To Get Vaccinated or Not? The Vaccination Decision-Making by Healthcare Professionals Working in Haematology: A Qualitative Study.

Haematological patients are more susceptible to infections. Vaccination has always been the most effective primary prevention strategy, even during the COVID-19 pandemic. However, the efficacy of vaccines for some haematological patients is low. Although vaccination of Healthcare Workers (HCWs) could protect patients from vaccine-preventable diseases, there is evidence of a high level of hesitation among healthcare workers in Italy. The aim of this study was to explore the attitudes towards vaccination of HCWs caring for haematology patients. Qualitative descriptive design was conducted. Twenty-one HCWs were interviewed. Content analysis was applied to the qualitative data. The following themes were generated from the analysis: "Trust", "Decision-making process focusing on individual health", "Decision-making process focusing on community health", "Changing opinion", and "Two sides of vaccination commitment". The most hesitant HCWs were oriented towards individual health. They perceived a lack of benefit from vaccines, feared side effects, or were influenced by negative experiences of others. In contrast, community-health-oriented HCWs showed more positive attitudes towards vaccination. Some hesitant HCWs changed their opinion on vaccination because they began to reflect on the importance of vaccination for the community. The change in opinion of some HCWs interviewed provided insight into the importance of focusing organisational efforts on collective responsibility.

Outcome of COVID-19 patients with haematological malignancies after the introduction of vaccination and monoclonal antibodies: results from the HM-COV 2.0 study.

Patients with haematological malignancies (HM) and SARS-CoV-2 infection present a higher risk of severe COVID-19 and mortality. The aim of the study was to investigate whether vaccination and monoclonal antibodies (mAbs) have modified the outcomes of HM patients with COVID-19. This is a single-centre retrospective study in HM patients hospitalized due to SARS-CoV-2 infection from March 2020 to April 2022. Patients were divided into PRE-V-mAb group (patients hospitalized before the introduction of vaccination and mAbs) and POST-V-mAb group (patients hospitalized after the use of vaccine and mAbs). A total of 126 patients were included (65 PRE-V-mAb and 61 POST-V-mAb). POST-V-mAb patients showed a significantly lower risk of intensive care unit (ICU) admission (8.2% vs. 27.7%, p = 0.005), shorter viral shedding [17 (IQR 10-28) vs. 24 days (IQR 15-50), p = 0.011] and shorter hospitalization length [13 (IQR 7-23) vs. 20 (IQR 14-41) days, p = 0.0003] compared to the PRE-V-mAb group. Nevertheless, both in-hospital and 30-day mortality rates did not significantly differ between the two groups (29.5% POST-V-mAb vs. 36.9% PRE-V-mAb and 21.3% POST-V-mAb vs. 29.2% PRE-V-mAb, respectively). At the multivariable analysis, an active malignancy (p = 0.042), a critical COVID-19 at admission (p = 0.025) and the need for high-level of oxygen support at respiratory worsening [either HFNC/CPAP (p = 0.022) or mechanical ventilation (p = 0.011)] were independently associated with in-hospital mortality. In the subgroup of POST-V-mAb patients, receiving therapy with mAbs was a protective factor (p = 0.033). Despite the new therapeutic and preventive strategies available, HM patients with COVID-19 disease represent an extremely vulnerable group with still high mortality rates.

LGL leukemia patients exhibit substantial protective humoral responses following SARS-CoV-2 vaccination.

Large granular lymphocyte leukemia is a rare chronic lymphoproliferative disorder of cytotoxic cells. Other hematological malignancies such as CLL and multiple myeloma have been associated with poor vaccination response and markedly increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mortality rates, specifically in patients who have undergone immunosuppressive therapy. Given the immunosuppressive therapies often used to treat the disease, large granular lymphocytic (LGL) patients may be especially vulnerable to SARS-CoV-2 infection. A questionnaire was sent to all patients in the LGL Leukemia Registry at the University of Virginia (UVA) to obtain information on vaccination status, type of vaccine received, side effects of vaccination, patient treatment status before, during, and after vaccination, antibody testing, history of coronavirus disease 2019 (COVID-19) infection, and presence or absence of booster vaccination. Antibody testing of 27 patients who had quantitative SARS-CoV-2 Spike Protein IgG levels determined by University of Virginia medical laboratories via the Abbott Architect SARS-CoV-2 IgG II assay were collected. The assay was scored as reactive at a threshold of ≥50.0 AU/mL or nonreactive with a threshold of <50.0 AU/mL. LGL patients without treatment as well as patients who held treatment prior to their vaccination have a robust humoral response to SARS-CoV-2 vaccines. Patients who did not hold their immunosuppressive treatments have signifigantly diminished vaccine response compared to those who held their immunosuppressive treatment. Our findings support a dual strategy of pausing immunotherapy during the vaccination window and administration of the SARS-CoV-2 booster to all LGL leukemia patients to maximize protective antibodies.

