Emergence of drug resistance with conventional cytotoxic
therapy is a major challenge towards the curability of many
cancers, especially in patients undergoing autologous BMT with ex-vivo purged hematopoietic support. We have explored the potential role of
photoradiation therapy in purging hematopoietic stem cells of various
hematological malignancies.
Benzoporphyrin derivative, monoacid ring A (
BPD-MA),
dihematoporphyrin ether (DHE), and MC-540 were evaluated for the "ex-vivo" purging of
residual tumor cells from autologous bone marrow (BM) grafts.
BPD-MA and DHE photosensitizing activity was tested against two human large cell
lymphoma cell lines and colony forming-unit
leukemia (CFU-L) derived from patients with
acute myelogenous leukemia (AML). In mixing experiments four log elimination of tumor cell lines was observed after 1 hr of incubation with
BPD-MA or DHE followed by white light exposure. By comparison, using the same concentration of
BPD-MA or DHE, the mean recovery of normal BM progenitors was 4-5.2% for granulocyte-macrophage colony forming unit (CFU-GM) and 5-9.8% for burst forming unit erythroid (BFU-E). The T
lymphoblastic leukemia cell line CEM and its
vinblastine (VBL)-resistant subline CEM/VBL100, along with the acute promyelocyte
leukemia cell line HL-60 and its
vincristine (VCR)-resistant subline HL-60/VCR, were also tested. Our results demonstrated the preferential cytotoxicity of
BPD-MA and DHE toward neoplastic cell lines and CFU-L from AML patients. In addition, DHE was slightly more effective in purging
tumor cells expressing the p-170
glycoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)