SUCCESSFUL IN-VITRO PURGING OF LEUKEMIC BLASTS FROM MARROW BY CORTIVAZOL, A PYRAZOLOSTEROID - A PRECLINICAL STUDY FOR AUTOLOGOUS TRANSPLANTATION IN ACUTE LYMPHOBLASTIC-LEUKEMIA AND NON-HODGKINS-LYMPHOMA

An important new approach to curative treatment of leukemia is vigorou s treatment of autologous marrow to remove residual abnormal cells in vitro prior to reinfusion. This in vitro 'purging' must destroy the ma lignant cells while preserving sufficient normal precursors to allow r e-establishment of normal in vivo function. We have confirmed that cor tivazol (CVZ), a glucocorticoid with an unusual structure, can kill de xamethasone (DEX)-resistant leukemic cells and have examined its abili ty to purge DEX-sensitive (CEM-C7) and -resistant (ICR-27) human leuke mic blasts artificially mixed with normal marrow mononuclear cells in vitro. By carefully defining time and dose, we established a 'therapeu tic window' that allowed 'cure' of the artificial remission marrow. A sufficient number of viable normal myeloid precursor cells (CFU-GM) re mained to suggest that normal marrow precursors adequate for successfu l marrow transplantation could survive such treatment. CVZ could be a useful drug for in vitro purging of bone marrow for autologous transpl antation in patients with acute lymphoblastic leukemia or non-Hodgkin' s lymphoma, sensitive or resistant to standard glucocorticoid.