Argiris Symeonidis

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• Emeritus Professor of Hematology
• University of Patras Medical School at University of Patras

We investigated peripheral blood T-lymphocyte subpopulations and intracellular expression of IFN-γ, IL-4, IL-10, and IL-13, by whole blood flow cytometry, in 22 type I Gaucher disease (GD) patients. Results were compared with those of 19 sex- and age-matched controls. Patients with GD exhibited decreased frequencies and absolute numbers of CD3+/CD4...

Descriptive epidemiology of the myelodysplastic syndromes (MDS) is always interesting and may reveal time-dependent and geographical variations, as well as occupational exposure. Epidemiological data in Greece are not available by now. We have collected and analyzed medical records of all patients with a documented diagnosis of MDS, performed by an...

  We determined nine immune function parameters at diagnosis in patients with myelodysplastic syndromes (MDS) and correlated the results with the FAB classification and prognosis by univariate and multivariate analyses. Patients with refractory anaemia (RA) and refractory anaemia with ring sideroblasts (RAS) tended to have a higher CD4/CD8 ratio an...

Iron is an essential element for cell growth and development, contributing to DNA synthesis and regulating the G(1)-phase to S-phase transition. Moreover, iron is important for the virulence of the majority of microorganisms, and the function of the genes regulating iron uptake is coupled with the manifestations of the virulence phenotype. All fung...

We investigated erythropoietin (Epo) response in a cohort of diabetic patients with various types of anemia to approach the pathogenesis of some cases of "unexplained" anemia encountered among diabetics. Serum Epo levels were determined totally in 747 evaluable subjects with normal renal and hepatic function, of whom 694 had anemia. Among anemic pa...

Infections are an important cause of morbidity and mortality in patients with lower-risk myelodysplastic syndromes (LR-MDS). Studies regarding risk factors for infections are, however, limited in this population. This study aimed to investigate the prevalence and risk factors for infections and infection-related death in patients with LR-MDS. This...

Background Patients with higher-risk (HR) myelodysplastic syndrome (MDS), ineligible for allogeneic hematopoietic stem cell transplantation (alloHSCT), require prompt therapeutic interventions, such as treatment with hypomethylating agents (HMAs) to restore normal DNA methylation patterns, mainly of oncosuppressor genes, and consequently to delay d...

Background In our previous study on erythropoiesis-stimulating agent (ESA) treatment in lower risk myelodysplastic syndromes from the European MDS (EUMDS) Registry, we showed that patients treated with ESAs had longer survival compared with patients who receive red blood cell transfusion (RBCT). In this study, with a longer follow up time and more...

Lower risk (LR) myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem and progenitor disorders caused by the accumulation of somatic mutations in various genes including epigenetic regulators that may produce convergent DNA methylation patterns driving specific gene expression profiles. The integration of genomic, epigenomic, and tra...

Proteasome inhibitors (PIs) constitute the most common type of induction treatment for multiple myeloma. Interactions between the proteasome, autophagy, and reactive oxygen species (ROS) have been shown in the past, thus emphasizing the need for a better understanding of the underlying pathophysiology. For this study, bone marrow mononuclear cells...

Myelofibrosis (MF) is a myeloproliferative neoplasm that was most commonly treated with hydroxyurea (HU) prior to approval of ruxolitinib (RUX), now the standard of care. Factors that influence changes in MF treatment in real-world settings are not well understood. The METER study (NCT05444972) was a multi-country retrospective chart review of MF t...

Introduction. Luspatercept has been recently approved for the treatment of red blood cell (RBC) transfusion-dependent (TD) Lower-Risk (LR) Myelodysplastic Syndrome (MDS) patients and can be administered either in the frontline or after erythropoietin failure. Our aim is to report its efficacy and safety in this study population in the everyday clin...

