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RM Lemoli, C Gasparetto, DA Scheinberg, MA Moore, BD Clarkson and SC Gulati
Laboratory of Hematopoietic Cell Kinetics, Memorial Sloan-Kettering Cancer
Center, New York, NY 10021.
We report the results of a preclinical study comparing four different
purging protocols using a promyelocytic human cell line HL-60 and myeloid
leukemic progenitor cells (colony-forming unit-leukemic [CFU- L]) from
acute myelogenous leukemia (AML) patients assayed in semisolid culture. We
studied the antileukemic effect of (1) Single-cycle complement-mediated
lysis by two different monoclonal antibodies (MoAbs) (M195 [CD33] and F23
[CD13] 40 micrograms/mL), reactive with distinct antigens found on early
myeloid cells and monocytes, used alone and in combinations; (2)
4-Hydroperoxycyclophosphamide (4-HC) (80 mumol/L or 100 mumol/L) alone; or
(3) combined with VP-16 (5 micrograms/mL) and (4) a cocktail of 1 through 3
as above (combined immunochemotherapy). More than 4 logs of HL-60 tumor
cell elimination were observed after 1 hour of incubation with both MoAbs
plus 4-HC + VP- 16 while the single treatment (immunotherapy or
chemotherapy) provided 1.5 and 3.5 logs of colony-forming inhibition,
respectively. When the same protocols were tested on cryopreserved leukemic
cells from eight patients with AML, we observed a mean value of CFU-L
inhibition of 92.3% +/- 2.5% SD, 95.5% +/- 1.4% SD, and 99% +/- 0.8% SD
after MoAbs and complement lysis, 4-HC, and 4-HC + VP-16 treatment,
respectively. The combined treatment of MoAbs and 4-HC + VP-16 produced
more than 3- log reduction of CFU-L colony formation. By comparison, the
mean recovery of committed normal bone marrow progenitors after incubation
with MoAbs and complement was 12% for CFU-granulocyte-macrophage (CFU- GM),
22.9% for burst-forming unit erythroid (BFU-E), and the recovery following
4-HC + VP-16 treatment was 4.4% for CFU-GM and 5.6% BFU-E. In subsequent
experiments, highly purified CD34+ blast cells, enriched by positive
selection, and stimulated in liquid culture by cytokines (interleukin-1
[IL-1], IL-3, and combination of both) or MO-conditioned medium (MoCM),
demonstrated that immunochemotherapy spares hematopoietic colony-forming
cells earlier than day 14 CFU-GM, in vitro.
This article has been cited by other articles:
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| Copyright © 1991 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||