Spontaneous Remission of Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report.

Spontaneous remissions (SRs) in blastic plasmacytoid dendritic cell neoplasms (BPDCNs) are infrequent, poorly documented, and transient. We report a 40-year-old man presenting with bycitopenia and soft tissue infection. The bone marrow exhibited 3% abnormal cells. Immunophenotyping of these cells revealed the antigens CD45+ (dim), CD34+, CD117+, CD123+ (bright), HLA-DR+ (bimodal), CD56+ (bright), CD33+, CD13+, CD2+, and CD22+ (dim) and the partial expression of the CD10+, CD36+, and CD7+ antigens. All other myeloid, monocytic, and lymphoid antigens were negative. Genetic studies showed a complex karyotype and mutations in the TP53R337C and KRASG12D genes. On hospital admission, the patient showed a subcutaneous nodule on the right hand and left lower limb. Flow cytometry multiparameter (FCM) analysis showed the presence of 29% abnormal cells with the previously described immunophenotype. The patient was diagnosed with BPDCN. The patient was treated with broad-spectrum antibiotics for soft tissue infection, which delayed therapy for BPDCN. No steroids or chemotherapeutic or hypomethylating agents were administered. His blood cell counts improved and skin lesions disappeared, until the patient relapsed five months after achieving spontaneous remission. About 60% of abnormal cells were identified. No changes in immunophenotype or the results of genetic studies were observed. The patient underwent a HyperCVAD chemotherapy regimen for six cycles. Consolidation therapy was performed via allogeneic bone marrow transplantation with an HLA-unrelated donor. One year after the bone marrow transplant, the patient died due to the progression of his underlying disease, coinciding with a respiratory infection caused by SARS-CoV-2. In the available literature, SRs are often linked to infections or other stimulators of the immune system, suggesting that powerful immune activation could play a role in controlling the leukemic clone. Nevertheless, the underlying mechanism of this phenomenon is not clearly understood. We hypothesize that the immune system would force the leukemic stem cell (LSC) to undergo a state of quiescence. This loss of replication causes the LSC progeny to die off, resulting in the SR of BPDCN.

Corrigendum: Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study.

[This corrects the article DOI: 10.3389/fimmu.2021.709861.].

Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study.

BACKGROUND: Immune hyperactivity is an important contributing factor to the morbidity and mortality of COVID-19 infection. Nasal administration of anti-CD3 monoclonal antibody downregulates hyperactive immune responses in animal models of autoimmunity through its immunomodulatory properties. We performed a randomized pilot study of fully-human nasal anti-CD3 (Foralumab) in patients with mild to moderate COVID-19 to determine if its immunomodulatory properties had ameliorating effects on disease. METHODS: Thirty-nine outpatients with mild to moderate COVID-19 were recruited at Santa Casa de Misericordia de Santos in Sao Paulo State, Brazil. Patients were randomized to three cohorts: 1) Control, no Foralumab (n=16); 2) Nasal Foralumab (100ug/day) given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n=11); and 3) Nasal Foralumab alone (100ug/day) given for 10 consecutive days (n=12). Patients continued standard of care medication. RESULTS: We observed reduction of serum IL-6 and C-reactive protein in Foralumab alone vs. untreated or Foralumab/Dexa treated patients. More rapid clearance of lung infiltrates as measured by chest CT was observed in Foralumab and Foralumab/Dexa treated subjects vs. those that did not receive Foralumab. Foralumab treatment was well-tolerated with no severe adverse events. CONCLUSIONS: This pilot study suggests that nasal Foralumab is well tolerated and may be of benefit in treatment of immune hyperactivity and lung involvement in COVID-19 disease and that further studies are warranted.

[Association between venous thrombosis and dyslipidemia]. / Asociación entre enfermedad tromboembólica venosa y dislipidemia.

