title: The effects of hyperthermia in bone marrow purging of breast cancer.
abstract: The number of autologous bone marrow transplants done for solid tumours, particularly breast cancer, has risen steadily over the last ten years. The role of bone marrow or peripheral blood progenitor cell purging in transplantation is incompletely understood. Theoretically, the reinfusion of untreated bone marrow containing tumour cells might result in relapse in some patients treated with high-dose chemotherapy and hematopoietic support. Therefore, safe and effective purging techniques may increase long-term, disease-free survivorship. In this study, hyperthermia was evaluated for its ability to purge CAMA-1 breast cancer cells from normal human bone marrow. Between two and nine trials of a range of temperatures (42-45 degrees C) and durations of treatment (1-4 h) were performed. The effect of hyperthermia on normal bone marrow alone and in mixes with breast cancer cells was also evaluated. Hyperthermia (45 degrees C, 4 h) produced > 5 logs of CAMA-1 cell kill. Exposures of 45 degrees C for 2 h and 44 degrees C for 4 h resulted in approximately three logs of cell kill, corresponding to < 1% survival of clonogenic cells. Normal bone marrow was considerably more vulnerable to heat treatments, however, with approximately 1% of progenitors remaining clonogenic after exposure of 43 degrees C for 2 h and 44 degrees C for 1 h. Therefore, although hyperthermia is able to achieve adequate CAMA-1 breast cancer cell kill, it remains more toxic to normal bone marrow as a purging method. To make hyperthermia useful in purging systems, mechanisms to selectively alter thermal sensitivity must be pursued.
authors.affiliation: Duke University Medical Center, Department of Radiation Oncology, Durham, North Carolina, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Ingram
authors.forename: T
authors.initials: T
authors.lastname: Samulski
authors.forename: R
authors.initials: R
authors.lastname: Dodge
authors.forename: L R
authors.initials: LR
authors.lastname: Prosnitz
authors.forename: P
authors.initials: P
authors.lastname: Peters
authors.forename: J
authors.initials: J
authors.lastname: Vredenburgh
mesh_terms: D016465:Bone Marrow Purging / Q000379:methods*; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000473:pathology / Q000601:surgery* / Q000628:therapy*; D016923:Cell Death; D005069:Evaluation Studies as Topic; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D066298:In Vitro Techniques; D014411:Neoplastic Stem Cells / Q000473:pathology; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay