{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:29:23Z","timestamp":1787509763055,"version":"build-2736575974"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100011725","name":"Servier","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pegaspargase is a pegylated formulation of\n                    <jats:italic>E. coli-<\/jats:italic>\n                    derived asparaginase, which when combined with multi-agent chemotherapy is an effective, well-established therapy for acute lymphoblastic leukemia (ALL). This study evaluated the efficacy, safety and pharmacokinetics of lyophilized pegaspargase in the Japanese population. The study had two parts; the primary endpoint for Part 1 was the incidence and nature of treatment-emergent adverse events (TEAEs), including those related to pegaspargase, to determine the number of patients who experience intolerable toxicity during a tolerability assessment period. The primary endpoint for Part 2 was the percentage of patients with plasma asparaginase activity of\u2009\u2265\u20090.1\u00a0IU\/ml 14\u00a0days after administration of the first dose of lyophilized pegaspargase. All 26 patients included in the safety analysis experienced at least one TEAE. Frequently reported TEAEs related to lyophilized pegaspargase included decreases in blood fibrinogen, antithrombin III, white blood cell count, and platelet count. No deaths were reported. Plasma asparaginase activity reached\u2009\u2265\u20090.1\u00a0IU\/ml 5\u00a0min after the first dose of lyophilized pegaspargase and was maintained for 14\u00a0days in all patients with evaluable samples. The results of this study show that lyophilized pegaspargase represents an effective and well-tolerated first-line treatment option in Japanese patients with ALL.\n                  <\/jats:p>","DOI":"10.1007\/s12185-025-03976-4","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T17:33:10Z","timestamp":1743528790000},"page":"284-294","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phase 2 multicenter study of pegaspargase in Japanese patients with previously untreated acute lymphoblastic leukemia"],"prefix":"10.1007","volume":"122","author":[{"given":"Katsuyoshi","family":"Koh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Kosaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoji","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Koga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien","family":"Tessier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelena","family":"Shvenke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bouchra","family":"Benettaib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizo","family":"Horibe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chitose","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"issue":"1","key":"3976_CR1","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1007\/s12185-013-1364-2","volume":"98","author":"K Horibe","year":"2013","unstructured":"Horibe K, Saito AM, Takimoto T, Tsuchida M, Manabe A, Shima M, et al. Incidence and survival rates of hematological malignancies in Japanese children and adolescents (2006\u20132010): based on registry data from the Japanese Society of Pediatric Hematology. Int J Hematol. 2013;98(1):74\u201388. https:\/\/doi.org\/10.1007\/s12185-013-1364-2.","journal-title":"Int J Hematol"},{"issue":"7","key":"3976_CR2","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1093\/jjco\/hyy071","volume":"48","author":"K Koh","year":"2018","unstructured":"Koh K, Kato M, Saito AM, Kada A, Kawasaki H, Okamoto Y, et al. Phase II\/III study in children and adolescents with newly diagnosed B-cell precursor acute lymphoblastic leukemia: protocol for a nationwide multicenter trial in Japan. Jpn J Clin Oncol. 