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1.
J Allergy Clin Immunol ; 148(1): 91-95, 2021 07.
Article in English | MEDLINE | ID: covidwho-1291943

ABSTRACT

BACKGROUND: The mechanisms underpinning allergic reactions to the BNT162b2 (Pfizer) COVID-19 vaccine remain unknown, with polyethylene glycol (PEG) contained in the lipid nanoparticle suspected as being the cause. OBJECTIVE: Our aim was to evaluate the performance of skin testing and basophil activation testing to PEG, polysorbate 80, and the BNT162b2 (Pfizer) and AZD1222 (AstraZeneca) COVID-19 vaccines in patients with a history of PEG allergy. METHODS: Three known individuals with PEG allergy and 3 healthy controls were recruited and evaluated for hypersensitivity to the BNT162b2 and AZD1222 vaccines, and to related compounds by skin testing and basophil activation, as measured by CD63 upregulation using flow cytometry. RESULTS: We found that the BNT162b2 vaccine induced positive skin test results in patients with PEG allergy, whereas the result of traditional PEG skin testing was negative in 2 of 3 patients. One patient was found to be cosensitized to both the BNT162b2 and AZD1222 vaccines because of cross-reactive PEG and polysorbate allergy. The BNT162b2 vaccine, but not PEG alone, induced dose-dependent activation of all patients' basophils ex vivo. Similar basophil activation could be induced by PEGylated liposomal doxorubicin, suggesting that PEGylated lipids within nanoparticles, but not PEG in its native state, are able to efficiently induce degranulation. CONCLUSIONS: Our findings implicate PEG, as covalently modified and arranged on the vaccine lipid nanoparticle, as a potential trigger of anaphylaxis in response to BNT162b2, and highlight shortcomings of current skin testing protocols for allergy to PEGylated liposomal drugs.


Subject(s)
Anaphylaxis/immunology , Basophils/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Doxorubicin/analogs & derivatives , Drug Hypersensitivity/immunology , Nanoparticles/adverse effects , Polyethylene Glycols/adverse effects , SARS-CoV-2/physiology , Adult , Cell Degranulation , Cells, Cultured , Doxorubicin/adverse effects , Doxorubicin/chemistry , Female , Humans , Lipids/chemistry , Male , Middle Aged , Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Skin Tests , Young Adult
2.
Ann Hematol ; 99(11): 2589-2598, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-746148

ABSTRACT

The induction therapy containing ixazomib, an oral proteasome inhibitor, has shown favorable efficacy and safety in clinical trials, but its experience in real-life remains limited. In routine practice, few patients received ixazomib-based induction therapy due to reasons including (1) patients' preference on oral regimens, (2) concerns on adverse events (AEs) of other intravenous/subcutaneous regimens, (3) requirements for less center visits, and (4) fears of COVID-19 and other infectious disease exposures. With the aim of assessing the real-life effectiveness and safety of ixazomib-based induction therapy, we performed this multi-center, observational study on 85 newly diagnosed multiple myeloma (NDMM) patients from 14 medical centers. Ixazomib-based regimens included ixazomib-lenalidomide-dexamethasone (IRd) in 44.7% of patients, ixazomib-dexamethasone (Id) in 29.4%, and Id plus another agent (doxorubicin, cyclophosphamide, thalidomide, or daratumumab) in 25.9%. Different ixazomib-based therapies were applied due to (1) financial burdens or limitations on local health insurance coverage, (2) concerns on treatment tolerance, and (3) drug accessibility issue. Ten patients received ixazomib maintenance. The median age was 67 years; 43.5% had ISS stage III disease; 48.2% had an Eastern Cooperative Oncology Group performance score ≥ 2; and 17.6% with high-risk cytogenetic abnormalities. Overall response rate for all 85 patients was 95.3%, including 65.9% very good partial response or better and 29.5% complete responses. The median time to response was 30 days. The response rate was similar across different ixazomib-based regimens. Median progression-free survival was not reached. Severe AEs (≥ grade 3) were reported in 29.4% of patients. No grade 3/4 peripheral neuropathy (PN) occurred. Patients received a median of 6 (range 1-20) cycles of ixazomib treatment; 56.6% remained on treatment at data cutoff; 15.3% discontinued treatment due to intolerable AEs. These results support that the ixazomib-based frontline therapy was highly effective with acceptable toxicity in routine practice and the ixazomib oral regimens could be good alternative options for NDMM patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Boron Compounds/administration & dosage , Glycine/analogs & derivatives , Multiple Myeloma/drug therapy , Peripheral Nervous System Diseases/chemically induced , Adolescent , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Boron Compounds/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Drug Administration Schedule , Female , Glycine/administration & dosage , Glycine/adverse effects , Humans , Lenalidomide/administration & dosage , Lenalidomide/adverse effects , Male , Middle Aged , Multiple Myeloma/mortality , Multiple Myeloma/pathology , Neoplasm Staging , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/physiopathology , Remission Induction , Survival Analysis , Thalidomide/administration & dosage , Thalidomide/adverse effects , Treatment Outcome
3.
Br J Haematol ; 191(3): 386-389, 2020 11.
Article in English | MEDLINE | ID: covidwho-697165

