Response to glucocorticoids and toxicity in childhood acute lymphoblastic leukemia: Role of polymorphisms of genes involved in glucocorticoid response

Marino, Sara; Verzegnassi, Federico; Tamaro, Paolo; Stocco, Gabriele; Bartoli, Fiora; Decorti, Giuliana; Rabusin, Marco

doi:10.1002/pbc.22163

Cited by 37 publications

(45 citation statements)

References 46 publications

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“…Glutathione-S-transferase M1 genotype might influence the severity of infection in childhood ALL. 31 In conclusion dexamethasone as a steroid therapy for adult patients with ALL/LBL at the dose given in the ALL-4 trial did not show any advantage compared to prednisolone. The toxicity of both drugs during induction therapy and consolidation was similar.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

Labar

Suciu²,

Willemze³

et al. 2010

Haematologica

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BackgroundCorticosteroids are a standard component of the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Our aim was to determine whether dexamethasone results in a better outcome than prednisolone. Design and MethodsAdult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma were randomized to receive, as part of their induction therapy on days 1-8 and 15-22, either dexamethasone 8 mg/m 2 or prednisolone 60 mg/m 2 . Those who reached complete remission were given two courses of consolidation therapy with high-dose cytarabine and mitoxantrone and methotrexate and asparaginase. Subsequently patients younger than 50 years, with a suitable donor, were to undergo allogeneic stem cell transplantation, whereas the others were planned to receive either an autologous stem cell transplant or high-dose maintenance chemotherapy with prophylactic central nervous system irradiation. Randomization was done with a minimization technique. The primary endpoint was event-free survival and the analyses was conducted on an intention-to-treat basis. ResultsBetween August 1995 and October 2003, 325 patients between 15 to 72 years of age were randomized to receive either dexamethasone (163 patients) or prednisolone (162 patients). After induction and the course of first consolidation therapy, 131 (80.4%) patients in the dexamethasone group and 124 (76.5%) in the prednisolone group achieved complete remission. No significant difference was observed between the two treatment groups with regards to 6-year event-free survival rates (±SE) which were 25.9% (3.6%) and 28.7% (3.5%) in the dexamethasone and prednisolone groups, respectively (P=0.82, hazard ratio 0.97; 95% confidence interval, 0.75-1.25). Disease-free survival after complete remission was also similar in the dexamethasone and prednisolone groups, the 6-year rates being 32.3% and 37.5%, respectively (hazard ratio 1.03; 95% confidence interval 0.76-1.40). The 6-year cumulative incidences of relapse were 49.8% and 53.5% (Gray's test: P=0.30) while the 6-year cumulative incidences of death were 18% and 9% (Gray's test: P=0.07). ConclusionsIn the ALL-4 trial in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma, treatment with dexamethasone did not show any advantage over treatment with prednisolone. (ClinicalTrials.gov Identifier: NCT00002700)

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Section: Discussionmentioning

confidence: 99%

Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

Labar

Suciu²,

Willemze³

et al. 2010

Haematologica

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“…It was described that G-allele carrier patients have a better response to ALL treatment which includes glucocorticoids, leading to a better outcome [39,40] A C C E P T E D M A N U S C R I P T…”

Section: Accepted Manuscriptmentioning

confidence: 99%

IL-10 gene polymorphism and influence of chemotherapy on cytokine plasma levels in childhood acute lymphoblastic leukemia patients

Hiroki

Amarante

Petenuci

et al. 2015

Blood Cells, Molecules, and Diseases

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“…The reasons for excluding 15 articles are shown in Figure 1. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Characteristics of included studies are presented in Table 1 (patients in trial Risk of bias assessment has been hampered by the fact that four of the eight studies, so far, have only published preliminary data in form of conference abstracts (AIEOP-BFM ALL 2000 and ALL-BFM 2000, respectively; COG AALL0232, EORTC 58951). Considering all trials, allocation generation and concealment information were available for one and two trials, respectively.…”

Section: Data Synthesis and Analysismentioning

confidence: 99%

Dexamethasone versus prednisone for induction therapy in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis

et al. 2011

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This systematic review and meta-analysis compared the efficacy and toxicity of dexamethasone (DEX) versus prednisone (PRED) for induction therapy in childhood acute lymphoblastic leukemia (ALL). We searched biomedical literature databases and conference proceedings for randomized controlled trials comparing DEX and PRED during induction therapy for childhood ALL. A total of eight studies were eligible for inclusion in this meta-analysis. DEX, in comparison with PRED, reduced events (that is, death from any cause, refractory or relapsed leukemia, or second malignancy; risk ratio (RR) 0.80; 95% confidence interval (CI), 0.68-0.94) and central nervous system relapse (RR 0.53; 95% CI, 0.44-0.65), but did not alter bone marrow relapse (RR 0.90; 95% CI, 0.69-1.18) or overall mortality (RR 0.91; 95% CI, 0.76-1.09). Patients receiving DEX had a higher risk of mortality during induction (RR 2.31; 95% CI, 1.46-3.66), neuro-psychiatric adverse events (RR 4.55; 95% CI, 2.45-8.46) and myopathy (RR 7.05; 95% CI, 3.00-16.58). There was no statistically significant difference in the risk of osteonecrosis, sepsis, fungal infection, diabetes or pancreatitis. DEX in induction therapy for children with ALL is more efficacious than PRED. However, DEX is also associated with more toxicity, and currently it remains unclear whether shortterm superiority of DEX will also result in better overall survival.

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Response to glucocorticoids and toxicity in childhood acute lymphoblastic leukemia: Role of polymorphisms of genes involved in glucocorticoid response

Abstract: GST-M1 genotype may influence the severity of infections in ALL children during GC administration.

Cited by 37 publications

References 46 publications

Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

IL-10 gene polymorphism and influence of chemotherapy on cytokine plasma levels in childhood acute lymphoblastic leukemia patients

Dexamethasone versus prednisone for induction therapy in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis

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