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1.
Front Oncol ; 12: 992137, 2022.
Article in English | MEDLINE | ID: covidwho-2080206

ABSTRACT

Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs.

2.
Haematologica ; 2022 05 12.
Article in English | MEDLINE | ID: covidwho-1841291

ABSTRACT

Patients with acute myeloid leukemia (AML) are at high risk of mortality from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients with COVID-19 diagnosis between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the prior 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with an improved survival when AML treatment could be delayed (80%; p<0.001). Overall survival in patients with COVID-19 diagnosis between January 2020 and August 2020 was significantly lower than those who were diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs 60% vs 61.9%, respectively; p=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.

3.
Nat Cancer ; 3(5): 552-564, 2022 05.
Article in English | MEDLINE | ID: covidwho-1764216

ABSTRACT

Patients with hematological malignancies are at increased risk of severe COVID-19 outcomes due to compromised immune responses, but the insights of these studies have been compromised due to intrinsic limitations in study design. Here we present the PROSECO prospective observational study ( NCT04858568 ) on 457 patients with lymphoma that received two or three COVID-19 vaccine doses. We show undetectable humoral responses following two vaccine doses in 52% of patients undergoing active anticancer treatment. Moreover, 60% of patients on anti-CD20 therapy had undetectable antibodies following full vaccination within 12 months of receiving their anticancer therapy. However, 70% of individuals with indolent B-cell lymphoma displayed improved antibody responses following booster vaccination. Notably, 63% of all patients displayed antigen-specific T-cell responses, which increased after a third dose irrespective of their cancer treatment status. Our results emphasize the urgency of careful monitoring of COVID-19-specific immune responses to guide vaccination schemes in these vulnerable populations.


Subject(s)
COVID-19 , Neoplasms , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Humans , SARS-CoV-2 , United Kingdom/epidemiology
4.
JAMA Netw Open ; 5(2): e220130, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1700096

ABSTRACT

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19-related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed.


Subject(s)
COVID-19/complications , Hematologic Neoplasms/mortality , Lung Neoplasms/mortality , SARS-CoV-2 , Aged , Aged, 80 and over , Cohort Studies , Drug Therapy , Female , Hematologic Neoplasms/complications , Hematologic Neoplasms/therapy , Humans , Immunotherapy , Lung Neoplasms/complications , Lung Neoplasms/therapy , Male , Middle Aged , Prospective Studies , Registries , United Kingdom
5.
Marchesi, Francesco, Salmanton-Garcia, Jon, Emarah, Ziad, Piukovics, Klára, Nucci, Marcio, Lopez-Garcia, Alberto, Racil, Zdenek, Farina, Francesca, Popova, Marina, Zompi, Sofia, Audisio, Ernesta, Ledoux, Marie-Pierre, Verga, Luisa, Weinbergerova, Barbora, Szotkowski, Tomas, Silva, Maria, Fracchiolla, Nicola Stefano, De Jonge, Nick, Collins, Graham, Marchetti, Monia, Magliano, Gabriele, GarcÍA-Vidal, Carolina, Biernat, Monika, Doesum, Jaap van, Machado, Marina, Demirkan, Fatih, Khabori, Murtadha Al, Zak, Pavel, Visek, Benjamin, Stoma, Igor, MÉNdez, Gustavo-Adolfo, Maertens, Johan, Khanna, Nina, Espigado, Ildefonso, Dragonetti, Giulia, Fianchi, Luana, Principe, Maria Ilaria Del, Cabirta, Alba, Ormazabal-VÉLez, Irati, Jaksic, Ozren, Buquicchio, Caterina, Bonuomo, Valentina, Batinić, Josip, Omrani, Ali, Lamure, Sylvain, Finizio, Olimpia, FernÁNdez, Noemí, Falces-Romero, Iker, Blennow, Ola, Bergantim, Rui, Ali, Natasha, Win, Sein, Praet, Jens V. A. N.; Tisi, Maria Chiara, Shirinova, Ayten, SchÖNlein, Martin, Prattes, Juergen, Piedimonte, Monica, Petzer, Verena, NavrÁTil, Milan, Kulasekararaj, Austin, Jindra, Pavel, Jiří, Glenthøj, Andreas, Fazzi, Rita, de Ramón, Cristina, Cattaneo, Chiara, Calbacho, Maria, Bahr, Nathan, El-Ashwl, Shaimaa Saber, Córdoba, Raúl, Hanakova, Michaela, Zambrotta, Giovanni, Sciumè, Mariarita, Booth, Stephen, Nunes-Rodrigues, Raquel, Sacchi, Maria Vittoria, GarcÍA-PoutÓN, Nicole, MartÍN-GonzÁLez, Juan-Alberto, Khostelidi, Sofya, GrÄFe, Stefanie, Rahimli, Laman, busca, alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Cornely, Oliver, pagano, Livio.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328805

