Gian Luca Forni

Gian Luca Forni
Galliera Hospital | galliera · Centro della Microcitemia, Anemie Congenite ed Alterazioni del Metabolismo del Ferro

MD

About

262
Publications
27,452
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
7,832
Citations
Citations since 2017
90 Research Items
3440 Citations
20172018201920202021202220230100200300400500600
20172018201920202021202220230100200300400500600
20172018201920202021202220230100200300400500600
20172018201920202021202220230100200300400500600
Additional affiliations
January 2011 - present
January 2006 - December 2011
Università degli Studi di Genova
Position
  • collaboration
January 1997 - January 2017
Galliera Hospital
Position
  • Chair

Publications

Publications (262)
Article
Full-text available
Gain-of-function (GoF) mutations in PIEZO1 cause dehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis, an autosomal dominant hemolytic anemia characterized by high reticulocyte count, a tendency to macrocytosis, and mild jaundice, as well as by other variably penetrant clinical features, such as perinatal edema, severe thromboemboli...
Article
Full-text available
We report data on survival and complications for a longitudinal cohort of 709 transfusion‐dependent β‐thalassemia major patients (51.1% males) born between 1970 and 1997 and followed through 2020 at seven major centers in Italy. Overall survival probability at 30 years was 83.6% (95%CI: 78.5–89.1) in the oldest birth cohort (1970–1974) compared wit...
Article
Full-text available
A real-world analysis was conducted in Italy among sickle cell disease (SCD) patients to evaluate the epidemiology of SCD, describe patients’ characteristics and the therapeutic and economic burden. A retrospective analysis of administrative databases of various Italian entities was carried out. All patients with ≥1 hospitalization with SCD diagnos...
Article
Background Iron-chelation therapy is life-saving in patients on a chronic transfusion regimen as it reduces organ damage related to iron deposition in the tissues. Deferasirox, an iron-chelator, is characterized by pharmacokinetics variability, and some patients may discontinue the treatment due to toxicities. Objective Understanding whether defer...
Article
Background: The correlation between thalassemia and malignancies other than hepatocellular carcinoma (HCC) and the possible relationship between other hemoglobinopathies and tumor risk have been poorly evaluated. Methods: Eight Italian specialized centers evaluated the incidence of malignant neoplasms in hemoglobinopathies as well as their sites...
Article
Full-text available
The purpose of this best practice paper is to review the current recommendations for the identification and prenatal diagnosis of hemoglobinopathies. Methods: The management committee of SITE selected and gathered a multidisciplinary team in order to formulate recommendations based on the available scientific evidence integrated with the opinions...
Article
Background: The treatment of endocrinopathies in haemoglobinopathies is a continually expanding research area; therefore, recommendations supporting the appropriateness of treatments are a pressing need for the medical community. Methods: The Management Committee of SITE selected and gathered a multidisciplinary and multiprofessional team includ...
Article
Full-text available
This Special Issue on “Emerging Therapies and Strategies in Thalassemia: Toward a New Era in management” aims to update researchers and clinicians regarding the field of thalassemia syndromes [...]
Article
Full-text available
Neurodegeneration with brain iron accumulation (NBIA) comprises various rare clinical entities with brain iron overload as a common feature. Magnetic resonance imaging (MRI) allows diagnosis of this condition, and genetic molecular testing can confirm the diagnosis to better understand the intracellular damage mechanism involved. NBIA groups disord...
Article
Background In patients with non-transfusion-dependent β-thalassaemia, haemoglobin concentrations lower than 10 g/dL are associated with a higher risk of morbidity, mortality, and impaired quality of life. No drugs are specifically approved for anaemia management in patients with non-transfusion-dependent β-thalassaemia, other than transfusion thera...
Conference Paper
Full-text available
Background: The use of Artificial Intelligence (AI) for personalized medicine has recently guided improvements in the diagnostic pathway of many diseases. The EU Project GENOMED4ALL: “Genomics and personalized Medicine for All through Artificial Intelligence in Haematological Diseases” aims at using European data of patients affected by Sickle Cel...
Article
Full-text available
Although numerous patient‐specific co‐factors have been shown to be associated with worse outcomes in COVID‐19, the prognostic value of thalassaemic syndromes in COVID‐19 patients remains poorly understood. We studied the outcomes of 137 COVID‐19 patients with a history of transfusion‐dependent thalassaemia (TDT) and transfusion independent thalass...
