Improving the role of hematopoietic support for high-dose cytotoxic therapy

Dose intensification of cytotoxic drugs is now being evaluated in several trials. Various methods are available to manage the hematopoietic toxicity. Hematopoietic growth factors can be used alone and/or in combination with hematopoietic stem cell rescue. Patients undergoing autologous stem cell transplantation (AuSCT) have their own bone marrow and/or peripheral blood used for hematopoietic engraftment. In several malignancies, the bone marrow is involved with tumor, and in such situations, the success of AuSCT may improve if hematopoietic elements are enriched (positive selection) or if contaminating cancer cells are purged by negative selection. In patients undergoing allogeneic bone marrow 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 with selective purging of T lymphocytes, but further modifications are needed to improve hematopoietic engraftment. Methods for purging hematopoietic stem cells are discussed, with emphasis on the therapeutic role of purging. Growing stem cells from a small amount of bone marrow presents a new possibility. Furthermore, genetic engineering can enhance immune surveillance and decrease drug resistance. Analysis of the clinical trials utilizing various doses of cytotoxic therapy with proper methods of hematopoietic rescue will help avoid unnecessary dose escalation and help decide the optimum use of cancer treatment modalities.