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1.
Blood Adv ; 6(6): 1671-1683, 2022 03 22.
Article in English | MEDLINE | ID: covidwho-1649450

ABSTRACT

Chronic lymphocytic leukemia (CLL), the most common leukemia worldwide, is associated with increased COVID-19 mortality. Previous studies suggest only a portion of vaccinated CLL patients develop severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibodies. Whether the elicited antibodies are functional and/or accompanied by functional T-cell responses is unknown. This prospective cohort study included patients with CLL who received SARS-CoV-2 and PCV13 vaccines (not concurrently). The primary cohort included adults with CLL off therapy. Coprimary outcomes were serologic response to SARS-CoV-2 (receptor binding domain [RBD] immunoassay) and PCV13 vaccines (23-serotype IgG assay). Characterization of SARS-CoV-2 antibodies and their functional activity and assessment of functional T-cell responses was performed. Sixty percent (18/30) of patients demonstrated serologic responses to SARS-CoV-2 vaccination, appearing more frequent among treatment-naïve patients (72%). Among treatment-naïve patients, an absolute lymphocyte count ≤24 000/µL was associated with serologic response (94% vs 14%; P < .001). On interferon-γ release assays, 80% (16/20) of patients had functional spike-specific T-cell responses, including 78% (7/9) with a negative RBD immunoassay, a group enriched for prior B-cell-depleting therapies. A bead-based multiplex immunoassay identified antibodies against wild-type and variant SARS-CoV-2 (α, ß, γ, and δ) in all tested patients and confirmed Fc-receptor binding and effector functions of these antibodies. Of 11 patients with negative RBD immunoassay after vaccination, 6 (55%) responded to an additional mRNA-based vaccine dose. The PCV13 serologic response rate was 29% (8/28). Our data demonstrate that SARS-CoV-2 vaccination induces functional T-cell and antibody responses in patients with CLL and provides the framework for investigating the molecular mechanisms and clinical benefit of these responses. This trial was registered at www.clinicaltrials.gov as #NCT05007860.


Subject(s)
COVID-19 , Leukemia, Lymphocytic, Chronic, B-Cell , Adult , Antibodies, Neutralizing , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunogenicity, Vaccine , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Prospective Studies , SARS-CoV-2
3.
Leukemia ; 35(12): 3444-3454, 2021 12.
Article in English | MEDLINE | ID: covidwho-1493064

ABSTRACT

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41-0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02-1.04; HR = 1.79, 95% CI:1.04-3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.


Subject(s)
COVID-19/complications , COVID-19/mortality , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , COVID-19/diagnosis , COVID-19/virology , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Leukemia, Lymphocytic, Chronic, B-Cell/virology , Mortality , Prognosis , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
4.
Leukemia ; 36(2): 476-481, 2022 02.
Article in English | MEDLINE | ID: covidwho-1437661

ABSTRACT

We studied clinical and immunological outcome of Covid-19 in consecutive CLL patients from a well-defined area during month 1-13 of the pandemic. Sixty patients (median age 71 y, range 43-97) were identified. Median CIRS was eight (4-20). Patients had indolent CLL (n = 38), had completed (n = 12) or ongoing therapy (n = 10). Forty-six patients (77%) were hospitalized due to severe Covid-19 and 11 were admitted to ICU. Severe Covid-19 was equally distributed across subgroups irrespective of age, gender, BMI, CLL status except CIRS (p < 0.05). Fourteen patients (23%) died; age ≥75 y was the only significant risk factor (p < 0.05, multivariate analysis with limited power). Comparing month 1-6 vs 7-13 of the pandemic, deaths were numerically reduced from 32% to 18%, ICU admission from 37% to 15% whereas hospitalizations remained frequent (86% vs 71%). Seroconversion occurred in 33/40 patients (82%) and anti-SARS-CoV-2 antibodies were detectable at six and 12 months in 17/22 and 8/11 patients, respectively. Most (13/17) had neutralizing antibodies and 19/28 had antibodies in saliva. SARS-CoV-2-specific T-cells (ELISpot) were detected in 14/17 patients. Covid-19 continued to result in high admission even among consecutive and young early- stage CLL patients. A robust and durable B and/or T cell immunity was observed in most convalescents.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , B-Lymphocytes/immunology , COVID-19/complications , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/transmission , COVID-19/virology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Leukemia, Lymphocytic, Chronic, B-Cell/virology , Male , Middle Aged , Prognosis , SARS-CoV-2/isolation & purification
7.
Cancer J ; 27(4): 328-333, 2021.
Article in English | MEDLINE | ID: covidwho-1354352

