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dc.contributor.authorEbbesen, Maria S
dc.contributor.authorNygaard, Ulrikka
dc.contributor.authorRosthøj, Susanne
dc.contributor.authorSørensen, Ditte
dc.contributor.authorNersting, Jacob
dc.contributor.authorVettenranta, Kim
dc.contributor.authorWesenberg, Finn
dc.contributor.authorKristinsson, Jon
dc.contributor.authorHarila-Saari, Arja
dc.contributor.authorSchmiegelow, Kjeld
dc.date.accessioned2017-05-11T10:45:24Z
dc.date.available2017-05-11T10:45:24Z
dc.date.issued2017-04
dc.date.submitted2017
dc.identifier.citationHepatotoxicity During Maintenance Therapy and Prognosis in Children With Acute Lymphoblastic Leukemia. 2017, 39 (3):161-166 J. Pediatr. Hematol. Oncol.en
dc.identifier.issn1536-3678
dc.identifier.pmid28060115
dc.identifier.doi10.1097/MPH.0000000000000733
dc.identifier.urihttp://hdl.handle.net/2336/620179
dc.descriptionTo access publisher's full text version of this article click on the hyperlink belowen
dc.description.abstractHepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine aminotransferases (ALAT) levels and relapse rate. We included 385 patients enrolled in the NOPHO ALL-92 protocol. Data on ALAT levels, 6 MP and MTX doses, cytotoxic MTX/6 MP metabolites, and thiopurine methyltransferase (TPMT) activity were prospectively registered. In total, 91% of the patients had a mean ALAT (mALAT) level above upper normal limit (40 IU/L) and ALAT levels were positively correlated to 6 MP doses (rs=0.31; P<0.001). In total, 47 patients suffered a relapse, no difference in mALAT levels were found in these compared with nonrelapse patients (median, 107 vs. 98 IU/L; P=0.39). mALAT levels in patients classified as TPMT high activity (TPMT) were higher than in TPMT low-activity patients (median, 103 vs. 82 IU/L; P=0.03). In a Cox regression model risk of relapse was not associated with ALAT levels (P=0.56). ALAT levels increased 2.7%/month during the last year of maintenance therapy (P<0.001). In conclusion, elevated ALAT levels are associated with TPMT and may indicate treatment adherence in these patients. If liver function is normal, elevated ALAT levels should not indicate treatment adaptation.
dc.description.sponsorshipDanish Cancer Society The Danish Childhood Cancer Foundation The Children's Cancer Foundation, Sweden The National Medical Research Council The Nordic Cancer Union The Lundbeck Foundation The Otto Christensen Foundation The Gangsted Foundation The Gunnar Jorgensen Foundationen
dc.language.isoenen
dc.publisherLippincott Williams & Wilkinsen
dc.relation.urlhttp://ovidsp.uk.ovid.com/sp-3.25.0a/ovidweb.cgi?WebLinkFrameset=1&S=BCBLPDCMANHFLOCAFNGKEEPFNJBCAA00&returnUrl=ovidweb.cgi%3f%26Full%2bText%3dL%257cS.sh.22.23%257c0%257c00043426-201704000-00001%26S%3dBCBLPDCMANHFLOCAFNGKEEPFNJBCAA00&directlink=http%3a%2f%2fovidsp.uk.ovid.com%2fovftpdfs%2fPDHFFNPFEECAAN00%2ffs046%2fovft%2flive%2fgv023%2f00043426%2f00043426-201704000-00001.pdf&filename=Hepatotoxicity+During+Maintenance+Therapy+and+Prognosis+in+Children+With+Acute+Lymphoblastic+Leukemia.&pdf_key=PDHFFNPFEECAAN00&pdf_index=/fs046/ovft/live/gv023/00043426/00043426-201704000-00001en
dc.rightsArchived with thanks to Journal of pediatric hematology/oncologyen
dc.subjectBráðahvítblæðien
dc.subjectLifrarsjúkdómaren
dc.subjectPED12en
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphomaen
dc.subject.meshChemical and Drug Induced Liver Injuryen
dc.titleHepatotoxicity During Maintenance Therapy and Prognosis in Children With Acute Lymphoblastic Leukemia.en
dc.typeArticleen
dc.contributor.department[ 1 ] Univ Copenhagen, Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark Show the Organization-Enhanced name(s) [ 2 ] Univ Copenhagen, Dept Publ Hlth, Sect Biostat, Copenhagen, Denmark Show the Organization-Enhanced name(s) [ 3 ] Univ Copenhagen, Inst Clin Med, Copenhagen, Denmark [ 4 ] Univ Hosp, Dept Pediat, Tampere, Finland Show the Organization-Enhanced name(s) [ 5 ] Univ Hosp, Dept Pediat, Oslo, Norway Show the Organization-Enhanced name(s) [ 6 ] Univ Hosp, Dept Pediat, Reykjavik, Iceland Show the Organization-Enhanced name(s) [ 7 ] Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Stockholm, Sweden Show the Organization-Enhanced name(s) [ 8 ] Karolinska Inst, Stockholm, Swedenen
dc.identifier.journalJournal of pediatric hematology/oncologyen
dc.rights.accessClosed - Lokaðen
html.description.abstractHepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine aminotransferases (ALAT) levels and relapse rate. We included 385 patients enrolled in the NOPHO ALL-92 protocol. Data on ALAT levels, 6 MP and MTX doses, cytotoxic MTX/6 MP metabolites, and thiopurine methyltransferase (TPMT) activity were prospectively registered. In total, 91% of the patients had a mean ALAT (mALAT) level above upper normal limit (40 IU/L) and ALAT levels were positively correlated to 6 MP doses (rs=0.31; P<0.001). In total, 47 patients suffered a relapse, no difference in mALAT levels were found in these compared with nonrelapse patients (median, 107 vs. 98 IU/L; P=0.39). mALAT levels in patients classified as TPMT high activity (TPMT) were higher than in TPMT low-activity patients (median, 103 vs. 82 IU/L; P=0.03). In a Cox regression model risk of relapse was not associated with ALAT levels (P=0.56). ALAT levels increased 2.7%/month during the last year of maintenance therapy (P<0.001). In conclusion, elevated ALAT levels are associated with TPMT and may indicate treatment adherence in these patients. If liver function is normal, elevated ALAT levels should not indicate treatment adaptation.


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