Hepatic sinusoidal obstruction syndrome and short-term application of 6-thioguanine in pediatric acute lymphoblastic leukemia

  1. Stanulla, Martin ORCID logo
  2. Schaeffeler, Elke
  3. Möricke, Anja
  4. Buchmann, Swantje
  5. Zimmermann, Martin
  6. Igel, Svitlana
  7. Schmiegelow, Kjeld
  8. Flotho, Christian
  9. Hartmann, Hans
  10. Illsinger, Sabine
  11. Sauerbrey, Axel
  12. Junk, Stefanie V.
  13. Schütte, Peter
  14. Hinze, Laura
  15. Lauten, Melchior
  16. Modlich, Simon
  17. Kolb, Reinhard
  18. Rossig, Claudia
  19. Schwabe, Georg
  20. Gnekow, Astrid K.
  21. Fleischhack, Gudrun ORCID logo
  22. Schlegel, Paul Gerhard
  23. Schünemann, Holger J.
  24. Kratz, Christian P.
  25. Cario, Gunnar
  26. Schrappe, Martin
  27. Schwab, Matthias

Download
s41375-021-01203-7.pdf 796,27KB
WeightNameValue
1000 Titel
  • Hepatic sinusoidal obstruction syndrome and short-term application of 6-thioguanine in pediatric acute lymphoblastic leukemia
1000 Autor/in
  1. Stanulla, Martin |
  2. Schaeffeler, Elke |
  3. Möricke, Anja |
  4. Buchmann, Swantje |
  5. Zimmermann, Martin |
  6. Igel, Svitlana |
  7. Schmiegelow, Kjeld |
  8. Flotho, Christian |
  9. Hartmann, Hans |
  10. Illsinger, Sabine |
  11. Sauerbrey, Axel |
  12. Junk, Stefanie V. |
  13. Schütte, Peter |
  14. Hinze, Laura |
  15. Lauten, Melchior |
  16. Modlich, Simon |
  17. Kolb, Reinhard |
  18. Rossig, Claudia |
  19. Schwabe, Georg |
  20. Gnekow, Astrid K. |
  21. Fleischhack, Gudrun |
  22. Schlegel, Paul Gerhard |
  23. Schünemann, Holger J. |
  24. Kratz, Christian P. |
  25. Cario, Gunnar |
  26. Schrappe, Martin |
  27. Schwab, Matthias |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-03-13
1000 Erschienen in
1000 Quellenangabe
  • 35(9):2650-2657
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41375-021-01203-7 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410596/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Long-term treatment with 6-thioguanine (6-TG) for pediatric acute lymphoblastic leukemia (ALL) is associated with high rates of hepatic sinusoidal obstruction syndrome (SOS). Nevertheless, current treatment continues to use short-term applications of 6-TG with only sparse information on toxicity. 6-TG is metabolized by thiopurine methyltransferase (TPMT) which underlies clinically relevant genetic polymorphism. We analyzed the association between hepatic SOS reported as a serious adverse event (SAE) and short-term 6-TG application in 3983 pediatric ALL patients treated on trial AIEOP-BFM ALL 2000 (derivation cohort) and defined the role of TPMT genotype in this relationship. We identified 17 patients (0.43%) with hepatic SOS, 13 of which with short-term exposure to 6-TG (P < 0.0001). Eight of the 13 patients were heterozygous for low-activity TPMT variants, resulting in a 22.4-fold (95% confidence interval 7.1-70.7; P ≤ 0.0001) increased risk of hepatic SOS for heterozygotes in comparison to TPMT wild-type patients. Results were supported by independent replication analysis. All patients with hepatic SOS after short-term 6-TG recovered and did not demonstrate residual symptoms. Thus, hepatic SOS is associated with short-term exposure to 6-TG during treatment of pediatric ALL and SOS risk is increased for patients with low-activity TPMT genotypes.
