{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T05:53:09Z","timestamp":1781502789454,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006506","name":"Minist\u00e9rio da Sa\u00fade","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006506","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Busulfan is given in the conditioning regimens preceding hematopoietic stem cell transplantation (HSCT), and plasma levels can be monitored. A targeted, individualized systemic exposure (SE) dose can be achieved by calculating the area under the plasma concentration versus time curve (AUC). The objective of this study was to determine a cutoff value for safety for the AUC for busulfan plasma levels in patients undergoing HSCT. A total of 149 consecutive HSCT patients were studied. After an oral test dose of busulfan, we set target doses of 4000, 5000, or 6000 \u00b5Mol\u2e31min\/day, and analyzed the AUC of oral or intravenous Bu. These patients were compared with 53 historical control subjects who had received myeloablative conditioning regimen without busulfan pharmacokinetic monitoring. Using a test dose and the administration route had no impact on the sinusoidal obstructive syndrome (SOS) incidence, transplant\u2010related mortality or 1\u2010year overall survival. However, patients receiving busulfan at doses set up at AUC &gt; 5000 had an increased risk to develop SOS after HSCT (hazard ratio 3.39,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.034, 95% CI 1.09\u201310.52). Adjusting the busulfan dose according to SE levels target dose during conditioning is associated with lower rates of oral severe mucositis and SOS. A cutoff of 5000 \u00b5Mol\u2e31min is safe and does not impair survival.\n                  <\/jats:p>","DOI":"10.1002\/hon.2789","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T22:35:13Z","timestamp":1597185313000},"page":"773-781","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Targeted\u2010dose of busulfan: Higher risk of sinusoidal obstructive syndrome observed with systemic exposure dose above 5000 \u00b5Mol\u2e31min. A historically controlled clinical trial"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3440-5677","authenticated-orcid":false,"given":"Iracema","family":"Esteves","sequence":"first","affiliation":[{"name":"Hospital Israelita Albert Einstein  S\u00e3o Paulo Brazil"},{"name":"Universidade Federal de S\u00e3o Paulo (UNIFESP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio Pires Souza","family":"Santos","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreza Alice Feitosa","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Seber","sequence":"additional","affiliation":[{"name":"Hospital Samaritano  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Kinio","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Associa\u00e7\u00e3o Fundo de Incentivo \u00e0 Pesquisa (AFIP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jairo Jos\u00e9 do Nascimento","family":"Sobrinho","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Carlos","family":"Barros","sequence":"additional","affiliation":[{"name":"Transplantation Hospital Dr. Euryclides de Jesus Zerbini  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Salvador Rodrigues","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Universidade Federal de S\u00e3o Paulo (UNIFESP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Folloni","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein  S\u00e3o Paulo Brazil"},{"name":"Bone Marrow Transplantation Unit Itaci Hospital, Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson","family":"Hamerschlak","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borje S.","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation and Cellular Therapy The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"de Lima","sequence":"additional","affiliation":[{"name":"Case Western Reserve University, University Hospitals of Cleveland  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio Rodrigues","family":"Kerbauy","sequence":"additional","affiliation":[{"name":"Universidade Federal de S\u00e3o Paulo (UNIFESP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,28]]},"reference":[{"key":"e_1_2_11_1_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-144-6-200603210-00007"},{"key":"e_1_2_11_1_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-23204"},{"key":"e_1_2_11_1_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1703014"},{"issue":"2","key":"e_1_2_11_1_5_1","first-page":"135","article-title":"Risk factors for hepatic veno\u2010occlusive disease after high\u2010dose busulfan\u2010containing regimens followed by autologous bone marrow transplantation: a study in 136 children","volume":"10","author":"M\u00e9resse V","year":"1992","journal-title":"Bone Marrow Transplant"},{"key":"e_1_2_11_1_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00694339"},{"key":"e_1_2_11_1_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00688324"},{"key":"e_1_2_11_1_8_1","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1182\/blood.V108.11.2939.2939","article-title":"Busulfan area\u2010under\u2010the\u2010curve finding study within a busulfan\/fludarabine (BuFlu) conditioning regimen before allogeneic hematopoietic cell transplantation (HCT)","volume":"108","author":"Field T","year":"2006","journal-title":"Blood"},{"key":"e_1_2_11_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1083-8791(00)70064-4"},{"key":"e_1_2_11_1_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/bbmt.2002.v8.pm12374454"},{"key":"e_1_2_11_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2014.12.016"},{"key":"e_1_2_11_1_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2013.188"},{"key":"e_1_2_11_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2013.04.005"},{"key":"e_1_2_11_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2011.02.011"},{"key":"e_1_2_11_1_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3046.2011.01529.x"},{"key":"e_1_2_11_1_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2010.60"},{"key":"e_1_2_11_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2007.09.015"},{"key":"e_1_2_11_1_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2017.02.020"},{"key":"e_1_2_11_1_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.8.3055"},{"key":"e_1_2_11_1_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199810000-00017"},{"key":"e_1_2_11_1_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2005.12.028"},{"key":"e_1_2_11_1_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-02-0414"},{"key":"e_1_2_11_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2010.09.022"},{"key":"e_1_2_11_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cden.2004.07.009"},{"issue":"2","key":"e_1_2_11_1_25_1","first-page":"9","article-title":"New strategies for management of oral mucositis in cancer patients","volume":"4","author":"Peterson DE","year":"2006","journal-title":"J Support Oncol"},{"key":"e_1_2_11_1_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/ecc.12344"},{"key":"e_1_2_11_1_27_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-128-12_Part_1-199806150-00002"},{"issue":"3","key":"e_1_2_11_1_28_1","first-page":"259","article-title":"New therapeutical indications of ursodeoxycholic acid","volume":"14","author":"Copaci I","year":"2005","journal-title":"Rom J Gastroenterol"},{"key":"e_1_2_11_1_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12558"},{"issue":"5","key":"e_1_2_11_1_30_1","first-page":"439","article-title":"A comparison of clinical criteria for the diagnosis of veno\u2010occlusive disease of the liver after bone marrow transplantation","volume":"10","author":"Blostein MD","year":"1992","journal-title":"Bone Marrow Transplant"},{"key":"e_1_2_11_1_31_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i29.3918"},{"key":"e_1_2_11_1_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-04-1216"},{"key":"e_1_2_11_1_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2010.02.009"},{"key":"e_1_2_11_1_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2006.08.037"},{"key":"e_1_2_11_1_35_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1176350951"},{"key":"e_1_2_11_1_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-10-4023"},{"key":"e_1_2_11_1_37_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i16.1851"},{"issue":"1","key":"e_1_2_11_1_38_1","first-page":"28","article-title":"Experi\u00eancia brasileira com transplante de medula \u00f3ssea em leucemias agudas [Bone marrow transplantation in acute leukemias: the Brazilian experience]","volume":"29","author":"Souza CA","year":"2007","journal-title":"Rev Bras Hematol Hemoter"},{"key":"e_1_2_11_1_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-019-0521-5"}],"container-title":["Hematological Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhon.2789","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hon.2789","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hon.2789","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hon.2789","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T05:11:00Z","timestamp":1781500260000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hon.2789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,28]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1002\/hon.2789"],"URL":"https:\/\/doi.org\/10.1002\/hon.2789","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/HON.2789\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.2789\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.2789\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.2789\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.2789\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.2789\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.2789\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.2789\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0278-0232","1099-1069"],"issn-type":[{"value":"0278-0232","type":"print"},{"value":"1099-1069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,28]]},"assertion":[{"value":"2019-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}