Use of thrombopoietic growth factors in acute leukemia.
Several hematopoietic growth factors have been shown to affect megakaryocyte development, and two, interleukin (IL)-11 and thrombopoietin (TPO) are presently being evaluated for use in patients with thrombocytopenia. In two studies patients who required one or more platelet transfusions during their first course of chemotherapy were found to require fewer platelet transfusions if their second cycle was augmented with IL-11. The drug was generally safe, with cardiovascular compromise the only significant complication occurring in a minority of patients. Although these reports included patients with various malignancies, studies of IL-11 in patients with myeloproliferative disorders have not been presented. In several clinical trials in cancer patients treatment with TPO was safe, and when administered early following a moderately aggressive cytotoxic insult was effective in accelerating platelet recovery. In addition, in both pre-clinical and clinical trials, TPO given to stem cell donors during mobilization lead to accelerated hematopoietic recovery. Finally, TPO appears safe when administered to patients with acute myelogenous leukemia (AML), both with respect to acute toxicity and long-term outcome of the leukemia. However, when used following a 7-day course of standard chemotherapy, the agent does not appear to accelerate platelet recovery. As such, additional clinical trials to test different growth factor regimens are ongoing. A number of studies have suggested that megakaryocytic growth factors may play a role in the biology of myeloproliferative disorders. Given the potential for adversely affecting patients with these disorders, the affects of IL-11 or TPO in patients with AML must continue to be carefully studied.
Kaushansky
K
K
Division of Hematology, University of Washington Medical Center, Seattle 98195, USA.
D000208:Acute Disease; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use*; D007951:Leukemia, Myeloid / Q000150:complications* / Q000188:drug therapy; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D017713:Platelet Transfusion; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy* / Q000628:therapy; D013926:Thrombopoietin / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D017370:Interleukin-11; D013926:Thrombopoietin