Allogeneic stem cell transplantation for the treatment of advanced solid tumors

Allogeneic stem cell transplantation has emerged as a potentially curative treatment modality for patients with hematological malignancies. The graft-versus-leukemia effect, an immune mechanism mediated by the donor immune system, is an important component of the therapeutic effect of allogeneic transplantation. Recent data from experimental animal models and from preliminary clinical experience suggest that a graft-versus-tumor effect, analogous to the graft-versus-leukemia effect, may be generated against solid tumors such as renal cell cancer, breast cancer, and other malignancies. The use of non-myeloablative, immunosuppressive conditioning regimens offers the opportunity to achieve a full-donor engraftment with reduced transplant-related complications and mortality, enabling also patients of advanced age and with co-morbidities to receive an allografting. Advanced renal cell cancer, an essentially incurable disease, has emerged from pilot studies as a disease susceptible to the graft-versus-tumor effect. Future studies will demonstrate if the tumor responses observed after allografting will translate into a clinically meaningful survival advantage. Other tumors in which tumor responses have been observed are: breast cancer, ovarian cancer, colorectal cancer, soft-tissue sarcoma, and others. Advanced melanoma may not be amenable to graft-versus-tumor effect. Future studies will point to the identification, isolation and cloning of target antigen(s) of graft-versus-tumor effect, to further reduce toxicities and to achieve a selective cell-mediated immunotherapy.