ABSTRACT

ABSTRACT: Coronavirus disease 2019 (COVID-19) has markedly impacted on the management of patients with chronic lymphocytic leukemia (CLL) and their outcome in the last year. The cumulative incidence of COVID-19 in patients with CLL in 1 year was approximately 3% in the recent Italian CAMPUS CLL survey; large retrospective studies have documented a higher mortality in patients with CLL hospitalized for severe COVID-19 compared with the general population. Controversial results for CLL-directed treatment have been reported, with some studies suggesting a potential benefit for BTK inhibitors. Reducing the number of hospital visits, delaying treatment whenever possible, and using oral therapy have become the mainstay of management in these patients. Available results with severe acute respiratory syndrome coronavirus 2 vaccines indicate an immune serological response in 40% of patients only, with a detrimental effect of recent therapy with or without anti-CD20 therapy, older age, and hypogammaglobulinemia. Further studies are needed to determine the best strategies in patients with CLL regarding (i) management of concomitant COVID-19, (ii) identification of patients in whom CLL therapy can be safely postponed, (iii) CLL treatment algorithms, and (iv) optimal severe acute respiratory syndrome coronavirus 2 vaccination strategies.


Subject(s)
COVID-19 , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , COVID-19 Vaccines , Humans , Protein Kinase Inhibitors/therapeutic use
8.
Cancer J ; 27(4): 297-305, 2021.
Article in English | MEDLINE | ID: covidwho-1354351

ABSTRACT

ABSTRACT: Despite multiple advances in the treatment landscape of chronic lymphocytic leukemia (CLL) during recent years, cellular therapies, such as allogeneic hematopoietic cell transplantation and chimeric antigen-engineered T cells, represent valuable therapeutic options for patients with multiply relapsed or poor-risk disease. This brief overview will summarize current results of cellular therapies in CLL including Richter transformation, suggest an indication algorithm and strategies for performing cellular therapies in these conditions, and discuss the impact of COVID-19 (coronavirus disease 2019) on allogeneic hematopoietic cell transplantation and chimeric antigen-engineered T cells in CLL.


Subject(s)
Cell- and Tissue-Based Therapy , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Antineoplastic Agents , COVID-19 , Cell- and Tissue-Based Therapy/trends , Hematopoietic Stem Cell Transplantation , Humans , Immunotherapy, Adoptive , Receptors, Chimeric Antigen
9.
Blood ; 138(18): 1768-1773, 2021 11 04.
Article in English | MEDLINE | ID: covidwho-1322916
11.
Blood ; 137(23): 3165-3173, 2021 06 10.
Article in English | MEDLINE | ID: covidwho-1190021

ABSTRACT

Patients with chronic lymphocytic leukemia (CLL) have an increased risk for severe COVID-19 disease and mortality. The goal of this study was to determine the efficacy of COVID-19 vaccine in patients with CLL. We evaluated humoral immune responses to the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine in patients with CLL and compared responses with those obtained in age-matched healthy control subjects. Patients received 2 vaccine doses, 21 days apart, and antibody titers were measured by using the Elecsys Anti-SARS-CoV-2 S assay after administration of the second dose. In a total of 167 patients with CLL, the antibody response rate was 39.5%. A comparison between 52 patients with CLL and 52 sex- and aged-matched healthy control subjects revealed a significantly reduced response rate among patients (52% vs 100%, respectively; adjusted odds ratio, 0.010; 95% confidence interval, 0.001-0.162; P < .001). The response rate was highest in patients who obtained clinical remission after treatment (79.2%), followed by 55.2% in treatment-naive patients and 16.0% in patients under treatment at the time of vaccination. In patients treated with either Bruton's tyrosine kinase inhibitors or venetoclax ± anti-CD20 antibody, response rates were considerably low (16.0% and 13.6%). None of the patients exposed to anti-CD20 antibodies <12 months before vaccination responded. In a multivariate analysis, the independent predictors of response were younger age, female sex, lack of currently active treatment, immunoglobulin G levels ≥550 mg/dL, and immunoglobulin M levels ≥40 mg/dL. In conclusion, antibody-mediated response to the BNT162b2 mRNA COVID-19 vaccine in patients with CLL is markedly impaired and affected by disease activity and treatment. This trial was registered at www.clinicaltrials.gov as #NCT04746092.


