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J Atzpodien, SC Gulati, A Strife and BD Clarkson
To assess the potential of photoradiation therapy for the in vitro purging
of residual tumor cells from autologous bone marrow (BM) transplants, we
studied normal marrow and tumor cell clonogenicity in response to different
light-activated compounds by using the fluorescent dyes dihematoporphyrin
ether (DHE) and merocyanine-540 (MC- 540). After photoradiation of cells
with white light, both DHE and MC- 540 showed high cytocidal activity
toward lymphoid and myeloid neoplastic cells but had a significantly lesser
effect on normal granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and
mixed colony- forming (CFU-GEMM) progenitor cells. Acute promyelocytic
leukemia (HL- 60), non-B, non-T, CALLA-positive acute lymphoblastic
leukemia (Reh), and diffuse histocytic B cell lymphoma (SK-DHL-2) cell
lines were exposed to different drug concentrations in combination with
white light at a constant illumination rate of 50,000 lux. With DHE doses
varying from 2.0 to 2.5 micrograms/mL and MC-540 concentrations of 15 to 20
micrograms/mL, clonogenic tumor cells could be reduced by more than 4 logs
when treated alone or in mixtures with normal irradiated human marrow
cells. However, preferential cytotoxicity towards neoplastic cells was
highly dependent on the mode of light activation. MC-540 had no substantial
effect on malignant lymphoid (SK-DHL-2) and myeloid (HL-60) cells and on
normal marrow myeloid (CFU-GM) precursors when drug incubation was
performed in the dark and followed by light exposure of washed cells. Equal
doses of MC-540 (15 to 20 micrograms/mL) could preferentially eliminate
tumor cells under conditions of simultaneous light and drug treatment (30
minutes at 37 degrees C). When using DHE (2.5 micrograms/mL), 29.3%, 46.8%,
and 27.5% of normal marrow CFU-GM, BFU-E, and CFU-GEMM, respectively, were
spared after sequential drug and light exposure of cells, whereas
simultaneous treatment reduced both normal (CFU-GM) and neoplastic cells
below the limits of detection. In summary, our results indicate the
usefulness of various photoradiation models for the ex vivo treatment of
leukemic and lymphomatous bone marrow autografts.
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| Copyright © 1987 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||