Cancer stem cells: relevance to clinical transplantation

Despite blood or marrow transplantation (BMT) being arguably the most active modality against hematologic malignancies, relapses remain the major reason for failure. Many cancers have now been shown to harbor cells that are phenotypically and biologically similar to normal cells with self-renewal capacity; these so-called cancer stem cells (CSCs) typically constitute only a small fraction of the total tumor burden, but are hypothesized to be responsible for relapse after conventional-dose therapy. Here, we review whether CSCs may have relevance to BMT.

CSCs appear to be relatively resistant to standard anticancer therapies in vitro. The often-dramatic responses induced by chemotherapy in most hematologic malignancies are likely a consequence of their impressive activity against the bulk tumor cells. Although the clinical importance of CSCs remains unproven, new evidence suggests that the limited durability of many of these responses reflect resistant CSCs. It is possible that CSCs are also relatively resistant to both high-dose myeloablative conditioning and allogeneic graft-versus-tumor effects. Data on the ability of most hematologic CSCs to circulate even early in the natural history of a malignancy also raises concerns about contamination of autografts contributing to relapse.

Emerging data for the first time suggest CSCs may be responsible for relapse, even after BMT. However, BMT may be a particularly compelling setting to test CSC-targeting strategies because it provides the most effective clinical debulking of hematologic malignancies, and because CSC-targeting strategies may also enhance allogeneic antitumor immunity.