{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:16:55Z","timestamp":1789604215552,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The prognosis of children with acute lymphoblastic leukemia (ALL) has improved considerably over the past five decades. However, to achieve cure in patients with refractory or relapsed disease, novel treatment options are necessary.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In the multicenter trial Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (CoALL)08\u201009, one additional treatment element consisting of the rarely used chemotherapeutic agent amsacrine combined with etoposide and methylprednisolone (AEP) (amsacrine 2 \u00d7 100\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , etoposide 2 \u00d7 500\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , and methylprednisolone 4 \u00d7 1000\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) was incorporated into the first\u2010line treatment of pediatric patients with poor treatment responses at the end of induction (EOI), measured by minimal residual disease (MRD). These patients were stratified into a high\u2010risk intensified arm (HR\u2010I), including an AEP element at the end of consolidation. Patients with induction failure (IF), that is, with lack of cytomorphological remission EOI, were eligible for hematopoietic stem cell transplantation (HSCT) after remission had been reached. These patients received AEP as a part of their MRD\u2010guided bridging\u2010to\u2010transplant treatments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A significant improvement in probability of overall survival (pOS) was noted for the CoALL08\u201009 HR\u2010I patients compared to MRD\u2010matched patients from the preceding CoALL07\u201003 trial in the absence of severe or persistent treatment\u2010related toxicities. Relapse rate and probability of event\u2010free survival (pEFS) did not differ significantly between trials. In patients with IF, stable or improved MRD responses after AEP were observed without severe or persistent treatment\u2010related toxicities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In conclusion, AEP is well tolerated as a component of the HR treatment and is useful in bridging\u2010to\u2010transplant settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.29997","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T08:29:06Z","timestamp":1663748946000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Amsacrine combined with etoposide and methylprednisolone is a feasible and safe component in first\u2010line intensified treatment of pediatric patients with high\u2010risk acute lymphoblastic leukemia in CoALL08\u201009 trial"],"prefix":"10.1002","volume":"69","author":[{"given":"Kerstin","family":"Mezger","sequence":"first","affiliation":[{"name":"Clinic of Paediatric Haematology and Oncology University Medical Centre Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Ebert","sequence":"additional","affiliation":[{"name":"Clinic of Paediatric Haematology and Oncology University Medical Centre Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah Elisa","family":"Muhle","sequence":"additional","affiliation":[{"name":"Clinic of Paediatric Haematology and Oncology University Medical Centre Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo zur","family":"Stadt","sequence":"additional","affiliation":[{"name":"Clinic of Paediatric Haematology and Oncology University Medical Centre Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Borkhardt","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology Medical Faculty Duesseldorf  Duesseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Dilloo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Faber","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology University Hospital Mainz  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Feuchtinger","sequence":"additional","affiliation":[{"name":"Dr. von Hauner Children's Hospital Ludwig Maximilian University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Imschweiler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Helios Hospital  Krefeld Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Jorch","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Hospital Bielefeld  Bielefeld Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnulf","family":"Pekrun","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Hospital Bremen\u2010Mitte  Bremen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Schmid","sequence":"additional","affiliation":[{"name":"Dr. von Hauner Children's Hospital Ludwig Maximilian University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Schramm","sequence":"additional","affiliation":[{"name":"Clinic of Paediatric Haematology and Oncology University Medical Centre Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of Pediatric Haematology and Oncology Medical School Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin A","family":"Horstmann","sequence":"additional","affiliation":[{"name":"Clinic of Paediatric Haematology and Oncology University Medical Centre Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2167-3805","authenticated-orcid":false,"given":"Gabriele","family":"Escherich","sequence":"additional","affiliation":[{"name":"Clinic of Paediatric Haematology and Oncology University Medical Centre Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.252"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.37.8018"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(20000415)88:8<1964::AID-CNCR27>3.0.CO;2-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2007.07.002"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102015\u201009\u2010670729"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555\u2010019\u201009834\u20100"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00255a003"},{"issue":"12","key":"e_1_2_9_9_1","first-page":"1701","article-title":"Amsacrine combined with etoposide and high\u2010dose methylprednisolone as salvage therapy in acute lymphoblastic leukemia in children","volume":"90","author":"Horstmann MA","year":"2005","journal-title":"Haematologica"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1704113"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v60.2.484.484"},{"issue":"11","key":"e_1_2_9_12_1","first-page":"977","article-title":"Amsacrine in refractory adult acute leukemia: a pilot study of the Southeastern Cancer Study Group","volume":"67","author":"Winton EF","year":"1983","journal-title":"Cancer Treat Rep"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1985.3.4.562"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u201093\u20101\u201017"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.257"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2021.279357"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000576"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1473575"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404586"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.2307\/2281868"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12520"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010020\u201001024\u20100"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.251"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.02529"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_201810_16158"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15761"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409\u2010018\u20100307\u20101"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000449"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12562"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102141.2005.05736.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102014\u201003\u2010560847"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw557"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31099"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408\u2010018\u20100117\u20100"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.0987"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/16078454.2018.1549802"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018025726"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2016.1161185"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29997","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pbc.29997","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29997","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T19:07:51Z","timestamp":1692644871000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.29997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,21]]},"references-count":37,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/pbc.29997"],"URL":"https:\/\/doi.org\/10.1002\/pbc.29997","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,21]]},"assertion":[{"value":"2022-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e29997"}}