2018;48(7):684\u201391. https:\/\/doi.org\/10.1093\/jjco\/hyy071.","journal-title":"Jpn J Clin Oncol"},{"issue":"3","key":"3976_CR3","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.cll.2021.04.003","volume":"41","author":"DC Luca","year":"2021","unstructured":"Luca DC. Update on lymphoblastic leukemia\/lymphoma. Clin Lab Med. 2021;41(3):405\u201316. https:\/\/doi.org\/10.1016\/j.cll.2021.04.003.","journal-title":"Clin Lab Med"},{"key":"3976_CR4","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.902117","volume":"10","author":"L Maese","year":"2022","unstructured":"Maese L, Rau RE. Current use of asparaginase in acute lymphoblastic leukemia\/lymphoblastic lymphoma. Front Pediatr. 2022;10: 902117. https:\/\/doi.org\/10.3389\/fped.2022.902117.","journal-title":"Front Pediatr"},{"key":"3976_CR5","doi-asserted-by":"publisher","unstructured":"Hatta Y, Hayakawa F, Yamazaki E. JSH practical guidelines for hematological malignancies, 2018: I. leukemia-3. acute lymphoblastic leukemia\/lymphoblastic lymphoma (ALL\/LBL). Int J Hematol. 2020;112(4):439\u201358. https:\/\/doi.org\/10.1007\/s12185-020-02965-z.","DOI":"10.1007\/s12185-020-02965-z"},{"issue":"1","key":"3976_CR6","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/ped.13457","volume":"60","author":"M Kato","year":"2018","unstructured":"Kato M, Manabe A. Treatment and biology of pediatric acute lymphoblastic leukemia. Pediatr Int. 2018;60(1):4\u201312. https:\/\/doi.org\/10.1111\/ped.13457.","journal-title":"Pediatr Int"},{"issue":"9","key":"3976_CR7","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1097\/MPH.0b013e3181483df1","volume":"29","author":"P Wacker","year":"2007","unstructured":"Wacker P, Land VJ, Camitta BM, Kurtzberg J, Pullen J, Harris MB, et al. Allergic reactions to E. coli L-asparaginase do not affect outcome in childhood B-precursor acute lymphoblastic leukemia: a Children\u2019s Oncology Group Study. J Pediatr Hematol Oncol. 2007;29(9):627\u201332. https:\/\/doi.org\/10.1097\/MPH.0b013e3181483df1.","journal-title":"J Pediatr Hematol Oncol."},{"issue":"5","key":"3976_CR8","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/s0142-9612(00)00193-9","volume":"22","author":"FM Veronese","year":"2001","unstructured":"Veronese FM. Peptide and protein PEGylation: a review of problems and solutions. Biomaterials. 2001;22(5):405\u201317. https:\/\/doi.org\/10.1016\/s0142-9612(00)00193-9.","journal-title":"Biomaterials"},{"issue":"16","key":"3976_CR9","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1016\/S1470-2045(15)00363-0","volume":"16","author":"AE Place","year":"2015","unstructured":"Place AE, Stevenson KE, Vrooman LM, Harris MH, Hunt SK, O\u2019Brien JE, et al. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05\u2013001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015;16(16):1677\u201390. https:\/\/doi.org\/10.1016\/S1470-2045(15)00363-0.","journal-title":"Lancet Oncol"},{"key":"3976_CR10","doi-asserted-by":"publisher","unstructured":"Brown PA, Shah B, Fathi A, Wieduwilt M, Advani A, Aoun P, et al. NCCN Guidelines Insights: Acute Lymphoblastic Leukemia, Version 1.2017. J Natl Compr Canc Netw. 2017;15(9):1091\u2013102. https:\/\/doi.org\/10.6004\/jnccn.2017.0147.","DOI":"10.6004\/jnccn.2017.0147"},{"issue":"suppl 5","key":"3976_CR11","doi-asserted-by":"publisher","first-page":"v69","DOI":"10.1093\/annonc\/mdw025","volume":"27","author":"D Hoelzer","year":"2016","unstructured":"Hoelzer D, Bassan R, Dombret H, Fielding A, Ribera JM, Buske C, et al. Acute lymphoblastic leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v69\u201382. https:\/\/doi.org\/10.1093\/annonc\/mdw025.","journal-title":"Ann Oncol"},{"key":"3976_CR12","doi-asserted-by":"publisher","unstructured":"Brown P, Inaba H, Annesley C, Beck J, Colace S, Dallas M, et al. Pediatric acute lymphoblastic leukemia, version 2.