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Thrombopoietic Factors in Chronic Bone Marrow Failure States: The Platelet Problem Revisited

Department of Bioimmunotherapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Razelle Kurzrock, Professor of Medicine, Director, Phase I Clinical Trials Program, Box 422, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Phone: 713-794-1226; Fax: 713-745-2374; E-mail: rkurzroc{at}mdanderson.org.

Thrombocytopenia is a serious clinical problem in several different clinical settings. In chronic bone marrow failure states, which include aplastic anemia, myelodysplastic syndrome, and graft failure, the prolonged nature of thrombocytopenia often leads to alloimunization after repeated platelet transfusions, the consequence of which is a platelet-refractory state and enhanced risk of bleeding. Despite the introduction of several thrombopoietic factors into clinical trials, an effective way to alleviate thrombocytopenia has been elusive, and the problem in chronic bone marrow failure states has remained poorly addressed by clinical investigations. Even so, several studies by our group and others suggest that a subset of patients suffering from chronic bone marrow failure can respond to appropriate growth factor therapy. The temporal pace of response appears, however, to be much slower than that observed after administering growth factors which act on neutrophils. On the other hand, durable responses can be secured in some patients given thrombopoietic factors for long periods of time. Herein, we provide an overview of the clinical research investigations of thrombopoietic factors in chronic bone marrow failure, and the emerging insights these studies provide for understanding the process of thrombopoiesis and its therapy in this setting.

Key Words: Thrombocytopenia • aplastic anemia • myelodysplatic syndrome

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