ABSTRACT

The COVID-19 pandemic has dramatically challenged care for cancer patients, especially those with active treatment who represent a vulnerable population for SARS-CoV-2 infection. Aggressive lymphoid neoplasms, such as diffuse large B cell lymphoma and high-grade B cell lymphoma, need to be treated without delay in order to get the best disease outcome. Because of that, our clinical practice was changed to minimise the risk of SARS-CoV-2 infection while continuing haematological treatment. In this report, we analyse the management of front-line therapy in 18 patients during the COVID-19 outbreak, as well as the results of the implemented measures in their outcome.


Subject(s)
COVID-19/epidemiology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Pandemics , Plasmablastic Lymphoma/drug therapy , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , Bacterial Infections/complications , Bacterial Infections/drug therapy , COVID-19/complications , COVID-19/drug therapy , COVID-19/prevention & control , COVID-19 Testing , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Febrile Neutropenia/chemically induced , Febrile Neutropenia/prevention & control , Female , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Infection Control/methods , Male , Middle Aged , Prednisone/administration & dosage , Prednisone/adverse effects , Rituximab/administration & dosage , Spain/epidemiology , Superinfection/drug therapy , Vincristine/administration & dosage , Vincristine/adverse effects
4.
Transpl Infect Dis ; 22(6): e13367, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-596059

ABSTRACT

The clinical course and outcomes of immunocompromised patients, such as transplant recipients, with COVID-19 remain unclear. It has been postulated that a substantial portion of the disease burden seems to be mediated by the host immune activation to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we present a simultaneous heart-kidney transplant (SHKT) recipient who was hospitalized for the management of respiratory failure from volume overload complicated by failure to thrive, multiple opportunistic infections, and open non-healing wounds in the setting of worsening renal dysfunction weeks prior to the first case of SARS-CoV-2 being detected in the state of Connecticut. After his third endotracheal intubation, routine nucleic acid testing (NAT) for SARS-CoV-2, in anticipation of a planned tracheostomy, was positive. His hemodynamics, respiratory status, and ventilator requirements remained stable without any worsening for 4 weeks until he had a negative NAT test. It is possible that the immunocompromised status of our patient may have prevented significant immune activation leading up to clinically significant cytokine storm that could have resulted in acute respiratory distress syndrome and multisystem organ failure.


Subject(s)
COVID-19/immunology , Cardiomyopathy, Dilated/surgery , Heart Transplantation , Immunocompromised Host/immunology , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Transplantation , Malnutrition/immunology , Opportunistic Infections/immunology , Antibiotics, Antineoplastic/adverse effects , BK Virus , Bacteremia/complications , Bacteremia/immunology , COVID-19/complications , COVID-19 Nucleic Acid Testing , Cardiomyopathy, Dilated/chemically induced , Cardiomyopathy, Dilated/complications , Cardiotoxicity , Doxorubicin/adverse effects , Graft Rejection/prevention & control , Gram-Positive Bacterial Infections/complications , Gram-Positive Bacterial Infections/immunology , Humans , Incidental Findings , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Malnutrition/complications , Methicillin-Resistant Staphylococcus aureus , Middle Aged , Mycophenolic Acid/therapeutic use , Opportunistic Infections/complications , Polyomavirus Infections/complications , Polyomavirus Infections/immunology , Postoperative Complications/therapy , Prednisone/therapeutic use , Renal Dialysis , SARS-CoV-2 , Staphylococcal Infections/complications , Staphylococcal Infections/immunology , Surgical Wound Infection/complications , Surgical Wound Infection/immunology , Tacrolimus/therapeutic use , Tracheostomy , Tumor Virus Infections/complications , Tumor Virus Infections/immunology , Vancomycin-Resistant Enterococci , Viremia/complications , Viremia/immunology , Water-Electrolyte Imbalance/complications , Water-Electrolyte Imbalance/therapy
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