ArticlePloS one2019
Asparaginase combined with discontinuous dexamethasone improves antileukemic efficacy without increasing osteonecrosis in preclinical models.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- An Integrated Method to Evaluate the Treatment Efficacy and Immunogenicity of B-Cell Acute Lymphoblastic Leukemia Therapeutic Enzyme Formulations.Small methods · 2026Article
- Investigating diet to control asparagine uptake as an adjunct to asparaginase treatment.Frontiers in oncology · 2025Article
- [Osteonecrosis-severe side effect of treatment for acute lymphoblastic leukemia].Orthopadie (Heidelberg, Germany) · 2022Review
- Effects of zoledronic acid on osteonecrosis and acute lymphoblastic leukemia treatment efficacy in preclinical models.Pediatric blood & cancer · 2021Article
- Review
- Effect of post-consolidation regimen on symptomatic osteonecrosis in three DCOG acute lymphoblastic leukemia protocols.Haematologica · 2021Article
- The Metabolic Remodelling in Lung Cancer and Its Putative Consequence in Therapy Response.Advances in experimental medicine and biology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
introductionCombination therapy for acute lymphoblastic leukemia (ALL) is highly effective but results in significant toxicity including osteonecrosis. Asparaginase is known to potentiate both the antileukemic and osteonecrosis-inducing effects of dexamethasone. The schedule of dexamethasone alters osteonecrosis risk. However, the effects of the interaction with asparaginase are unknown when dexamethasone is given on a discontinuous schedule.
methodsUsing the murine model of osteonecrosis, we compared the frequency of osteonecrosis in mice receiving discontinuous dexamethasone (3.5 days/ week) with mice receiving asparaginase and discontinuous dexamethasone. We then tested the effect on antileukemic efficacy using six pediatric ALL xenografts.
resultsThe addition of asparaginase to discontinuous dexamethasone did not alter the rate of osteonecrosis compared to dexamethasone alone (7/35 in dexamethasone with asparaginase combination vs. 10/36 in dexamethasone alone, p = 0.62) despite increasing steady-state plasma dexamethasone levels (103.9 nM vs. 33.4 nM, p = 9.2x10-7). Combination therapy with asparaginase and dexamethasone demonstrated synergistic antileukemic effects across all six xenografts studied.
conclusionsWhen discontinuous dexamethasone was given, its anti-leukemic activity synergized with asparaginase but the osteonecrosis-worsening effects of asparaginase (above dexamethasone alone) were not observed. Thus, there is a favorable drug interaction (unchanged toxicity, synergistic efficacy) between discontinuous dexamethasone and asparaginase.
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Registered trials
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