In-hospital mortality among immunosuppressed patients with COVID-19: Analysis from a national cohort in Spain

Background Whether immunosuppressed (IS) patients have a worse prognosis of COVID-19 compared to non-IS patients is not known. The aim of this study was to evaluate the clinical characteristics and outcome of IS patients hospitalized with COVID-19 compared to non-IS patients. Methods We designed a retrospective cohort study. We included all patients hospitalized with laboratory-confirmed COVID-19 from the SEMI-COVID-19 Registry, a large multicentre national cohort in Spain, from March 27th until June 19th, 2020. We used multivariable logistic regression to assess the adjusted odds ratios (aOR) of in-hospital death among IS compared to non-IS patients. Results Among 13 206 included patients, 2 111 (16.0%) were IS. A total of 166 (1.3%) patients had solid organ (SO) transplant, 1081 (8.2%) had SO neoplasia, 332 (2.5%) had hematologic neoplasia, and 570 (4.3%), 183 (1.4%) and 394 (3.0%) were receiving systemic steroids, biological treatments, and immunosuppressors, respectively. Compared to non-IS patients, the aOR (95% CI) for in-hospital death was 1.60 (1.43–1.79) for all IS patients, 1.39 (1.18–1.63) for patients with SO cancer, 2.31 (1.76–3.03) for patients with haematological cancer and 3.12 (2.23–4.36) for patients with SO transplant. The aOR (95% CI) for death for patients who were receiving systemic steroids, biological treatments and immunosuppressors compared to non-IS patients were 2.16 (1.80–2.61), 1.97 (1.33–2.91) and 2.06 (1.64–2.60), respectively. IS patients had a higher odds than non-IS patients of in-hospital acute respiratory distress syndrome, heart failure, myocarditis, thromboembolic disease and multiorgan failure. Conclusions IS patients hospitalized with COVID-19 have a higher odds of in-hospital complications and death compared to non-IS patients.

ETV6: A Candidate Gene for Predisposition to “Blend Pedigrees”? A Case Report from the NEXT-Famly Clinical Trial

Background. The identification of germline mutations in familial leukemia predisposition genes by next generation sequencing is of pivotal importance. Lately, some “blend pedigrees” characterized by both solid and hematologic malignancies have been described. Some genes were recognized as related to this double predisposition, while the involvement of others is still a matter of debate. ETV6 was associated with hematologic malignancies, in particular myeloid malignancies, and recently described as mutated also in oncologic patients. No clear evidences in its involvement in blend pedigrees are known. Case Presentation. We present our recent experience in the identification of an ETV6-mutated “blend pedigree,” suggesting the involvement of ETV6 in the predisposition to both solid and hematologic neoplasia. The pedigree recognition started with a MDS case enrolled in the NEXT-Famly protocol. The patient presented 9 relatives affected by solid tumors and hematological malignancies. Following the clinical trial protocol, the patient underwent NGS analysis, which confirmed the presence of a mutation on the noncoding region of ETV6 both on tumor and on germline DNA. The mutation resulted was shared by the still alive affected relatives. Conclusion. This evidence supports the involvement of ETV6 in the predisposition to both solid and hematologic neoplasia and the importance of the investigation of the noncoding regions of the genes as recently suggested by different expert groups.

Cumulative incidence of hematological neoplasms and dynamic of this in different regions of the Cherkasy oblast in 1980, 1989, 2001 and 2014 years

The purpose of the study was to analyze the cumulative incidence of hematological neoplasia and evaluate the dynamics of this in different regions of Cherkasy oblast in 1980, 1989, 2001, 2014 yy. Materials and methods. The epidemiological parameters of hematological neoplasms in the radiation-contaminated (RC), chemically contaminated (CC), radiation and chemically contaminated (RCC), conditionally clean (CNC) regions of Cherkassy oblast (CO) in 1980, 1989, 2001, 2014 yy. were analyzed. Classification of CO territories to the RC, CC, RCC, CNC regions was conducted based on reports of the dosimetry certification of all settlements of Ukraine after the Chernobyl accident and the results of determination of the level of chemical contamination by the sanitary and epidemiological service during 1980-2014 yy. Results. It was determined, that, at the limit of statistical significant (p = 0.057), on the RC territory of CO in 2001 year the relative risk for the cumulative incidence of hematologic neoplasia was on 1.41 times higher (18,682 (95 % confidence interval (CI) = 14,426 – 16,879) against 13,187 (95 % CI = 9,495 – 16,879)), compared with CNC region. In addition, in the RC territory from 1989 to 2001 year the increasing at 9,342 times (1,999 (95% CI = 0.69–3.305) versus 18,682 (95% CI = 14.426 – 16.879)) of cumulative incidence of the hematopoietic and lymphoid systems neoplasm was detected. It is proved, that in the CNC region from 2001 to 2014 year at 1,791 times (13,187 (95% CI = 9.495 – 16.879) versus 23,619 (95% CI = 18.412 – 28.826)) higher level of the cumulative incidence of hematologic neoplasia was observed. Conclusions. In the CO, which was polluted by the radiation factor because of the Chernobyl nuclear power plant accident, 5 years after that, in 2001 was detected the increasing of the relative risk of hematologic neoplasia, compared to that on the CNC region. In addition, on the RC territory from 1989 to 2001 year the increasing at 9,342 times of the incidence of hematopoietic and lymphoid system tumors was observed. This is evidence of pro-leukemic effects of ionization radiation and, probably, the increase in the diagnostic potential of the hematological service of the CO.

