[Selective photodynamic destruction of leukemic cells]

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 employment 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.

By determining cell viability using tetrazolium salt reduction (MTT), by flow cytometrypropidium 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/cm2) 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).

Photodynamic therapy based on the application of 5-aminolevulinic acid is a perspective method for the specific destruction of leukemic cells in autologous transplants.