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-Hodgkin's lymphoma.
An important new approach to curative treatment of leukemia is vigorous treatment of autologous marrow to remove residual abnormal cells in vitro prior to reinfusion. This in vitro 'purging' must destroy the malignant cells while preserving sufficient normal precursors to allow re-establishment of normal in vivo function. We have confirmed that cortivazol (CVZ), a glucocorticoid with an unusual structure, can kill dexamethasone (DEX)-resistant leukemic cells and have examined its ability to purge DEX-sensitive (CEM-C7) and -resistant (ICR-27) human leukemic blasts artificially mixed with normal marrow mononuclear cells in vitro. By carefully defining time and dose, we established a 'therapeutic window' that allowed 'cure' of the artificial remission marrow. A sufficient number of viable normal myeloid precursor cells (CFU-GM) remained to suggest that normal marrow precursors adequate for successful marrow transplantation could survive such treatment. CVZ could be a useful drug for in vitro purging of bone marrow for autologous transplantation in patients with acute lymphoblastic leukemia or non-Hodgkin's lymphoma, sensitive or resistant to standard glucocorticoid.
Juneja
H S
HS
Department of Internal Medicine, University of Texas Medical Branch at Galveston, USA.
Harvey
W H
WH
Brasher
W K
WK
Thompson
E B
EB
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D016465:Bone Marrow Purging / Q000379:methods*; D003907:Dexamethasone; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D006098:Granulocytes; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D011281:Pregnatrienes; D014410:Tumor Stem Cell Assay
D018931:Antineoplastic Agents, Hormonal; D011281:Pregnatrienes; D003907:Dexamethasone; C005924:cortivazol