Levocarnitine for pegasparaginase-induced hepatotoxicity in acute lymphoblastic leukemia

Trang, Elena; Ngo, Dat; Chen, Jason; Aldoss, Ibrahim; Salhotra, Amandeep; Pullarkat, Vinod

doi:10.1080/10428194.2020.1805108

Cited by 10 publications

(4 citation statements)

References 7 publications

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“…It has been proposed that l -carnitine be incorporated into ALL treatment to reduce hepatotoxic effects in adult ALL. 18 , 19 , 20 However, in a mouse model, it did not reduce asparaginase-associated hepatotoxic effects. 21 IGHMBP2 was initially discovered to bind to the immunoglobulin mu chain switch (S mu) region, 22 but its function related to IgM has not been well established.…”

Section: Discussionmentioning

confidence: 91%

Association of Inherited Genetic Factors With Drug-Induced Hepatic Damage Among Children With Acute Lymphoblastic Leukemia

et al. 2022

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ImportanceAcute lymphoblastic leukemia (ALL) is the most common childhood cancer. Hepatotoxic effects, including hyperbilirubinemia and elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, are common during all phases of therapy and are linked to several chemotherapeutic agents, including asparaginase, mercaptopurine, and methotrexate.ObjectiveTo determine which genetic variants were associated with hyperbilirubinemia and elevated ALT and AST levels in children, adolescents, and young adults treated for ALL.Design, Setting, and ParticipantsThis retrospective analysis of a multiethnic genome-wide association study was conducted between January 1, 2019, and April 15, 2022, including patients treated as part of Children’s Oncology Group (COG) trials with centers in the United States, Canada, and Australia, which accrued data from December 29, 2003, to January 21, 2011 (AALL0232), and from January 22, 2007, to July 24, 2014 (AALL0434). Germline genotypes were interrogated using genome-wide arrays and imputed using a National Institutes of Health TOPMed Imputation server. Mixed-effects logistic regressions were used to account for multiple episodes for an individual patient. Genotype × treatment phase interaction was tested to uncover phase-specific genetic risk factors.ExposuresTotal duration of multiagent protocol chemotherapy ranging from 2.5 to 3.5 years.Main Outcomes and MeasuresThe primary outcomes were National Cancer Institute Common Terminology Criteria for Adverse Events (version 4) hyperbilirubinemia of grade 3 or higher and elevated liver ALT and AST levels.ResultsA total of 3557 participants were included in the analysis (2179 [61.3%] male; median age, 11.1 [range, 1-30] years). Among 576 known variants associated with these liver function test results in the general population, UGT1A1 variant rs887829 and PNPLA3 variant rs738409 were associated with increased risk of hyperbilirubinemia (odds ratio [OR], 2.18 [95% CI, 1.89-2.53]; P = 6.7 × 10−27) and ALT and AST levels (OR, 1.27 [95% CI, 1.15-1.40]; P = 3.7 × 10−7), respectively, during treatment for ALL. Corresponding polygenic risk scores were associated with hepatotoxic effects across all therapy phases and were largely driven by UGT1A1 and PNPLA3 variants. Genome-wide association analysis revealed an age-specific variant near the CPT1A gene that was only associated with elevated ALT and AST levels among patients younger than 10 years (OR, 1.28 [95% CI, 1.18-1.39]; P = 8.7 × 10−10).Conclusions and RelevanceThese results suggest a strong genetic basis for interpatient variability in hyperbilirubinemia and aminotransferase level elevations during leukemia chemotherapy.

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Section: Discussionmentioning

confidence: 91%

Association of Inherited Genetic Factors With Drug-Induced Hepatic Damage Among Children With Acute Lymphoblastic Leukemia

et al. 2022

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“…Compared with control groups, the pooled effect results of AST ( I 2 = 89%, P -value < 0.00001, MD = −9.42 IU L −1 , 95% CI: −21.64 to 2.80) and ALT ( I 2 = 96%, P -value < 0.00001, MD = −16.28 IU L −1 , 95% CI: −33.57 to 1.00) were not significantly different. For AST and ALT, the removal of one trial with higher risk bias 29 in influence analysis did not improve the significance of the pooled effects of AST (MD = −11.05 IU L −1 , 95% CI: −23.08 to 0.99), but the pooled effects of ALT (MD = −19.71 IU L −1 , 95% CI: −36.45 to −2.96) had significant differences following the removal (Fig. 5).…”

Section: Resultsmentioning

confidence: 99%

“…13 out of the 15 studies were RCTs, while 2 were retro-spective studies. 28,29 These trials were carried out in different countries including Iran, Korea, Italy, China, Sweden, and USA. The total number of participants was 1452 individuals, mean age ranged from 30 to 60 years old, including 619 individuals with intervention and 833 in the control group.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

Effects of l-carnitine supplementation on glucolipid metabolism: a systematic review and meta-analysis

Xie

Qiu

et al. 2023

Food Funct.

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“…These results indicate that L-carnitine effectively enhanced immune function of the patients, and improved their quality of life. These outcomes might be attributed to the fact that Lcarnitine enhanced the immune function of patients, thereby reducing the side effects of hemodialysis, and improving the quality of life of patients [16].…”

Section: Discussionmentioning

confidence: 99%

Effect of combined use of L carnitine and hemodialysis on clinical efficacy and quality of life of uremic patients

Liu¹,

Zhang²

2022

Trop. J. Pharm Res

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Purpose: To investigate the clinical efficacy of combined use of L-carnitine and hemodialysis in the treatment of uremic patients, and its effect on their quality of life. Methods: A total of 160 uremic patients who were admitted to Lujiang County People's Hospital from November 2018 to August 2020 were selected and divided equally into dialysis group (hemodialysis), and combined group (L-carnitine + hemodialysis). Some clinical indices and parameters, including safety profile, National Institutes of Health Stroke Scale (NIHSS) score, CD4+ and CD4+/CD8+, and plasma protein levels were evaluated for both study groups. Results: Patients treated with L-carnitine + hemodialysis in the combined group resulted in significantly higher clinical treatment effectiveness than those in the dialysis group (p < 0.05). However, safety profiles were comparable in the two groups (p > 0.05). No significant difference in NIHSS score between the two groups before treatment, but L-carnitine + hemodialysis led to a better NIHSS score than in the dialysis group after treatment (p < 0.05). However, there were better levels of CD4+ and CD4+/CD8+ in the combined group than in the dialysis group (p < 0.05). Similarly, although pre-treatment plasma protein levels in the two groups were comparable, there were significantly lower plasma protein levels in the combined group than in the dialysis group post-treatment (p < 0.05). Conclusion: The combination of L-carnitine and hemodialysis in the treatment of uremia patients improves the clinical management of the patients, enhances their quality of life, and shows good safety profile. However, further clinical trials should be carried out prior to the application of the combined treatment in clinical practice.

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Levocarnitine for pegasparaginase-induced hepatotoxicity in acute lymphoblastic leukemia

Cited by 10 publications

References 7 publications

Association of Inherited Genetic Factors With Drug-Induced Hepatic Damage Among Children With Acute Lymphoblastic Leukemia

Association of Inherited Genetic Factors With Drug-Induced Hepatic Damage Among Children With Acute Lymphoblastic Leukemia

Effects of l-carnitine supplementation on glucolipid metabolism: a systematic review and meta-analysis

Effect of combined use of L carnitine and hemodialysis on clinical efficacy and quality of life of uremic patients

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