Profound graft-versus-tumor response in metastatic breast cancer with nonmyeloablative allografting.

Allogeneic transplants from human leukocyte antigen (HLA)compatible donors can cure hematologic malignancies which cannot be cured with chemotherapy alone. This technique was first applied to metastatic breast cancer in 1996 [1], where response in lymph node and bone metastases was attributed to an immune response induced by myeloablative allogeneic transplant. This report demonstrated that breast cancer cell lines expressed class I antigen-restricted major histocompatibility complex molecules and that cytotoxic minor histocompatibility antigen-specific T cells recognizing breast cancer cells were present in the patient after transplant. Subsequently, a series of 10 patients receiving ablative allogeneic transplant for advanced breast cancer indicated response in 50% with post-transplant immune response induced by withdrawal of immune suppressive drugs [2]. In the same year, immune response induced by interleukin-2activated T-lymphocytes following autologous transplantation was reported [3]. The use of infusions of sibling-derived HLA-matched lymphocytes as immunotherapy have been reported to produce tumor responses in breast cancer [4]. The high treatment-related morbidity and mortality associated with myeloablative conditioning regimens led to the introduction of reduced intensity regimens in the late 1990s, which relied on a graft-versus-leukemia effect to achieve response. With suggestion that there is a graft-versus-tumor effect possible in breast cancer, we pioneered a protocol in 1997 which combined the antitumor effect of high-dose chemotherapy and autologous stem-cell infusion with reduced intensity allogeneic stem-cell transplant for patients with HLA-matched sibling donors. The results in 17 patients with Annals of Oncology letters to the editor