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1.
Visentin, Andrea, Scarfò, Lydia, Chatzikonstantinou, Thomas, Kapetanakis, Anargyros, Demosthenous, Christos, Karakatsoulis, Georgios, Andres, Martin, Antic, Darko, Allsup, David, Baile, Mónica, Bron, Dominique, Capasso, Antonella, Catherwood, Mark, Collado, Rosa, Cordoba, Raul, Cuéllar-García, Carolina, Delgado, Julio, Dimou, Maria, Doubek, Michael, De Paoli, Lorenzo, De Paolis, Maria Rosaria, Del Poeta, Giovanni, Efstathopoulou, Maria, Shimaa, El-Ashwah, Enrico, Alicia, Farina, Lucia, Ferrari, Angela, Foglietta, Myriam, Furstenau, Moritz, Garcia-Marco, Jose A.; Gentile, Massimo, Gimeno, Eva, Maria, Gomes da Silva, Gutwein, Odit, Hakobyan, Yervand, Herishanu, Yair, Hernandez, jose Angel, Herold, Tobias, Iyengar, Sunil, Itchaki, Gilad, Jaksic, Ozren, Janssens, Ann, Kalashnikova, Olga, Kalicinska, Elzbieta, Kater, Arnon P.; Kersting, Sabina, Labrador, Jorge, Lad, Deepesh, Laurenti, Luca, Levin, Mark-David, Lista, Enrico, Malerba, Lara, Marasca, Roberto, Marchetti, Monia, Marquet Palomanes, Juan, Mattsson, Mattias, Mauro, Francesca Romana, Mayor-Bastida, Carlota, Morawska, Marta, Motta, Marina, Munir, Talha, Murru, Roberta, Milosevic, Ivana, Miras Calvo, Fatima, Niemann, Carsten Utoft, Olivieri, Jacopo, Orsucci, Lorella, Papaioannou, Maria, Pavlovsky, Miguel Arturo, Piskunova, Inga S.; Pocali, Barbara, Popov, Viola Maria, Quaglia, Francesca Maria, Quaresmini, Giulia, Raa, Doreen te, Reda, Gianluigi, Rigolin, Gian Matteo, Ruchlemer, Rosa, Shrestha, Amit, Šimkovič, Martin, Špaček, Martin, Sportoletti, Paolo, Stanca Ciocan, Oana, Tadmor, Tamar, Vandenberghe, Elisabeth, Varettoni, Marzia, Vitale, Candida, Van Der Spek, Ellen, Van Gelder, Michel, Wasik-Szczepanek, Ewa, Yáñez, Lucrecia, Yassin, Mohamed A.; Coscia, Marta, Eichhorst, Barbara, Rambaldi, Alessandro, Stavroyianni, Niki, Trentin, Livio, Stamatopoulos, Kostas, Ghia, Paolo.
Blood ; 140:2333-2337, 2022.
Article in English | ScienceDirect | ID: covidwho-2120438
3.
Eur J Cancer ; 172: 65-75, 2022 09.
Article in English | MEDLINE | ID: covidwho-1906969

ABSTRACT

IMPORTANCE: Patients with cancer have an increased risk of severe disease and mortality from COVID-19, as the disease and antineoplastic therapy cause reduced vaccine immunogenicity. Booster doses have been proposed to enhance protection, and efficacy data are emerging from several studies. OBJECTIVE: To evaluate the proportion of COVID-19 primary vaccination non-responders with cancer who seroconvert after a booster dose. METHODS: PubMed, EMBASE, CENTRAL and medRxiv were searched from 1st January 2021 to 10th March 2022. Quality was assessed using the Joanna Briggs Institute Critical Appraisal checklist. RESULTS: After the eligibility assessment, 22 studies were included in this systematic review and 17 for meta-analysis of seroconversion in non-responders, pooling a total of 849 patients with haematological cancer and 82 patients with solid cancer. Haematological cancer non-responders exhibited lower seroconversion at 44% (95% CI 36-53%) than solid cancer at 80% (95% CI 69-87%). Individual patient data meta-analysis found the odds of having a meaningful rise in antibody titres to be significantly associated with increased duration between the second and third dose (OR 1.02, 95% CI 1.00-1.03, P ≤ 0.05), age of patient (OR 0.960, 95% CI 0.934-0.987, P ≤ 0.05) and cancer type. With patients with haematological cancer as a reference, patients with lung cancer had 16.8 times the odds of achieving a meaningful increase in antibody titres (OR 16.8, 95% CI 2.95-318, P ≤ 0.05) and gastrointestinal cancer patients had 25.4 times the odds of achieving a meaningful increase in antibody titres (OR 25.4, 95% CI 5.26-492.21, P ≤ 0.05). CONCLUSIONS: administration of a COVID-19 vaccine booster dose is effective in improving seroconversion and antibody levels. Patients with haematological cancer consistently demonstrate poorer response to booster vaccines than patients with solid cancer.


