The use of photodynamic therapy in bone marrow purging.
High-dose chemotherapy and autologous bone marrow transplantation are an effective combination for treating a number of malignant disorders. Clinical trials have demonstrated a potential role for this regimen in the management of acute leukemia and non-Hodgkin's lymphoma. Autologous bone marrow transplantation continues to be limited by high relapse rates, as compared with allogeneic bone marrow transplantation. Two factors are thought to account for this observation. First, autologous transplants lack the immunologic "graft-versus-host" advantage of allogeneic transplants. Second, autologous grafts have the possibility of tumor cell contamination. Methods to reduce tumor cell contamination in autografts include exposure to chemical agents or monoclonal antibodies; long-term marrow cultures; and immunologic manipulation, either with immunomagnetic devices or antibody/complement combinations. Photodynamic therapy (PDT) with porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) or benzoporphyrin derivative (BPD verteporfin; BPD-MA; BPD-Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) may be an effective means of purging bone marrow. The ability of malignant cells to selectively accumulate photosensitizing agents may account for efficacy of PDT in bone marrow purging. The efficacy of porfimer sodium and BPD has been evaluated in cell lines known to express multidrug resistance (MDR), and the results compared with corresponding MDR-negative cell lines. Multidrug resistance-positive cell lines appear relatively resistant to BPD; porfimer sodium remains active. The reason for the differential effect of MDR positivity on the cytotoxicity of porfimer sodium and BPD is unclear, but is believed to be related to the larger size of the porfimer sodium molecule. Clinical trials evaluating PDT in bone marrow transplantation are under way.
Mulroney
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University of California, San Diego Cancer Center 92103-8421.
Glück
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D016465:Bone Marrow Purging / Q000379:methods*; D016026:Bone Marrow Transplantation; D002986:Clinical Trials as Topic; D004351:Drug Resistance; D017324:Hematoporphyrin Derivative / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D010778:Photochemotherapy; D011166:Porphyrins / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014407:Tumor Cells, Cultured; D000077362:Verteporfin
D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D000077362:Verteporfin; D017324:Hematoporphyrin Derivative