BACKGROUND AND OBJECTIVE: Venous and arterial thrombosis, despite being historically considered as distinct conditions, share certain risk factors. Dyslipidemia is a clinical condition with a relatively high prevalence in the population and has been associated with an increased thrombotic risk. Lipids and lipoproteins modulate the expression and/or function of thrombotic, fibrinolytic and rheological factors. PATIENTS AND METHOD: We have developed a descriptive, retrospective, comparative, cross-sectional study including a group of 313 patients with venous thromboembolism (VTE). We collected basic demographic data, cardiovascular risk factors and thrombotic complications. All patients were subjected to a lipid profile study with determination of total cholesterol, high density lipoprotein cholesterol (cHDL), low density lipoprotein cholesterol (cLDL) and triglycerides. RESULTS: The multivariable analysis showed that dyslipidemia was a risk factor for VTE (odds ratio [OR] 3.87, 95% confidence interval [95% CI] 2.72-5.56; P<.0001). Of a total of 313 patients included in the study, 31% (n=97) had a recurrent thrombotic event and 23% (n=72) developed post-thrombotic syndrome. cHDL levels below 35 mg/dl and cLDL levels higher than 180 mg/dl represented risk factors for the development of recurrent thrombosis, OR 3.12 (95% CI 1.35-7.74; P=.008) and OR 2.35 (95% CI 1.24-4.45; P=.008), respectively, and post-thrombotic syndrome, OR 3.44 (95% CI 1.43-8.83; P=.005) and OR 2.35 (95% CI 1.24-4.45; P=.008). CONCLUSIONS: Our study confirmed the association between dyslipidemia and VTE and showed a risk of thrombosis nearly 4 times higher in individuals with this disease. In addition, alterations in the lipid profile were also related to a higher prevalence of thrombotic complications, recurrence and post-thrombotic syndrome.

Immunophenotype in chronic myelomonocytic leukemia: is it closer to myelodysplastic syndromes or to myeloproliferative disorders?

Chronic myelomonocytic leukemia (CMML) is a heterogeneous disease balanced between myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD). We used flow cytometry to describe and compare the immunophenotypic profile of 20 patients with CMML, 38 patients with MDS, and 20 patients with MPD. CMML and MDS only showed statistically significant differences (P<0.05) in CD56 monocyte expression. CMML and MPD showed significant differences in CD45 myeloid distribution, myeloid antigenic profile, CD56 and CD2 monocyte expression, and B-cell development. These data support the classic concept of CMML as part of MDS diseases and encourage including immunophenotyping among the studies to be performed in these diseases.

Asociación entre enfermedad tromboembólica venosa y dislipidemia / Association between venous thrombosis and dyslipidemia

Fundamento y objetivo: La trombosis venosa y la trombosis arterial, a pesar de haber sido consideradas durante años como 2 entidades distintas, comparten ciertos factores de riesgo. La dislipidemia es una condición clínica con una prevalencia relativamente elevada en la población, que se ha asociado a un incremento del riesgo trombótico. Los lípidos y lipoproteínas modulan la expresión y/o función de factores trombóticos, fibrinolíticos y reológicos. Pacientes y método: Se ha desarrollado un estudio descriptivo, retrospectivo, comparativo y transversal en el que se ha incluido un grupo de 313 pacientes con enfermedad tromboembólica venosa (ETEV). Se recogieron los datos de filiación básica, factores de riesgo cardiovascular clásicos y complicaciones trombóticas. En todos los pacientes se estudió el perfil lipídico: colesterol total, colesterol unido a high density lipoproteins (HDL, «lipoproteínas de alta densidad»), colesterol unido a low density lipoproteins (LDL, «lipoproteínas de baja densidad») y triglicéridos. Resultados: La dislipidemia es un factor de riesgo para la ETEV, con una odds ratio (OR) de 3,87 (intervalo de confianza del 95% [IC 95%] 2,72-5,56; p < 0,0001). El 31% (n = 97) de los pacientes sufrió un episodio recurrente y el 23% (n = 72) desarrolló síndrome postrombótico. Los valores de colesterol HDL < 35 mg/dl y los de colesterol LDL > 180 mg/dl resultaron ser factores de riesgo para el desarrollo de trombosis recurrente, con una OR de 3,12 (IC 95% 1,35-7,74; p = 0,008) y de 2,35 (IC 95% 1,24-4,45; p = 0,008), respectivamente, y síndrome postrombótico: OR 3,44 (IC 95% 1,43-8,83; p = 0,005) y OR 2,35 (IC 95% 1,24-4,45; p = 0,008). Conclusiones: Existe una asociación entre la dislipidemia y la ETEV, siendo el riesgo de trombosis casi 4 veces mayor en individuos con esta enfermedad. Las alteraciones del perfil lipídico también están relacionadas con una mayor prevalencia de recurrencia y síndrome postrombótico (AU)

