title: Outcome and toxicities associated to chemotherapy in children with acute lymphoblastic leukemia and Gilbert syndrome. Usefulness of UGT1A1 mutational screening.
abstract: 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 <  .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.
authors: Department of Pediatric Hematology. Hospital Sant Joan de Déu, University of Barcelona, Spain.
authors: R
authors: R
authors: Berrueco
authors: Department of Pediatric Hematology. Hospital Sant Joan de Déu, University of Barcelona, Spain.
authors: A
authors: A
authors: Alonso-Saladrigues
authors: Laboratory Department, Molecular Genetics. Hospital Sant Joan de Déu, University of Barcelona, Spain.
authors: L
authors: L
authors: Martorell-Sampol
authors: Department of Pediatric Hematology. Hospital Sant Joan de Déu, University of Barcelona, Spain.
authors: A
authors: A
authors: Català-Temprano
authors: Department of Pediatric Hematology. Hospital Sant Joan de Déu, University of Barcelona, Spain.
authors: A
authors: A
authors: Ruiz-Llobet
authors: Department of Pediatric Hematology. Hospital Sant Joan de Déu, University of Barcelona, Spain.|Laboratory Department, Hematology. Hospital Sant Joan de Déu, University of Barcelona, Spain.
authors: T
authors: T
authors: Toll
authors: Laboratory Department, Hematology. Hospital Sant Joan de Déu, University of Barcelona, Spain.
authors: M
authors: M
authors: Torrebadell
authors: Laboratory Department, Hematology. Hospital Sant Joan de Déu, University of Barcelona, Spain.
authors: M
authors: M
authors: Naudó
authors: Laboratory Department, Hematology. Hospital Sant Joan de Déu, University of Barcelona, Spain.
authors: M
authors: M
authors: Camós
authors: Department of Pediatric Hematology. Hospital Sant Joan de Déu, University of Barcelona, Spain.
authors: S
authors: S
authors: Rives
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000706:statistics & numerical data*; D005260:Female; D005500:Follow-Up Studies; D005878:Gilbert Disease / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced / Q000175:diagnosis* / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D014018:Tissue Distribution; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme
keywords: Gilbert syndrome; acute lymphoblastic leukemia; children