Purging of peripheral blood stem cell grafts

The shortage of HLA-matched sibling donors for bone marrow transplant patients has stimulated interest in the use of alternative donors. As a result, there has been a dramatic increase in the use of autologous marrow transplantation, which avoids the complications of graft-versus-host disease, but may deprive the patient of a potentially beneficial graft-versus-disease response and runs the risk of returning occult tumor cells with the graft. There is increasing evidence that these cells may be associated with disease relapse post-transplant, and many methods have been developed for their removal ex vivo. Combinations of negative and positive selection may achieve elimination of tumor cells to the limits of detection of the most sensitive assays currently available. The marked trend toward the use of autologous grafts derived from blood rather than marrow has raised the question as to whether peripheral blood stem cell (PBSC) preparations should be purged of tumor. Data indicate that these grafts generally contain a lower tumor burden, although the stem cell mobilization procedure may recruit tumor cells into the peripheral circulation. Enrichment of CD34+ cells from apheresis products appears, at present, to be less efficient than from marrow and provides at best about a 2-3 log depletion of tumor. This has prompted proposals to follow positive selection by a small-scale purging procedure. Technical issues, such as preprocessing and pooling of collections prior to purging, remain to be addressed. Ultimately, the development of successful purging procedures for PBSC grafts will simply reemphasize the necessity of improving the efficacy of high-dose therapy.