Article
Full-text available
Background: The treatment of endocrinopathies in haemoglobinopathies is a continually expanding research area; therefore, recommendations supporting the appropriateness of treatments are a pressing need for the medical community. Methods: The Management Committee of SITE selected and gathered a multidisciplinary and multi-professional team, incl...
Article
Full-text available
Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by recurrent acute vaso-occlusive crises (VOCs and anemia). Gold standard treatments are hydroxycarbamide (HC) and/or different red blood cell (RBC) transfusion regimens to limit disease progression. Here, we report a retrospective study on 1,579 SCD pat...
Article
Iron is essential in cellular life, however, when in excess, it favors the production of reactive oxygen species (ROS) that, when overwhelm the physiological cellular antioxidant system, produce an oxidative stress state leading to cellular damages and organ failure. What is not yet completely clear is whether the damage is related more to the amou...
Article
Pulmonary arterial hypertension (PAH) is a life-threatening complication of β-thalassemia, especially in untransfused patients with thalassemia intermedia. Pinto and colleagues analyzed the outcome of 24 patients with PAH documented by right heart catheterization, and they report that with a median follow-up of 4 years, 54% died, most of which deat...
Article
Full-text available
Lifespan treatment in transfusion-dependent β-thalassemia (TDT) is expected to impact quality of life. This study aimed at evaluating health-related quality of life (HRQoL), well-being, and the burden of TDT on Italian patients. Patients (≥14 years) were invited to complete a cross-sectional, online volunteer survey. HRQoL was measured by the 36-it...
Article
Full-text available
Methemoglobinemia is a rare disorder associated with oxidization of divalent ferro-iron of hemoglobin (Hb) to ferri-iron of methemoglobin (MetHb). Methemoglobinemia can result from either inherited or acquired processes. Acquired forms are the most common, mainly due to the exposure to substances that cause oxidation of the Hb both directly or indi...
Article
Full-text available
Background: Hemoglobin A (Hb A) (α2β2) in the normal adult subject constitutes 96-98% of hemoglobin, and Hb F is normally less than 1%, while for hemoglobin A2 (Hb A2) (α2δ2), the normal reference values are between 2.0 and 3.3%. It is important to evaluate the presence of possible delta gene mutations in a population at high risk for globin gene...
Article
Introduction. Sickle Cell Disease (SCD) is an evolving public health issue with a significant impact on patient survival, quality of life and costs for health systems also in Italy, a multiethnic country where epidemiology has deeply changed. We present final results from the GREATalyS study that aimed to better understand the SCD burden in Italy i...
Article
Iron overload and chronic viral hepatitis underlie the increased incidence of hepatocellular carcinoma in patients with Beta thalassemia, as recently emerged due to the prolonged survival. Conversely, there are very few studies examining the relationship between thalassemia and other malignancies. Although some Authors have indicated an increase in...
Article
Introduction: Patients (pts) with non-transfusion-dependent β-thalassemia (NTDT) suffer from chronic anemia due to ineffective erythropoiesis. Low hemoglobin (Hb) levels in pts with anemia are associated with development of clinical complications and poor quality of life (QoL). There are no approved treatments for NTDT-associated anemia. Luspaterce...
Article
Full-text available
Hereditary erythrocytes disorders include a large group of conditions with heterogeneous molecular bases and phenotypes. We analyzed here a case series of 155 consecutive patients with clinical suspicion of hereditary erythrocyte defects referred to the Medical Genetics Unit from 2018 to 2020. All of the cases followed a diagnostic workflow based o...
Article
Full-text available
This expert opinion originally developed by a panel of the Italian Society of Thalassemias and Hemoglobinopathies (SITE), reviewed and adopted by the European Hematology Association (EHA) through the EHA Scientific Working Group on Red Cells and Iron, has been developed as priority decision-making algorithm on evidence and consensus with the aim to...
Article
Full-text available
Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusion-dependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX).We developed a multicentre follow-up study of 426 TDT p...
Article
Full-text available
Thalassemia syndromes are characterized by the inability to produce normal hemoglobin. Ineffective erythropoiesis and red cell transfusions are sources of excess iron that the human organism is unable to remove. Iron that is not saturated by transferrin is a toxic agent that, in transfusion-dependent patients, leads to death from iron-induced cardi...