The unique heterogenous landscape of myelodysplastic syndromes/neoplasms (MDS) has resulted in continuous redefinition of disease sub-entities, in view of the novel translational research data that have clarified several areas of the pathogenesis and the progression of the disease. The new international classifications (WHO 2022, ICC 2022) have inc...

MiRNAs have been identified as participants in leukemogenesis by controlling several cellular functions, such as differentiation, proliferation, and apoptosis. Their role in myelodysplastic neoplasms (MDS) pathogenesis is researched due to implementations in early identification, classification, and therapeutical options. IPSS-R, being the most wid...

Prior studies have suggested that immune thrombotic thrombocytopenic purpura (iTTP) may display seasonal variation; however, methodologic limitations and sample sizes have diminished the ability to perform a rigorous assessment. This 5‐year retrospective study assessed the epidemiology of iTTP and determined whether it displays a seasonal pattern....

Background As new treatment options for patients with higher-risk myelodysplastic syndromes are emerging, identification of prognostic markers for hypomethylating agent (HMA) treatment and understanding mechanisms of their delayed and short-term responses are essential. Early fetal hemoglobin (HbF) induction has been suggested as a prognostic indic...

Novel therapies have improved outcomes for multiple myeloma (MM) patients, but most ultimately relapse, making treatment decisions for relapsed/refractory MM (RRMM) patients increasingly challenging. We report the final analysis of a single‐arm, phase 2 study evaluating the oral proteasome inhibitor (PI) ixazomib combined with daratumumab and dexam...

The precise link between inflammation and pathogenesis of myelodysplastic syndrome (MDS) is yet to be fully established. We developed a novel method to measure ASC/NLRP3 protein specks which are specific for the NLRP3 inflammasome only. We combined this with cytokine profiling to characterise various inflammatory markers in a large cohort of patien...

Treatment decision and response assessment in myelodysplastic syndromes (MDS) can be enhanced by the implementation of advanced diagnostic and prognostic assays for the detection of multiple molecular features. Higher-risk (HR) MDS, ineligible for allogeneic hematopoietic stem cell transplantation (alloHSCT), require prompt therapeutic intervention...

Predominantly antibody deficiencies (PAD) represent the most common type of primary immunodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifestations, and outcome. Considering that the prevalence of PAD in Greece is unknown, and there is limited knowledge on the clinical and laboratory characteristics of affe...

The effectiveness of proteasome inhibitors against solid tumors is limited as the emergence of resistance is rapid. Although many mechanisms have been proposed and verified, no definite answer has been given, highlighting the complexity of the resistant phenotype. In this study, a Bortezomib-resistant prostate cancer cell line is created, and a bro...

Chronic myelomonocytic leukemia (CMML) is a heterogeneous disease presenting with either myeloproliferative or myelodysplastic features. Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only potentially curative option, but the inherent toxicity of this procedure makes the decision to proceed to allo-HCT challenging, particularl...

Background As new treatment options for patients with higher-risk myelodysplastic syndromes are emerging, identification of prognostic markers for hypomethylating agent (HMA) treatment and understanding mechanisms of their delayed and short-term responses are essential. Early fetal hemoglobin (HbF) induction has been suggested as a prognostic indic...

Proteasome inhibitors such as Bortezomib represent an established type of targeted treatment for several types of hematological malignancies, including multiple myeloma, Waldenstrom’s macroglobulinemia, and mantle cell lymphoma, based on the cancer cell’s susceptibility to impairment of the proteasome-ubiquitin system. However, a major problem limi...

Predominantly antibody deficiencies (PAD) represent the most common type of primary immu-nodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifesta-tions, complications and outcome. Considering that the prevalence of PAD in Greece is unknown and there is limited knowledge on clinical and laboratory characterist...

Iron overload from repeated transfusions has a negative impact on cardiac function, and iron chelation therapy may help prevent cardiac dysfunction in transfusion‐dependent patients with myelodysplastic syndromes (MDS). TELESTO (NCT00940602) was a prospective, placebo‐controlled, randomised study to evaluate the iron chelator deferasirox in patient...

