Preclinical assessment of purging with VP-16-213: Key role for long-term marrow cultures Journal Article

  

Authors:	Kushner, B. H.; Kwon, J. H.; Gulati, S. C.; Castro-Malaspina, H.
Article Title:	Preclinical assessment of purging with VP-16-213: Key role for long-term marrow cultures
Abstract:	An evaluation of the effects of VP-16 on normal human marrow cells and representative lymphoma-leukemia cell lines was performed to assess this agent's applicability to ex vivo marrow purging. Tumoricidal dose curves were defined using malignant lymphoid (SK-DHL2 and Reh) and myeloid (HL-60) cells admixed with a 20-fold excess of irradiated marrow cells to simulate a borderline remission marrow. One-hour treatment yielded ID50 of <5 μmol/L of VP-16 for clonogenic units from each cell line; rare-to-zero clonogenic units survived exposure to 50 to 100 μmol/L. CFU-Mix, BFU-E, and CFU-GM were equal in their sensitivity to VP-16 (ID50s 25 to 30 μmol/L). Marrows treated with 75 μmol/L were completely depleted of these colony-forming cells but produced CFU-GM in one-stage long-term marrow cultures (LTMCs). This dose had little adverse effect on the proliferative capacity of marrow stromal progenitors, as measured by CFU-F (ID50 271 μmol/L) and by the unperturbed development of adherent layers in LTMCs. Furthermore, these stromal layers were able to support hematopoiesis as well as controls in co-culture experiments with autologous marrow cells (two-stage LTMCs). In conclusion, doses of VP-16 but cleanse marrow of lymphoma-leukemia cells spare hematopoietic and stromal progenitors as demonstrated by LTMCs. These data favor the use of VP-16 in the clinical autotransplant setting.
Keywords:	human cell; dose response; drug efficacy; methodology; bone marrow; etoposide; cell line; in vitro study; histology; cell culture; leukemia cell; lymphoma cell; drug response; drug administration; therapy; normal human; pharmacokinetics; etiology; colony formation; human; priority journal; blood and hemopoietic system
Journal Title:	Blood
Volume:	69
Issue:	1
ISSN:	0006-4971
Publisher:	American Society of Hematology
Date Published:	1987-01-01
Start Page:	65
End Page:	71
Language:	English
DOI:	10.1182/blood.v69.1.65.65
PUBMED:	3790729
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0023130328&doi=10.1182%2fblood.v69.1.65.65&partnerID=40&md5=33d1c590774c55ce9ab8aa7207f736a3
Notes:	Article -- Export Date: 5 February 2021 -- Source: Scopus

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