Nonmyeloablative transplantation for solid tumors: a new frontier for allogeneic immunotherapy

Abstract

The failure of conventional chemotherapy to improve survival in a large percentage of patients with advanced solid tumors has prompted the development of alternative anticancer approaches. Conventional allogeneic hematopoietic stem cell transplantation (HSCT) relies on myeloablative conditioning to eradicate the underlying disease, as well as suppress the patient's immune response, allowing engraftment of the donor's lymphohematopoietic system. Such preparative regimens are frequently associated with serious hematologic and nonhematologic toxicities, resulting in substantial morbidity and mortality. A significant curative component of allogeneic HSCT is the immune-mediated graft-versus-tumor (GVT) effect. Nonmyeloablative preparative regimens were designed to suppress host immunity to allow for sufficient engraftment of the donor immune system for the subsequent generation of GVT effects. These relatively low-dose preparative regimens are generally well tolerated and are associated with a reduction in the risk of transplant-related mortality. Nonmyeloablative HSCT provides a safer platform to explore the efficacy of allogeneic HSCT in patients with solid tumors. Initial reports have demonstrated that GVT may occur against several different solid tumors, including renal cell carcinoma, ovarian cancer, breast cancer and others. Based on these preliminary encouraging results, further exploration of nonmyeloablative HSCT for solid tumors is clearly warranted. The development of strategies to decrease graft-versus-host disease while enhancing post-transplant antitumor immunity will hopefully be forthcoming in the near future.