title: Comparison of hypersensitivity rates to intravenous and intramuscular PEG-asparaginase in children with acute lymphoblastic leukemia: A meta-analysis and systematic review.
abstract: 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.
  
  
  
  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.
  
  
  
  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 standard-risk (SR) patients (IV vs. IM: HR ↑35.2% and SR ↓2.9%).
  
  
  
  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.
authors: Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada.
authors: Haroon
authors: H
authors: Hasan
authors: Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors: Omar Mohammad
authors: OM
authors: Shaikh
authors: Division of Oncology/Hematology/BMT, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.|Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Shahrad Rod
authors: SR
authors: Rassekh
authors: School of Nursing, Faculty of Applied Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors: A Fuchsia
authors: AF
authors: Howard
authors: Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada.|Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Karen
authors: K
authors: Goddard
mesh_terms: D061605:Administration, Intravenous / Q000009:adverse effects*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000209:etiology*; D006801:Humans; D007273:Injections, Intramuscular / Q000009:adverse effects*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011379:Prognosis
chemical_list: D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase
keywords: PEG-asparaginase; acute lymphoblastic leukemia; hypersensitivity; intramuscular; intravenous; meta-analysis