SOHO State of the Art Updates and Next Questions: Management of Asparaginase Toxicity in Adolescents and Young Adults with Acute Lymphoblastic Leukemia

Schmiegelow, Kjeld; Rank, Cecilie Utke; Stock, Wendy; Dworkin, Emily; Sluis, Inge van der

doi:10.1016/j.clml.2021.07.009

Cited by 15 publications

(15 citation statements)

References 137 publications

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“…Unfortunately, some patients have notable hypersensitivity reactions to the L‐ASNase enzyme, due to its bacterial origin, and it becomes necessary to change the formulation 14 . Diverse sources of the microbial enzyme have been implemented, and currently, three are commercially available for treating patients (native E. coli L‐ASNases, E. coli PEG‐L‐ASNase, and E. chrysanthemi L‐ASNases) 15 .…”

Section: Discussionmentioning

confidence: 99%

An acute lymphoblastic leukemia cell‐based preclinical assay revealed functional differences between commercial brands of L‐asparaginase administered in Colombia

Reyes

Agudelo

Silva

et al. 2023

Pediatric Blood & Cancer

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Background: L-asparaginase (L-ASNase) is an essential component of chemotherapy strategies due to its differential action between normal and leukemic cells. Recently, concerns about the efficiency of commercial formulations administered in developing countries have been reported, and available methods have limitations for directly determining the quality of the formulation of the medications. Procedure:We developed a cell-based protocol to analyze the activity of different L-ASNase formulations used in Colombia to induce apoptosis of the NALM-6 cell line after 24, 48, and 72 hours, using flow cytometry. Then we compared results and determined the statistically significant differences.Results: Three statistically different groups, ranging from full to no activity against leukemic cells, using 0.05, 0.5, and 5.0 IU/ml concentrations, were identified. Group 1 (asparaginase codified [ASA]2-4) exhibited very low to no activity against B-cell acute lymphoblastic leukemia (B-ALL) cells. Group 2 (ASA6) exhibited intermediate-level activity, and group 3 (ASA1 and ASA5) exhibited high activity.Conclusions: Differences found between the therapeutic formulations of L-ASNase distributed in Colombia raise concerns about the quality of the treatment administered to patients in low-and middle-income countries. Therefore, we recommend a preclinical evaluation of formulations of L-ASNase in order to prevent therapeutical impacts on the outcome of ALL patients.

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Section: Discussionmentioning

confidence: 99%

An acute lymphoblastic leukemia cell‐based preclinical assay revealed functional differences between commercial brands of L‐asparaginase administered in Colombia

Reyes

Agudelo

Silva

et al. 2023

Pediatric Blood & Cancer

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“…Unfortunately, some patients have important allergic reactions to L-ASNase enzyme due to their bacterial origin and it is necessary to change the formulation 11 . Diverse sources of microbial L-ASNase have been implemented and currently three are commercially available to treat patients (Native E. coli L-ASNases,E.…”

Section: Discussionmentioning

confidence: 99%

An acute lymphoblastic leukemia cell-based preclinical assay revealed functional differences of commercial L-asparaginase administered in Colombia

Contreras-Acosta

Reyes

Agudelo

et al. 2022

Preprint

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L-asparaginase (L-ASNase) is an essential component of chemotherapy schemes due to its differential action over normal and leukemic cells. Recently, concerns on the performance of commercial formulations administered in developing countries have been reported. To address this problem, we developed a cell-based protocol to compare the activity of different L-ASNase formulations used in Colombia. We found three statistically different groups, ranging from full to no activity on leukemic cells using 0.05, 0.5 and 5.0 IU/mL concentrations. According to our results, we advise a preclinical evaluation for formulations of L-ASNase distributed in developing countries which could impact the outcome of patients.

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“…22 However, another study showed that the age factor did not significantly cause hepatotoxicity in ALL patients who received asparaginase, but patients who experienced hepatotoxicity tended to be older than those who did not experience toxicity. 6,23 A study reported that hepatotoxicity due to L-asparaginase chemotherapy is related to older age. 24 Obesity was identified as a predictor of hepatotoxicity where obese children have a 2.18-fold risk of developing hepatotoxicity during therapy.…”

Section: Parametermentioning

confidence: 99%

Risk Factors for Hepatotoxicity From L-Asparaginase Chemotherapy In Children With Acute Lymphoblastic Leukemia

Hikmat¹,

Andarsini²,

Setyoboedi³

et al. 2023

Pharmacogn J.

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Introduction: L-asparaginase chemotherapy often causes hepatotoxicity and affects complete remission in pediatric acute lymphoblastic leukemia (ALL). This study aims to investigate the risk factors that affect the incidence of hepatotoxicity caused by L-asparaginase chemotherapy in ALL children. Methods: An observational study with prospective sampling was conducted at Dr. Soetomo Hospital, Surabaya. The inclusion criteria included ALL children aged 1-18 years, undergoing ALL Induction phase chemotherapy based on the 2018 Indonesian Children's ALL protocol as evidenced by bone marrow aspiration, receiving L-asparaginase chemotherapy, and obtaining written consent from parents or guardians. Each child had 3 ml of blood drawn from a peripheral vein to assess their complete blood count, alanine transaminase (ALT) levels, and albumin level. Results: Thirty-two children with ALL were collected. Two of them were excluded due to allergic reaction and enable to continue the L-asparaginase chemotherapy. Thirty of them were eligible participants. Approximately 53.3% of ALL children aged ≤ seven years. Fourteen (47%) children with ALL were included in the standard-risk group and 16 (53%) of them included high-risk group. There were significant differences in ALT levels between the four stages of observation (p=<0.001). Twenty-two ALL children had hepatotoxicity (73.3%), while 8 had non-hepatotoxicity (26.7%). Two risk factors had a significant influence on the occurrence of hepatotoxicity due to L-asparaginase chemotherapy including age and hypoalbuminemia (p=0.045, p=0.028). Conclusion: Age and hypoalbuminemia were the risk factors that might affect the incidents of hepatotoxicity. Clinical monitoring before and after treatment needs to be done to prevent poor outcomes.

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SOHO State of the Art Updates and Next Questions: Management of Asparaginase Toxicity in Adolescents and Young Adults with Acute Lymphoblastic Leukemia

Cited by 15 publications

References 137 publications

An acute lymphoblastic leukemia cell‐based preclinical assay revealed functional differences between commercial brands of L‐asparaginase administered in Colombia

An acute lymphoblastic leukemia cell‐based preclinical assay revealed functional differences between commercial brands of L‐asparaginase administered in Colombia

An acute lymphoblastic leukemia cell-based preclinical assay revealed functional differences of commercial L-asparaginase administered in Colombia

Risk Factors for Hepatotoxicity From L-Asparaginase Chemotherapy In Children With Acute Lymphoblastic Leukemia

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