Subject(s)
COVID-19 , Leukemia, Lymphocytic, Chronic, B-Cell , Aged , COVID-19 Vaccines , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , RNA, Messenger/genetics , SARS-CoV-2
12.
Acta Haematol ; 144(5): 508-518, 2021.
Article in English | MEDLINE | ID: covidwho-1102241

ABSTRACT

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been first described in December 2019 in Wuhan, China, and has led to a worldwide pandemic ever since. Initial clinical data imply that cancer patients are particularly at risk for a severe course of SARS-CoV-2. In patients with chronic lymphocytic leukemia (CLL), infections are a main contributor to morbidity and mortality driven by an impaired immune system. Treatment initiation is likely to induce immune modulation that further increases the risk for severe infections. This article aims to give an overview on pathogenesis and risk of infectious complications in patients with CLL. In this context, we discuss current data of SARS-CoV-2 infections in patients with CLL and how the pandemic impacts their management.


Subject(s)
COVID-19/epidemiology , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , COVID-19/complications , COVID-19/pathology , COVID-19/therapy , COVID-19/virology , Humans , Immunization, Passive , Immunocompromised Host , Immunotherapy , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Palliative Care , Pandemics , Protein Kinase Inhibitors/therapeutic use , SARS-CoV-2/isolation & purification
13.
Blood ; 136(10): 1134-1143, 2020 09 03.
Article in English | MEDLINE | ID: covidwho-656981

ABSTRACT

Given advanced age, comorbidities, and immune dysfunction, chronic lymphocytic leukemia (CLL) patients may be at particularly high risk of infection and poor outcomes related to coronavirus disease 2019 (COVID-19). Robust analysis of outcomes for CLL patients, particularly examining effects of baseline characteristics and CLL-directed therapy, is critical to optimally manage CLL patients through this evolving pandemic. CLL patients diagnosed with symptomatic COVID-19 across 43 international centers (n = 198) were included. Hospital admission occurred in 90%. Median age at COVID-19 diagnosis was 70.5 years. Median Cumulative Illness Rating Scale score was 8 (range, 4-32). Thirty-nine percent were treatment naive ("watch and wait"), while 61% had received ≥1 CLL-directed therapy (median, 2; range, 1-8). Ninety patients (45%) were receiving active CLL therapy at COVID-19 diagnosis, most commonly Bruton tyrosine kinase inhibitors (BTKi's; n = 68/90 [76%]). At a median follow-up of 16 days, the overall case fatality rate was 33%, though 25% remain admitted. Watch-and-wait and treated cohorts had similar rates of admission (89% vs 90%), intensive care unit admission (35% vs 36%), intubation (33% vs 25%), and mortality (37% vs 32%). CLL-directed treatment with BTKi's at COVID-19 diagnosis did not impact survival (case fatality rate, 34% vs 35%), though the BTKi was held during the COVID-19 course for most patients. These data suggest that the subgroup of CLL patients admitted with COVID-19, regardless of disease phase or treatment status, are at high risk of death. Future epidemiologic studies are needed to assess severe acute respiratory syndrome coronavirus 2 infection risk, these data should be validated independently, and randomized studies of BTKi's in COVID-19 are needed to provide definitive evidence of benefit.


