0000000000412091
AUTHOR
Rosario Di Maggio
Development of a Severity Score System for Thalassemia Syndromes
Introduction Thalassemia Syndromes (TS) are a group of inherited haemoglobin disorders characterized by different phenotype severity falling among heterozygote state, no transfusion dependent thalassemia (NTDT) and transfusion dependent Thalassemia (TDT) (Graffeo et al, 2018; Taher & Saliba, 2017). Several factors, independently by genotype and globin chain unbalance, modulate the severity of ineffective erythropoiesis (Rivella et al, 2015). Considering the complexity of this pathophysiology, one tool to evaluate patients on an individual basis is needed. The aim of this study was to develop a severity scoring system with a view to initiate timely interventions that would prevent any fu…
A Patient with Sickle Cell Disease and Recurrent Venous Thromboembolism after Renal Transplantation
Venous thromboembolism (VTE) is a life-threatening complication, especially in case of recurrence. The appropriate duration of anticoagulant treatment following the first event is crucial. Risk factors that increase the risk of recurrence of VTE are many, and include medications, kidney disease, renal transplantation (RT), and a diagnosis of sickle cell disease (SCD). There are currently no guidelines that define the duration of anticoagulant therapy after the first event in a patient with RT. We report a case of recurring episodes of VTE after RT in a SCD patient. Our case suggests that the use of a long-term anticoagulant treatment may be recommended in patients with SCD and RT after the …
Hematopoietic Stem Cell Mobilization for Gene Therapy: The Combination of G-CSF+Plerixafor in Patients with Beta-Thalassemia Major Provides High Yields of CD34+ Cells with Primitive Signatures
Abstract Hematopoietic stem cell engineering is a promising therapy to cure b-thalassemia, in particular for patients who lack a suitable BM donor for allogeneic transplantation. Since the engrafted gene-corrected stem cells will not have any selective advantage over the unmodified ones, the effectiveness of the therapy in this setting largely depends on the infusion of high numbers of gene-modified cells and on the conditioning regimen. The quality of the infused cells is also crucial for the clinical outcome and the duration of the therapeutic effect. HSPCs mobilization, particularly when G-CSF and plerixafor are used in combination, has been proved to be the optimal approach to harvest a…
The Challenge of Using CB-HSCs As Source for Gene Therapy: Lentiviral Vector Transduction, Phenotypic Characterization and Global Gene Expression Profile of Ex-Vivo Expanded CB CD34+ Cells
Abstract Introduction: Genetic modification of autologous hematopoietic stem and progenitor cells (HSPC) is a promising clinical intervention to cure inherited monogenic diseases. Successful gene therapy trials have already been conducted using CD34+ cells from bone marrow and from mobilized peripheral blood. In this regard, cord blood (CB) represents an attractive source of HSCs due to its high concentration of high proliferative HSPC and increased susceptibility to be transduced by lentiviral vectors. Unfortunately, the major disadvantage is the limited number of HSC in the CB collection. Consequently, ex-vivo expansion of CB-HSC is desirable to extend clinical applications. Purposes: To …
Polycythemia Vera as a Predisposing Factor for Aortic Stenosis: Prevalence and Correlation with Blood Cells Count and Mutational Status
Abstract The association between Polycythemia Vera (PV) and thrombosis is multi-factorial involving the complex interaction between activated leukocytes, platelets and endothelium. Recent reports have postulated that PV patients may over express adhesive molecules on red cell surface, likely by JAK2 mutation (Wautier M et al. Blood.2007;110(3):894–901). This process activates endothelium with production of vascular growth factors and other mechanisms leading to atherosclerosis. Aortic Stenosis (AS) is the commonest valvular heart disease in western countries; its pathogenesis is mainly related to a degenerative process sharing many characteristics with atherosclerosis. At the present is not…
Long-term use of deferiprone significantly enhances left-ventricular ejection function in thalassemia major patients
A multicenter randomized open-label long-term sequential deferiprone–deferoxamine (DFP-DFO) versus DFP alone trial (sequential DFP-DFO) performed in patients with thalassemia major (TM) was retrospectively reanalyzed to assess the variation in the left ventricular ejection fraction (LVEF) [1].
β-Thalassemia heterozygote state detrimentally affects health expectation.
Background: Thalassemia minor (Tm) individuals, are generally considered healthy. However, the prognosis of Tm individuals has not been extensively studied. The aim of this study was to evaluate the prognosis of Tm versus controls without β-thalassemia carrier state. Methods: A total of 26,006 individuals seeking thalassemia screening at the AOOR Villa Sofia-V. Cervello, Palermo (Italy) were retrospectively studied. Logistic penalised regression model was used to estimate risk of potential complications and survival techniques were used to study mortality. Results: We identified a total of 4943 Tm and 21,063 controls. Tm was associated with significantly higher risks of hospitalisation for …
The Sea Urchin sns5 Chromatin Insulator Improves the Likelihood of Lentiviral Vectors in Erythroid Milieu By Organizing an Independent Chromatin Domain at the Integration Site
Abstract Retroviral vectors are currently the most suitable vehicles for therapeutic gene transfer in hematopoietic stem cells. However, these vectors are known to integrate rather randomly throughout the genome, suffering the so called chromosomal position effects (PE). Such a critical occurrence most probably depends upon the ability of heterochromatin to spread in the inserted vector sequences. Moreover, the use of transgenes imply genotoxicity effects, since the cis-regulatory sequences harbored by the vector can disturb the proper transcription of the resident genes neighboring the integration site, potentially leading to malignant transformation. Due to their enhancer blocker activity…