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G D Demetri

Publications and source records attributed to G D Demetri.

56 records · Page 4Linked to original sources

Hematopoietic growth factors: current knowledge, future prospects.

The introduction of hematopoietic growth factors into clinical medicine represents one of the more exciting developments in oncology in the past several years. The identification, gene cloning, and large-scale production of hematopoietic growth factors represent important examples of the practical benefits that may accrue from application of the sophisticated technology derived from recombinant DNA research. Research, both at the bench and by the bedside, has proceeded at an extraordinarily rapid pace in this field over the past five years, leading to an abundance of new information, novel promising agents, and important clinical controversies related to the biology and appropriate clinical applications of hematopoietic growth factors. With these agents, for the first time in history, the production of human blood cells can be systematically manipulated in vivo in an effort to optimize physiology beyond the endogenous host response. Additionally, investigators utilizing purified hematopoietic growth factors as reagents may provide crucial insights into the mechanisms of blood cell production in health and in various disease states. This review aims to summarize the current state of knowledge regarding the control of blood cell production by specific factors and to put these data in the context of clinical medicine. The emphasis will be on factors that primarily influence myeloid (rather than lymphoid) cell growth, differentiation, and activation, and the clinical focus will be on applications in oncologic therapeutics and in the treatment of primary hematologic disorders. By reviewing what we know and what has already been done, we may be better able to define the important questions that remain and to formulate the means to answer our current uncertainties about the activities and clinical uses of hematopoietic growth factors.

Animals↗

The emergence of peripheral blood progenitor cells to support intensive chemotherapy for patients with breast cancer.

Increasing evidence supports the hypothesis that "dose" is critical to the clinical outcomes of cytotoxic chemotherapy for patients with breast cancer. Clinical trials continue to investigate whether higher doses of chemotherapy lead to proportionate improvements in the outcomes of patients. Delivery of dose-intensive chemotherapy has been facilitated by technological advancements in supportive care. Improved antiemetics have led to increased patient tolerance of the most acute symptoms of aggressive chemotherapeutic dosing. Chemotherapy-induced myelosuppression may be minimized in a lineage-specific manner by appropriate use of hematopoietic cytokines such as filgrastim (granulocyte colony-stimulating factor), sargramostim (granulocyte-macrophage colony-stimulating factor), and/or epoetin alfa (erythropoietin). However, cumulative myelotoxicity occurs with dose-intensive chemotherapy over multiple cycles despite adjunctive cytokine support. Additionally, no cytokine has yet been demonstrated to support platelet production to any clinically significant degree although several regulators of platelet production (such as thrombopoietin, IL-6, and IL-11) are in clinical trials. Many cytokines can induce the mobilization of hematopoietic progenitor and stem cells from the bone marrow into the circulating blood pool, where these cells may be harvested. Clinical use of these cytokine-mobilized peripheral blood progenitor cells (also known as PBPCs or, commonly, as blood stem cells) has documented the effectiveness of these cells to reconstitute multilineage blood production following very high-dose chemotherapy. The ease with which PBPCs can be collected and their reproducible clinical effectiveness to support patients through intensive treatment protocols have led to a virtual elimination of bone marrow as the source of cellular support for myeloablative chemotherapy in many transplant centers. Novel investigative approaches are also possible with PBPCs. In this review, the historical background of PBPCs is summarized, and the potential benefits (including economic advantages) of PBPCs to support dose-intensive chemotherapy for treating breast cancer are discussed. While dose intensification of breast cancer chemotherapy to the degree requiring PBPC support remains controversial and, in most centers, investigational, there is no doubt that PBPCs are an effective adjunct to the hematopoietic support of patients undergoing transplant-level cytotoxic treatments. Further study will undoubtedly lead to increased use of PBPCs in novel treatments for patients with breast cancer and other solid tumors.

Bone Marrow Transplantation↗