Browsing by Author "Antić, Darko (23979576100)"

Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and very aggressive hematological malignancy derived from precursor of the plasmacytoid dendritic cell. We present a case with cervix uteri involvement without skin lesions, which is, to the best of our knowledge, the first case of BPDCN localized in the cervix. Case outline A 66-year-old previously healthy women initially presented with a four-week history of vaginal bleeding. Gynecologic examination revealed a tumorous bleeding formation on cervix uteri. Except paleness of the skin, physical examination results were normal. Complete blood counts showed anemia and thrombocytopenia. Computed tomography scans showed an expansive tumorous formation at the level of the isthmus and cervix uteri, 60 × 42 mm in size. Cervical biopsy was done and final pathohistological diagnosis was BPDCN. Karyotype analysis results from the bone marrow aspiration specimen demonstrated tetrasomy of chromosome 2 and monosomy of chromosome 16. The patient did not accept treatment and died two months after the initial diagnosis was established. Conclusion Attributes such as aggressive clinical course of BPDCN, demonstrated unusual localization, infrequency, and the absence of consensus about standard treatment options, demand constructive clinical reasoning and tight cooperation between medical professionals of various fields. © 2020, Serbia Medical Society. All rights reserved.

Introduction/Objective Prognostication of chronic lymphocytic leukemia (CLL) has been substantially improved in recent times. Among several prognostic models (PMs) focused on the prediction of time to first treatment (TTFT), progression-risk score (PRS), and MD Anderson Cancer Center score 2011 (MDACC 2011) are the most relevant, while CLL-International Prognostic Index (CLL-IPI), although originally developed to predict overall survival (OS), is also being used to estimate TTFT. The aim of this study was to investigate CLL-IPI, PRS, and MDACC 2011 prognostic values regarding TTFT and OS. Methods The analyzed cohort included 57 unselected Serbian CLL patients from a single institution, with the basic characteristics reflecting more aggressive disease than in the general de novo CLL population. The eligible patients were assigned investigated PMs, and TTFT and OS analyses were performed. Results Patients with higher risk scores according to CLL-IPI, PRS, and MDACC 2011 underwent treatment significantly earlier than patients with lower risk scores (p = 0.002, p = 0.019, and p < 0.001, respectively). In multivariate analysis, MDACC 2011 and CLL-IPI retained their significance regarding TTFT (p = 0.001 and p = 0.018, respectively), while PRS did not. CLL-IPI was the only significant predictor of OS both at the univariate (p = 0.005) and multivariate (p = 0.013) levels. Conclusion CLL-IPI, PRS, and particularly MDACC 2011 are able to predict TTFT even in cohorts with more advanced-disease patients, while for prediction of OS, CLL-IPI is the only applicable among the three PMs. These results imply that PMs should be investigated in more diverse CLL populations, as it is in real-life setting. © 2021, Serbia Medical Society. All rights reserved.

Acknowledgements Members of the EPICOVIDEHA registry: Joseph Meletiadis, Florian Reizine, Jan Novák, Summiya Nizamuddin, Roberta Di Blasi, Alexandra Serris, Pavel Jindra, Sylvain Lamure, François Danion, Maria Chiara Tisi, Mario Virgilio Papa, Nurettin Erben, ľuboš DrgoňA, Nathan C. Bahr, Murtadha Al-Khabori, Ayten Shirinova, Jörg Schubert, Lisset Lorenzo De La Peña, José-Ángel Hernández-Rivas, Elena Busch, Josip Batinić, Giuseppe Sapienza, Mohammad Reza Salehi, Reham Abdelaziz Khedr, Nina Khanna, Baerbel Hoell-Neugebauer, Ana Groh, Eleni Gavriilaki, Rita Fazzi, Rémy Duléry, Roberta Della Pepa, Mario Delia, Nicola Coppola, Maria Calbacho, Darko Antić, Hossein Zarrinfer, Ayel Yahia, Vivien Wai-Man, Ana Torres-TIenza, Alina Daniela Tanasa, Andrés Soto-Silva, Laura Serrano, Enrico Schalk, Ikhwan Rinaldi, Gaëtan Plantefeve, Monica Piedimonte, Maria Enza Mitra, Carolina Miranda-Castillo, Jorge Loureiro-Amigo, Ira Lacej, Martin Kolditz, María-Josefa Jiménez-Lorenzo, Guillemette Fouquet, Omar-Francisco Coronel-Ayala, Mathias Brehon, Panagiotis Tsirigotis, Anastasia Antoniadou, Gina Varricchio, Maria Vehreschild, Agostino Tafuri, José-María Ribera-Santa Susana, Joyce Marques De Almeida, María Fernández-Galán, Avinash Aujayeb, Athanasios Tragiannidis, Malgorzata Mikulska, Sein Win, Elizabeth De Kort, Hans-Beier Ommen, Donald C. Vinh, Hans Martin Orth, Sandra Malak, Przemyslaw Zdziarski, Modar Saleh, Chi Shan Kho, Fabio Guolo, M. Mansour Ceesay, Christopher H. Heath, Sergey Gerasymchuk, Monica Fung, Maximilian Desole, Erik De Cabo, Tania Cushion, Fazle Rabbi Chowdhury, Louis Yi Ann Chai, Fevzi Altuntaş, Charlotte Flasshove. The original article has been updated. © The Author(s) 2024.

