Nejvíce citovaný článek - PubMed ID 33861303
Patients with chronic lymphocytic leukemia (CLL) exhibit diverse clinical outcomes. An expanding array of genetic tests is now employed to facilitate the identification of patients with high-risk disease and inform treatment decisions. These tests encompass molecular cytogenetic analysis, focusing on recurrent chromosomal alterations, particularly del(17p). Additionally, sequencing is utilized to identify TP53 mutations and to determine the somatic hypermutation status of the immunoglobulin heavy variable gene. Concurrently, a swift advancement of targeted treatment has led to the implementation of novel strategies for patients with CLL, including kinase and BCL2 inhibitors. This review explores both current and emerging diagnostic tests aimed at identifying high-risk patients who should benefit from targeted therapies. We outline existing treatment paradigms, emphasizing the importance of matching the right treatment to the right patient beyond genetic stratification, considering the crucial balance between safety and efficacy. We also take into consideration the practical and logistical issues when choosing a management strategy for each individual patient. Furthermore, we delve into the mechanisms underlying therapy resistance and stress the relevance of monitoring measurable residual disease to guide treatment decisions. Finally, we underscore the necessity of aggregating real-world data, adopting a global perspective, and ensuring patient engagement. Taken together, we argue that precision medicine is not the mere application of precision diagnostics and accessibility of precision therapies in CLL but encompasses various aspects of the patient journey (e.g., lifestyle exposures and comorbidities) and their preferences toward achieving true personalized medicine for patients with CLL.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Patients treated with B-cell-targeting therapies like Rituximab or Ibrutinib have decreased serological response to various vaccines. In this study, we tested serological and cellular response to SARS-CoV-2 mRNA vaccines in 16 patients treated with Ibrutinib, 16 treated with maintenance Rituximab, 18 patients with chronic lymphocytic leukaemia (CLL) with watch and wait status and 21 healthy volunteers. In comparison with the healthy volunteers, where serological response was achieved by 100% subjects, patients on B-cell-targeting therapy (Ibrutinib and Rituximab) had their response dramatically impaired. The serological response was achieved in 0% of Rituximab treated, 18% of Ibrutinib treated and 50% of untreated CLL patients. Cell-mediated immunity analysed by the whole blood Interferon-γ Release immune Assay developed in 80% of healthy controls, 62% of Rituximab treated, 75% of Ibrutinib treated and 55% of untreated CLL patients. The probability of cell-mediated immune response development negatively correlates with disease burden mainly in CLL patients. Our study shows that even though the serological response to SARS-CoV-2 vaccine is severely impaired in patients treated with B-cell-targeting therapy, the majority of these patients develop sufficient cell-mediated immunity. The vaccination of these patients therefore might be meaningful in terms of protection against SARS-CoV-2 infection.
- Klíčová slova
- Cellular immune response, Ibrutinib, Rituximab, SARS-COV-2, Vaccination,
- MeSH
- buněčná imunita MeSH
- chronická lymfatická leukemie * farmakoterapie MeSH
- COVID-19 * prevence a kontrola etiologie MeSH
- humorální imunita MeSH
- lidé MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- rituximab terapeutické užití MeSH
- SARS-CoV-2 MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ibrutinib MeSH Prohlížeč
- rituximab MeSH
- vakcíny proti COVID-19 MeSH
Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals.
- MeSH
- antivirové látky MeSH
- COVID-19 * epidemiologie prevence a kontrola MeSH
- dospělí MeSH
- hematologické nádory * komplikace terapie MeSH
- lidé MeSH
- monoklonální protilátky MeSH
- protilátky virové MeSH
- SARS-CoV-2 MeSH
- testování na COVID-19 MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antivirové látky MeSH
- monoklonální protilátky MeSH
- protilátky virové MeSH
Vaccination is an important tool in the fight against the COVID-19 pandemic in patients with haematologic malignancies. The paper provides an analysis of the course of breakthrough SARS-CoV-2 infection in a group of vaccinated patients with haematological malignancy and a comparison with a historical cohort of 96 non-vaccinated patients with haematologic malignancies and bone marrow failure syndromes (two patients) in the treatment of COVID-19. A severe or critical course of COVID-19 was significantly less frequent in the group of vaccinated patients (10.2% vs. 31.4%, p = 0.003). The need for hospitalisation due to COVID-19 was significantly lower in vaccinated patients (27.1% vs. 72.6%, p < 0.0001) and the duration of hospitalisation was significantly shorter (10 vs. 14 days, p = 0.045). Vaccinated patients were insignificantly less likely to require oxygen therapy during infection. COVID-19 mortality was significantly higher in non-vaccinated patients (15.6% vs. 5.1%, p = 0.047). The paper demonstrated a significant positive effect of vaccination against COVID-19 on a less severe clinical course of infection, lower need for hospitalisation and mortality. However, the results need to be evaluated even in the context of new antivirals and monoclonal antibodies against SARS-CoV-2 or virus mutations with different biological behaviour.
