Abstract:
Background. Residual leukemic cells if present in autologous bone marrow grafts or CD34
+
concentrates obtained
from peripheral blood may increase the risk of relapse after autotransplantation. We are presenting the employement
of a new method which was introduced into the photodynamic therapy, namely enhancement of synthesis of the
photosensitizing compound, protoporphyrin IX, in cancer cells, following application of its metabolic precursor,
5-aminolevulinic acid, for the specific destruction of leukemic cells.
Methods and Results. By determining cell viability using tetrazolium salt reduction (MTT), by flow cytometry-
propidium iodide assay and by determining cell proliferation using bromodeoxyuridine incorporation we studied the
effect of photodynamic therapy based on the application of 5-aminolevulinic acid on the cells of leukemic cell lines
HL60 (human promyelocytic leukemia), HEL (erythroleukemia), DAUDI (B-cell leukemia), JURKAT (T-cell
lymphoma), blast cells of patients with acute myelogenous leukemia as well as on normal lymphocytes and normal
human bone marrow progenitors. In in vitro experiments photodynamic therapy based on an administration of
5-aminolevulinic acid (1 mM, 4 h, 18 J/cm
2
) lowered the number of viable leukemic cells by over 2 orders (with the
exception of HEL cells) and eliminated blast cells in mononuclear cell preparations of six out of seven patients with
acute myelogenous leukemia. On the other hand the viability of normal resting lymphocytes was little affected by
photodynamic therapy (number of necrotic cells increased from 6 to 11 %) and also the clonogenic activity of the
progenitor cells of normal bone marrows did not decrease substantially (CFU-GM to 60 % and BFU-E to 55 % of
the original activity).
Conclusions. Photodynamic therapy based on the application of 5-aminolevulinic acid is a perspective method
for the specific destruction of leukemic cells in autologous transplants.
Key words:
leukemia, photodynamic therapy, 5-aminolevulinic acid, autologous transplantation, bone marrow purging.
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