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Outcome and toxicities associated to chemotherapy in children with acute lymphoblastic leukemia and Gilbert syndrome. Usefulness of UGT1A1 mutational screening
Author(s) -
Berrueco R.,
AlonsoSaladrigues A.,
MartorellSampol L.,
CatalàTemprano A.,
RuizLlobet A.,
Toll T.,
Torrebadell M.,
Naudó M.,
Camós M.,
Rives S.
Publication year - 2015
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.25457
Subject(s) - medicine , pediatric cancer , chemotherapy , toxicity , pediatrics , blood cancer , methotrexate , lymphoblastic leukemia , population , retrospective cohort study , cancer , gastroenterology , leukemia , environmental health
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 < 0.0001) and a slower methotrexate clearance when it was administered during a 24‐hr infusion at high doses (patients with GS: 74 hr ± 19 vs. patients without GS: 64 hr ± 8; P < 0.002). However, no relevant toxicity or delays in treatment were found in them. Finally, changes in treatment due to hyperbilirubinemia were only done in 5 patients with GS. Conclusions Differences in outcome were not found in patients with GS. Universal screening for GS appears to be not necessary in pediatric patients with ALL. However, when hyperbilirubinemia is observed, it must be rule out in order to avoid unnecessary changes in treatment. Pediatr Blood Cancer 2015;62:1195–1201. © 2015 Wiley Periodicals, Inc.