Academic Journal
Hepatic sinusoidal obstruction syndrome and short-term application of 6-thioguanine in pediatric acute lymphoblastic leukemia
| العنوان: | Hepatic sinusoidal obstruction syndrome and short-term application of 6-thioguanine in pediatric acute lymphoblastic leukemia |
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| المؤلفون: | Stanulla, Martin, Schaeffeler, Elke, Möricke, Anja, Buchmann, Swantje, Zimmermann, Martin, Igel, Svitlana, Schmiegelow, Kjeld, Flotho, Christian, Hartmann, Hans, Illsinger, Sabine, Sauerbrey, Axel, Junk, Stefanie V., Schütte, Peter, Hinze, Laura, Lauten, Melchior, Modlich, Simon, Kolb, Reinhard, Rossig, Claudia, Schwabe, Georg, Gnekow, Astrid K., Fleischhack, Gudrun, Schlegel, Paul Gerhard, Schünemann, Holger J., Kratz, Christian P., Cario, Gunnar, Schrappe, Martin, Schwab, Matthias |
| المصدر: | http://lobid.org/resources/99370672770606441#!, 35(9):2650-2657. |
| سنة النشر: | 2021 |
| المجموعة: | Publisso (ZB MED-Publikationsportal Lebenswissenschaften) |
| مصطلحات موضوعية: | Adolescent [MeSH], Female [MeSH], Follow-Up Studies [MeSH], Hepatic Veno-Occlusive Disease/prevention, Humans [MeSH], Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology [MeSH], Time Factors [MeSH], Acute lymphocytic leukaemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy [MeSH], Article, Infant [MeSH], Male [MeSH], Antimetabolites, Antineoplastic/administration, Prognosis [MeSH], Chemotherapy, Thioguanine/administration, Child [MeSH], Child, Preschool [MeSH] |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://repository.publisso.de/resource/frl:6443834; https://doi.org/10.1038/s41375-021-01203-7; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410596/ |
| DOI: | 10.1038/s41375-021-01203-7 |
| الاتاحة: | https://repository.publisso.de/resource/frl:6443834 https://doi.org/10.1038/s41375-021-01203-7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410596/ |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.7EA72AAD |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41375-021-01203-7 |
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