title: Glutathione S-transferase homozygous deletions and relapse in childhood acute lymphoblastic leukemia: a novel study design in a large Italian AIEOP cohort.
abstract: OBJECTIVE
  In the AIEOP-BFM 2000 trial, 15% of pediatric patients treated according to risk-adapted polychemotherapeutic regimens relapsed. The present study aimed to investigate the influence of GST-M1 and GST-T1 deletions on clinical outcome of children with acute lymphoblastic leukemia treated according to the AIEOP-BFM ALL 2000 study protocol.
  
  
  METHODS
  A novel-design, two-phase study was applied to select a subsample of 614 children to be genotyped for the deletions of GST genes. Cumulative incidence of relapse was then estimated by weighted Kaplan-Meier analysis, and the Cox model was applied to evaluate the effect of GST-M1 and GST-T1 isoenzyme deletions on relapse.
  
  
  RESULTS
  No overall effect was found, but the GST-M1 deletion was associated with better clinical outcome within prednisone poor-responder patients (hazard ratio [HR]: 0.45; 95% CI: 0.23-0.91; p = 0.026), whereas the GST-T1 deletion was associated with worse outcome in the standard-risk group (HR: 4.62; 95% CI: 1.04-20.6; p = 0.045) and within prednisone good responders (HR: 1.62; 95% CI: 1.02-2.58; p = 0.041).
  
  
  CONCLUSIONS
  Our results show that GST-M1 and GST-T1 homozygous deletions have opposite correlation with relapse, the former being protective and the latter unfavourable in specific subsets of acute lymphoblastic leukemia patients.
authors.affiliation: IRCCS Burlo Garofolo, UO Pediatric Hemato-Oncology, Via dell'Istria 65/1, 34137 Trieste, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Franca
authors.forename: Paola
authors.initials: P
authors.lastname: Rebora
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cazzaniga
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
authors.forename: Giuliana
authors.initials: G
authors.lastname: Decorti
authors.forename: Franca
authors.initials: F
authors.lastname: Fagioli
authors.forename: Emanuela
authors.initials: E
authors.lastname: Giarin
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Poggi
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Marco
authors.initials: M
authors.lastname: Rabusin
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007223:Infant; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D005982:Glutathione Transferase