Subject(s)
Coronavirus Infections/complications , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Pneumonia, Viral/complications , Adult , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Aged , Aged, 80 and over , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/therapy , Female , Humans , Immunization, Passive , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Male , Middle Aged , Pandemics , Pneumonia, Viral/therapy , Protein Kinase Inhibitors/therapeutic use , SARS-CoV-2 , Survival Analysis , Treatment Outcome
14.
Curr Oncol ; 27(3): e332-e335, 2020 06.
Article in English | MEDLINE | ID: covidwho-646931

ABSTRACT

The emergence of the covid-19 disease pandemic caused by the 2019 novel coronavirus has required a re-evaluation of treatment practices for clinicians caring for patients with chronic lymphocytic leukemia (cll). The American Society for Hematology (ash) has provided a series of recommendations for the treatment of patients with cll during the pandemic, covering a range of topics, including testing for covid-19, cll treatment initiation and selection, use of immunoglobulin therapy, in-person monitoring, and treatment of patients with cll and covid-19. We summarize the ash recommendations and discuss their applicability as guidelines for the treatment of cll during the covid-19 pandemic in Canada.


Subject(s)
Antineoplastic Agents/therapeutic use , Coronavirus Infections/epidemiology , Immunologic Factors/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Pneumonia, Viral/epidemiology , Adenine/analogs & derivatives , Ambulatory Care/methods , Appointments and Schedules , Betacoronavirus , COVID-19 , Canada/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Disease Management , Hospitalization , Humans , Immunoglobulins, Intravenous/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Pandemics , Piperidines , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Practice Guidelines as Topic , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , SARS-CoV-2
15.
Eur J Haematol ; 105(4): 508-511, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-612274

ABSTRACT

The number of people suffering from the new coronavirus SARS-CoV-2 continues to rise. In SARS-CoV-2, superinfection with bacteria or fungi seems to be associated with increased mortality. The role of co-infections with respiratory viral pathogens has not yet been clarified. Here, we report the course of COVID-19 in a CLL patient with secondary immunodeficiency and viral co-infection with parainfluenza.


Subject(s)
COVID-19/complications , Coinfection/complications , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Paramyxoviridae Infections/complications , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/therapy , Humans , IgG Deficiency/complications , IgG Deficiency/immunology , IgG Deficiency/therapy , Immunoglobulins, Intravenous/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Male , Middle Aged , Pandemics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology
17.
Intern Med J ; 50(6): 667-679, 2020 06.
Article in English | MEDLINE | ID: covidwho-271531

ABSTRACT

The COVID-19 pandemic poses a unique challenge to the care of patients with haematological malignancies. Viral pneumonia is known to cause disproportionately severe disease in patients with cancer, and patients with lymphoma, myeloma and chronic lymphocytic leukaemia are likely to be at particular risk of severe disease related to COVID-19. This statement has been developed by consensus among authors from Australia and New Zealand. We aim to provide supportive guidance to clinicians making individual patient decisions during the COVID-19 pandemic, in particular during periods that access to healthcare resources may be limited. General recommendations include those to minimise patient exposure to COVID-19, including the use of telehealth, avoidance of non-essential visits and minimisation of time spent by patients in infusion suites and other clinical areas. This statement also provides recommendations where appropriate in assessing indications for therapy, reducing therapy-associated immunosuppression and reducing healthcare utilisation in patients with specific haematological malignancies during the COVID-19 pandemic. Specific decisions regarding therapy of haematological malignancies will need to be individualised, based on disease risk, risks of immunosuppression, rates of community transmission of COVID-19 and available local healthcare resources.


Subject(s)
Consensus , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Infection Control/methods , Leukemia, Lymphocytic, Chronic, B-Cell/physiopathology , Lymphoma/physiopathology , Multiple Myeloma/physiopathology , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Australia , Betacoronavirus/immunology , COVID-19 , Comorbidity , Coronavirus Infections/immunology , Coronavirus Infections/virology , Drug Therapy , Guideline Adherence , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Lymphoma/immunology , Lymphoma/therapy , Multiple Myeloma/immunology , Multiple Myeloma/therapy , New Zealand , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Practice Guidelines as Topic , Risk Assessment , SARS-CoV-2 , Salvage Therapy/methods , Stem Cell Transplantation/methods
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