Predictive model for BNT162b2 vaccine response in cancer patients based on blood cytokines and growth factors.

Background: Patients with cancer, especially hematological cancer, are at increased risk for breakthrough COVID-19 infection. So far, a predictive biomarker that can assess compromised vaccine-induced anti-SARS-CoV-2 immunity in cancer patients has not been proposed. Methods: We employed machine learning approaches to identify a biomarker signature based on blood cytokines, chemokines, and immune- and non-immune-related growth factors linked to vaccine immunogenicity in 199 cancer patients receiving the BNT162b2 vaccine. Results: C-reactive protein (general marker of inflammation), interleukin (IL)-15 (a pro-inflammatory cytokine), IL-18 (interferon-gamma inducing factor), and placental growth factor (an angiogenic cytokine) correctly classified patients with a diminished vaccine response assessed at day 49 with >80% accuracy. Amongst these, CRP showed the highest predictive value for poor response to vaccine administration. Importantly, this unique signature of vaccine response was present at different studied timepoints both before and after vaccination and was not majorly affected by different anti-cancer treatments. Conclusion: We propose a blood-based signature of cytokines and growth factors that can be employed in identifying cancer patients at persistent high risk of COVID-19 despite vaccination with BNT162b2. Our data also suggest that such a signature may reflect the inherent immunological constitution of some cancer patients who are refractive to immunotherapy.

Supportive care and symptom management in patients with advanced hematological malignancies: a literature review.

BACKGROUND AND OBJECTIVE: Recent advances have led to cure or long-term disease control for patients with hematological malignancy (HM). Unfortunately, some of them still have poor prognoses and are often associated with significant symptom burden and poor quality of life for patients and families. These patients usually require supportive care including red blood cell and platelet transfusion, due to disease itself and the oncological treatment, apart from their symptom management. However, there is currently lack of the literatures review in these aspects. The objective of this review is to summarize practical supportive care recommendations for physicians or nurses practicing in palliative care (PC)/hematology-oncology unit, starting with core approaches in use of blood products for anemia and thrombocytopenia, management of tumor lysis syndrome, PC and oncology nursing care. METHODS: Evidence for this review was obtained from a search of the Cochrane database, PubMed, guidelines of European Society of Medical Oncology, British society of Hematology, American Society of Clinical Oncology, National Comprehensive Cancer Network and peer-reviewed journal articles. KEY CONTENT AND FINDINGS: For asymptomatic cancer patients who are anaemic, a threshold of haemoglobin level of 7 g/dL is considered to be safe and generally favored for blood transfusion. 'Single-unit' red cell transfusion is safer and at least as effective as 'double-unit' transfusion. Prophylactic platelet transfusion should be given to stable patients without bleeding and with platelet count less than 10×109/L. In febrile patients, the threshold is lifted to 20×109/L. There are also recommendations for the use of blood products during COVID-19 pandemic. In general, HM patients were more prone to painful infections when compared with solid cancer patients. Thus, antibiotics to treat underlying infections should be applied whenever possible and as required to control pain. CONCLUSIONS: This narrative review showed the recent literatures in the supportive care and symptom management of advanced HM patients. However, it is limited by some of the 'evidence-based' recommendations for interventions (including symptom management) based on early phase of HM populations rather than those receiving end-of-life care.

COVID-19 infection in patients with haematological disease - A tertiary centre experience from north India.

This retrospective study was aimed to understand the clinical, laboratory, radiological parameters and the outcome of COVID-19 patients with underlying haematological disease. All patients with known haematological disease admitted with COVID-19-positive status from April to August 2020 in the COVID-19 facility of a tertiary care centre in north India, were included. Their medical records were analyzed for outcome and mortality risk factors. Fifty four patients, 37 males, were included in the study. Of these, 36 patients had haematological malignancy and 18 had benign disorder. Fever (95.5%), cough (59.2%) and dyspnoea (31.4%) were the most common symptoms. Nine patients had severe disease at diagnosis, mostly malignant disorders. Overall mortality rate was 37.0 per cent, with high mortality seen in patients with aplastic anaemia (50.0%), acute myeloid (46.7%) and lymphoblastic leukaemia (40.0%). On univariate analysis, Eastern Cooperative Oncology Group performance status >2 [odd ratio (OR) 11.6], COVID-19 severity (OR 8.2), dyspnoea (OR 5.7) and blood product transfusion (OR 6.4) were the predictors of mortality. However, the presence of moderate or severe COVID-19 (OR 16.6, confidence interval 3.8-72.8) was found significant on multivariate analysis. The results showed that patients with haematological malignancies and aplastic anaemia might be at increased risk of getting severe COVID-19 infection and mortality as compared to the general population.

