{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T22:48:51Z","timestamp":1781909331067,"version":"3.54.5"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Asparaginase is an essential drug for acute lymphoblastic leukaemia (ALL) treatment, but has several side effects, and its discontinuation often compromises patient outcomes. In the prospective Japan Association of Childhood Leukaemia Study ALL\u201002 protocol, two major changes were made: (1) additional chemotherapies to compensate for the reduction of treatment intensity when asparaginase was discontinued and (2) more intensive concomitant corticosteroid administration, relative to our previous ALL\u201097 protocol. In ALL\u201002 study, 1192 patients were included and L\u2010asparaginase was discontinued for 88 (7.4%). Discontinuation due to allergy was markedly decreased relative to the ALL\u201097 protocol (2.3% vs 15.4%). Event\u2010free survival (EFS) among patients with T\u2010ALL was compromised when L\u2010asparaginase was discontinued, as well as among patients with high\u2010risk B\u2010cell ALL, especially when discontinued before maintenance therapy. Moreover, multivariate analysis identified discontinuation of L\u2010asparaginase as an independent poor prognostic factor for EFS. In the current study, additional chemotherapies failed to fully compensate for L\u2010asparaginase discontinuation, illustrating the difficulty of replacing asparaginase with other classes of drugs, although this study was not designed to evaluate the effect of these modifications. Concomitant intensive corticosteroid treatment may help to reduce allergy to asparaginase. These results will assist in further optimization of asparaginase use.<\/jats:p>","DOI":"10.1111\/bjh.18745","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T08:43:01Z","timestamp":1678351381000},"page":"1200-1208","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Impact of asparaginase discontinuation on outcomes of children with acute lymphoblastic leukaemia receiving the Japan Association of Childhood Leukaemia Study <scp>ALL<\/scp>\u201002 protocol"],"prefix":"10.1111","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3391-8403","authenticated-orcid":false,"given":"Hisashi","family":"Ishida","sequence":"first","affiliation":[{"name":"Department of Pediatrics Okayama University Hospital  Okayama 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