The use of lenalidomide in frontline therapy for patients with newly diagnosed multiple myeloma (MM) has increased the number of those who become refractory to lenalidomide at second line. In this context, we assessed the efficacy of daratumumab in combination with ixazomib and dexamethasone (Dara‐Ixa‐dex) in the prospective phase 2 study DARIA. El...

Background: The landscape of first-line treatment for acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy has changed remarkably after venetoclax approval. Accumulating real-world data further apprises us with more knowledgeable use. To assess the efficacy and safety challenges in the real-life setting of the combination of...

Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and an elevated risk of transformation to acute myeloid leukemia (AML). Available disease-modifying treatment approaches are limited. The ineffectiveness of proteasome inhibitors (PIs) in MDS patien...

Introduction Renal impairment (RI), a common complication of multiple myeloma (MM), is associated with increased risk of early death. Reversal of MM-associated RI is a key predictor of improved survival. Regimens containing bortezomib and dexamethasone are the treatment backbone for newly diagnosed (ND) patients (pts) with MM and severe RI, even th...

Background: Current standard of care for HR-MDS patients, i.e. hypomethylating agent (HMAs) treatment with azacytidine (AZA) or decitabine (DAC), is associated with a 30-50% response rate, and many efforts have been made to identify predictive factors for response. Fetal hemoglobin (HbF) levels have been proposed as a prognostic index for DAC treat...

Introduction Relapse in patients (pts) with multiple myeloma (MM) is a common occurrence, resulting in a continued need for novel treatment approaches. Isatuximab (Isa), a monoclonal antibody (mAb), combined with pomalidomide (Pom) and dexamethasone (Dex), is indicated for the treatment of pts with relapsed/refractory multiple myeloma who have rece...

Background : Myelofibrosis (MF) is a rare myeloproliferative disorder associated with significant morbidity and mortality. The hallmarks of MF pathobiology include aberrant myeloproliferation, cytokine-induced inflammation, bone marrow reticulin fibrosis, extramedullary hematopoiesis, cytopenias, and constitutional symptoms. Hydroxyurea was the mos...

Myelodysplastic syndromes (MDS) are a group of heterogeneous disorders caused by the accumulation of somatic mutations in the hematopoietic stem and progenitor compartment. Besides del(5q), SF3B1 or TP53 mutations, referred to as defining genetic abnormalities, mutation patterning hardly structured the classification of MDS. Mutations in epigenetic...

Introduction – Purpose: Proteasome inhibitors (PIs) are a group of pharmaceutical substances that target the 26S proteasome, the major protein degradation pathway of neoplastic and normal cells. Although inhibition of this cellular function is an effective treatment for several hematological malignancies, there is no clear evidence to support its a...

Given the limited real-world data of caplacizumab, our multicenter real-world study was designed to assess the safety and efficacy of caplacizumab in immune thrombotic thrombocytopenic pupura (iTTP), compared to historic controls. We have studied 70 patients: 23 in the caplacizumab and 47 in the historic control group. Plasma exchange was applied i...

Proteasome inhibitors are a group of drugs targeting the Ubiquitin-Proteasome System, the main protein degradation pathway utilized by both, normal and cancer cells. Cancer cells rely heavily on this pathway to replace damaged, misfolded or excessive amount of proteins, as a result of rapid biosynthetic rates, metabolic dysregulation, as well as of...

Proteasome inhibitors such as Bortezomib, represent an established type of targeted treatment for several types of hematological malignancies, including multiple myeloma, Waldenstrom’s macroglobulinemia and mantle cell lymphoma, based on the cancer cell’s susceptibility upon impairment of the proteasome-ubiquitin system. However, a major problem li...

Bortezomib (Velcade®, PS-341) is the first proteasome inhibitor approved by the FDA for the treatment of multiple myeloma which binds reversibly and with high specificity to the 26S proteasome β5 subunit. The development of resistance against bortezomib limits the treatment effectiveness, highlighting the need for investigation of the underlying me...

