Data di Pubblicazione:
1987
Citazione:
Myeloablation with diaziquone: in vitro assessment / B.H. Kushner, S. Siena, H. Castro-Malaspina. - In: BLOOD. - ISSN 0006-4971. - 69:6(1987 Jun), pp. 1747-1752.
Abstract:
The promising antineoplastic agent diaziquone is associated with prolonged aplasia and rare instances of bone marrow necrosis, but only mild extramedullary toxicity. To explore the drug's potential as a myeloablative agent prior to bone marrow transplantation, we compared its effects on hematopoietic versus marrow stromal cells. After short-term (one to six hours) or prolonged (three to seven days) exposure to the drug, marrow was assayed for hematopoietic (CFU-Mix, BFU-E, CFU-GM) and stromal (CFU-F) colony-forming cells and studied in long-term marrow culture (LTMC). One- and three-hour treatments produced little cytotoxicity, even at 5000 ng/mL. After six-hour treatments with this dose, marrow was depleted of CFU-Mix, BFU-E, and CFU-GM, but produced CFU-GM in LTMCs, indicating an ongoing input of CFU-GM from a surviving pre-CFU-Mix population. In contrast, elimination of the latter may be inferred from the absence of CFU-GM in LTMCs exposed for three to seven days to diaziquone at only 150 ng/mL. Under these conditions, CFU-F recovery was 40% and adherent stromal layers in LTMCs were similar to untreated controls regarding rate of development and cellular composition. Our in vitro pre-CFU-Mix-ablative regimen correlates with clinical data that show prolonged but reversible myelosuppression at steady-state diaziquone plasma levels of 101 +/- 10 ng/mL (mean +/- standard error of mean) during 7-day constant infusions.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Aziridines; Azirines; Bone Marrow Transplantation; Cells, Cultured; Humans; Stem Cells; Time Factors; Benzoquinones; Bone Marrow Cells
Elenco autori:
B.H. Kushner, S. Siena, H. Castro-Malaspina
Link alla scheda completa:
Link al Full Text: