{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:13:18Z","timestamp":1790359998494,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,4,28]],"date-time":"2017-04-28T00:00:00Z","timestamp":1493337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U10CA180886"],"award-info":[{"award-number":["U10CA180886"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U10CA180899"],"award-info":[{"award-number":["U10CA180899"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U10CA098543"],"award-info":[{"award-number":["U10CA098543"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U10CA098413"],"award-info":[{"award-number":["U10CA098413"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006058","name":"St. Baldrick's Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006058","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood & Cancer"],"published-print":{"date-parts":[[2017,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n The prognostic impact of central nervous system (CNS) involvement in children with acute myeloid leukemia (AML) has varied in past trials, and controversy exists over the degree of involvement requiring intensified CNS therapy. Two recent Children's Oncology Group protocols, AAML03P1 and AAML0531, directed additional intrathecal (IT) therapy to patients with CNS2 (\u22645 white blood cell [WBC] with blasts) or CNS3 (>5 WBC with blasts or CNS symptoms) disease at diagnosis.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We examined disease characteristics and outcomes of the 1,344 patients on these protocols, 949 with CNS1 (no blasts), 217 with CNS2, and 178 with CNS3, with the latter two receiving additional IT therapy.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Young age (\n P<\/jats:italic>\n = 0.003), hyperleukocytosis (\n P<\/jats:italic>\n \u00a0< 0.001), and the presence of inversion 16 (\n P<\/jats:italic>\n \u00a0< 0.001) were the only factors more prevalent in patients with CNS2 or CNS3 disease. Complete remission at the end of induction (EOI) 2 was achieved less often in patients with CNS involvement (\n P<\/jats:italic>\n \u00a0< 0.001). From diagnosis, event\u2010free survival (EFS) for patients with CNS involvement was significantly worse (\n P<\/jats:italic>\n \u00a0< 0.001), whereas overall survival (OS) was not (\n P<\/jats:italic>\n = 0.16). From the EOI1, there was a higher relapse rate (RR) and worse disease\u2010free survival (DFS), but less impact on OS (CNS1:DFS 58.9%, RR 34.1%, OS 69.3%; CNS2:DFS 53.2%, RR 40.9%, OS 74.7%; CNS3:DFS 45.2%, RR 48.8%, OS 60.8%;\n P<\/jats:italic>\n = 0.006,\n P<\/jats:italic>\n \u00a0< 0.001,\n P<\/jats:italic>\n = 0.045, respectively). Multivariable analysis showed that independently CNS2 and CNS3 status adversely affected RR and DFS. Traumatic diagnostic lumbar puncture was not associated with worse outcome.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n CNS leukemia confers greater relapse risk despite more aggressive locally directed therapy. Novel approaches need to be investigated in this group of patients.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/pbc.26612","type":"journal-article","created":{"date-parts":[[2017,4,28]],"date-time":"2017-04-28T15:07:22Z","timestamp":1493392042000},"source":"Crossref","is-referenced-by-count":52,"title":["Central nervous system disease in pediatric acute myeloid leukemia: A report from the Children's Oncology Group"],"prefix":"10.1002","volume":"64","author":[{"given":"Donna L.","family":"Johnston","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology Children's Hospital of Eastern Ontario Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd A.","family":"Alonzo","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine University of Southern California Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Gerbing","sequence":"additional","affiliation":[{"name":"Children's Oncology Group Monrovia California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Aplenc","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Woods","sequence":"additional","affiliation":[{"name":"Aflac Cancer Center and Blood Disorders Service Children's Healthcare of Atlanta Emory University Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soheil","family":"Meshinchi","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology Seattle Children's Hospital Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Gamis","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology\/Bone Marrow Transplantation Children's Mercy Hospitals and Clinic Kansas City Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,28]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"1","article-title":"A review of central nervous system leukaemia in paediatric acute myeloid leukaemia","volume":"1","author":"Johnston DL","year":"2011","journal-title":"J Hematol 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