Prednison therapy of acute lymphatic leukemia in children

Hyman, Chester; Sturgeon, Phillips

doi:10.1002/1097-0142(195609/10)9:5<965::aid-cncr2820090517>3.0.co;2-l

Cited by 24 publications

(11 citation statements)

References 7 publications

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“…1,2 Traditionally, prednisone has been the most commonly used glucocorticoid in remission induction, whereas dexamethasone has been applied during the reintensification phase.…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000

Möricke

Zimmermann

Valsecchi

et al. 2016

Blood

223

196

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Key Points• Dexamethasone vs prednisone in induction of pediatric ALL led to significant relapse reduction and increased treatment-related mortality.• No overall survival benefit was achieved with dexamethasone except in the subset of patients with T-cell ALL and good early treatment response.Induction therapy for childhood acute lymphoblastic leukemia (ALL) traditionally includes prednisone; yet, dexamethasone may have higher antileukemic potency, leading to fewer relapses and improved survival. After a 7-day prednisone prephase, 3720 patients enrolled on trial Associazione Italiana di Ematologia e Oncologia Pediatrica and BerlinFrankfurt-Münster (AIEOP-BFM) ALL 2000 were randomly selected to receive either dexamethasone (10 mg/m 2 per day) or prednisone (60 mg/m 2 per day) for 3 weeks plus tapering in induction. The 5-year cumulative incidence of relapse (6 standard error) was 10.8 6 0.7% in the dexamethasone and 15.6 6 0.8% in the prednisone group (P < .0001), showing the largest effect on extramedullary relapses. The benefit of dexamethasone was partially counterbalanced by a significantly higher induction-related death rate (2.5% vs 0.9%, P 5 .00013), resulting in 5-year event-free survival rates of 83.9 6 0.9% for dexamethasone and 80.8 6 0.9% for prednisone (P 5 .024). No difference was seen in 5-year overall survival (OS) in the total cohort (dexamethasone, 90.3 6 0.7%; prednisone, 90.5 6 0.7%). Retrospective analyses of predefined subgroups revealed a significant survival benefit from dexamethasone only for patients with T-cell ALL and good response to the prednisone prephase (prednisone good-response [PGR]) (dexamethasone, 91.4 6 2.4%; prednisone, 82.6 6 3.2%; P 5 .036). In patients with precursor B-cell ALL and PGR, survival after relapse was found to be significantly worse if patients were previously assigned to the dexamethasone arm. We conclude that, for patients with PGR in the large subgroup of precursor B-cell ALL, dexamethasone especially reduced the incidence of better salvageable relapses, resulting in inferior survival after relapse. This explains the lack of benefit from dexamethasone in overall survival that we observed in the total cohort except in the subset of T-cell ALL patients with PGR. This trial was registered at www.clinicaltrials.gov

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“…1,2 Traditionally, prednisone has been the most commonly used glucocorticoid in remission induction, whereas dexamethasone has been applied during the reintensification phase.…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000

Möricke

Zimmermann

Valsecchi

et al. 2016

Blood

223

196

View full text Add to dashboard Cite

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“…By themselves, GCs can achieve clinical remission in ALL, and with the addition of other chemotherapeutic agents, contribute to over eighty percent of patients achieving long-term event-free and overall survival (1, 2). Additionally, early response to GCs is a positive prognostic indicator and those patients who lack a robust response more frequently experience negative outcomes (3–5).…”

Section: Introductionmentioning

confidence: 99%

Modulation of Glucocorticoid Resistance in Pediatric T-cell Acute Lymphoblastic Leukemia by Increasing BIM Expression with the PI3K/mTOR Inhibitor BEZ235

Hall

Reynolds

Kang

2016

Clinical Cancer Research

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Purpose The aim of our study is to evaluate the preclinical therapeutic activity and mechanism of action of BEZ235, a dual PI3K/mTOR inhibitor, in combination with dexamethasone in ALL. Experimental Design The cytotoxic effects of BEZ235 and dexamethasone as single agents and in combination were assessed in a panel of ALL cell lines and xenograft models. The underlying mechanism of BEZ235 and dexamethasone was evaluated using immunoblotting, TaqMan RT-PCR, siRNA, immunohistochemistry and immunoprecipitation. Results Inhibition of the PI3K/AKT/mTOR pathway with the dual PI3K/mTOR inhibitor BEZ235 enhanced dexamethasone-induced anti-leukemic activity in in vitro (continuous cell lines and primary ALL cultures) and systemic in vivo models of T-ALL (including a patient-derived xenograft). Through inhibition of AKT1, BEZ235 was able to alleviate AKT1-mediated suppression of dexamethasone-induced apoptotic pathways leading to increased expression of the pro-apoptotic BCL-2 protein BIM. Downregulation of MCL-1 by BEZ235 further contributed to the modulation of dexamethasone resistance by increasing the amount of BIM available to induce apoptosis, especially in PTEN-null T-ALL where inhibition of AKT only partially overcame AKT-induced BIM suppression. Conclusion Our data support the further investigation of agents targeting the PI3K/mTOR pathway to modulate glucocorticoid resistance in T-ALL.

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“…Dex is also one of the most commonly used chemotherapeutic drugs to treat different cancer [2,3]. Cancer patients undergoing chemotherapy are also given Dex to counteract certain side effects of their antitumor treatment.…”

Section: Introductionmentioning

confidence: 99%

Effect of Formulation and Processing Variables on Dexamethasone Entrapment and Release of Niosomes

2015

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Multilamellar niosomes entrapping Dexamethasone (Dex) were prepared by thin film hydration, sonication, respectively. The influence of different processing variables (sonication time, temperature) and formulation variable (cholesterol content) on Dex entrapment efficiency % (EE) was demonstrated. Also, the Dex release from the prepared niosomes in phosphate buffer (pH 7.4) was illustrated. Results indicated that cholesterol increased or decreased the noisome size and EE % depending on its concentration within the formulae. The maximum loading efficiency was 29.2 % when the span 60:cholesterol molar ratio was 100:50 and the hydrating step was conducted by 30 min sonication. Increasing sonication time also increased and then decreased the EE % of Dex into niosomes. Finally, results indicated that in vitro release profiles of Dex from all niosome formulations is an apparently biphasic release process and 5-15 % of drug released from niosomes after 8 h incubation in buffer, depending on the type of niosome.

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Prednison therapy of acute lymphatic leukemia in children

Cited by 24 publications

References 7 publications

Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000

Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000

Modulation of Glucocorticoid Resistance in Pediatric T-cell Acute Lymphoblastic Leukemia by Increasing BIM Expression with the PI3K/mTOR Inhibitor BEZ235

Effect of Formulation and Processing Variables on Dexamethasone Entrapment and Release of Niosomes

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