Developments in purging in autotransplantation.

Abstract

High-dose therapy and bone marrow transplantation has been shown to be a potentially curative modality for patients with hematologic malignancies. Several obstacles to the use of this approach include the availability of histocompatible siblings and the increased toxicity even in HLA-matched patients owing to graft-versus-host disease and interstitial pneumonitis. The use of autologous marrow in support of high-dose therapy has lower toxicity; however, there is the issue that residual tumor cells may be reinfused into the patient. There are several laboratory studies demonstrating that residual tumor cells persist in the marrow despite histologic remission. In addition, case reports suggest that contaminated marrow has led to widespread early relapse owing to reinfusion of tumor cells. A variety of techniques have been developed that can deplete up to 5 logs of tumor cells from the marrow. These techniques include very specific immunologic as well as less specific pharmacologic purging. Both approaches have been refined so that normal hematopoietic stem cell reconstitution is relatively preserved. Although a large number of studies have been reported that have utilized ex vivo marrow purging, few have examined whether there has been an impact on disease-free survival. Although randomized studies have not been performed to date, several recent studies in ANLL and B-cell NHL strongly suggest that there is a relationship between the quality of elimination of the disease ex vivo in the marrow and disease-free survival. With further improvements in marrow treatment, whereby all detectable cells are depleted, as determined by highly sensitive molecular biologic techniques, and randomized trials involving purged and unpurged BM, the question of the impact of ex vivo marrow treatment can be better answered.