Purging with 4-hydroperoxycyclophosphamide

Over the past 10 years, very-high-dose cytotoxic therapy with rescue of marrow function by autologous bone marrow transplantation (BMT) has been shown to be effective treatment for patients with lymphomas and acute leukemias. However, a major concern has been that infusion of occult tumor cells with the autologous marrow will contribute to relapse. Accordingly, multiple techniques for treating autologous marrow grafts in vitro, to remove or "purge" occult tumor, have been developed. Despite controversy regarding the necessity and efficacy of purging, most autologous transplants for acute leukemia and many for lymphoma are currently purged. Most studies have used immunologic or cytotoxic agents for purging. The most widely used cytotoxic purging agents have been the cyclophosphamide congeners, 4-hydroperoxycyclophosphamide (4-HC) and mafosfamide. Since the first 4-HC-purged autologous marrow transplant was performed in 1980, over 700 patients have received 4-HC-purged autologous bone marrow transplants at Johns Hopkins alone. This review will chronicle the development of 4-HC as a purging agent.