Subject(s)
COVID-19 , Hematologic Neoplasms , Neoplasms , COVID-19/prevention & control , COVID-19 Vaccines , Hematologic Neoplasms/therapy , Humans , Immunization, Secondary , Neoplasms/therapy
4.
Haematologica ; 107(3): 625-634, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1714970

ABSTRACT

Patients with chronic lymphocytic leukemia (CLL) have a suboptimal humoral response to vaccination. Recently, BNT162b2, an mRNA COVID-19 vaccine with a high efficacy of 95% in immunocompetent individuals, was introduced. We investigated the safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with CLL from nine medical centers in Israel, Overall 400 patients were included, of whom 373 were found to be eligible for the analysis of antibody response. The vaccine appeared to be safe and only grade 1-2 adverse events were seen in 50% of the patients. Following the second dose, an antibody response was detected in 43% of the cohort. Among these CLL patients, 61% of the treatment-na ve patients responded to the vaccine, while responses developed in only 18% of those with ongoing disease, 37% of those previously treated with a BTK inhibitor and 5% of those recently given an anti-CD20 antibody. Among patients treated with BCL2 as monotherapy or in combination with anti-CD20, 62% and 14%, respectively, developed an immune response. There was a high concordance between neutralizing antibodies and positive serological response to spike protein. Based on our findings we developed a simple seven-factor score including timing of any treatment with anti-CD20, age, treatment status, and IgG, IgA, IgM and hemoglobin levels. The sum of all the above parameters can serve as a possible estimate to predict whether a given CLL patient will develop sufficient antibodies. In conclusion, the BNT162b2 mRNA COVID-19 vaccine was found to be safe in patients with CLL, but its efficacy is limited, particularly in treated patients.


Subject(s)
COVID-19 , Leukemia, Lymphocytic, Chronic, B-Cell , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , RNA, Messenger/genetics , SARS-CoV-2
5.
Blood ; 139(5): 678-685, 2022 02 03.
Article in English | MEDLINE | ID: covidwho-1551192

ABSTRACT

Patients with chronic lymphocytic leukemia (CLL) have an impaired antibody response to coronavirus disease 2019 (COVID-19) vaccination. Here, we evaluated the antibody response to a third BNT162b2 mRNA vaccine in patients with CLL/small lymphocytic lymphoma (SLL) who failed to achieve a humoral response after standard 2-dose vaccination regimen. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were measured 3 weeks after administration of the third dose. In 172 patients with CLL, the antibody response rate was 23.8%. Response rate among actively treated patients (12.0%; n = 12/100) was lower compared with treatment-naïve patients (40.0%; n = 16/40; OR = 4.9, 95% CI 1.9-12.9; P < .001) and patients off-therapy (40.6%; n = 13/32; OR = 5.0, 95% CI 1.8-14.1; P < .001), (P < .001). In patients actively treated with Bruton's tyrosine kinase (BTK) inhibitors or venetoclax ± anti-CD20 antibody, response rates were extremely low (15.3%, n = 9/59, and 7.7%, n = 3/39, respectively). Only 1 of the 28 patients (3.6%) treated with anti-CD20 antibodies <12 months prior to vaccination responded. In a multivariate analysis, the independent variables that were associated with response included lack of active therapy (OR = 5.6, 95% CI 2.3-13.8; P < .001) and serum immunoglobulin A levels ≥80 mg/dL (OR = 5.8, 95% CI 2.1-15.9; P < .001). In patients with CLL/SLL who failed to achieve a humoral response after standard 2-dose BNT162b2 mRNA vaccination regimen, close to a quarter responded to the third dose of vaccine. The antibody response rates were lower during active treatment and in patients with a recent exposure (<12 months prior to vaccination) to anti-CD20 therapy. This trial was registered at www.clinicaltrials.gov as #NCT04862806.


Subject(s)
/therapeutic use , COVID-19/prevention & control , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Aged , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antibody Formation , COVID-19/blood , COVID-19/immunology , Female , Humans , Immunity, Humoral , Leukemia, Lymphocytic, Chronic, B-Cell/blood , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Male , Middle Aged , SARS-CoV-2/immunology
6.
In Vivo ; 35(5): 2951-2955, 2021.
Article in English | MEDLINE | ID: covidwho-1436484

ABSTRACT

BACKGROUND/AIM: We present the case of a 19-year-old male patient diagnosed concomitantly with extensive thromboses (including two intra-cardiac masses and Budd-Chiari syndrome), as well as acute myeloid leukemia. This necessitated prompt deployment of a monitoring and treatment strategy which included twice-daily blood count assessment, multiple platelet transfusions and anti-coagulation therapy with dose-adjustment per blood count during both induction and consolidation chemotherapy. Multiple factors are believed to contribute to the development of thrombosis in acute leukemia such as diffuse intravascular coagulation, cytokine release and chemotherapy. CASE REPORT: Our patient presented early on in the COVID-19 pandemic, delaying his seeking out medical treatment and we suspect this to have contributed to his 'catastrophic' thrombotic presentation. Well-structured guidelines to help clinicians manage these patients are lacking, and most data are from retrospective analyses or case reports. Our patient continued full-dose anticoagulant therapy until successfully undergoing allogeneic stem cell transplant. The thrombi eventually diminished in size, and the patient was not diagnosed with any further thrombotic events. CONCLUSION: Our case highlights the feasibility of intensive monitoring and provision of platelet transfusion as necessary in order to safely administer low molecular weight heparin from the outset of chemotherapy.


