Choline Magnesium Trisalicylate

Purpose: Nuclear factor-κB (NF-κB) is constitutively expressed in many acute myelogenous leukemia (AML) cells and AML stem cells. Ex vivo treatment of AML cells with inhibitors of NF-κB results in diminished AML cell survival and enhances the cytotoxic effects of chemotherapeutic agents. The purpose of this study was to determine if standard anti-inflammatory agents modulate AML cell nuclear NF-κB when administered in conjunction with induction chemotherapy.Experimental Design: Patients with newly diagnosed AML were treated with dexamethasone, choline magnesium trisalicylate, or both for 24 hours prior to and 24 hours following initiation of standard induction chemotherapy. AML cell nuclear NF-κB was measured at baseline, 24, and 48 hours.Results: Choline magnesium trisalicylate ± dexamethasone decreased nuclear NF-κB, whereas dexamethasone alone was associated with an increase in nuclear NF-κB in AML cells.Conclusions: These results show the feasibility of NF-κB modulation in conjunction with induction chemotherapy for patients with AML using inexpensive readily available medications. A follow-up study to determine the effects of NF-κB modulation on clinical end points is warranted.

Aspirin-exacerbated respiratory disease (AERD) is an adult-onset condition that manifests as asthma, rhinosinusitis/nasal polyps, and sensitivity to aspirin and other cyclooxygenase-1 (COX-1)-inhibitor nonsteroidal anti-inflammatory drugs (NSAIDs). There is no cross-sensitivity to highly selective COX-2 inhibitors. AERD is chronic and does not improve with avoidance of COX-1 inhibitors. The diagnosis of AERD is made through provocative challenge testing. Following a positive aspirin challenge, patients can be desensitized to aspirin and NSAIDs. The desensitized state can be maintained indefinitely with continued daily administration. After desensitization, there is an approximately 48-hour refractory period to adverse effects from aspirin. The pathogenesis of AERD remains unknown, but these patients have been shown to have multiple abnormalities in arachidonic acid metabolism and in cysteinyl leukotriene 1 receptors. AERD patients can take up to 650 mg of acetaminophen for analgesic or antipyretic relief. Patients can also use weak COX-1 inhibitors, such as sodium salicylate or choline magnesium trisalicylate. Treatment of AERD patients with antileukotriene medications has been helpful but not preferential when compared with non-AERD patients. An alternative treatment for many AERD patients is aspirin desensitization. This is particularly effective in reducing upper-airway mucosal congestion, nasal polyp formation, and systemic steroids.