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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.

Abstract
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.
AuthorsH S Juneja, W H Harvey, W K Brasher, E B Thompson
JournalLeukemia (Leukemia) Vol. 9 Issue 10 Pg. 1771-8 (Oct 1995) ISSN: 0887-6924 [Print] England
PMID7564524 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents, Hormonal
  • Pregnatrienes
  • Dexamethasone
  • cortivazol
Topics
  • Antineoplastic Agents, Hormonal (pharmacology)
  • Bone Marrow Purging (methods)
  • Dexamethasone
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Resistance
  • Female
  • Granulocytes
  • Humans
  • Lymphoma, Non-Hodgkin (therapy)
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma (therapy)
  • Pregnatrienes
  • Tumor Stem Cell Assay

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