Temporal response of murine bone marrow to local hyperthermia

Hemopoietic insufficiency resulting from single or multiple agents used in cancer therapy often becomes a dose limiting toxicity. Since hyperthermia is finding increased clinical application with whole body or extended field treatments for a variety of neoplastic diseases, we wished to examine its potential effects on normal bone marrow. One hind leg of anesthetized mice received up to one hour water bath heating to 41-44 degrees C. With temperatures of 42 degrees C or greater, there was a dose and heating time dependent initial depletion of both CFU-S and CFU-GM that was not appreciably affected by migration of stem cells to or from the heated field. CFU-S and CFU-GM returned to normal values by 2 to 3 weeks after 1 hour heating to 42 degrees C. However, at 43 degrees or 44 degrees C for 1 hour, CFU-GM only transiently returned to normal, falling to 55% and 33% of control respectively by 3 months. Total nucleated cell counts reflected a similar dose and time dependent depletion and repopulation. Finally, bone marrow differential counts from heated marrow suggested that equivalent repopulation along each differentiation pathway occurred during recovery after thermal injury. These data indicate that temperatures greater than 42 degrees C for one hour caused a long term delay in hemopoietic repopulation, which may contribute to a significant toxicity when hyperthermia is used in combination with chemotherapeutic drugs or local irradiation incorporating the same treatment field.