Nonmyeloablative allogeneic stem cell transplantation in metastatic renal cell carcinoma: a new therapeutic option or just a clinical experiment?

Nonmyeloablative stem cell transplantation (NST) and donor lymphocyte infusions (DLI) are currently under clinical investigation as an innovative therapeutic option for patients with metastatic renal cell carcinoma (RCC). The underlying concept, adopted from patients with hematologic malignancies, aims at a reduction of conditioning toxicity and exploits the graft versus malignancy effect of donor T-lymphocytes after transplantation. Clinical data from more than 100 patients treated worldwide have been published so far. The data provide evidence that NST is feasible with a very low rate of engraftment failure. Objective remissions in these heterogenous studies were observed in 23% of the patients overall. Remissions after NST developed only after complete engraftment of donor lymphoid cells had occurred. Objective responses were almost always accompanied by graft versus host disease (GvHD) after withdrawal of immunosuppression and/or DLI. GvHD and infections were the main contributors to a substantial transplant related morbidity and mortality, the major drawback of allogeneic stem cell transplantation. Therefore, clinical studies are necessary to further investigate and improve the selection of patients with metastatic RCC or other solid tumors for NST and to reduce post-transplant complications. This article reviews the results, side effects and potential future developments of NST in the treatment of solid tumors.