- Klíčová slova
- COVID-19, SARS-CoV-2, haematological malignancy, monoclonal antibodies, mortality, vaccination,
- Publikační typ
- časopisecké články MeSH
With the arrival of the highly transmissible Omicron variants (BA.4 and BA.5), dentistry faces another seasonal challenge to preserve the biosafety of dental care and education. With the aim of protecting patients, students, teachers and healthcare professionals, this paper introduces a prospective sustainable biosafety setting for everyday dental care and education. The setting developed by dental clinicians, epidemiologists, and teachers of dentistry consists of a combination of modern technologies focused on the air-borne part of the viral pathway. The introduced biosafety setting has been clinically evaluated after 18 months of application in the real clinical environment. The protocol has three fundamental pillars: (1) UVC air disinfection; (2) air saturation with certified virucidal essences with nebulizing diffusers; (3) complementary solutions including telehealth and 3D printing. A pseudonymous online smart form was used as the evaluation method. The protocol operates on the premise that everybody is a hypothetical asymptomatic carrier. The results of a clinical evaluation of 115 patient feedbacks imply that no virus transmission from patient to patient or from doctor to nurse was observed or reported using this protocol, and vice versa, although nine patients retrospectively admitted that the clinic visit is likely to be infectious. Despite these promising results, a larger clinical sample and exposition to the current mutated strains are needed for reliable conclusions about protocol virucidal efficiency in current dental environments.
- Klíčová slova
- COVID-19, UVC, biosafety, dental education, dentistry, infection, orthodontics, prevention, sustainability, teledentistry, virucidal oil dispersion,
- MeSH
- COVID-19 * prevence a kontrola MeSH
- lidé MeSH
- omezování biologických rizik MeSH
- prospektivní studie MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 * genetika MeSH
- stomatologická péče MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. METHODS: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. RESULTS AND CONCLUSION: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.
- Klíčová slova
- COVID-19, consensus manuscript, hematological malignancies,
- MeSH
- COVID-19 * MeSH
- hematologické nádory * epidemiologie terapie MeSH
- konsensus MeSH
- lidé MeSH
- pandemie MeSH
- testování na COVID-19 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- směrnice pro lékařskou praxi MeSH
In a Plenary Paper, Mittelman and colleagues assess the relative clinical efficacy of mRNA vaccination on COVID-19 disease incidence and outcomes in patients with hematologic malignancies compared with healthy matched controls. This population-based study from Israel links prior observations of poor serologic responses to vaccination to higher risk for breakthrough infection, hospitalization, and death in patients with blood cancer, especially those on active antineoplastic therapy. In an accompanying Letter to Blood, Pagano et al provide supportive data using a multination survey approach to capture outcomes for COVID-19 in vaccinated patients with hematologic neoplasms. They also emphasize the higher risk among patients with lymphoid malignancies. Together, these findings argue for both continued deployment of booster programs and ongoing public health guidance for this vulnerable group.
- MeSH
- COVID-19 * imunologie mortalita prevence a kontrola MeSH
- dospělí MeSH
- hematologické nádory * imunologie mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- SARS-CoV-2 imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vakcína BNT162 aplikace a dávkování MeSH
- vakcína firmy Moderna proti COVID-19 aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- Názvy látek
- vakcína BNT162 MeSH
- vakcína firmy Moderna proti COVID-19 MeSH
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.
- Klíčová slova
- COVID-19, EHA, Epidemiology, Hematological malignancies, Pandemic,
- MeSH
- COVID-19 komplikace diagnóza epidemiologie terapie MeSH
- dospělí MeSH
- hematologické nádory komplikace epidemiologie terapie MeSH
- hospitalizace MeSH
- jednotky intenzivní péče MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- registrace MeSH
- rizikové faktory MeSH
- SARS-CoV-2 izolace a purifikace MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa epidemiologie MeSH