Comparison of hypersensitivity rates to intravenous and intramuscular PEG‐asparaginase in children with acute lymphoblastic leukemia: A meta‐analysis and systematic review

Abstract

Background: Pegylated-asparaginase (PEG-ASP) is a critical treatment for pediatric acute lymphoblastic leukemia (ALL) and has traditionally been delivered via intramuscular (IM) injection. In an attempt to reduce pain and anxiety, PEG-ASP has increasingly been delivered via intravenous (IV) administration. The study objective was to perform a meta-analysis and systematic review to compare and generate pooled hypersensitivity rates for IM and IV PEG-ASP. Methods:A systematic literature search was conducted for all epidemiological studies that investigated IV and IM hypersensitivity rates for pediatric ALL. Included studies were critically appraised using the GRACE checklist. Pooled estimates and odds ratios with 95% confidence intervals (CIs) for IM and IV hypersensitivity rates were derived based on either a random or fixed effects model. Results:Four studies satisfied the inclusion criteria and were of adequate quality. The random effects pooled hypersensitivity rates were 23.5% (95% CI 14.7-33.7) and 8.7% (95% CI 5.4-12.8) for IV and IM, respectively. The fixed effects pooled odds ratio after adjusting for publication bias was 2.49 (95% CI 1.62-3.83), indicating a significantly higher risk of hypersensitivity for IV over IM PEG-ASP. This risk is far more pronounced for high-risk (HR) patients compared with standardrisk (SR) patients (IV vs. IM: HR ↑35.2% and SR ↓2.9%). Conclusions:Although administering PEG-ASP through IV is preferable for patients, it poses a significantly higher risk of hypersensitivity when compared with IM administration, especially for HR patients. We recommend pediatric oncologists consider treating patients with HR pediatric ALL with IM PEG-ASP to reduce the risk of hypersensitivity. K E Y W O R D Sacute lymphoblastic leukemia, hypersensitivity, intramuscular, intravenous, meta-analysis, PEGasparaginase Abbreviations: ALL, acute lymphoblastic leukemia; B-ALL, B-cell acute lymphoblastic

Reply to: Comment on: Comparison of hypersensitivity rates to intravenous and intramuscular PEG‐asparaginase in children with acute lymphoblastic leukemia: A meta‐analysis and systematic review

“…However, as Dholaria and colleagues, along with others, have demonstrated, the rate of hypersensitivity is confounded by risk type among other factors. This has been detailed in our manuscript and in other reviews …”

“…We thank Dholaria and colleagues for their letter in response to our manuscript titled, “ Comparison of Hypersensitivity Rates to Intravenous and Intramuscular PEG‐Asparaginase in Children with Acute Lymphoblastic Leukemia: A meta‐analysis and systematic review .”…”

“…Meta‐analysis of hypersensitivity rates summarizing absolute risk difference for IV versus IM route of administration of pegylated asparaginase for the treatment of pediatric acute lymphoblastic leukemia. Panel A reflects the meta‐analysis without the inclusion of data reported by Dholaria and colleagues (i.e., data included in our manuscript) . Please note the data from the MacDonald (2016) study remains unchanged from the data presented in their abstract published in 2014, which was included in our manuscript .…”

“…Panel A reflects the meta‐analysis without the inclusion of data reported by Dholaria and colleagues (i.e., data included in our manuscript) . Please note the data from the MacDonald (2016) study remains unchanged from the data presented in their abstract published in 2014, which was included in our manuscript . Panel B reflects the meta‐analysis with inclusion of data reported by Dholaria and colleagues…”

Clinical Characteristics of Intravenous PEG-Asparaginase Hypersensitivity Reactions in Patients Undergoing Treatment for Acute Lymphoblastic Leukemia

“…Rates of clinical hypersensitivity to E. coli asparaginase generally range from 10–30%, and rates of 3–24% have been reported with PEG-asparaginase (Vrooman et al, 2010). Children receiving PEG-asparaginase IV have been found to have a greater risk of hypersensitivity than intramuscular (IM) administration (Hasan, Shaikh, Rassekh, Howard, & Goddard, 2017), but the time to IV PEG-asparaginase reaction onset has not been extensively studied. This lack of evidence creates challenges for nurses caring for patients receiving IV PEG-asparaginase, as the ideal post-infusion monitoring time has not been established (Woods et al, 2017).…”