Modulation of hematopoiesis and survival after high-dose chemotherapy or radiotherapy: review and discussion of possible mechanisms.

This paper reviews ways by which growth of transplanted or surviving hematopoietic stem cells might be enhanced to improve survival in the case of autologous marrow transplantation. Most of the treatments known to have such effects have been used in isologous mouse models and improve animal survival by enhancing hematopoietic recovery after high doses of whole body irradiation or chemotherapy. Although some of these were studied 20 years ago, the use of such treatments in man has awaited the realization that some disseminated cancer can only be eliminated by use of various treatments where hematopoietic damage is the limiting factor. Although increasing the number of transplanted pluripotent stem cells is the most certain way to hasten return of needed blood cells in transplant patients, several of the treatments listed in the paper have growth enhancing effects on both surviving host stem cells and transplanted cells. There are recent studies which indicate that such priming treatments may also be effective in other normal tissues such as gut and bladder epithelium. At least one study in man has intentionally applied this approach with the expected benefit and others may have done so inadvertently. Much work remains to find new combinations to select the best priming treatments and intervals in man and to determine whether or not such treatments are effective against tumors.