Hypersensitivity reactions to L-asparaginase do not impact on the remission duration of adults with acute lymphoblastic leukemia

Open Access
Publisher Website
Google Scholar
Abstract
Among its multiple toxic effects, L-asparaginase induces allergic reactions that may reduce its biological effect. The impact of hypersensitivity reactions on the duration of leukemia-free survival (LFS) was assessed in adults with newly diagnosed acute lymphoblastic leukemia (ALL) receiving intensive multi-agent chemotherapy. In CALGB study 8811 (Blood 1995; 85: 2025–2037), 197 adults were scheduled to receive 14 doses of Escherichia coli L-asparaginase (6000 U/m2 SC) during 7 of the first 12 weeks of chemotherapy. No further L-asparaginase was given. Chemotherapy was given for 24 months. The median follow-up time has been 5.7 years. Of the 141 patients who remained on study after 12 weeks, 82 (58%) had received all 14 planned doses; 38 (27%) had 12–13 L-asparaginase doses documented in their treatment record; 21 (15%) patients had received ⩽11 doses due to a variety of toxic effects. The mean number of doses received prior to experiencing any hypersensitivity reaction was seven (range 1–11). Seven patients had mild hypersensitivity reactions, but all seven eventually received 12–14 doses of E. coli L-asparaginase. Twenty-one other patients had severe hypersensitivity reactions that required discontinuation of E. coli L-asparaginase; 20 of these patients were switched to Erwinia L-asparaginase to complete their treatment. Ultimately, 12 of these 20 patients received 14 doses of L-asparaginase in total, and six received 12–13 doses. Thus, only three of the 21 patients who had severe hypersensitivity reactions received ⩽11 total L-asparaginase doses. Other L-asparaginase-related complications included pancreatitis (15 patients), hypofibrinogenemia P = 0.68). LFS did not correlate with a history of severe hypersensitivity reaction (P = 0.67). In general, E. coli L-asparaginase was well tolerated in these adult patients, and most patients received all of the planned therapy. Patients who had mild L-asparaginase hypersensitivity reactions and patients who switched to Erwinia L-asparaginase because of more severe allergic reactions did not have significantly shorter LFS than the remaining adults treated on this ALL protocol. The possibility that E. coli L-asparaginase is inactivated or destroyed in those individuals who have become hypersensitive to it becomes less important when allergic patients are secondarily treated with Erwinia L-asparaginase.

This publication has 0 references indexed in Scilit: