Chemotherapy-Induced Unconjugated Hyperbilirubinemia Complicated by Other Trigger Factors in a Child with T-Cell Acute Lymphoblastic Leukaemia and UGT1A1 Mutation-Associated Gilbert Syndrome
Abstract
1. Introduction
2. Case Presentation
3. Discussion
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Wagner, K.H.; Shiels, R.G.; Lang, C.A.; Seyed Khoei, N.; Bulmer, A.C. Diagnostic criteria and contributors to Gilbert’s syndrome. Crit. Rev. Clin. Lab. Sci. 2018, 55, 129–139. [Google Scholar] [CrossRef] [PubMed]
- Thoguluva Chandrasekar, V.; Faust, T.W.; John, S. Gilbert Syndrome. In StatPearls; StatPearls Publishing LLC.: Treasure Island, FL, USA, 2024. [Google Scholar]
- Ye, N.; Zhou, Z.; Gong, H.; Teng, J.; Han, Y.; Yang, C.; Ye, J. Gilbert syndrome with systemic lupus erythematosus presenting with persistent unconjugated hyperbilirubinemia: A case report. Exp. Ther. Med. 2020, 20, 91. [Google Scholar] [CrossRef] [PubMed]
- Singh, A.; Koritala, T.; Jialal, I. Unconjugated Hyperbilirubinemia. In StatPearls; StatPearls Publishing LLC.: Treasure Island, FL, USA, 2024. [Google Scholar]
- Çağan Appak, Y.; Aksoy, B.; Özyılmaz, B.; Özdemir, T.R.; Baran, M. Gilbert Syndrome and Genetic Findings in Children: A Tertiary-Center Experience from Turkey. Turk. Arch. Pediatr. 2022, 57, 295–299. [Google Scholar] [CrossRef] [PubMed]
- Karas, S.; Innocenti, F. All You Need to Know About UGT1A1 Genetic Testing for Patients Treated with Irinotecan: A Practitioner-Friendly Guide. JCO Oncol. Pract. 2022, 18, 270–277. [Google Scholar] [CrossRef]
- Raetz, E.A.; Teachey, D.T. T-cell acute lymphoblastic leukemia. Hematol. Am. Soc. Hematol. Educ. Program 2016, 2016, 580–588. [Google Scholar] [CrossRef] [PubMed]
- Weeramange, C.J.; Binns, C.M.; Chen, C.; Rafferty, R.J. Inhibition of UDP-glucose dehydrogenase by 6-thiopurine and its oxidative metabolites: Possible mechanism for its interaction within the bilirubin excretion pathway and 6TP associated liver toxicity. J. Pharm. Biomed. Anal. 2018, 151, 106–115. [Google Scholar] [CrossRef] [PubMed]
- Maruo, Y.; Sato, H.; Bamba, N.; Iwai, M.; Sawa, H.; Fujino, H.; Taga, T.; Ota, S.; Shimada, M. Chemotherapy-induced Unconjugated Hyperbilirubinemia Caused by a Mutation of the Bilirubin Uridine-5[acute]-Diphosphate-Glucuronosyltransferase Gene. J. Pediatr. Hematol./Oncol. 2001, 23, 45–47. [Google Scholar] [CrossRef]
- Nomura, A.; Maruo, Y.; Taga, T.; Takeuchi, Y. Contribution of UGT1A1 variations to chemotherapy-induced unconjugated hyperbilirubinemia in pediatric leukemia patients. Pediatr. Res. 2016, 80, 252–257. [Google Scholar] [CrossRef] [PubMed]
- Berrueco, R.; Alonso-Saladrigues, A.; Martorell-Sampol, L.; Catala, A.; Llobet, A.; Toll, T.; Torrebadell, M.; Naudó, M.; Camós, M.; Rives, S. Outcome and toxicities associated to chemotherapy in children with acute lymphoblastic leukemia and Gilbert syndrome. Usefulness of UGT1A1 mutational screening: Gilbert Syndrome and Pediatric Acute Leukemia. Pediatr. Blood Cancer 2015, 62, 1195–1201. [Google Scholar] [CrossRef] [PubMed]
- Ruiz-Argüelles, G.J.; Ruiz-Delgado, G.J.; David Gómez-Rangel, J.; Gómez-Almaguer, D. Gilbert’s syndrome disclosed during the treatment of hematological malignancies. Hematology 2005, 10, 59–60. [Google Scholar] [CrossRef] [PubMed]
