key: cord-0933522-x1p5ysjz
authors: Zarnegar‐Lumley, Sara; Stone, Cosby A.; Smith, Christine M.; Hall, Laura L.; Luck, Kate E.; Koo, Grace; Plager, Jessica H.; Phillips, Elizabeth J.; Friedman, Debra L.
title: Oncologist counseling practice and COVID‐19 vaccination outcomes for patients with history of PEG‐asparaginase hypersensitivity
date: 2022-03-30
journal: Pediatr Blood Cancer
DOI: 10.1002/pbc.29686
sha: c21bb83b74f8d03cfd447b6d5fe9a0d1bae991f2
doc_id: 933522
cord_uid: x1p5ysjz

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an effective strategy to prevent serious coronavirus disease 2019 (COVID‐19) and is important for oncology patients. mRNA‐based COVID‐19 vaccines are contraindicated in those with a history of severe or immediate allergy to any vaccine component, including polyethylene glycol (PEG)2000. Patients with acute lymphoblastic leukemia/lymphoma receive asparaginase conjugated to PEG5000 (PEG‐ASNase) and those with PEG‐ASNase‐associated hypersensitivity may be unnecessarily excluded from receiving mRNA COVID‐19 vaccines. We, therefore, surveyed oncologists on COVID‐19 vaccine counseling practice and vaccination outcomes in COVID‐19 vaccination‐eligible patients and show safe receipt of mRNA vaccines despite PEG‐ASNase hypersensitivity.

Concern for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with cancer and impaired immunity is significant and warranted. [10] [11] [12] Primary vaccination with mRNA coronavirus disease 2019 vaccines manufactured by Pfizer-BioN-Tech 13 and Moderna 14 has led to significantly reduced severity of COVID-19 illness and death. 15 However, these vaccines contain a PEG formulation, PEG2000, to stabilize the lipid nanoparticle carrier molecule for the mRNA spike protein construct. 16 PEG was hypothesized to be a potential allergen in previously sensitized patients in early reports of anaphylaxis to mRNA COVID-19

vaccines. 17 The Centers for Disease Control and Prevention includes severe or immediate allergic reaction of any severity to a component of the COVID-19 vaccine as a contraindication to vaccine administration. 18 This raised concern about the safety of mRNA COVID-19 vaccines in patients with prior PEG-ASNase hypersensitivity. The American Society of Hematology recommended patient referral for skin testing to PEG to determine safety of mRNA vaccine administration. 19 Recently published consensus recommendations from a multidisciplinary panel of experts in anaphylaxis management advise against prevaccination excipient skin testing outside of the research setting, given the unknown exact cause of hypersensitivity and variable predictive value of skin testing. 20 In a recent study from Vanderbilt University Medical Center (VUMC) and Texas Children's Hospital, 19 patients with a prior designation of PEG-ASNase allergy were referred to allergy clinics; 14 patients had skin testing performed, yielding negative results with subsequent safe administration of mRNA COVID-19 vaccine. 7 Five patients had previously tolerated oral laxative, PEG3350, so no skin testing was performed and there was no reaction to vaccine. 7 The Hospital for Sick Children implemented a screening questionnaire to assess PEG-ASNase allergy severity or reaction to PEG3350. 21 One allergy referral was made for a patient with PEG-ASNase and PEG3350 hypersensitivity; the remaining 32 PEG-ASNase-allergic patients received vaccine under medical observation without skin testing, and no allergic reaction was reported. 21 The aim of our study was to better understand oncologists' vaccine counseling and referral practices for patients with prior PEG-ASNase hypersensitivity and to report any allergic reactions to vaccine. This study was approved by the VUMC Institutional Review Board. 

Seventy-five responses were entered into the database, with two ineligible entries due to patient age <12 years. Characteristics of patients and PEG-ASNase hypersensitivity reactions are described (Table 1) .

COVID-19 vaccine counseling and administration practice are described in Table 2 

Due to the presence of PEG in mRNA COVID-19 vaccines, pediatric oncologists are faced with how best to counsel patients with prior PEG-ASNase hypersensitivity. Our study, which included patients 12 years and older, indicated that the majority of patients were Abbreviations: mRNA, m-ribonucleic acid; PEG, polyethylene glycol. a One response was not provided to question "vaccine received?" b Non-mRNA: Johnson & Johnson/Janssen. c mRNA (Pfizer-BioNTech n = 39, Moderna n = 3).

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