1000 Sacherschließung
lokal Adolescent [MeSH]
lokal Female [MeSH]
lokal Follow-Up Studies [MeSH]
lokal Hepatic Veno-Occlusive Disease/prevention
lokal Humans [MeSH]
lokal Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology [MeSH]
lokal Time Factors [MeSH]
lokal Acute lymphocytic leukaemia
lokal Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy [MeSH]
lokal Article
lokal Infant [MeSH]
lokal Male [MeSH]
lokal Antimetabolites, Antineoplastic/administration
lokal Prognosis [MeSH]
lokal Chemotherapy
lokal Thioguanine/administration
lokal Child [MeSH]
lokal Child, Preschool [MeSH]
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-3834-0727|https://frl.publisso.de/adhoc/uri/U2NoYWVmZmVsZXIsIEVsa2U=|https://frl.publisso.de/adhoc/uri/TcO2cmlja2UsIEFuamE=|https://frl.publisso.de/adhoc/uri/QnVjaG1hbm4sIFN3YW50amU=|https://frl.publisso.de/adhoc/uri/WmltbWVybWFubiwgTWFydGlu|https://frl.publisso.de/adhoc/uri/SWdlbCwgU3ZpdGxhbmE=|https://frl.publisso.de/adhoc/uri/U2NobWllZ2Vsb3csIEtqZWxk|https://frl.publisso.de/adhoc/uri/RmxvdGhvLCBDaHJpc3RpYW4=|https://frl.publisso.de/adhoc/uri/SGFydG1hbm4sIEhhbnM=|https://frl.publisso.de/adhoc/uri/SWxsc2luZ2VyLCBTYWJpbmU=|https://frl.publisso.de/adhoc/uri/U2F1ZXJicmV5LCBBeGVs|https://frl.publisso.de/adhoc/uri/SnVuaywgU3RlZmFuaWUgVi4=|https://frl.publisso.de/adhoc/uri/U2Now7x0dGUsIFBldGVy|https://frl.publisso.de/adhoc/uri/SGluemUsIExhdXJh|https://frl.publisso.de/adhoc/uri/TGF1dGVuLCBNZWxjaGlvcg==|https://frl.publisso.de/adhoc/uri/TW9kbGljaCwgU2ltb24=|https://frl.publisso.de/adhoc/uri/S29sYiwgUmVpbmhhcmQ=|https://frl.publisso.de/adhoc/uri/Um9zc2lnLCBDbGF1ZGlh|https://frl.publisso.de/adhoc/uri/U2Nod2FiZSwgR2Vvcmc=|https://frl.publisso.de/adhoc/uri/R25la293LCBBc3RyaWQgSy4=|https://orcid.org/0000-0001-5714-007X|https://frl.publisso.de/adhoc/uri/U2NobGVnZWwsIFBhdWwgR2VyaGFyZA==|https://frl.publisso.de/adhoc/uri/U2Now7xuZW1hbm4sIEhvbGdlciBKLg==|https://frl.publisso.de/adhoc/uri/S3JhdHosIENocmlzdGlhbiBQLg==|https://frl.publisso.de/adhoc/uri/Q2FyaW8sIEd1bm5hcg==|https://frl.publisso.de/adhoc/uri/U2NocmFwcGUsIE1hcnRpbg==|https://frl.publisso.de/adhoc/uri/U2Nod2FiLCBNYXR0aGlhcw==
1000 Hinweis
  • DeepGreen-ID: ab68b18403ca4f4f898161ef3975028e ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
1000 Label
1000 Dateien
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6443834.rdf
1000 Erstellt am 2023-04-27T11:00:09.455+0200
1000 Erstellt von 322
1000 beschreibt frl:6443834
1000 Zuletzt bearbeitet 2023-10-20T11:33:13.626+0200
1000 Objekt bearb. Fri Oct 20 11:33:13 CEST 2023
1000 Vgl. frl:6443834
1000 Oai Id
  1. oai:frl.publisso.de:frl:6443834 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source