Pretreatment with triprolidine, CV-6209, or dexamethasone (Dex) mitigates the severity of asparaginase-induced allergies. Mice sensitized to E. coli asparaginase were pretreated with triprolidine, cimetidine, the PAF receptor antagonist CV-6209, single-dose dexamethasone, or a combination of the agents as per Fig. 1B; multiple-dose dexamethasone or oral dexamethasone was given as per Fig. 1C. All pretreatment agents except for cimetidine and oral dexamethasone given 7 days after the initial asparaginase immunization dose (at day 0) were able to mitigate the severity of the reaction compared with nonpretreated, sensitized mice (P < 0.03); however, the combination of antihistamine and CV-6209 showed the best ability to reduce the severity of the reaction compared with nonpretreated, sensitized mice (P = 1.2 × 10−5).