Neutralizing monoclonal antibodies in haematological patients paucisymptomatic for COVID-19: The GIMEMA EMATO-0321 study.

COVID-19 continues to be a relevant issue among patients with haematological malignancies (HM). Vaccines are frequently not effective in subjects on active treatment. In this multicentre retrospective study of Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA), we collected data from 91 paucisymptomatic HM patients treated with anti-spike neutralizing monoclonal antibodies (nMoAbs) to determine time to viral clearance, referencing it to the expected value of 28 days from an historical group of untreated paucisymptomatic patients. Secondary endpoints included rate of hospitalization, intensive care unit (ICU) admission, COVID-19 related death and safety. SARS-CoV-2 molecular swab negativity was obtained in 86 patients (95%), with a median time of 18 days (IQR 13-26; p < 0.0001). We did not find significant variations according to age, diagnosis, treatment type, vaccination status or nMoAbs type. Rate of hospitalization due to COVID-19 progression was 12% (11/91), with 2 patients (2.2%) requiring ICU admission. With a median follow-up of 2.33 months, the overall mortality was 5.5% (5/91), with 3 deaths due to COVID-19. Side effects were rare and self-limiting. Our data suggest that nMoAbs can limit the detrimental effect of immunosuppressive treatments on COVID-19 clinical progression and time to viral clearance. The original trial was registered at www.clinicaltrials.gov as #NCT04932967.

COVID-19 vaccination in cancer patients: a narrative review.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected over 220 million individuals worldwide, and has been shown to cause increased disease severity and mortality in patients with active cancer versus healthy individuals. Vaccination is important in reducing COVID-19-associated morbidity and mortality. Thus, the aim of this article was to review the existing knowledge on effectiveness, immunogenicity and safety of COVID-19 vaccines in patients with cancer. Fifty-four articles were included following a search of PubMed and Google Scholar databases for studies published between January 2020 and September 2021 that investigated humoral and cell-mediated immune responses following COVID-19 vaccination in patients with cancer. Immunogenicity of vaccines was found to be lower in patients with cancer versus healthy individuals, and humoral immune responses were inferior in those with haematological versus solid cancers. Patient-, disease-, and treatment-related factors associated with poorer vaccine responses should be identified and corrected or mitigated when possible. Consideration should be given to offering patients with cancer second doses of COVID vaccine at shorter intervals than in healthy individuals. Patients with cancer warrant a third vaccine dose and must be prioritized in vaccination schedules. Vaccine adverse effect profiles are comparable between patients with cancer and healthy individuals.

Key findings from the UKCCMP cohort of 877 patients with haematological malignancy and COVID-19: disease control as an important factor relative to recent chemotherapy or anti-CD20 therapy.

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.

Clinical profile and outcome of COVID-19 in haematological malignancies: experience from tertiary care centre in India.

There is limited evidence on various clinical aspects of SARS-CoV-2 infection in patients with haematological cancers. The risk factors, prognosis, and outcome of patients with haematological cancers with coexistent COVID-19 need to be explored in different subsets of population. A single-institutional prospective observational study was conducted at a tertiary level medical institute in North India. The clinical details of the recruited patients having haematological malignancies and diagnosed with COVID-19 between 15 March 2020 and 31 May 2021 were prospectively collected through the electronic patient database system. The outcomes with respect to 28-day and 56-day mortality and the associated risk factors for prognostication were analysed. Of the 5750 hospital admissions (inpatient and day-care) during the study period, two hundred and forty-two patients (4.2%) were diagnosed with COVID-19. Acute leukaemia was the most common haematological malignancy, seen in 117 (48.3%) patients. Eighty-nine (36.8%) patients had moderate-to-severe COVID-19 while 153 (63.2%) patients presented with mild infection. The 28-day and 56-day mortality rates in our cohort were 13.3% and 19.8% respectively. Amongst the risk factors associated with poor outcome, the severity of COVID-19 (HR = 1.8, 95% CI 1.16-10.35; p = 0.04), presence of secondary infection (HR = 2.1, 95% CI 2.45-21.3; p = 0.023), and need for invasive mechanical ventilation (HR = 2.3, 95% CI 1.8-18.43; p = 0.01) were prognostically significant on multivariate log rank analysis. The risk of SARS-CoV-2 infection does not increase with haematological malignancies; however, the outcome remains poor in patients with severe COVID-19, requirement of invasive mechanical ventilation, and pre-existing bacterial/fungal infection at presentation.

Lymphocyte subsets in haematological patients with COVID-19: Multicentre prospective study.

