Search

Hypersensitivity reactions (HSRs) to chemotherapy may prevent patients from receiving the most effective therapy. This review was undertaken to identify evidence-based preventive premedication strategies that reduce the likelihood of HSR in the first instance and improve the safety of subsequent infusions in patients who have demonstrated HSR to a certain class of chemotherapy. PubMed was searched until October 2021 using the key words: "hypersensitivity to chemotherapeutic drugs," "hypersensitivity to antineoplastic agents," "taxanes hypersensitivity," "platinum compound hypersensitivity," "premedication," "dexamethasone," "prednisone," "hydrocortisone," "antihistamine," "diphenhydramine," "cetirizine," "famotidine," "meperidine," "aspirin," "ibuprofen," and "montelukast." The search was restricted to articles published in English. A total of 73 abstracts were selected for inclusion in the review. Most premedication regimens have been derived empirically rather than determined through randomized trials. Based on the available evidence, we provide an update on likely HSR mechanisms and a practical guide for classifying systemic HSR. The evidence indicates that a combination of prevention strategies using newer antihistamines, H2 antagonists, leukotriene receptor antagonists, and corticosteroids and other interventions used judiciously reduces the occurrence and severity of HSR and improves safety.

Messenger RNA coronavirus disease 2019 (COVID-19) vaccines have been associated with allergic reactions. A history of anaphylaxis has been suggested as a risk factor for such reactions. Polyethylene glycol (PEG) has been proposed as a possible culprit allergen.To investigate possible PEG or polysorbate allergy among patients reporting prior reactions to COVID-19 vaccines or PEG and to report their subsequent tolerance of COVID-19 vaccines.From January 1, 2021, to October 31, 2021, adult patients referred to the McGill University Health Centre allergy clinics who were considered at risk of anaphylaxis were prospectively recruited. The entry criteria were any documented history of reaction to a COVID-19 vaccine or reported allergy to PEG or polysorbate. Evaluated patients underwent skin prick testing (SPT) with PEG and polysorbate. After SPT, placebo-controlled vaccine challenges were carried out.Of the 44 patients recruited, 40 (90.1%) had reacted to the first vaccine dose, with 18 (45%) of them had anaphylactic reaction. All patients underwent SPT and 5 (11.3%) had a positive test result. A total of 39 patients (88.6%) underwent COVID-19 vaccine challenge at the allergy clinic. Most tolerated the vaccine, with 18 (40.1%) received a single full dose, 20 (45.4%) 2 split doses, and 6 (13.6%) a graded dosing protocol. Of the 40 patients who reacted to the first dose, 2 had immediate nonsevere allergic reactions to the second dose.In this cohort of patients with a history of anaphylaxis and increased risk of allergic reactions to the COVID-19 vaccines, after allergist evaluation, including negative PEG skin testing result, the vaccine was safely administered without any serious adverse events.

BACKGROUND: The tumor necrosis family factor receptor (TNFR) family member 4-1BB (CD137) is encoded by TNFRSF9 and expressed on activated T cells. 4-1BB provides a co-stimulatory signal that enhances CD8(+) T cell survival, cytotoxicity, and mitochondrial activity, thereby promoting immunity against viruses and tumors. The ligand for 4-1BB (4-1BBL) is expressed on antigen-presenting cells and Epstein-Barr virus (EBV) transformed B cells. OBJECTIVE: We investigated the genetic basis of recurrent sino-pulmonary infections, persistent EBV viremia, and EBV-induced lymphoproliferation in two unrelated patients. METHODS: Whole exome sequencing, immunoblotting, immunophenotyping, and in vitro assays of lymphocyte and mitochondrial function were performed. RESULTS: The two patients shared a homozygous G109S missense mutation in 4-1BB that abolished protein expression and ligand binding. The patients’ CD8(+) T cells had reduced proliferation, impaired expression of interferon-γ (IFN-γ) and perforin, and diminished cytotoxicity against allogeneic and HLA matched EBV-B cells. Mitochondrial biogenesis, membrane potential, and function were significantly reduced in the patients’ activated T cells. An inhibitory antibody against 4-1BB recapitulated the patients’ defective CD8(+) T cell activation and cytotoxicity against EBV-infected B cells in vitro. CONCLUSION: This novel immunodeficiency demonstrates the critical role of 4-1BB co-stimulation in host immunity against EBV infection.