ABSTRACT

Patients with acute myeloid leukemia (AML) are at high risk of mortality from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients with COVID-19 diagnosis between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the prior 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died. Death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%). Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with an improved survival when AML treatment could be delayed. Patients with COVID-19 diagnosis between January and August 2020 had a significantly lower survival. COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296800

ABSTRACT

SUMMARY SARS-CoV-2 vaccination protects against COVID-19. Antibodies and antigen-specific T-cell responses against the spike domain can be used to measure vaccine immune response. Individuals with lymphoma have defects in humoral and cellular immunity that may compromise vaccine response. In this prospective observational study of 457 participants with lymphoma, 52% of participants vaccinated on treatment had undetectable anti-spike IgG antibodies compared to 9% who were not on treatment. Marked impairment was observed in those receiving anti- CD20 antibody within 12 months where 60% had undetectable antibodies compared to 11% on chemotherapy, which persisted despite three vaccine doses. Overall, 63% had positive T-cell responses irrespective of treatment. Individuals with indolent B-cell lymphoma have impaired antibody and cellular responses that were independent of treatment. The significant reduction and heterogeneity in immune responses in these individuals emphasise the urgent need for immune response monitoring and alternative prophylactic strategies to protect against COVID- 19.

7.
Br J Haematol ; 196(4): 892-901, 2022 02.
Article in English | MEDLINE | ID: covidwho-1511287

ABSTRACT

Patients with haematological malignancies have a high risk of severe infection and death from SARS-CoV-2. In this prospective observational study, we investigated the impact of cancer type, disease activity, and treatment in 877 unvaccinated UK patients with SARS-CoV-2 infection and active haematological cancer. The primary end-point was all-cause mortality. In a multivariate analysis adjusted for age, sex and comorbidities, the highest mortality was in patients with acute leukaemia [odds ratio (OR) = 1·73, 95% confidence interval (CI) 1·1-2·72, P = 0·017] and myeloma (OR 1·3, 95% CI 0·96-1·76, P = 0·08). Having uncontrolled cancer (newly diagnosed awaiting treatment as well as relapsed or progressive disease) was associated with increased mortality risk (OR = 2·45, 95% CI 1·09-5·5, P = 0·03), as was receiving second or beyond line of treatment (OR = 1·7, 95% CI 1·08-2·67, P = 0·023). We found no association between recent cytotoxic chemotherapy or anti-CD19/anti-CD20 treatment and increased risk of death within the limitations of the cohort size. Therefore, disease control is an important factor predicting mortality in the context of SARS-CoV-2 infection alongside the possible risks of therapies such as cytotoxic treatment or anti-CD19/anti-CD20 treatments.


Subject(s)
Antigens, CD20/immunology , Antineoplastic Agents, Immunological/therapeutic use , COVID-19/complications , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Adult , Antineoplastic Agents, Immunological/adverse effects , COVID-19/etiology , COVID-19/immunology , Female , Hematologic Neoplasms/immunology , Humans , Leukemia/complications , Leukemia/drug therapy , Leukemia/immunology , Male , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Multiple Myeloma/immunology , Prospective Studies , Risk Factors
8.
J Hematol Oncol ; 14(1): 168, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1468074

ABSTRACT

BACKGROUND: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. METHODS: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. RESULTS: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March-May 2020) and the second wave (October-December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. CONCLUSIONS: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.


