IMPROVING THE ROLE OF HEMATOPOIETIC SUPPORT FOR HIGH-DOSE CYTOTOXIC THERAPY

Dose intensification of cytotoxic drugs is now being evaluated in seve ral trials. Various methods are available to manage the hematopoietic toxicity. Hematopoietic growth factors can be used alone and/or in com bination with hematopoietic stem cell rescue. Patients undergoing auto logous stem cell transplantation (AuSCT) have their own bone marrow an d/or peripheral blood used for hematopoietic engraftment. In several m alignancies, the bone barrow is involved with tumor, and in such situa tions, the success of AuSCT may improve if hematopoietic elements are enriched (positive selection) or if contaminating cancer cells are pur ged by negative selection. In patients undergoing allogeneic bone marr ow transplantation, T lymphocytes, from donor cells, contribute to the development of graft-versus-host disease (GVHD), which can result in major morbidity and mortality: The incidence of GVHD has decreased wit h selective purging of T lymphocytes, but further modifications are ne eded to improve hematopoietic engraftment. Methods for purging hematop oietic stem cells are discussed, with emphasis on the therapeutic role of purging. Growing stem cells from a small amount of bone marrow pre sents a new possibility. Furthermore, genetic engineering can enhance immune surveillance and decrease drug resistance. Analysis of the clin ical trials utilizing various doses of cytotoxic therapy with proper m ethods of hematopoietic rescue will help avoid unnecessary dose escala tion and help decide the optimum use of cancer treatment modalities.