Abstract
The heterogeneity of Myelodysplastic Syndrome (MDS) has spurred interest in combining agents with different mechanisms of action in an attempt to improve the frequency and robustness of responses. Laboratory studies in patients with MDS have shown a shift in the relative levels of TNF-α receptor 1 and 2 in favor of receptor 2 in patients with more advanced MDS. Receptor 2 conveys only proliferative (not apoptotic) signals, and blockade of TNF-α may thus interfere with disease progression, while possibly protecting normal hematopoietic precursors. Therefore, we combined an established regimen of azacitidine with administration of the soluble TNF receptor antagonist etanercept in patients with advanced MDS. Twenty-three patients were treated with azacitidine, 75mg/m2/day for 7 days combined with etanercept, 25mg sc twice a week for two weeks every 28 days. Eighteen patients with MDS (4 RAEB-1, 11 RAEB-2, 1 CMML-1, and 2 CMML-2) have completed at least 3 months of therapy and were considered evaluable. Five of these patients had intermediate-1 risk, seven intermediate-2 and six high risk MDS by IPSS. Using the revised International Working Group (IWG) criteria for MDS, 14 patients (78%) responded: 5 patients (28%) had complete remissions (CR), 8 patients (44%) had partial remissions (PR) and 1 patient (6%) had hematologic improvement of neutrophils. Three patients have been on therapy for two years with sustained responses. Two patients developed pneumonias. The most common grade ¾ adverse events were hematological toxicity (78%). This therapeutic combination may be superior to treatment with azacitidine alone and warrants further study.
The roles of TNF-α and the soluble TNF receptor I on sleep architecture in OSA