THE EFFECTS OF HYPERTHERMIA IN BONE-MARROW PURGING OF BREAST-CANCER

The number of autologous bone marrow transplants done for solid tumour s, particularly breast cancer, has risen steadily over the last ten ye ars. The role of bone marrow or peripheral blood progenitor cell purgi ng in transplantation is incompletely understood. Theoretically, the r einfusion of untreated bone marrow containing tumour cells might resul t in relapse in some patients treated with high-dose chemotherapy and hematopoietic support. Therefore, safe and effective purging technique s may increase long-term, disease-free survivorship. In this study, hy perthermia 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. Hyper thermia (45 degrees C, 4 h) produced >5 logs of CAMA-1 cell kill. Expo sures of 45 degrees C for 2 h and 44 degrees C for 4 h resulted in app roximately three logs of cell kill, corresponding to <1% survival of c lonogenic cells. Normal bone marrow was considerably more vulnerable t o heat treatments, however, with approximately 1% of progenitors remai ning clonogenic after exposure of 43 degrees C for 2 h and 44 degrees C for 1 h. Therefore, although hyperthermia is able to achieve adequat e CAMA-1 breast cancer cell kill, it remains more toxic to normal bone marrow as a purging method. To make hyperthermia useful in purging sy stems, mechanisms to selectively alter thermal sensitivity must be pur sued.