Introduction and Purpose: The proteasome is a multi-enzymatic protein complex that degrades excessive, misfolded or damaged proteins inside the cells. Inhibition of the chymotrypsin-like (ChT-L) proteasomal activity is a therapeutic target for several neoplastic diseases, for which proteasome inhibitors (PIs) are effective. There is no evidence whe...

Myelodysplastic syndromes (MDS) consist of a group of hematological malignancies characterized by ineffective hematopoiesis, cytogenetic abnormalities, and often a high risk of transformation to acute myeloid leukemia (AML). So far, there have been only a very limited number of studies assessing the epigenetics component contributing to the pathoph...

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders with maturation and differentiation defects exhibiting morphological dysplasia in one or more hematopoietic cell lineages. They are associated with peripheral blood cytopenias and by increased risk for progression into acute myelogenous leukemia. A...

Regional real-world evidence on the safety and efficacy of tyrosine kinase inhibitors in patients with chronic myeloid leukemia (CML) is limited. This multicenter, observational, prospective study, ERASER, evaluated the safety and tolerability of nilotinib in routine clinical practice in Greece. Adult patients with newly diagnosed BCR/ABL+ chronic...

The BM, the major hematopoietic organ in humans, consists of a pleiomorphic environment of cellular, extracellular, and bioactive compounds with continuous and complex interactions between them, leading to the formation of mature blood cells found in the peripheral circulation. Systemic and local inflammation in the BM elicit stress hematopoiesis a...

Information on causes of death (CoDs) and the impact of myelodysplastic syndromes (MDS) on survival in patients with lower‐risk MDS (LR‐MDS) is limited. A better understanding of the relationship between disease characteristics, clinical interventions and CoDs may improve outcomes of patients with LR‐MDS. We prospectively collected data on patients...

Monocytopenia is a common finding in patients with myelodysplastic syndrome (MDS), but although monocytes may exhibit prognostic significance in MDS due to their role in innate immunity, they have not been incorporated in any prognostic scoring system for MDS. In this study, we analyzed national registry data from 1719 adults with MDS. Monocytopeni...

The Phase 3 ICARIA-MM (NCT02990338) and IKEMA (NCT03275285) studies demonstrated that isatuximab (Isa) plus pomalidomide (P) and dexamethasone (d; Isa-Pd) or carfilzomib (K) and d (Isa-Kd) improved progression-free survival (PFS) versus Pd or Kd in patients with relapsed and/or refractory multiple myeloma. In this post hoc analysis of patients with...

Chronic myelomonocytic leukemia (CMML) and the remaining, less frequent hybrid, mixed, or overlap myelodysplastic syndromes/myeloproliferative neoplasms (MDSs/MPNs) are difficult to treat neoplastic hematological disorders, exhibiting substantial clinical and prognostic heterogeneity, for which clear therapeutic guidelines or effective treatment op...

PANTHER was a global, randomized phase 3 trial of pevonedistat plus azacitidine (n = 227) vs azacitidine monotherapy (n = 227) in patients with newly diagnosed higher-risk myelodysplastic syndromes (MDS) (n = 324), higher-risk chronic myelomonocytic leukemia (n = 27), or acute myeloid leukemia (AML) with 20-30% blasts (n = 103). The primary endpoin...

Simple Summary Multiple myeloma (MM) is characterized by the presence of deregulated bone metabolism. Restoring bone turnover is essential for patients with MM. We prospectively evaluated the impact of the anti-CD38 monoclonal antibody daratumumab on markers of bone remodeling among patients with relapsed/refractory MM. Overall, daratumumab improve...

The EUMDS Registry started in 2008 as a prospective, non-interventional longitudinal study, enrolling newly diagnosed patients with IPSS low or intermediate-1 MDS from 16 European countries and Israel.