- Xu, R.; Cui, X.; Huang, N.; Xu, J.; Dong, X. PB2283 Treatment of Gilbert Syndrome complicated by blood diseases: A series of case reports. HemaSphere 2019, 3, 1020. [Google Scholar] [CrossRef]
- Cupp, M.J.; Higa, G.M. Doxorubicin dosage guidelines in a patient with hyperbilirubinemia of Gilbert’s syndrome. Ann. Pharmacother 1998, 32, 1026–1029. [Google Scholar] [CrossRef] [PubMed]
- Ha, V.H.; Jupp, J.; Tsang, R.Y. Oncology Drug Dosing in Gilbert Syndrome Associated with UGT1A1: A Summary of the Literature. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2017, 37, 956–972. [Google Scholar] [CrossRef]
- Maruo, Y.; D’Addario, C.; Mori, A.; Iwai, M.; Takahashi, H.; Sato, H.; Takeuchi, Y. Two linked polymorphic mutations (A(TA)7TAA and T-3279G) of UGT1A1 as the principal cause of Gilbert Syndrome. Hum. Genet. 2004, 115, 525–526. [Google Scholar] [CrossRef] [PubMed]
- Eklund, J.W.; Trifilio, S.; Mulcahy, M.F. Chemotherapy dosing in the setting of liver dysfunction. Oncology 2005, 19, 1057–1063; discussion 1063–1054, 1069. [Google Scholar] [PubMed]
- Kishi, S.; Cheng, C.; French, D.; Pei, D.; Das, S.; Cook, E.H.; Hijiya, N.; Rizzari, C.; Rosner, G.L.; Frudakis, T.; et al. Ancestry and pharmacogenetics of antileukemic drug toxicity. Blood 2007, 109, 4151–4157. [Google Scholar] [CrossRef] [PubMed]
- King, D.; Armstrong, M.J. Overview of Gilbert’s syndrome. Drug Ther. Bull. 2019, 57, 27–31. [Google Scholar] [CrossRef]
- McDonald, G.B.; Evans, A.T.; McCune, J.S.; Schoch, G.; Ostrow, J.D.; Gooley, T.A. Mortality outcomes after busulfan-containing conditioning treatment and haemopoietic cell transplantation in patients with Gilbert’s syndrome: A retrospective cohort study. Lancet Haematol. 2016, 3, e516–e525. [Google Scholar] [CrossRef]
Test | Result(s) |
---|---|
Serum bilirubin |
|
Faecal urobilinogen | Decreased |
UFEME a | No bilirubin |
Liver function tests (ALT b, AST c, ALP d, GGT e, albumin, total protein, and PT f ) | Normal |
Liver biopsy | Normal |
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Khoo, M.S.; Jamalullail, S.N.; Loh, C.-K.; Lau, S.C.D.; Alias, H. Chemotherapy-Induced Unconjugated Hyperbilirubinemia Complicated by Other Trigger Factors in a Child with T-Cell Acute Lymphoblastic Leukaemia and UGT1A1 Mutation-Associated Gilbert Syndrome. Curr. Oncol. 2025, 32, 91. https://doi.org/10.3390/curroncol32020091
Khoo MS, Jamalullail SN, Loh C-K, Lau SCD, Alias H. Chemotherapy-Induced Unconjugated Hyperbilirubinemia Complicated by Other Trigger Factors in a Child with T-Cell Acute Lymphoblastic Leukaemia and UGT1A1 Mutation-Associated Gilbert Syndrome. Current Oncology. 2025; 32(2):91. https://doi.org/10.3390/curroncol32020091
Chicago/Turabian StyleKhoo, Mohammad Shukri, Sharifah Naiema Jamalullail, C-Khai Loh, Sie Chong Doris Lau, and Hamidah Alias. 2025. "Chemotherapy-Induced Unconjugated Hyperbilirubinemia Complicated by Other Trigger Factors in a Child with T-Cell Acute Lymphoblastic Leukaemia and UGT1A1 Mutation-Associated Gilbert Syndrome" Current Oncology 32, no. 2: 91. https://doi.org/10.3390/curroncol32020091
APA StyleKhoo, M. S., Jamalullail, S. N., Loh, C.-K., Lau, S. C. D., & Alias, H. (2025). Chemotherapy-Induced Unconjugated Hyperbilirubinemia Complicated by Other Trigger Factors in a Child with T-Cell Acute Lymphoblastic Leukaemia and UGT1A1 Mutation-Associated Gilbert Syndrome. Current Oncology, 32(2), 91. https://doi.org/10.3390/curroncol32020091