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Photoradiation methods for purging autologous bone marrow grafts
S Gulati1, J Atzpodien, R M Lemoli
1Laboratory of Hematopoietic Cell Kinetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Progress in Clinical and Biological Research
|January 1, 1990
Summary
Photoradiation therapy using Dihematoporphyrin Ether (DHE) and Merocyanine-540 (MC-540) effectively purges leukemia and lymphoma cells from bone marrow transplants. This phototherapy shows high cancer cell kill rates while sparing normal progenitor cells, suggesting clinical trial potential.
Area of Science:
- Biomedical Engineering
- Photodynamic Therapy
- Cancer Research
Background:
- Autologous bone marrow transplants can retain residual tumor cells.
- Effective purging of these cells is crucial for successful transplantation.
- Photoradiation therapy offers a potential method for ex vivo tumor cell elimination.
Purpose of the Study:
- To evaluate the efficacy of Dihematoporphyrin Ether (DHE) and Merocyanine-540 (MC-540) mediated photoradiation therapy for purging cancer cells from bone marrow.
- To assess the selective toxicity of these agents towards neoplastic cells versus normal hematopoietic progenitor cells.
- To determine optimal conditions for photoradiation therapy to maximize tumor cell kill and minimize damage to healthy cells.
Main Methods:
- In vitro exposure of leukemia and lymphoma cell lines (HL-60, Reh, SK-DHL-2) and normal human marrow progenitor cells (CFU-GM, BFU-E, CFU-GEMM) to DHE and MC-540 with white light.
- Comparison of sequential (drug incubation followed by light) and simultaneous (drug and light exposure concurrently) treatment protocols.
- Quantification of residual tumor cells and normal progenitor cell viability post-treatment.
Main Results:
- Both DHE and MC-540 demonstrated high cytocidal activity against lymphoid and myeloid neoplastic cells.
- Normal hematopoietic progenitor cells (CFU-GM, BFU-E, CFU-GEMM) were significantly less affected by the photoradiation.
- Simultaneous light and MC-540 treatment preferentially eliminated tumor cells, reducing them by over 4 logs.
- Sequential DHE treatment spared a significant percentage of normal progenitor cells, while simultaneous treatment eradicated both tumor and normal cells.
Conclusions:
- Photoradiation therapy with DHE and MC-540 is a promising method for purging residual tumor cells in autologous bone marrow transplantation.
- The selective toxicity is dependent on the mode of light activation, with simultaneous treatment showing preferential tumor cell elimination.
- These findings support the development of phototherapy protocols for clinical trials in leukemia and lymphoma treatment.