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

Franca, R., Rebora, P., Basso, G., Biondi, A., Cazzaniga, G., Crovella, S., et al. (2012). Glutathione S-Transferase homozygous deletions on relapse in childhood Acute Lymphoblastic Leukemia: a novel study design in a large Italian AIEOP cohort. PHARMACOGENOMICS, 13(16), 1905-1916 [10.2217/pgs.12.169].

Glutathione S-Transferase homozygous deletions on relapse in childhood Acute Lymphoblastic Leukemia: a novel study design in a large Italian AIEOP cohort.

REBORA, PAOLA;BIONDI, ANDREA;Cazzaniga, G;VALSECCHI, MARIA GRAZIA;
2012

Abstract

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
Articolo in rivista - Articolo scientifico
Acute Lymphoblastic Leukemia; Glutathione S-Transferase; polymorphism; prognostic genetic factors; relapse; polychemotherapy; two-phase design
English
2012
13
16
1905
1916
none
Franca, R., Rebora, P., Basso, G., Biondi, A., Cazzaniga, G., Crovella, S., et al. (2012). Glutathione S-Transferase homozygous deletions on relapse in childhood Acute Lymphoblastic Leukemia: a novel study design in a large Italian AIEOP cohort. PHARMACOGENOMICS, 13(16), 1905-1916 [10.2217/pgs.12.169].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/39120
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