SUCCESSFUL PURGING OF MURINE PLASMACYTOMA BY MAFOSFAMIDE (ASTA-Z)

Mafosfamide (ASTA-Z) is a chemotherapeutic agent currently in use for in vitro purging of tumor-bearing human BM cells prior to autologous b one marrow transplantation (ABMT). We tested the efficacy of ASTA-Z ag ainst mouse plasmacytoma cells MOPC-315 (MOPC), a model of human multi ple myeloma. BALB/c mice were injected intraperitoneally with differen t doses of MOPC preincubated with ASTA-Z. All control mice receiving g reater than or equal to 10(4) MOPC intraperitoneally (ip) died within 23 days. All recipients of ASTA-Z pretreated MOPC remained healthy for > 180 days. To simulate the clinical situation, BALB/c mice received lethal doses of 10(3) MOPC ip prior to ABMT. Subsequently, mice were t reated with cyclophosphamide 200 mg/kg one day prior to syngeneic BMT with 10(7) BMC containing 10(6) MOPC; 90% of the mice receiving unpurg ed syngeneic BMC died within 45 days whereas all mice transplanted wit h ASTA-Z-treated BMC/MOPC mixtures remained disease-free for > 100 day s. Our results suggest that a similar approach may be successful in pa tients with multiple myeloma and residual disease prior to cryopreserv ation of their BM for ABMT. Bone marrow purging with ASTA-Z is effecti ve and under certain conditions could be critical for prevention of re lapse following ABMT, provided that effective elimination of residual disease in the host can be achieved by the conditioning regimen prior to ABMT.