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020;18(1):81\u2013112. https:\/\/doi.org\/10.6004\/jnccn.2020.0001.","DOI":"10.6004\/jnccn.2020.0001"},{"issue":"6","key":"3976_CR13","doi-asserted-by":"publisher","first-page":"1986","DOI":"10.1182\/blood.v99.6.1986","volume":"99","author":"VI Avramis","year":"2002","unstructured":"Avramis VI, Sencer S, Periclou AP, Sather H, Bostrom BC, Cohen LJ, et al. A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children\u2019s Cancer Group study. Blood. 2002;99(6):1986\u201394. https:\/\/doi.org\/10.1182\/blood.v99.6.1986.","journal-title":"Blood"},{"issue":"8","key":"3976_CR14","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1007\/s12325-019-00988-5","volume":"36","author":"AM Faschinger","year":"2019","unstructured":"Faschinger AM, Sessler N. Development of a lyophilized formulation of pegaspargase and comparability versus liquid pegaspargase. Adv Ther. 2019;36(8):2106\u201321. https:\/\/doi.org\/10.1007\/s12325-019-00988-5.","journal-title":"Adv Ther"},{"issue":"34","key":"3976_CR15","doi-asserted-by":"publisher","first-page":"3874","DOI":"10.1200\/JCO.2014.55.5763","volume":"32","author":"AL Angiolillo","year":"2014","unstructured":"Angiolillo AL, Schore RJ, Devidas M, Borowitz MJ, Carroll AJ, Gastier-Foster JM, et al. Pharmacokinetic and pharmacodynamic properties of calaspargase pegol Escherichia coli L-asparaginase in the treatment of patients with acute lymphoblastic leukemia: results from Children\u2019s Oncology Group Study AALL07P4. J Clin Oncol. 2014;32(34):3874\u201382. https:\/\/doi.org\/10.1200\/JCO.2014.55.5763.","journal-title":"J Clin Oncol"},{"issue":"8","key":"3976_CR16","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1634\/theoncologist.12-8-991","volume":"12","author":"PA Dinndorf","year":"2007","unstructured":"Dinndorf PA, Gootenberg J, Cohen MH, Keegan P, Pazdur R. FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist. 2007;12(8):991\u20138. https:\/\/doi.org\/10.1634\/theoncologist.12-8-991.","journal-title":"Oncologist"},{"issue":"7","key":"3976_CR17","doi-asserted-by":"publisher","first-page":"1740","DOI":"10.1080\/10428194.2018.1542146","volume":"60","author":"RJ Schore","year":"2019","unstructured":"Schore RJ, Devidas M, Bleyer A, Reaman GH, Winick N, Loh ML, et al. Plasma asparaginase activity and asparagine depletion in acute lymphoblastic leukemia patients treated with pegaspargase on Children\u2019s Oncology Group AALL07P4(). Leuk Lymphoma. 2019;60(7):1740\u20138. https:\/\/doi.org\/10.1080\/10428194.2018.1542146.","journal-title":"Leuk Lymphoma"},{"issue":"31","key":"3976_CR18","doi-asserted-by":"publisher","first-page":"3496","DOI":"10.1200\/JCO.20.03692","volume":"39","author":"LM Vrooman","year":"2021","unstructured":"Vrooman LM, Blonquist TM, Stevenson KE, Supko JG, Hunt SK, Cronholm SM, et al. Efficacy and toxicity of pegaspargase and calaspargase pegol in childhood acute lymphoblastic leukemia: results of DFCI 11\u2013001. J Clin Oncol. 2021;39(31):3496\u2013505. https:\/\/doi.org\/10.1200\/JCO.20.03692.","journal-title":"J Clin Oncol"},{"issue":"9","key":"3976_CR19","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1002\/psp4.12838","volume":"11","author":"RJ Svensson","year":"2022","unstructured":"Svensson RJ, Jonsson EN. Efficient and relevant stepwise covariate model building for pharmacometrics. CPT Pharmacometrics Syst Pharmacol. 2022;11(9):1210\u201322. https:\/\/doi.org\/10.1002\/psp4.12838.","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"issue":"1","key":"3976_CR20","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1111\/j.1365-2141.2009.07923.x","volume":"148","author":"G Hempel","year":"2010","unstructured":"Hempel G, Muller HJ, Lanvers-Kaminsky C, Wurthwein G, Hoppe A, Boos J. A population pharmacokinetic model for pegylated-asparaginase in children. Br J Haematol. 