Selective Photodynamic Destruction of Leukemic Cells

Overview

Background.
Residual leukemic cells if present in autologous bone marrow grafts or CD34+concentrates obtainedfrom peripheral blood may increase the risk of relapse after autotransplantation. We are presenting the employementof a new method which was introduced into the photodynamic therapy, namely enhancement of synthesis of thephotosensitizing 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 theeffect of photodynamic therapy based on the application of 5-aminolevulinic acid on the cells of leukemic cell linesHL60 (human promyelocytic leukemia), HEL (erythroleukemia), DAUDI (B-cell leukemia), JURKAT (T-celllymphoma), blast cells of patients with acute myelogenous leukemia as well as on normal lymphocytes and normalhuman bone marrow progenitors. In in vitro experiments photodynamic therapy based on an administration of5-aminolevulinic acid (1 mM, 4 h, 18 J/cm2) lowered the number of viable leukemic cells by over 2 orders (with theexception of HEL cells) and eliminated blast cells in mononuclear cell preparations of six out of seven patients withacute myelogenous leukemia. On the other hand the viability of normal resting lymphocytes was little affected byphotodynamic therapy (number of necrotic cells increased from 6 to 11 %) and also the clonogenic activity of theprogenitor cells of normal bone marrows did not decrease substantially (CFU-GM to 60 % and BFU-E to 55 % ofthe original activity).Conclusions. Photodynamic therapy based on the application of 5-aminolevulinic acid is a perspective methodfor the specific destruction of leukemic cells in autologous transplants.

Key words:
leukemia, photodynamic therapy, 5-aminolevulinic acid, autologous transplantation, bone marrow purging.