Article
Background. Patients with pre-existent chronic morbidities are likely to be more severely affected by SARS-Cov2 infection. In Italy, the "Società Italiana Talassemie ed Emoglobinopatie" (SITE) has recently estimated the number of patients (Pts) with Hemoglobinopathies followed by Italian Specialized Centers (SITE Network). Five thousand Transfusion...
Article
Introduction Asplenic patients are at high risk of potentially fatal invasive infections, such as sepsis, meningitis, and pneumonia. It has been shown that infection from influenza viruses can precede or increase the risk of bacterial infection and of serious complications of the underlying disease. International and national guidelines recommend a...
Article
Background: Migration has impacted the spread of thalassaemia which is gradually becoming a global health problem. Italy, with an approximate estimation of 7,000 patients, does not have an accurate national record for haemoglobinopathies. This cross-sectional evaluation includes data for approximately 50% of beta-thalassaemia patients in Italy to...
Article
Full-text available
β-thalassemia major is an inherited hemoglobinopathy that requires lifelong red blood cell transfusions and iron chelation therapy to prevent complications due to iron overload. Traditionally, β-thalassemia has been more common in certain regions of the world such as the Mediterranean, Middle East, and Southeast Asia. However, the prevalence of β-t...
Article
Full-text available
Manual erythroexchange (MEEX) was proven to be effective and safe in the management of sickle cell disease (SCD). The goal is to quickly reduce the percentage of hemoglobin S (HbS%). A national survey of the Italian Society for Thalassemia and Hemoglobinopathies (SITE) observed a great variability among MEEX protocols none of which were found to be...
Article
Full-text available
Rare inherited anemias are a subset of anemias caused by a genetic defect along one of the several stages of erythropoiesis or in different cellular components that affect red blood cell integrity, and thus its lifespan. Due to their low prevalence, several complications on growth and development, and multi-organ system damage are not yet well defi...
Article
Full-text available
Fyn is a tyrosine kinase belonging to the Src family (Src-Family-Kinase, SFK), ubiquitously expressed. Previously, we report that Fyn is important in stress erythropoiesis. Here, we show that in red cells Fyn specifically stimulates G6PD activity, resulting in a 3-fold increase enzyme catalytic activity (kcat) by phosphorylating tyrosine (Tyr)-401....
Article
Full-text available
The analysis confirmed the increase in D-dimer values (1700 ng/mL with 95%CI 1367–2515, normal range <500 ng/mL) and showed a mild reduction of ADAMTS13 activity (47% with 95%CI 40–55, normal range 60–130%). Although not statistically significant, there was a trend of inverse correlation between D-dimer and ADAMTS13 (R = −0.355, P = 0.233). Our res...
Article
We here report the successful recovery from coronavirus disease-19 (COVID-19) pneumonia in a patient with β-thalassemia major (β-TM) and severe pulmonary arterial hypertension (PAH), focusing on the patient’s comorbidities, therapeutic course and drug interaction.
Article
Full-text available
Sickle-cell disease (SCD) is a worldwide distributed hemoglobinopathy, characterized by hemolytic anemia associated with vaso-occlusive events. These result in acute and chronic multiorgan damage. Bone is early involved, leading to long-term disability, chronic pain and fractures. Here, we carried out a retrospective study to evaluate sickle bone d...
Article
Full-text available
Background Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. Metho...
Article
Full-text available
Sickle cell disease (SCD) is an inherited red blood cell disorder caused by a structural abnormality of hemoglobin called sickle hemoglobin (HbS). Clinical manifestations of SCD are mainly characterized by chronic hemolysis and acute vaso-occlusive crisis, which are responsible for severe acute and chronic organ damage. SCD is widespread in sub-Sah...
Article
Full-text available
Purpose To assess the agreement of one-dimensional transient elastography (1D-TE), two-dimensional shear wave elastography (2D-SWE), and magnetic resonance elastography (MRE) in a consecutive cohort of patients affected by hepatitis C virus (HCV) and to understand which patient-related factors are associated with disagreement. Methods Ninety-one c...
