2019
DOI: 10.1080/10428194.2019.1680839
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Efficacy and toxicity of reduced vs. standard dose pegylated asparaginase in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia

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Cited by 31 publications
(27 citation statements)
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“…The uptake of glutamine by its major transporter SLC1A5 (ACST2) is required for leucine import by the glutamine/leucine antiporter (see below) and mTORC1 activation (Nicklin et al, 2009), thereby promoting CD4 + T-cell differentiation into Th1 and Th17 cells (Nakaya et al, 2014). The bacterial enzyme asparaginase, commonly used as an anticancer agent in lymphoblastic leukemia, catalyzes the deamination of asparagine and, to a lesser extent, glutamine, to aspartic acid and glutamic acid, respectively (Derman et al, 2020). The absence of asparagine affects T-cell activation and IL-2 production through inhibition of the mTORC1 pathway (Torres et al, 2016).…”
Section: Other Amino Acids Important For T-cell Signaling and Activationmentioning
confidence: 99%
“…The uptake of glutamine by its major transporter SLC1A5 (ACST2) is required for leucine import by the glutamine/leucine antiporter (see below) and mTORC1 activation (Nicklin et al, 2009), thereby promoting CD4 + T-cell differentiation into Th1 and Th17 cells (Nakaya et al, 2014). The bacterial enzyme asparaginase, commonly used as an anticancer agent in lymphoblastic leukemia, catalyzes the deamination of asparagine and, to a lesser extent, glutamine, to aspartic acid and glutamic acid, respectively (Derman et al, 2020). The absence of asparagine affects T-cell activation and IL-2 production through inhibition of the mTORC1 pathway (Torres et al, 2016).…”
Section: Other Amino Acids Important For T-cell Signaling and Activationmentioning
confidence: 99%
“…In a pediatric study using a more sensitive technique, an effective serum asparagine depletion was obtained with an enzymatic activity as low as 0.02 IU/ml [65]; also, in adult patients, 80-90% of the cases receiving Peg-ASP 500-1000 IU/m 2 reached drug levels > 0.1 IU/ml, that persisted for 14 days in 77% with 1000 IU/m 2 and for 7 days in 59% with 500 IU/m 2 [66]. Finally, a recent study reported that adults with comorbidities receiving a reduced dose of PEG-ASP < 1000 IU/m 2 experienced fewer toxicities while still attaining therapeutic activity levels > 0.1 IU/ mL [67]. The final consensus of the panel against the utility of routinely searching anti-asparaginase antibodies reflects the data mentioned above.…”
Section: Discussionmentioning
confidence: 95%
“…However, alternate doses and dosing schedules of peg-asparaginase have also been explored in an effort to reduce toxicities. Derman and colleagues were able to show, retrospectively, that patients who were treated per the CALGB 10403 regimen, off trial, with reduced doses of peg-asparaginase (≤1000 IU/m 2 ) were able to achieve adequate asparagine depletion and fewer total grade 3 or 4 toxicities, compared with patients who received standard dose peg-asparaginase (doses ≥1000 IU/m 2 ), without compromising RFS or OS [ 30 ]. However, rates of new VTE between the reduced dose peg-asparaginase group and the standard dose group were, essentially unchanged (20 vs 15.4%, p = 0.726).…”
Section: Discussionmentioning
confidence: 99%