Immunotoxin Elimination of Leukemic B - Lineage Progenitors

Autoiogous bone marrow transplantation (BMT) ~ is being evaluated at several medical centers as an alternative approach to aliogeneic BMT for the t rea tment of acute lymphoblastic leukemia (ALL) patients who do not have matched sibling donors (1, 2). A major limitation o f autologous B M T is the likely presence o f residual leukemia in the remission marrow (2). This difficulty makes ex vivo purging of autologous stem cell grafts before transplantation essential for therapeutic efficacy (3). Cur ren t ex vivo purging strategies involve the t rea tment of autologous marrow with cyclophosphamide congeners (3-5), mAb plus complement (6-9), and immunotoxins (IT) (10-18). O u r laboratory is commit ted to the evaluation of the clinical potential of I T in autoiogous B M T for ALL. We have begun a phase I trial in T A L L using intact ricin IT as purgative reagents to eliminate occult leukemic T-lineage blasts f rom autologous marrow grafts pr ior to reinfusion (18). In common B-lineage ALL, our Bone Marrow Transplant T e a m at the University of Minnesota has emphasized the use of mAb plus complement for ex vivo bone marrow t rea tment (19). Despite such ex vivo manipulation of autologous stem cell grafts, r ecur ren t leukemia in autotransplanted patients remains tile major cause for t rea tment failure in ALL (19-21). Available methods do not de te rmine whether relapses occur because o f incom-