PEG-asparaginase and native Escherichia coli L-asparaginase in acute lymphoblastic leukemia in children and adolescents: a systematic review

Medawar, Camile Valle; Mosegui, Gabriela Bittencourt Gonzalez; Vianna, Cid Manso de Mello; Costa, Talita Martins Alves da

doi:10.1016/j.htct.2019.01.013

Cited by 27 publications

(14 citation statements)

References 15 publications

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“…The difference in PFS and OS was not significant between groups. This is consistent with the systematic evaluation result of Medawar (33), which was based on populations of the USA, Puerto Rico, and Canada. Studies from the United States and India conducted evaluations on local patients and also demonstrated that there were no significant differences between the two groups in terms of event-free survival and OS (11)(12)(13).…”

Section: Discussionsupporting

confidence: 91%

Efficacy and safety of PEG-asparaginase versus E. coli L-asparaginase in Chinese children with acute lymphoblastic leukemia: a meta-analysis

Dai

Huang

2021

Transl Pediatr

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Background: Multiagent chemotherapy is the primary treatment for acute lymphoblastic leukemia (ALL), of which asparaginases including Escherichia coli L-asparaginase (E. coli L-Asp) and pegylated-asparaginase (PEG-Asp), are cornerstone components. The study aimed to conduct a meta-analysis to compare the efficacy and safety of PEG-Asp with E. coli L-Asp in Chinese children with ALL. Methods: A systematic literature search was conducted to collect randomized controlled trials (RCTs) on PEG-Asp versus E. coli L-Asp in Chinese children with ALL. Two reviewers independently selected articles and extracted data. Risk-of-bias assessment was conducted with Cochrane recommendation tool. Pooled estimates and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for all outcomes in Review Manager 5.3. Results: Out of the 470 publications screened, 15 studies were included, involving 1,194 patients. Pooled estimates showed that there were no significant differences in complete responses (CR), overall response rate (ORR), gastrointestinal symptoms, and coagulation abnormalities rate between the PEG-Asp and E. coli L-Asp groups (all P>0.05). Hypersensitivity (RR =0.63; 95% CI, 0.40-1.01; Ρ=0.05) and hepatic injury rate (RR =0.45; 95% CI, 0.27-0.75; Ρ=0.002) were lower in the PEG-Asp group. The frequency of administration and length of hospital stay of patients in the PEG-Asp group were less than those in the E. coli L-Asp group (both Ρ<0.0001).Conclusions: Current evidence pointed out a similar efficacy in the two groups. The PEG-Asp group showed a lower hypersensitivity and hepatic injury rate. In addition, using PEG-Asp decreased the frequency of administration and the length of hospital stay, which, to some extent, might reduce patients' burden caused by medical resource consumption.

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Section: Discussionsupporting

confidence: 91%

Efficacy and safety of PEG-asparaginase versus E. coli L-asparaginase in Chinese children with acute lymphoblastic leukemia: a meta-analysis

Dai

Huang

2021

Transl Pediatr

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“…The serendipitous detection of strong antileukemic properties of guinea pig serum 2 was attributed by Broom et al 3 to L-asparaginase activity, and indeed low (μM) K m bacterial asparaginases (Class 1 in revised classification 4 ) of type II 5 , notably E. coli EcAII, but not type I (e.g. EcAI with mM K m 6 ) became potent drugs in the treatment of acute lymphoblastic leukemia (ALL) 7 . Later, it was realized that plants possess different, Ntn-type, asparaginases (some of which, e.g.…”

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confidence: 99%

Crystal structures of the elusive Rhizobium etli l-asparaginase reveal a peculiar active site

et al. 2021

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Rhizobium etli, a nitrogen-fixing bacterial symbiont of legume plants, encodes an essential l-asparaginase (ReAV) with no sequence homology to known enzymes with this activity. High-resolution crystal structures of ReAV show indeed a structurally distinct, dimeric enzyme, with some resemblance to glutaminases and β-lactamases. However, ReAV has no glutaminase or lactamase activity, and at pH 9 its allosteric asparaginase activity is relatively high, with Km for l-Asn at 4.2 mM and kcat of 438 s−1. The active site of ReAV, deduced from structural comparisons and confirmed by mutagenesis experiments, contains a highly specific Zn2+ binding site without a catalytic role. The extensive active site includes residues with unusual chemical properties. There are two Ser-Lys tandems, all connected through a network of H-bonds to the Zn center, and three tightly bound water molecules near Ser48, which clearly indicate the catalytic nucleophile.

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“…Moreover, L-ASP formulation was believed to affect the treatment outcome, and it was replaced by PEG-ASP that has a longer half-life and is potentially less immunogenic. However, recent research shows that L-ASP and PEG-ASP demonstrate similar efficacy and safety [57]. Place et al [58] reported that with a median follow-up of 6.0 years, the 5-year OS was 89% (95% CI = 85-93) for L-ASP and 90% (95% CI = 85-93) for PEG-ASP (P = 0.58).…”

Section: Discussionmentioning

confidence: 99%

St. Jude Total Therapy studies from I to XVII for childhood acute lymphoblastic leukemia: a brief review

Omar

Basiouny²,

Elnoby

et al. 2022

J Egypt Natl Canc Inst

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The therapy design of childhood acute lymphoblastic leukemia (ALL) has evolved over the past 60 years. The St. Jude Children’s Research Hospital has developed 17 treatment protocols from 1962 to 2017, aiming to have the most effective and least toxic treatment form. This review summarizes each protocol’s objectives, inclusion criteria, treatment phases, pharmacological agents, irradiation therapy, response criteria, risk stratification, type of relapse, and overall survival. The enhancement and successful application of preventive therapy for ALL and following a risk-stratified approach have progressively improved the cure rate of childhood ALL, with relatively few adverse sequelae. Moreover, St. Jude’s scientific theme serves as a reminder of the principal factor of research directed to a catastrophic disease such as ALL.

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PEG-asparaginase and native Escherichia coli L-asparaginase in acute lymphoblastic leukemia in children and adolescents: a systematic review

Cited by 27 publications

References 15 publications

Efficacy and safety of PEG-asparaginase versus E. coli L-asparaginase in Chinese children with acute lymphoblastic leukemia: a meta-analysis

Efficacy and safety of PEG-asparaginase versus E. coli L-asparaginase in Chinese children with acute lymphoblastic leukemia: a meta-analysis

Crystal structures of the elusive Rhizobium etli l-asparaginase reveal a peculiar active site

St. Jude Total Therapy studies from I to XVII for childhood acute lymphoblastic leukemia: a brief review

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