Subject(s)
COVID-19 , Leukemia, Myeloid, Acute , Thrombosis , Adult , Humans , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/diagnosis , Male , Pandemics , Retrospective Studies , SARS-CoV-2 , Thrombosis/diagnosis , Thrombosis/etiology , Young Adult
7.
Leuk Lymphoma ; 62(14): 3384-3393, 2021 12.
Article in English | MEDLINE | ID: covidwho-1360252

ABSTRACT

This national Israeli multicenter retrospective study aimed to characterize the clinical course of COVID-19 infection among patients with hematological malignancies, with special emphasis on treatment efficacy and outcome. Clinical and laboratory data from haemato-oncological patients diagnosed with COVID-19 from 16 medical centers were centrally reported. Multivariate regression analyses were used to determine variables associated with severe disease, hospitalization, and mortality. In total, 313 patients were included: 103 (35.7%) developed severe/critical respiratory infection, 178 (61.4%) were hospitalized, and 60 (20.0%) died. Age > 70 years was associated with severe/critical disease (p = 0.036) and mortality (p = 0.023), hypertension with severe/critical disease (p = 0.046) and hospitalization (p = 0.001), active haemato-oncological treatment with hospitalization (p = 0.009), and remdesivir treatment was associated with decreased mortality (p = 0.021). Convalescent plasma, enoxaparin, and corticosteroids resulted in no clinical benefit. In conclusion, COVID-19 infection seems particularly severe in patients with hematological malignancies, and of all examined therapies, remdesivir appears to be the most effective.


Subject(s)
COVID-19 , Hematologic Neoplasms , Aged , COVID-19/therapy , Hematologic Neoplasms/complications , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Humans , Immunization, Passive , Retrospective Studies , SARS-CoV-2
9.
Support Care Cancer ; 29(12): 7591-7599, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1269151

ABSTRACT

BACKGROUND: The COVID-19 pandemic required reevaluation of the therapeutic approach and added emotional stress for patients with hematological malignancies at high risk of contracting the virus. We aimed to evaluate how it affected such patients during the second lockdown in Israel. METHODS: This national survey included Hebrew-speaking patients with hematological malignancy. This included three tools with 28 items of sociodemographic and medical baseline characteristics, management of hematological disease, and evaluation of emotional coping during COVID-19 pandemic; the Hebrew version of the Patient Health Questionnaire 9; and 3 qualitative open-ended questions. Data was analyzed by mixed methods which combined both quantitative and qualitative thematic analyses. RESULTS: Four hundred eight patients responded to the survey. The management of their hematological disease included a decrease in the number of visits to the hematology clinic (37.0%), delay of some treatment schedules (9.1%), and prescription of replacement therapies permitting less visits to the clinic (2.2%). The frequency and intensity of "feeling afraid" regarding COVID-19 infection was increased (mean ± SD: 4 ± 1 to 5 ± 2 in a 1-7 Likert scale), and a high rate of depression was recorded, which appeared to be more evident in patients with chronic myeloid leukemia (CML) (p < 0.001). CONCLUSION: The management of hematological malignancies during pandemics should always take into consideration patients' fears, as well as the development of depression related to isolation and loneliness, in addition to the high risk of severe disease. Patients with CML had a high rate of depression which obviously needs to be managed very carefully during and after the COVID-19 pandemic.


Subject(s)
COVID-19 , Hematologic Neoplasms , Communicable Disease Control , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Humans , Pandemics , SARS-CoV-2
10.
Leukemia ; 35(7): 1864-1872, 2021 07.
Article in English | MEDLINE | ID: covidwho-1216445

ABSTRACT

Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients. The new recommendations adapt the 2017 consensus for the diagnosis and management with cHCL to the current COVID-19 pandemic. They underline the option of active surveillance in patients with low but stable blood counts, consider the use of targeted and non-immunosuppressive agents as first-line treatment for cHCL, and give recommendations on preventive measures against COVID-19.


Subject(s)
COVID-19/complications , Leukemia, Hairy Cell/therapy , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Consensus , Humans , Leukemia, Hairy Cell/complications , Pandemics , Practice Guidelines as Topic , SARS-CoV-2/isolation & purification , Severity of Illness Index
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