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 s
upport. We have explored the potential role of photoradiation therapy
in purging hematopoietic stem cells of various hematological malignanc
ies. Benzoporphyrin derivative, monoacid ring A (BPD-MA), dihematoporp
hyrin ether (DHE), and MC540 were evaluated for the ''ex-vivo'' purgin
g of residual tumor cells from autologous bone marrow (BM) grafts. BPD
-MA and DHE photosensitizing activity was tested against two human lar
ge cell lymphoma cell lines and colony forming-unit leukemia (CFU-L) d
erived from patients with acute myelogenous leukemia (AML). In mixing
experiments four log elimination of tumor cell lines was observed afte
r 1 hr of incubation with BPD-MA or DHE followed by white light exposu
re. By comparison, using the same concentration of BPD-MA or DHE, the
mean recovery of normal BM progenitors was 4-5.2% for granulocyte-macr
ophage colony forming unit (CFU-GM) and 5-9.8% for burst forming unit
erythroid (BFUE). The T lymphoblastic leukemia cell line CEM and its v
inblastine (VBL)-resistant subline CEM/VBL100, along with the acute pr
omyelocyte leukemia cell line HL-60 and its vincristine (VCR)-resistan
t subline HL-60/VCR, were also tested. Our results demonstrated the pr
eferential cytotoxicity of BPD-MA and DHE toward neoplastic cell lines
and CFU-L from AML patients. In addition, DHE was slightly more effec
tive in purging tumor cells expressing the p-170 glycoprotein. These r
esults suggest that photoradiation would be useful for ''ex-vivo'' pur
ging of malignant cells. Other methods to deal with decreasing drug re
sistance are also detailed.