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

Abstract

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.

Second-line strategies for metastatic renal cell carcinoma: classics and novel approaches

“…Altogether, clinical data from more than 100 patients treated worldwide have been published so far and have been reviewed by Roigas and Massenkeil (2005). The data provide evidence that NST is feasible with a decreasing rate of engraftment failure.…”

Experimental Verification of Hypothesis of Antitumor Potential Presence in Mesenchymal Stem Cells

“…On the one hand, SCs are considered as convenient transporters of anticancer substances to tumor cells [6][7][8][9]. On the other hand, experts fear an enhancement of carcinogenesis process during SCs introduction into the body [1,3,10]. There are several additional aspects of this problem.…”

Influence of CD80, Interleukin-2, and Interleukin-7 Expression in Human Renal Cell Carcinoma on the Expansion, Function, and Survival of Tumor-Specific CTLs

“…Both natural killer cells and MHCrestricted CTLs could be specifically recruited to RCC in vivo (3,4). Furthermore, RCC patients showed tumor regression following allogeneic stem cell transplantation with subsequent donor lymphocyte infusions (5,6). Nevertheless, only a small percentage of patients achieved durable responses following various forms of immunotherapy and the basis of effective antitumor immunity remains unclear.…”