2010;148(1):119\u201325. https:\/\/doi.org\/10.1111\/j.1365-2141.2009.07923.x.","journal-title":"Br J Haematol"},{"issue":"6","key":"3976_CR21","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1007\/s13318-017-0410-5","volume":"42","author":"G Wurthwein","year":"2017","unstructured":"Wurthwein G, Lanvers-Kaminsky C, Hempel G, Gastine S, Moricke A, Schrappe M, et al. Population pharmacokinetics to model the time-varying clearance of the PEGylated asparaginase Oncaspar((R)) in children with acute lymphoblastic leukemia. Eur J Drug Metab Pharmacokinet. 2017;42(6):955\u201363. https:\/\/doi.org\/10.1007\/s13318-017-0410-5.","journal-title":"Eur J Drug Metab Pharmacokinet"},{"issue":"5","key":"3976_CR22","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2020-000858","volume":"5","author":"PW Burke","year":"2020","unstructured":"Burke PW, Hoelzer D, Park JH, Schmiegelow K, Douer D. Managing toxicities with asparaginase-based therapies in adult ALL: summary of an ESMO Open-Cancer Horizons roundtable discussion. ESMO Open. 2020;5(5):e000858. https:\/\/doi.org\/10.1136\/esmoopen-2020-000858.","journal-title":"ESMO Open"},{"issue":"1","key":"3976_CR23","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s13561-019-0257-3","volume":"9","author":"X Hu","year":"2019","unstructured":"Hu X, Wildman KP, Basu S, Lin PL, Rowntree C, Saha V. The cost-effectiveness of pegaspargase versus native asparaginase for first-line treatment of acute lymphoblastic leukaemia: a UK-based cost-utility analysis. Health Econ Rev. 2019;9(1):40. https:\/\/doi.org\/10.1186\/s13561-019-0257-3.","journal-title":"Health Econ Rev"},{"issue":"11","key":"3976_CR24","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1007\/s40261-022-01207-w","volume":"42","author":"G Gourzoulidis","year":"2022","unstructured":"Gourzoulidis G, Koulentaki M, Kattamis A, Bouzani M, Giatra C, Chotzagiannoglou V, et al. Cost-utility analysis of pegaspargase for the treatment of acute lymphoblastic leukemia in Greece. Clin Drug Investig. 2022;42(11):999\u20131008. https:\/\/doi.org\/10.1007\/s40261-022-01207-w.","journal-title":"Clin Drug Investig"},{"key":"3976_CR25","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1182\/blood-2023-182464","volume":"142","author":"M Kato","year":"2023","unstructured":"Kato M, Okamoto Y, Imamura T, Kada A, Saito AM, Iijmia-Yamashita Y, et al. A nationwide clinical trial ALL-B12: an optimized therapy for pediatric B-precursor acute lymphoblastic leukemia with excellent overall survival and minimal non-relapse mortality: a report from the Japan Children\u2019s Cancer Group. Blood. 2023;142(Supplement 1):519.\u00a0https:\/\/doi.org\/10.1182\/blood-2023-182464.","journal-title":"Blood"}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-025-03976-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-025-03976-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-025-03976-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T08:33:49Z","timestamp":1757147629000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-025-03976-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,31]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["3976"],"URL":"https:\/\/doi.org\/10.1007\/s12185-025-03976-4","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,31]]},"assertion":[{"value":"22 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 March 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 March 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Katsuyoshi Koh, Yoshiyuki Kosaka, Naoko Maeda, Atsushi Ogawa, Ryoji Kobayashi, Daisuke Hasegawa, Keizo Horibe, and Chitose Ogawa have no conflict of interest to disclose. Yasuhiro Okamoto received payment for a medical interview from Nihon Servier. Nobuhiro Koga, Adrien Tessier, Yelena Shvenke, Jian Zhu, and Bouchra Benettaib are employees of Servier.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}