Subject(s)
COVID-19/complications , Hematologic Neoplasms/complications , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Europe/epidemiology , Female , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Registries , Risk Factors , SARS-CoV-2/isolation & purification , Young Adult
11.
Lancet Oncol ; 21(10): 1309-1316, 2020 10.
Article in English | MEDLINE | ID: covidwho-726907

ABSTRACT

BACKGROUND: Patients with cancer are purported to have poor COVID-19 outcomes. However, cancer is a heterogeneous group of diseases, encompassing a spectrum of tumour subtypes. The aim of this study was to investigate COVID-19 risk according to tumour subtype and patient demographics in patients with cancer in the UK. METHODS: We compared adult patients with cancer enrolled in the UK Coronavirus Cancer Monitoring Project (UKCCMP) cohort between March 18 and May 8, 2020, with a parallel non-COVID-19 UK cancer control population from the UK Office for National Statistics (2017 data). The primary outcome of the study was the effect of primary tumour subtype, age, and sex and on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence and the case-fatality rate during hospital admission. We analysed the effect of tumour subtype and patient demographics (age and sex) on prevalence and mortality from COVID-19 using univariable and multivariable models. FINDINGS: 319 (30·6%) of 1044 patients in the UKCCMP cohort died, 295 (92·5%) of whom had a cause of death recorded as due to COVID-19. The all-cause case-fatality rate in patients with cancer after SARS-CoV-2 infection was significantly associated with increasing age, rising from 0·10 in patients aged 40-49 years to 0·48 in those aged 80 years and older. Patients with haematological malignancies (leukaemia, lymphoma, and myeloma) had a more severe COVID-19 trajectory compared with patients with solid organ tumours (odds ratio [OR] 1·57, 95% CI 1·15-2·15; p<0·0043). Compared with the rest of the UKCCMP cohort, patients with leukaemia showed a significantly increased case-fatality rate (2·25, 1·13-4·57; p=0·023). After correction for age and sex, patients with haematological malignancies who had recent chemotherapy had an increased risk of death during COVID-19-associated hospital admission (OR 2·09, 95% CI 1·09-4·08; p=0·028). INTERPRETATION: Patients with cancer with different tumour types have differing susceptibility to SARS-CoV-2 infection and COVID-19 phenotypes. We generated individualised risk tables for patients with cancer, considering age, sex, and tumour subtype. Our results could be useful to assist physicians in informed risk-benefit discussions to explain COVID-19 risk and enable an evidenced-based approach to national social isolation policies. FUNDING: University of Birmingham and University of Oxford.


Subject(s)
Coronavirus Infections/mortality , Neoplasms/mortality , Pandemics , Pneumonia, Viral/mortality , Adult , Aged , Aged, 80 and over , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/pathology , Coronavirus Infections/virology , Female , Hospitalization , Humans , Male , Middle Aged , Neoplasms/pathology , Neoplasms/virology , Pneumonia, Viral/complications , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Prospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2
12.
Eur J Haematol ; 105(4): 476-483, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-599960

ABSTRACT

OBJECTIVES: We sought to characterise the outcomes of patients with haematological malignancy and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hospital in our regional network of 7 hospitals. METHODS: Consecutive hospitalised patients with haematological malignancy and SARS-CoV-2 infection were identified from 01/03/2020 to 06/05/2020. Outcomes were categorised as death, resolved or ongoing. The primary outcome was preliminary case fatality rate (pCFR), defined as the number of cases resulting in death as a proportion of all diagnosed cases. Analysis was primarily descriptive. RESULTS: 66 Patients were included, overall pCFR was 51.5%. Patients ≥ 70 years accounted for the majority of hospitalised cases (42, 63%) and fatalities (25, 74%). Mortality was similar between females (52%) and males (51%). Immunosuppressive or cytotoxic treatment within 3 months of the diagnosis of SARS-CoV-2 infection was associated with a significantly higher pCFR of 70%, compared with 28% in those not on active treatment (P = .0013, 2 proportions z test). CONCLUSIONS: Mortality rates in patients with haematological malignancy and SARS-CoV-2 infection in hospital are high supporting measures to minimise the risk of infection in this population.


Subject(s)
COVID-19/complications , Hematologic Neoplasms/complications , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , COVID-19/mortality , COVID-19/prevention & control , Cytotoxins/adverse effects , Female , Hematologic Neoplasms/therapy , Hospitalization , Humans , Immunosuppression Therapy/adverse effects , Male , Middle Aged , Pandemics , Prospective Studies , SARS-CoV-2 , United Kingdom/epidemiology
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