Impaired adaptive immune response in COVID-19 convalescent patients with hematological malignancies.

OBJECTIVES: The immune dysregulation during SARS-CoV-2 has the potential to worsen immune homeostasis after recovery. Patients with hematological malignancies with COVID-19 have changes both in the innate and adaptive immune responses. Little is known about the severity of immune dysfunction following recovery from COVID-19 in hematological patients. METHODS: Here, we performed a comprehensive analysis of the lymphocyte subsets in peripheral blood mononuclear cells by FACS Canto II in 55 patients, including 42 with hematological malignancies 4-6 weeks after COVID-19. RESULTS: Hematological COVID-19 convalescents had deep reduction in CD3+ T cells, including helper T cells (CD3 + CD4+), naïve helper T cells (CD3 + CD4 + CD45RA+), and memory CD4+ T cells among with extremely low levels of Treg cells and decreased expression of both TCRα/ß and TCRγ/δ. Severe immune dysregulation in hematological convalescents was expressed by increased activation of T lymphocytes, both as elevated levels of activated T cells (CD3 + HLA-DR+) and activated cytotoxic T cells (CD3 + CD8 + HLA-DR+). CONCLUSIONS: Our findings showed a profound impairment of the adaptive immune response in hematological convalescents which might be a result of persistent activation of T cells. Convalescents with lymphoid malignancies showed more pronounced depletion of key T lymphocytes subpopulations in creating an effective adaptive response and immune memory.

A survey across orbital lymphoma in Poland: Multicenter retrospective study of polish lymphoma research group (PLRG).

OBJECTIVE: To investigate the prevalence of histopathological subtypes, the clinical stage at presentation and treatment modalities in Polish patients with orbital lymphoma (OL) and to determine prognostic outcomes. METHODS: The retrospective study of 107 patients with OL treated in a 14-year period in Polish hematological centers. The analysis included histopathological subtype, disease clinical advancement, treatment modalities, progression-free survival (PFS), and overall survival (OS). RESULTS: The median patient age was 60 years (range 51-71). Mucosa-associated lymphoid tissue (MALT) lymphoma accounted for slightly more than half of all cases of orbital lymphoma (51%). The second most common subtype was diffuse large B-cell lymphoma (DLBCL) (29%). Primary orbital lymphoma was diagnosed in 48% of all patients. According to the Ann Arbor, localized stage IE of orbital lymphoma was diagnosed only in 39% of all patients. Systemic involvement was observed in more than half of all patients (52%). The median follow-up period was 30 months (range 0-160 months). Patients with non-MALT lymphoma had a significantly inferior PFS compared to patients with MALT lymphoma, (p = 0.047). Patients with primary orbital lymphoma had a superior PFS compared to patients with secondary orbital lymphoma [median PFS 104.5 months vs. 33.4 months], (p = 0.069). Younger patients with MALT lymphoma were characterized by superior PFS (median PFS not reached) compared to other studied subgroups of patients (older patients with MALT lymphoma, younger and older non-MALT lymphoma patients) with a median PFS of 30.5, 32.2, 32.6 months respectively (p = 0.039). Patients treated with chemotherapy alone had inferior PFS compared to patients treated with combined therapies (p = 0.034). The median PFS across patients who received chemotherapy alone was 23.7 months, whereas across other patients was 73.9 months. CONCLUSIONS: Secondary lymphoma accounts for more than half of the orbital lymphoma in Polish population. The advanced clinical stage of the disease (non-IE according to Ann Arbor) concerns two-thirds of the overall population of patients with orbital lymphomas and one-third of MALT lymphoma patients. The high incidence of advanced stages of orbital lymphoma may indicate the need for combined treatment. Combined orbital lymphoma treatment is associated with superior PFS compared to chemotherapy alone in overall population of patients with orbital lymphoma.

The Risk of Autoimmunity Development following mRNA COVID-19 Vaccination.

The broad spectrum of interactions between autoimmune diseases and the SARS-CoV-2 vaccination is not fully understood. This study aims to evaluate the prevalence of anti-nuclear antibodies (ANA), anti-ENA, anticardiolipin antibodies (ACL), and anti-beta-2 glycoprotein I antibodies (anti-ß2GPI) before and after the SARS-CoV-2 mRNA vaccination in a real-life setting in healthcare professionals. The identification of risk factors associated with vaccine immunogenicity was evaluated. The study group consisted of employees of two hospitals (354 individuals). Samples for antibody assays were collected before vaccination and at 7-9 months after complete immunisation. There was no significant increase in the prevalence of ANA, ACL or anti-ß2GPI antibodies, or autoimmune diseases in subjects who were vaccinated 7-9 months after complete immunisation. In terms of detected anti-ENA, the anti-DFS70 antibodies were found in 6 times more subjects than before vaccination at the second blood draw (in 18 and 3 subjects, respectively) (p = 0.001). There were no significant relationships between a SARS-CoV-2 infection history, humoral response, cellular response, subject category, smoking, sex, body weight, ANA, anti-ENA, ACL, or anti-ß2GPI. This study revealed a possible association between the severity of vaccine adverse events (VAEs) and ANA titre. Individuals with more severe VAEs (>10 points) after the second dose of the vaccine had significantly higher ANA titre after complete immunization. When analysing the significance of time between the ANA, anti-ENA, ACL, and anti- ß2GPI assays and complete immunisation antibody values, no qualitative result was statistically significant. There was correlation between the time since complete immunization and ANA after.

