematopoietic stem cell transplantation in metastatic colorectal cancer as a novel adoptive cell therapy approach. The European group for blood and marrow transplantation experience.Biol Blood Marrow Transplant.2009;15(3):326-35.
Peccatori J, Barkholt L, Demirer T, et al. Prognostic factors for survival in patients with advanced renal cell carcinoma undergoing nonmyeloablative allogeneic stem cell transplantation. Cancer. 2005;104(10):2099-103.
Childs R, Chernoff A, Contentin N, et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000;343(11):750-8.
Ueno NT, Cheng YC, Rondon G, Tannir NM, et al. Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors. Blood. 2003;102(10):3829-36.
Blaise D, Bay JO, Faucher C, et al. Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors. Blood. 2004;103(2):435-41.
Barkholt L, Bregni M, Remberger M, et al. Allogeneic haematopoietic stem cell transplantation for metastatic renal carcinoma in Europe. Ann Oncol. 2006;17(7):1134-40.
Ueno NT, Rondon G, Mirza NQ, et al. Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer. J Clin Oncol. 1998;16(3):986-93.
Bregni M, Dodero A, Peccatori J, et al. Nonmyeloablative conditioning followed by hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer. Blood. 2002;99(11):4234-6.
Carella AM, Beltrami G, Lerma E, et al. Combined use of autografting and non-myeloablative allografting for the treatment of hematologic malignancies and metastatic breast cancer. Cancer Treat Res. 2002;110:101-12.
Bishop MR, Fowler DH, Marchigiani D, et al. Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer. J Clin Oncol. 2004;22(19):3886-92.
Barnes DW, Corp MJ, Loutit JF, et al. Treatment of murine leukaemia with X rays and homologous bone marrow; preliminary communication.Br Med J.1956;2(4993):626-7.
Moscovitch M, Slavin S. Anti-tumor effects of allogeneic bone marrow transplantation in (NZB X NZW)F1 hybrids with spontaneous lymphosarcoma. J Immunol. 1984;132(2):997-1000.
Morecki S, Yacovlev E, Gelfand Y, et al. Cell therapy with preimmunized effector cells mismatched for minor histocompatible antigens in the treatment of a murine mammary carcinoma. J Immunother. 2001;24(2):114-21.
Panigrahi S, Yacovlev E, Gelfand Y, et al. Intraportal and systemic allogeneic cell therapy in a murine model of hepatic metastatic breast cancer. Cytokines Cell Mol Ther. 2002;7(3):99-106.
Carnevale-Schianca F, Ricchiardi A, Capaldi A, et al. Allogeneic hemopoietic stem cell transplantation in solid tumors. Transplant Proc. 2005;37(6):2664-6.
Khouri IF, Keating M, Korbling M, et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol. 1998;16(8):2817-24.
Morecki S, Yacovlev E, Diab A, et al. Allogeneic cell therapy for a murine mammary carcinoma. Cancer Res. 1998;58(17):3891-5.
Kummar S, Ishii A, Yang HK, et al. Modulation of graft-versus-tumor effects in a murine allogeneic bone marrow transplantation model by tumor-derived transforming growth factor-betaI. Biol Blood Marrow Transplant.2001;7(1):25-30.
Bishop MR, Fowler DH, Marchigiani D, et al. Allogeneic Lymphocytes Induce Tumor Regression of Advanced Metastatic Breast Cancer. J Clin Oncol.2004;22(19):3886-92.
Carella AM, Beltrami G, Corsetti MT, et al. Reduced intensity conditioning for allograft after cytoreductive autograft in metastatic breast cancer. Lancet. 2005;366(9482):318-20.
Pedrazzoli P, Comoli P, Montagna D, et al. Is adoptive T-cell therapy for solid tumors coming of age? Bone Marrow Transplant. 2012;47(8):1013-9.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.