“Less is More”: The Role of Purging in Hematopoietic Stem Cell Transplantation

The epithet "less is more" is usually applied to the essentials of good design, but it might be equally true of autologous blood or marrow transplantation. Ever since autologous marrow transplantation was first used to reconstitute recipients of high-dose chemotherapy or radiotherapy, there has been much discussion about the relative contribution of residual tumor cells in the graft to the occurrence of subsequent relapse. It was not until the early 1990s that this risk was finally confirmed by the use of gene marking [1]. A retroviral vector was used to mark a proportion of the autologous remission bone marrow from patients with acute myeloid leukemia (AML) before marrow infusion after high-dose therapy. Two recipients relapsed and both had leukemic blasts with the marker, the neomycin-resistance gene. As the safety of autologous hematopoietic stem cell transplantation has increased, the use of high-dose therapy followed by stem cell "rescue" is becoming more widespread. The malignancies treated in this way include leukemia, lymphoma, myeloma, neuroblastoma, breast cancer, and ovarian tumors. In each of these conditions a number of important questions should be addressed: Can we identify and quantitate tumor cells in the grafts and establish their oncogenic potential? If so, how best can we remove them? Can they be removed without compromising the graft, and will such purging produce a clinically significant reduction in relapse risk? Finally, will the procedure be cost-effective?