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases. © 2021, The Author(s).

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases. © 2021, The Author(s).

Chronic inflammation has been identified in leukemias as an essential regulator of angiogenesis. B-chronic lymphocytic leukemia (CLL) cells secrete high levels of vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1 alpha (HIF1α). The aim was to assess the role of inflammation in activation of angiogenic factors: endothelial nitric oxide synthase (eNOS), HIF1α and VEGF via proliferation related signaling pathways and VEGF autocrine control. We isolated mononuclear cells (MNC) and CD19+ cells from peripheral blood of 60 patients with CLL. MNC were treated with pro-inflammatory interleukin-6 (IL-6) and VEGF, in combination with inhibitors of JAK1/2 (Ruxolitinib), mTOR (Rapamycin), NF-κB (JSH23), SMAD (LDN-193189) and PI3K/AKT (Ly294002) signaling pathways, to evaluate eNOS, VEGF and HIF1α expression by immunoblotting, immunocytochemistry and RT-qPCR. Also, we investigated IL-6 dependent neovascularization in human microvascular endothelial cells (HMEC-1) in co-culture with MNC of CLL. The angiogenic factors eNOS, VEGF and HIF1α had significantly higher frequencies in MNC of CLL in comparison to healthy controls (p < 0.001) and CD19+ cells of CLL. IL-6 increased the quantity of HIF1α (p < 0.05) and VEGF positive cells in the presence of JSH23 (p < 0.01). VEGF increased HIF1α (p < 0.05), and decreased eNOS gene expression (p < 0.01) in MNC of CLL. VEGF significantly (p < 0.001) increased the number of HIF1α positive MNC of CLL, prevented by inhibitors of JAK1/2, PI3K and mTOR signaling pathways. VEGF stimulation of SMAD (p < 0.05) and STAT5 (p < 0.01) signaling has been prevented by inhibitors of JAK1/2, mTOR, PI3K and SMAD signaling, individually (p < 0.01) or mutually (p < 0.001). Also, we showed that MNC of CLL and IL-6 individually stimulate neovascularization in co-culture with HMEC-1, without a cumulative effect. We demonstrated elevated angiogenic factors in CLL, while VEGF and IL-6 independently stimulated HIF1α. VEGF stimulation of HIF1α was mostly mTOR dependent, while IL-6 stimulation was NF-κB dependent. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.

Introduction Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder characterized by giant platelets thrombocytopenia, prolonged bleeding time, frequent hemorrhages with considerable morbidity. Data on the outcome of pregnancy and gynecological intervention in BSS are rare and there are no general therapeutic recommendations. Cases Outline We report two cases of BSS. In the first case a 29-year-old patient with BSS was admitted in 8 weeks of gestation. The diagnosis of BSS was made on the basis of prolonged bleeding time, giant-platelets thrombocytopenia, and absent ristocetin-induced platelet aggregation. In 38 week of gestation Cesarean section, with platelets transfusion preparation, was performed. Obstetric intervention passed without complication. Postoperative course was complicated with a three-week vaginal bleeding resistant to platelet transfusion. Neonate platelet count was normal. Our second case was a 28-year-old patient with BSS, hospitalized for ovarial tumor surgery. The patient was prepared for the intervention with platelets transfusion. The surgery was uncomplicated, but on the second postoperative day a massive vaginal bleeding, resistant to the platelet transfusion, developed. Bleeding control was achieved with activated recombinant factor VII. Twelve hours the patient developed later hypertensive crisis with epileptic seizure due to subarachnoid hemorrhage. Therapy was continued with platelet transfusion, antihypertensive and antiedema drugs. PH examination of tumor tissue showed hemorrhagic ovarial cyst. Conclusion Obstretic and gynecological intervention in women with BSS may be associated with a life-threatening bleeding thus requiring a multidisciplinary approach with adequate preparation. Because of the limited data in the literature, it is not possible to provide firm management recommendations and each case should be managed individually. © 2014, Serbia Medical Society. All rights reserved.

Scleredema adultorum (SA) is a rare sclerotic disorder characterized by non-pitting induration of the neck with acral progression, sparing hands and feet. We report on a 57-year-old male with severe SA associated with paraproteinemia, treated with methotrexate. Such widespread skin thickening followed by severe movement restriction and inability to function on daily basis, as in our patient, has never been described. Severe osteoarthritis and finding of HLA-B39 allele in association with SA has not been previously described either. To the best of our knowledge, up to 40 patients with SA associated with paraproteinemia has been reported so far, and currently, there is no established effective treatment protocol. In our patient, low-dose methotrexate resulted in stiffness reduction, increased motility of the trunk and extremities, and ability to function on daily basis. We believe that any information about treatment outcome in SA patients should be disseminated in order to establish consensual treatment protocol for this rare disease.