The assessment of the risk of COVID-19 infection and its course in the medical staff of a COVID-only and a non-COVID hospital.

BACKGROUND: Medical workers are a group that is particularly vulnerable to infection during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVES: The study aimed to assess the risk of COVID-19 infection and its course in the medical staff of a COVID-only and a non-COVID hospital. MATERIAL AND METHODS: The observational study included 732 participants who were medical workers. The study was conducted between June 2020 and December 2020, before widespread COVID-19 immunization was introduced. RESULTS: Of the 732 employees of the hospitals, 377 had a history of COVID-19. The risk of disease was twice as high in the medical staff of the COVID-only hospital compared to the medical staff of the non-COVID hospital (odds ratio (OR) = 2.0; p < 0.001). Among medical personnel, 20.6% of the participants were asymptomatic and 6.4% required hospitalization. For the non-COVID hospital, the employees who were most frequently infected with COVID-19 were nurses/paramedics/medical caretakers. The factor influencing the risk of infection was body mass index (BMI; OR = 1.05; p = 0.004). The risk of COVID-19 infection was lower in the influenza vaccine group (OR = 2.23, p < 0.001). CONCLUSIONS: The study results indicate that employees of the hospital treating only COVID patients have a higher risk of infection. Previous observations on factors predisposing to COVID-19 infection like gender and BMI were confirmed. However, the observations carried out on the studied population did not confirm the influence of other factors, such as the coexistence of chronic diseases (apart from diabetes) on the risk of developing COVID-19. In addition, we noticed that seasonal influenza vaccination has a beneficial effect in patients with COVID-19 infection.

Complete (Humoral and Cellular) Response to Vaccination against COVID-19 in a Group of Healthcare Workers-Assessment of Factors Affecting Immunogenicity.

Vaccination is the best way to limit the extent of the COVID pandemic. Knowledge of the duration of the immune response will allow the planning of a vaccination protocol. This study aims to validate the complete (humoral and cellular) immune responses over time in large population groups following the full vaccination of healthcare professionals in real-life conditions and to assess the relationship between antibody levels and T-cell activity in relation to the characteristics of the study group. The samples for the study were obtained from volunteers (staff of two hospitals) on three occasions: before vaccination, T0, then 4-9 weeks after full vaccination (two doses BNT162b2), T1, and 7-9 months after vaccination, T2. The humoral response was investigated by the titre of anti-SARS-CoV-2 IgG antibodies to S1 protein. Assays were performed three times at intervals. The cellular response was assessed in a subgroup of 189 subjects by QuanT-Cell SARS-CoV-2 (IGRA). The assay was performed once. A group of 344 subjects fully vaccinated with the BNT162b2 vaccine were included in the study. The humoral response was observed in 100% of subjects at both 4-7 weeks and 7-9 months, but antibody titres fell by almost 90% in this interval. The cellular response was observed in 94% (177/189) of subjects 7-9 months after the second dose of vaccine. In subjects with a negative cellular response, eight out of 12 smoked. A factor associated with greater immunogenicity of vaccination was past SARS-CoV-2 infection. The administration of full BNT162b2 vaccination (two doses) induces humoral and cellular responses detectable even more than six months after vaccination. Smoking may be a factor associated with impaired cellular response to vaccination.

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.

Response to the Therapy in Hairy Cell Leukemia: Systematic Review and Meta-Analysis.

Hairy cell leukemia is an uncommon chronic B-cell lymphoproliferative disorder. Various treatment options are available. The objective of the study was to evaluate through meta-analysis the pooled proportions of patients responding to each therapeutic agent. We conducted a systematic review and meta-analysis to estimate the pooled response rate to modern hairy cell leukemia therapies. Articles published between January 1992 and August 2017 were identified by searching PubMed, Web of Science, and the Cochrane Library. Weighted meta-analysis of proportion using a random-effects model was performed for each treatment option. Of 3287 articles viewed, 20 articles describing 21 studies were included in the meta-analysis. The pooled random effect of the response rate was up to 99% in both cladribine with rituximab at 0.99 (95% confidence interval [CI], 0.98-1.0) and vemurafenib treatment at 0.99 (95% CI, 0.95-1.0). The pooled random effect of the complete response rate was up to 97% (0.97; 95% CI, 0.88-1.0) in cladribine followed by rituximab. The most effective therapy in patients treatment naïve and in first relapse was cladribine with rituximab maintenance.

Efficacy and Safety of Bendamustine and Ibrutinib in Previously Untreated Patients With Chronic Lymphocytic Leukemia: Indirect Comparison.

Bendamustine and ibrutinib are commonly used in the treatment of patients suffering from chronic lymphocytic leukemia (CLL). In this study we compare efficacy and safety bendamustine versus ibrutinib therapy in previously untreated patients with CLL. Because there are no head-to-head comparisons between bendamustine and ibrutinib, we performed indirect comparison using Bucher method. A systematic literature review was performed and 2 studies published before June 2016 were taken into analysis. Treatment with ibrutinib significantly improves PFS determined by investigator (HR of 0.3; P = .01) and OS (HR of 0.21; P < .001. Our study indicates that ibrutinib therapy improves PFS, OS and is superior in terms of safety comparing with bendamustine therapy in CLL patients.