title: Preferential inactivation of paediatric solid tumour cells by sequential exposure to Merocyanine 540-mediated photodynamic therapy and Edelfosine: implications for the ex vivo purging of autologous haematopoietic stem cell grafts.
abstract: Paediatric solid tumours exhibit steep dose-response curves to alkylating agents and are therefore considered candidates for high-dose chemotherapy and autologous stem cell support. There is growing evidence that autologous stem cell grafts from patients with solid tumours are frequently contaminated with live tumour cells. The objective of this study was to perform, in a preclinical purging model, an initial assessment of the safety and efficacy of a two-step purging procedure that combined Merocyanine 540-mediated photodynamic therapy (MC540-PDT) with a brief exposure to the alkyl-lysophospholipid, Edelfosine. Human and murine bone marrow cells and Neuro-2a murine neuroblastoma, SK-N-SH human neuroblastoma, SK-ES-1 and U-2 OS human osteosarcoma, G-401 and SK-NEP-1 human Wilms' tumour, and A-204 human rhabdomyosarcoma cells were exposed to a fixed dose of MC540-PDT followed by a brief incubation with graded concentrations of Edelfosine. Survival was subsequently assessed by in vitro clonal assay or, in the case of CD34-positive haematopoietic stem cells, by an immunohistochemical method. Combination purging with MC540-PDT and Edelfosine depleted all tumour cells by >4 log while preserving at least 15% of murine granulocyte/macrophage progenitors (CFU-GM), 34% of human CFU-GM, and 31% of human CD34-positive cells. The data suggest that combination purging with MC540-PDT and Edelfosine may be useful for the ex vivo purging of autologous stem cell grafts from patients with paediatric solid tumours.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Anderson
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tsujino
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Miyagi
authors.forename: Reynée
authors.initials: R
authors.lastname: Sampson
authors.forename: Fritz
authors.initials: F
authors.lastname: Sieber
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000503:physiopathology*; D012516:Osteosarcoma / Q000378:metabolism / Q000503:physiopathology*; D010742:Phospholipid Ethers / Q000008:administration & dosage; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011744:Pyrimidinones / Q000008:administration & dosage; D012208:Rhabdomyosarcoma / Q000378:metabolism / Q000503:physiopathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009396:Wilms Tumor / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D010742:Phospholipid Ethers; D017319:Photosensitizing Agents; D011744:Pyrimidinones; C026659:edelfosine; C003954:merocyanine dye