RESUMO
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.
Assuntos
Antígenos CD20/imunologia , Antineoplásicos Imunológicos/uso terapêutico , COVID-19/complicações , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Adulto , Antineoplásicos Imunológicos/efeitos adversos , COVID-19/etiologia , COVID-19/imunologia , Feminino , Neoplasias Hematológicas/imunologia , Humanos , Leucemia/complicações , Leucemia/tratamento farmacológico , Leucemia/imunologia , Masculino , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/imunologia , Estudos Prospectivos , Fatores de RiscoRESUMO
Regulatory T (Treg) cells contribute to immune evasion by malignancies. To investigate their importance in non-Hodgkin lymphoma (NHL), we enumerated Treg cells in peripheral blood mononuclear cells (PBMCs) and involved tissues from 30 patients. CD25(+)FoxP3(+)CD127(low)CD4(+) Treg cells were increased markedly in PBMCs (median = 20.4% CD4 T cells, n = 20) versus healthy controls (median = 3.2%, n = 13, P < .001) regardless of lymphoma subtype, and correlated with disease stage and serum lactate dehydrogenase (R(s) = 0.79, P < .001). T-cell hyporesponsiveness was reversed by depleting CD25(+) cells, or by adding anti-CTLA-4, supporting the view that Treg cells explain the systemic immunosuppression seen in NHL. A high proportion of Treg cells was also present in involved tissues (median = 38.8% CD4 T cells, n = 15) versus reactive nodes (median = 11.6%, n = 2, P = .02). When autologous CD25(-) PBMC fractions were incubated with tumor cells from patients (n = 6) in vitro, there was consistent strong induction and then expansion of cells with the CD4(+)CD25(+)FoxP3(+) phenotype of classic "natural" Treg cells. This population was confirmed to be suppressive in function. Direct cell-cell interaction of tumor cells with CD25(-) PBMCs was important in Treg induction, although there was heterogeneity in the mechanisms responsible. We conclude that NHL cells are powerful inducers of Treg cells, which may represent a new therapeutic target.
Assuntos
Linfoma não Hodgkin/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Evasão Tumoral/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Citometria de Fluxo , Humanos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/citologiaRESUMO
Minor CLL-like clones are found in approximately 3% of healthy individuals. AIHA and ITP are common in CLL and may be causally linked. We investigated the presence of CLL phenotype lymphocytes in 11 cases of primary AIHA, 18 of ITP and 2 of Evans' Syndrome, compared with 26 age-matched healthy controls. A population of 'CLL phenotype' was seen in 6/31 patients compared to 1/26 healthy controls (chi(2)=3.9; p=0.05). Such clones may be important in the pathogenesis of autoimmune blood disorders.
Assuntos
Anemia Hemolítica Autoimune/sangue , Leucemia Linfocítica Crônica de Células B/genética , Linfócitos/metabolismo , Púrpura Trombocitopênica Idiopática/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Hemolítica Autoimune/genética , Estudos de Casos e Controles , Separação Celular , Citometria de Fluxo , Humanos , Pessoa de Meia-Idade , Fenótipo , Púrpura Trombocitopênica Idiopática/genética , SíndromeRESUMO
Recombinant activated factor VII (rVIIa) was initially used for the treatment of inhibitors in patients with haemophilia. However, its localised mode of action at sites of damage to the vessel combined with dramatic clinical observations in exsanguinating patients have resulted in huge interest in its use as a global haemostatic agent. Although it appears safe, with no obvious excess of thrombotic events, its use in assorted acquired bleeding disorders, especially those associated with the development of complex coagulopathies, such as in the post-trauma state, has proved to be less dramatic than hoped.