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Glutathione S-transferase homozygous deletions and relapse in childhood acute lymphoblastic leukemia: a novel study design in a large Italian AIEOP cohort.
MedLine Citation:
PMID:  23215883     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Aim: 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. Materials & 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). Conclusion: 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. Original submitted 1 August 2012; Revision submitted 27 September 2012.
Authors:
Raffaella Franca; Paola Rebora; Giuseppe Basso; Andrea Biondi; Giovanni Cazzaniga; Sergio Crovella; Giuliana Decorti; Franca Fagioli; Emanuela Giarin; Franco Locatelli; Vincenzo Poggi; Maria Grazia Valsecchi; Marco Rabusin
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pharmacogenomics     Volume:  13     ISSN:  1744-8042     ISO Abbreviation:  Pharmacogenomics     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100897350     Medline TA:  Pharmacogenomics     Country:  England    
Other Details:
Languages:  eng     Pagination:  1905-16     Citation Subset:  IM    
Affiliation:
I.R.C.C.S Burlo Garofolo, UO Pediatric Hemato-Oncology, Via dell'Istria 65/1, 34137 Trieste, Italy.
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