{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:16:37Z","timestamp":1789017397791,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"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":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteonecrosis is a major cause of acute and long\u2010lasting complications of acute lymphoblastic leukemia (ALL) therapy in children. Our study aimed to evaluate the prevalence, characteristics, risk factors, and outcome of osteonecrosis in children with ALL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedure<\/jats:title>\n                    <jats:p>The cohort included 559 children aged 1\u201320\u00a0years diagnosed with ALL between 2003 and 2018 at two tertiary medical centers in Israel and enrolled in two consecutive protocols: ALL\u2010IC BFM 2002 and AIEOP\u2010BFM ALL 2009. Symptomatic osteonecrosis was prospectively captured as an adverse event.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Osteonecrosis occurred in 51 patients (9.1%). Ninety\u2010four percent of the events were graded as moderate or severe (grades 3\u20134, Ponte di Legno Toxicity Working Group classification) and multiple bone involvement was common. Full resolution of osteonecrosis was documented in only 16% of the children (median follow\u2010up 4.2\u00a0years). Stepwise logistic regression identified five risk factors for osteonecrosis, with a high predictive value (AUC\u00a0=\u00a00.88): older ageat ALL diagnosis, high\u2010risk ALL group, T\u2010cell immunophenotype, female gender, and a novel risk factor: bone pain at the time of leukemia diagnosis. In addition, osteonecrosis was less common among children of Arab ethnicity. Thrombophilia and an elevated age\u2010adjusted body mass index were not confirmed as risk factors for osteonecrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Due to the low rates of osteonecrosis resolution and its debilitating long\u2010term impact, the identification of patients at high risk for osteonecrosis is important for their inclusion in further studies evaluating potential therapeutic adjustments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.29033","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T08:14:05Z","timestamp":1617178445000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Bone pain at leukemia diagnosis and other risk factors for symptomatic osteonecrosis in children with acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3994-0556","authenticated-orcid":false,"given":"Shlomit","family":"Barzilai\u2010Birenboim","sequence":"first","affiliation":[{"name":"The Rina Zaizov Division of Pediatric Hematology\u2010Oncology Schneider Children's Medical Center of Israel  Petach Tikva Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-5694","authenticated-orcid":false,"given":"Joanne","family":"Yacobovich","sequence":"additional","affiliation":[{"name":"The Rina Zaizov Division of Pediatric Hematology\u2010Oncology Schneider Children's Medical Center of Israel  Petach Tikva Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Zalcberg","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"Division of Pediatric Hematology, Oncology, and Bone Marrow Transplantation The Edmond and Lily Safra Children's Hospital, Sheba Medical Center  Ramat Gan Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nira","family":"Arad\u2010Cohen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\u2010Oncology Ruth Rappaport Children's Hospital, Rambam Health Care Campus, and Technion\u2010Israel Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galia","family":"Avrahami","sequence":"additional","affiliation":[{"name":"The Rina Zaizov Division of Pediatric Hematology\u2010Oncology Schneider Children's Medical Center of Israel  Petach Tikva Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil","family":"Gilad","sequence":"additional","affiliation":[{"name":"The Rina Zaizov Division of Pediatric Hematology\u2010Oncology Schneider Children's Medical Center of Israel  Petach Tikva Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Litichever","sequence":"additional","affiliation":[{"name":"The Rina Zaizov Division of Pediatric Hematology\u2010Oncology Schneider Children's Medical Center of Israel  Petach Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6938-2540","authenticated-orcid":false,"given":"Shai","family":"Izraeli","sequence":"additional","affiliation":[{"name":"The Rina Zaizov Division of Pediatric Hematology\u2010Oncology Schneider Children's Medical Center of Israel  Petach Tikva Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3495-7578","authenticated-orcid":false,"given":"Sarah","family":"Elitzur","sequence":"additional","affiliation":[{"name":"The Rina Zaizov Division of Pediatric Hematology\u2010Oncology Schneider Children's Medical Center of Israel  Petach Tikva Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.081265"},{"key":"e_1_2_9_3_1","unstructured":"National Institutes of Health and National Cancer Institute.Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0. Published May 28 2009; v4.03: June 14 2010.U.S. Department of Health and Human Services.https:\/\/evs.nci.nih.gov\/ftp1\/CTCAE\/CTCAE_4.03\/Archive\/CTCAE_4.0_2009\u201005\u201029_QuickReference_8.5.11.pdf. Accessed February 2018."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30035-3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2006.11.002"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjpo-2017-000122"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70315-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.18.3262"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.37.3217"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20244"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2405032"},{"issue":"7","key":"e_1_2_9_12_1","first-page":"747","article-title":"Associazione Italiana di Ematologia ed Oncologia Pediatrica. Osteonecrosis: an emerging complication of intensive chemotherapy for childhood acute lymphoblastic leukemia","volume":"88","author":"Aric\u00f2 M","year":"2003","journal-title":"Haematologica"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.147595"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2001.19.12.3066"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.095562"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-010-8217-z"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199912000-00033"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.8.2907"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(01)00663-9"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00029330-200604010-00012"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-200001000-00030"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.48.6522"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15752"},{"key":"e_1_2_9_24_1","unstructured":"Centers for Disease Control and Prevention.BMI Percentile Calculator for Child and Teen.CDC.https:\/\/www.cdc.gov\/healthyweight\/assessing\/bmi\/adult_bmi\/english_bmi_calculator\/bmi_calculator.html. Accessed February 2018."},{"key":"e_1_2_9_25_1","volume-title":"BMDP Statistical Software","author":"Dixon WJ","year":"1993"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27300"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000006"},{"issue":"3","key":"e_1_2_9_28_1","first-page":"195","article-title":"An expanded overview of postmenopausal osteoporosis","volume":"2","author":"Marcus R","year":"2002","journal-title":"J Musculoskelet Neuronal Interact"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.2539"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.160507"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-311969"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28040"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2014.06.023"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26559"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(01)00656-6"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00402-004-0760-8"},{"key":"e_1_2_9_37_1","first-page":"111","article-title":"The 677C>T mutation of the methylene\u2010tetrahydrofolate reductase gene in the pathogenesis of osteonecrosis of the femoral head","volume":"87","author":"Zalavras CG","year":"2002","journal-title":"Haematologica"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2005.12.062"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000157539.67567.03"},{"issue":"10","key":"e_1_2_9_40_1","first-page":"1326","article-title":"Low molecular weight heparin prevents the progression of precollapse osteonecrosis of the hip","volume":"96","author":"Chotanaphuti T","year":"2013","journal-title":"J Med Assoc Thai"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02886443"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-911X(199901)32:1<11::AID-MPO4>3.0.CO;2-F"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2017.1280605"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1466292"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26624"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-027204"},{"issue":"1","key":"e_1_2_9_47_1","first-page":"24","article-title":"Tenth european consensus conference on hyperbaric medicine: recommendations for accepted and non\u2010accepted clinical indications and practice of hyperbaric oxygen treatment","volume":"47","author":"Mathieu D","year":"2017","journal-title":"Diving Hyperb Med"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.4081\/or.2016.6150"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-200105000-00022"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20517"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70274-7"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000150312.53937.6f"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-010-1250-7"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29033","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pbc.29033","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T04:56:37Z","timestamp":1693198597000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.29033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,31]]},"references-count":52,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1002\/pbc.29033"],"URL":"https:\/\/doi.org\/10.1002\/pbc.29033","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,31]]},"assertion":[{"value":"2020-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e29033"}}