The thrombocytopenia of cancer: Prospects for effective cytokine therapy

The previous 10 years have witnessed the development of increasing needs for platelet transfusion in support of aggressive therapies of malignancy. Despite gains in our understanding of platelet preparation, storage, and transfusion, alternative therapies are clearly desirable. During the late 1980s at least six distinct cytokines that display effects on megakaryocyte growth and differentiation-IL-3, KL, GM-CSF, IL-6, IL-11, and LIF-and a synthetic growth factor, PIXY 321, were cloned and characterized. Although none of these cytokines fulfill all of the physiologic roles of thrombopoietin, in its absence several have undergone extensive preclinical and preliminary clinical testing. Of these, IL-11 and PIXY 321 hold promise for clinical amelioration of thrombocytopenia in cancer patients. With the recent cloning of thrombopoietin and its promise in preclinical trials, the role of each of these recombinant proteins in clinical medicine is undergoing careful evaluation. As with erythropoietin and G-CSF before it, given its normal role in the regulation of platelet production, Tpo would appear to provide the greatest physiologic stimulus to platelet production in states of natural and iatrogenic marrow failure. Careful clinical trials of the agent are needed to determine whether the hormone will fulfill this promise. The following decade will most certainly see the resolution of many of the complications of thrombocytopenia and its transfusional support.