The role of immune dysregulation in the course and prognosis of COVID-19 is not clearly established. In particular, immune status in specific populations such as haematological patients, who have an impaired immunological system, has not been described so far. Here, we performed a comprehensive analysis of peripheral blood lymphocyte subsets in 27 SARS-CoV-2-infected patients, including 16 patients with haematological malignancies. We identified T cell subpopulations, B cells, NK cells and TCR α/ß and É£/ƍ-expressing T cells during COVID-19 infection, with significant changes observed in immune profiles during the course of disease, especially in haematological patients. We observed an increase in activated T lymphocytes (CD3+HLA-DR+ and CD3+CD8+HLA-DR+) in the early stages of SARS-CoV-2 infection with a concomitant decrease in the CD4/CD8 ratio in haematological patients compared to non-haematological patients affected by COVID-19. We also found a decrease in É£/ƍ T cells in both studied groups of patients, with lower numbers of CD25+ T cells and CD16+CD56+ NK cells in haematological patients compared to non-haematological patients with COVID-19. Our findings demonstrate, for the first time, impaired adaptive immunity in patients with haematological malignancies infected with COVID-19, resulting in impaired cellular immune responses to SARS-CoV-2. This warrants further investigation of this disease group in COVID-19 patient cohorts.

Rapidly established telehealth care for blood cancer patients in Nepal during the COVID-19 pandemic using the free app Viber.

National lockdown to control the spread of COVID-19 in Nepal started in March 2020. This lockdown mandated closure of private and public transportation. The patients with hematological malignancies were at risk of delayed consultation, admission and missing scheduled chemotherapy. Since there is no official tele-health or e-health system established in hospitals, we decided to use Viber, a free text and call app to trace and provide information about patient admission and treatment schedule. This use of Viber during the pandemic was found to be very helpful, none of the patients missed chemotherapy and we were able to admit more patients than before. Patients found this strategy very convenient and cost-effective and suggested that we continue this service in future even after the lockdown is lifted. This preliminary experience of using Viber for cancer care consultations in Nepal at the time of the COVID-19 pandemic suggests the utility and acceptability of using mobile technology to improve access to health care services in a low-income country. Further pre-planned well conducted studies are needed to assess the outcomes of using this technology.

Nosocomial outbreak of SARS-CoV-2 infection in a haematological unit - High mortality rate in infected patients with haematologic malignancies.

BACKGROUND: Here we report nosocomial outbreak of COVID-19 among patients in a haematological unit. To our knowledge this is the first report from Central Europe comparing morbidity and mortality in infected and non-infected patients after exposure to SARS-CoV-2. METHODS: The outbreak involved 39 individuals: 19 patients and 20 health care workers. The SARS-CoV-2 test by nasopharyngeal swabs was performed by real-time RT-PCR. Exposed patients were divided into two groups: quarantine patients with and without COVID-19. All patients were prospectively examined at the following time points: 0, 7 days, 14 days, 21 days and 28 days after confirmation or exclusion of SARS-CoV-2. RESULTS: Infection was confirmed in a total of 5/20 health care workers and 10/19 patients. Among the patients positive for SARS-CoV-2 infection, the mortality rate was 36.8 %. The probability of death in patients infected with SARS-CoV-2 increased 8-fold (p = 0.03). Bacterial, fungal, and viral co-infection significantly decreased survival in these patients (p < 0.05). Additionally, the probability of death was much higher in patients older than 40 years of age (p = 0.032). CONCLUSION: This study showed significantly higher mortality rate in COVID-19 patients with haematologic diseases compared to the non-infected patient group. Haematologic patients with COVID-19 have 50 % less chance of survival.

Managing the front-line treatment for diffuse large B cell lymphoma and high-grade B cell lymphoma during the COVID-19 outbreak.

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.

Haematological cancers and the risk of severe COVID-19: Exploration and critical evaluation of the evidence to date.

From the outset of the COVID-19 pandemic, patients and healthcare professionals have been concerned that a history of haematological malignancy will lead to an increased risk of severe COVID-19. This led to the UK government advising patients with blood cancers to shield, massive re-organisation of NHS haematology and cancer services, and changes in treatment plans for thousands of patients. Given the unknown effects that relaxation of social-distancing measures will have on the infection rate, we review the evidence to date to see whether a history of haematological malignancy is associated with increased risk of COVID-19. Multivariable analysis of large population studies, taking other known risk factors into account, do indicate that patients with haematological malignancy, especially those diagnosed recently, are at increased risk of death from COVID-19 compared to the general population. The evidence that this risk is higher than for those with solid malignancies is conflicting. There is suggestive evidence from smaller cohort studies that those with myeloid malignancy may be at increased risk within the blood cancer population, but this needs to be confirmed on larger studies. Ongoing large collaborative efforts are required to gain further evidence regarding specific risk factors for severe complications of COVID-19.