Background and objective: Venous and arterial thrombosis, despite being historically considered as distinct conditions, share certain risk factors. Dyslipidemia is a clinical condition with a relatively high prevalence in the population and has been associated with an increased thrombotic risk. Lipids and lipoproteins modulate the expression and/or function of thrombotic, fibrinolytic and rheological factors. Patients and method: We have developed a descriptive, retrospective, comparative, cross-sectional study including a group of 313 patients with venous thromboembolism (VTE). We collected basic demographic data, cardiovascular risk factors and thrombotic complications. All patients were subjected to a lipid profile study with determination of total cholesterol, high density lipoprotein cholesterol (cHDL), low density lipoprotein cholesterol (cLDL) and triglycerides. Results: The multivariable analysis showed that dyslipidemia was a risk factor for VTE (odds ratio [OR] 3.87, 95% confidence interval [95% CI] 2.72-5.56; P < .0001). Of a total of 313 patients included in the study, 31% (n = 97) had a recurrent thrombotic event and 23% (n = 72) developed post-thrombotic syndrome. cHDL levels below 35 mg/dl and cLDL levels higher than 180 mg/dl represented risk factors for the development of recurrent thrombosis, OR 3.12 (95% CI 1.35-7.74; P = .008) and OR 2.35 (95% CI Background and objective: Venous and arterial thrombosis, despite being historically considered as distinct conditions, share certain risk factors. Dyslipidemia is a clinical condition with a relatively high prevalence in the population and has been associated with an increased thrombotic risk. Lipids and lipoproteins modulate the expression and/or function of thrombotic, fibrinolytic and rheological factors. Patients and method: We have developed a descriptive, retrospective, comparative, cross-sectional study including a group of 313 patients with venous thromboembolism (VTE). We collected basic demographic data, cardiovascular risk factors and thrombotic complications. All patients were subjected to a lipid profile study with determination of total cholesterol, high density lipoprotein cholesterol (cHDL), low density lipoprotein cholesterol (cLDL) and triglycerides. Results: The multivariable analysis showed that dyslipidemia was a risk factor for VTE (odds ratio [OR] 3.87, 95% confidence interval [95% CI] 2.72-5.56; P < .0001). Of a total of 313 patients included in the study, 31% (n = 97) had a recurrent thrombotic event and 23% (n = 72) developed post-thrombotic syndrome. cHDL levels below 35 mg/dl and cLDL levels higher than 180 mg/dl represented risk factors for the development of recurrent thrombosis, OR 3.12 (95% CI 1.35-7.74; P = .008) and OR 2.35 (95% CI 1.24-4.45; P = .008), respectively, and post-thrombotic syndrome, OR 3.44 (95% CI 1.43-8.83; P = .005) and OR 2.35 (95% CI 1.24-4.45; P = .008). Conclusions: Our study confirmed the association between dyslipidemia and VTE and showed a risk of thrombosis nearly 4 times higher in individuals with this disease. In addition, alterations in the lipid profile were also related to a higher prevalence of thrombotic complications, recurrence and postthrombotic syndrome (AU)