Current role of allogeneic stem cell transplantation in breast cancer.

The majority of patients with metastatic breast cancer will relapse and will die of their disease. Allogeneic stem cell transplantation (AlloSCT) with myeloablative conditioning regimens may provide cytoreduction and eradication of disease with two advantages: a cancer free-graft and an immune-mediated graft-versus-tumor (GVT) effect mediated by the donor's immune cells. The first report of an AlloSCT in solid tumors has been published in 1996 [1]. Since then, several small series have been published, especially in renal cell and breast cancer [2, 3–11]. With reduced-intensity conditioning regimens (RICT), the goal of transplantation is the achievement of a full donor engraftment and the induction of a GVT effect, rather than chemotherapy-related cytoreduction. Clinical responses suggestive of a GVT effects have been reported, and more than 1000 patients with refractory and advanced solid tumors, to date, have undergone RICT in EBMT centers. graft-versus-breast cancer effect In 1996, Eibl et al. reported a single patient with metastatic breast cancer who achieved a complete remission after a matched-sibling allogeneic donor transplant. They were also able to isolate from the blood of the patient minor histocompatible antigen-specific and major histocompatibility complex class I antigen-restricted cytotoxic T lymphocytes recognizing breast carcinoma target cells [1]. Subsequently, Ben-Yosef et al. provided evidence of breast cancer response following allogeneic transplantation for acute leukemia [12]. In 1998, Ueno et al. published a series of 10 patients with breast cancer who received a myeloablative conditioning and a matched sibling bone marrow donor transplant, observing two responses concurrently with acute graft-versus-host disease. However, the high toxicity of the conditioning and the heavy pretreatment of these patients, associated with a high tumor burden, precluded a meaningful evaluation of the effects of allogeneic transplantation [2]. A clear direct evidence of GVT in hematological malignancies came from the observation that donor lymphocyte infusions can induce remissions of malignant diseases without cytotoxic therapy in patients who relapse after AlloSCT [13]. The GVT effect is strongly associated with GVHD; the responses occur after withdrawal of immunosuppression and after establishment of complete donor chimerism; moreover, the time to response is delayed following transplant. Spontaneous GVT effects against solid tumors were first documented in the 1980s in mouse models following allogeneic transplantation. Most of the available data on animal models of allografting in solid tumors came from Shimon Slavin and his group in Jerusalem. They demonstrated that naı¨ve or immune donor cells, sensitized with either tumor or normal minor mismatched …