SynthesisPloS one2019
Hepatotoxicity during 6-thioguanine treatment in inflammatory bowel disease and childhood acute lymphoblastic leukaemia: A systematic review.
Synthesis in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- KASL clinical practice guidelines for management of autoimmune hepatitis 2022.Clinical and molecular hepatology · 2023Guideline
- DNA-thioguanine concentration and relapse risk in children and young adults with acute lymphoblastic leukemia: an IPD meta-analysis.Leukemia · 2022Pooled it
- DNA-TG and risk of sinusoidal obstruction syndrome in childhood acute lymphoblastic leukemia.Leukemia · 2022Trial
- [Emphasis on the etiological diagnosis and management of non-cirrhotic portal hypertension].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Novel Therapeutic Approaches in Pediatric Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Review
- Review
- The Effectiveness and Safety of First-Line Thioguanine in Thiopurine-Naïve Inflammatory Bowel Disease Patients.Inflammatory bowel diseases · 2024Article
- Uphill battle: Innovation of thiopurine therapy in global inflammatory bowel disease care.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2024Review
- Article
- Polymer-Based Nanoparticles as Drug Delivery Systems for Purines of Established Importance in Medicine.Nanomaterials (Basel, Switzerland) · 2023Review
- Thioguanine is Effective as Maintenance Therapy for Inflammatory Bowel Disease: A Prospective Multicentre Registry Study.Journal of Crohn's & colitis · 2023Article
- [Treatment of Autoimmune Hepatitis].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2023Review
- Maintenance therapy for acute lymphoblastic leukemia: basic science and clinical translations.Leukemia · 2022Review
- Article
- Increments in DNA-thioguanine level during thiopurine-enhanced maintenance therapy of acute lymphoblastic leukemia.Haematologica · 2021Article
- Biomarkers for gastrointestinal adverse events related to thiopurine therapy.World journal of gastroenterology · 2021Article
- Thiopurines in Inflammatory Bowel Disease. How to Optimize Thiopurines in the Biologic Era?Frontiers in medicine · 2021Review
- A comparative analysis of tioguanine versus low-dose thiopurines combined with allopurinol in inflammatory bowel disease patients.Alimentary pharmacology & therapeutics · 2020Article
- [A rare case of neonatal-onset hepatic sinusoidal obstruction syndrome].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatricsArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe recently established association between higher levels of DNA-incorporated thioguanine nucleotides and lower relapse risk in childhood acute lymphoblastic leukaemia (ALL) calls for reassessment of prolonged 6-thioguanine (6TG) treatment, while avoiding the risk of hepatotoxicity.
objectivesTo assess the incidence of hepatotoxicity in patients treated with 6TG, and to explore if a safe dose of continuous 6TG can be established. DATA SOURCES: Databases, conference proceedings, and reference lists of included studies were systematically searched for 6TG and synonyms from 1998-2018.
methodsWe included studies of patients with ALL or inflammatory bowel disorder (IBD) treated with 6TG, excluding studies with 6TG as part of an intensive chemotherapy regimen. We uploaded a protocol to PROSPERO (registration number CRD42018089424). Database and manual searches yielded 1823 unique records. Of these, 395 full-texts were screened for eligibility. Finally, 134 reports representing 42 studies were included. RESULTS AND
conclusionsWe included data from 42 studies of ALL and IBD patients; four randomised controlled trials (RCTs) including 3,993 patients, 20 observational studies including 796 patients, and 18 case reports including 60 patients. Hepatotoxicity in the form of sinusoidal obstruction syndrome (SOS) occurred in 9-25% of the ALL patients in two of the four included RCTs using 6TG doses of 40-60 mg/m2/day, and long-term hepatotoxicity in the form of nodular regenerative hyperplasia (NRH) was reported in 2.5%. In IBD patients treated with 6TG doses of approximately 23 mg/m2/day, NRH occurred in 14% of patients. At a 6TG dose of approximately 12 mg/m2/day, NRH was reported in 6% of IBD patients, which is similar to the background incidence. According to this review, doses at or below 12 mg/m2/day are rarely associated with notable hepatotoxicity and can probably be considered safe.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.