Outcome and toxicities associated to chemotherapy in children with acute lymphoblastic leukemia and Gilbert syndrome. Usefulness of UGT1A1 mutational screening

Background Acute lymphoblastic leukemia (ALL) is the most frequent cancer in childhood. Although intensive chemotherapy has improved survival in those patients, important side effects, including hyperbilirubinemia, are frequent. Gilbert syndrome (GS) is a frequent condition that causes a reduction i...

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Bibliographic Details
Published in:Pediatric blood & cancer 2015-07, Vol.62 (7), p.1195-1201
Main Authors: Berrueco, R., Alonso-Saladrigues, A., Martorell-Sampol, L., Català-Temprano, A., Ruiz-Llobet, A., Toll, T., Torrebadell, M., Naudó, M., Camós, M., Rives, S.
Format: Article
Language:English
Subjects:
acute lymphoblastic leukemia
Adolescent
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics
Child
Child, Preschool
children
DNA Mutational Analysis - utilization
Female
Follow-Up Studies
Gilbert Disease - drug therapy
Gilbert Disease - genetics
Gilbert Disease - mortality
Gilbert syndrome
Glucuronosyltransferase - genetics
Hematology
Humans
Hyperbilirubinemia - chemically induced
Hyperbilirubinemia - diagnosis
Hyperbilirubinemia - genetics
Infant
Infant, Newborn
Male
Mutation - genetics
Oncology
Pediatrics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality
Prognosis
Retrospective Studies
Survival Rate
Tissue Distribution
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Summary:Background Acute lymphoblastic leukemia (ALL) is the most frequent cancer in childhood. Although intensive chemotherapy has improved survival in those patients, important side effects, including hyperbilirubinemia, are frequent. Gilbert syndrome (GS) is a frequent condition that causes a reduction in glucuronidation and intermittent hyperbilirubinemia episodes. This could provoke a greater exposure to some cytotoxic agents used in ALL, increasing the risk of toxicity. On the other hand, unexplained hyperbilirubinemia could lead to unnecessary modifications or even treatment withdrawals, which could increase the risk of relapse, but data regarding this in ALL pediatric population are scarce. Methods Retrospective study to analyze toxicity, outcome and treatment modifications related to GS in children diagnosed with ALL. Results A total of 23 of 159 patients were diagnosed with GS. They had statistically higher hyperbilirubinemias during all treatment phases (P 
ISSN:1545-5009
1545-5017
DOI:10.1002/pbc.25457