Epidemiological Profile of Patients with Hematological Neoplasms in an Oncological Hospital of Mato Grosso

O objetivo do estudo foi analisar os aspectos epidemiológicos de pacientes adultos com diagnóstico de neoplasia hematológica, no período de 2004 a 2014, em um Hospital Oncológico em Mato Grosso. A coleta de dados foi realizada através de busca e análise de 590 prontuários. Entre os pacientes, 335 (56,8%) eram do sexo masculino (p<0,05). A maioria possuía mais de 50 anos (p<0,05), com idade média de 53,97±16,55 anos. Quanto ao local de procedência, 257 pacientes eram provenientes da região metropolitana de Cuiabá (43,6%) e 333 (56,4%) de outros locais (p<0,05). A maioria eram pacientes não brancos (p<0,05) e solteiros 342 (58%) (p<0,05). Em relação ao tratamento, 537 (91%) pacientes utilizavam quimioterapia (p<0,05), 57 (9,7%) fizeram uso da radioterapia (p<0,05). Cinquenta e quatro (9,2%) pacientes fizeram uso de ambas as terapias de forma associada (p<0,05) e 50 pacientes (8,4%) não fizeram uso de radioterapia e nem de quimioterapia. Referente aos tipos de neoplasia, os diagnósticos mais encontrados na análise foram de: leucemia mielóide crônica 131 (22,2%); linfoma não Hodking 119 (20,2%); mieloma múltiplo 93 (15,8%); trombocitemia essencial 49 (8,3%); linfoma de Hodking 39 (6,6%); leucemia linfocítica crônica 38 (6,4%); policetemia vera 34 (5,8%); leucemia mielóide aguda 27 (4,6%); síndrome mielodisplasica 21 (3,6); leucemia linfocítica aguda 13 (2,2%) e síndrome mieloproliferativa 10 (1,7%) (p<0,05). A partir dos resultados deste estudo, pode-se concluir que, em geral, os pacientes mais acometidos pelas neoplasias hematológicas tinham mais de 50 anos, eram homens, provenientes do interior do Estado, não brancos e solteiros.Palavras-chave: Doenças Hematológicas. Epidemiologia. Leucemia.AbstractThe objective of this study was to analyze the epidemiological aspects of adult patients diagnosed with hematologic neoplasia, from 2004 to 2014, at a Cancer Hospital in Mato Grosso. Data collection was performed through the search and analysis of 590 patient records. Among the patients, 335 (56.8%) were male (p <0.05). The majority was older than 50 years (p <0.05), with a mean age of 53.97 ± 14.95 years. Regarding origin, 257 patients came from the metropolitan region of Cuiabá (43.6%) and 333 (56.4%) from other sites (p <0.05). The majority was non-white patients (p <0.05) and unmarried 342 (58%) (p <0.05). About treatment, 537 (91%) patients used chemotherapy (p <0.05), 57 (9.7%) used radiotherapy (p <0.05). Fifty-four (9.2%) patients used both therapies in an associated way (p <0.05) and 50 patients (8.4%) did not use either radiotherapy or chemotherapy at any time of their treatment. Regarding the types of neoplasia, the diagnoses most found in the analysis were: chronic myelogenous leukemia 131 (22.2%); non Hodking lymphoma 119 (20.2%); multiple myeloma 93 (15.8%); essential thrombocythemia 49 (8.3%); Hodgkin's lymphoma 39 (6.6%); chronic lymphocytic leukemia 38 (6.4%); policetemia vera 34 (5.8%); acute myeloid leukemia 27 (4.6%); myelodysplastic syndrome 21 (3,6); acute lymphocytic leukemia 13 (2.2%) and myeloproliferative syndrome 10 (1.7%) (p <0.05). From the results of this study, it can be concluded that, in general, the most affected patients by hematological malignancies were older than 50 years, were men from the interior of the State, non-white and unmarried.Keywords: Hematologic Diseases. Epidemiology. Hodgkin Lymphoma. Leukemia.

The impact of Mir-9 regulation in normal and malignant hematopoiesis

MicroRNA-9 (MiR-9) dysregulation has been observed in various cancers. Recently, MiR-9 is considered to have a part in hematopoiesis and hematologic malignancies. However, its importance in blood neoplasms is not yet well defined. Thus, this study was conducted in order to assess the significance of MiR-9 role in the development of hematologic neoplasia, prognosis, and treatment approaches. We have shown that a large number of MiR-9 targets (such as FOXOs, SIRT1, CCND1, ID2, CCNG1, Ets, and NFkB) play essential roles in leukemogenesis and that it is overexpressed in different leukemias. Our findings indicated MiR-9 downregulation in a majority of leukemias. However, its overexpression was reported in patients with dysregulated MiR-9 controlling factors (such as MLLr). Additionally, prognostic value of MiR-9 has been reported in some types of leukemia. This study generally emphasizes on the critical role of MiR-9 in hematologic malignancies as a prognostic factor and a therapeutic target.