Article
Background Most MDS patients require regular packed red blood cells (RBC) transfusions and finally most become transfusion dependent. One of the unavoidable consequences of transfusion therapy is iron overload which has been found to be deleterious for different categories of patients including MDS patients. So far tissue and organ damage have been...
Article
Fyn is a tyrosine kinase belonging to the Src family (Src-Family-Kinase, SFK), ubiquitously expressed. Previously, we reported that Fyn is important in stress erythropoiesis. Here, we show that in red cells Fyn specifically stimulates G6PD activity, resulting in a 3-fold increase of the enzyme catalytic activity (kcat) by phosphorylating tyrosine (...
Article
Introduction and Aim Till today, the only curative and most widely used therapy for β-thalassemia (β-TDT) is allogeneic HSCT: the European Society for Bone Marrow Transplantation Hemoglobinopathy Registry reported over 90% overall survival in under-14 patients transplanted from an HLA identical family donor. However, with the new therapeutic scenar...
Article
Full-text available
Neuroferritinopathy (NF) is a movement disorder caused by alterations in the L-ferritin gene that generate cytosolic free iron. NF is a unique pathophysiological model for determining the direct consequences of cell iron dysregulation. We established lines of induced pluripotent stem cells from fibroblasts from two NF patients and one isogenic cont...
Article
Full-text available
Asplenia is a condition due to spleen absence or dysfunction, which leads to high risk of infections and thrombotic events with significant chance of mortality and morbidity. Antibiotic prophylaxis, specific vaccine schedules, and aggressive treatment of fever and infectious events in asplenic or hyposplenic patients is recommended, but adherence t...
Article
Full-text available
Sickle cell disease (SCD) is the most important hemoglobinopathy worldwide in terms of frequency and social impact, recently recognized as a global public health problem by the World Health Organization. It is a monogenic but multisystem disorder with high morbidity and mortality. Vaso-occlusion, hemolytic anemia and vasculopathy are the hallmarks...
Article
Thalassemia is among the most common monogenic diseases worldwide. Stem cell transplantation can be curative but is reserved for young patients, as probably gene therapy will be in the future. Adult thalassemia patients are treated with transfusion therapy and iron chelation, and improvements in the safety of transfusion protocols, use of iron chel...
Article
Background Superficial siderosis (SS) of the central nervous system is a rare and heterogeneous condition due to deposition of hemosiderin on the surface of the brain and spinal cord. The usually progressive clinical course is characterized by a combination of hearing loss, cerebellar ataxia, and myelopathy. There is no known treatment for SS, but...
Article
Full-text available
Single point mutations or small deletions in the Aγ - and Gγ-globin gene promoter region are associated to the nondeletional hereditary persistence of fetal hemoglobin (HPFH). Currently, DNA sequencing is most common technique adopted for detection of hemoglobin (Hb) mutations. However, some can be rapidly detected because they either destroy or cr...
Article
Full-text available
Background: Chronic red blood cell transfusion is the first-line treatment for severe forms of thalassaemia. This therapy is, however, hampered by a number of adverse effects, including red blood cell alloimmunisation. The aim of this systematic review was to collect the current literature data on erythrocyte alloimmunisation. Materials and metho...
Article
INTRODUCTION: Allogeneic hematopoietic cell transplantation (HCT) is a diffuse curative option for transfusion dependent thalassemia (TDT) and sickle cell disease (SCD). To verify transplant activity, distribution, demography, policies and outcomes the Hemoglobinopathy Registry was established inside the European Group for Blood and Marrow Transpla...
Article
Introduction. Despite the increasing of number of patients with Sickle Cell Disease (SCD) in Italy, due to multi-ethnic migratory phenomena, a large percentage of Caucasian sickle population is already present in Italy mainly with b-thal/HbS genotype. Red cell transfusion is one effective treatment for both acute and chronic complications of SCD, w...
Article
Introduction: β-thalassemia is an inherited hemoglobinopathy associated with an erythroid maturation defect characterized by ineffective erythropoiesis and impaired RBC maturation. Luspatercept is a first-in-class erythroid maturation agent under development to treat patients with β-thalassemia. Luspatercept binds to select TGFβ superfamily ligands...
Article
Background The hemoglobin (Hb) response to the activin receptor type IIA ligand trap ACE-011 (Sotatercept) in non-transfusion-dependent thalassemia (NTDT), and the transfusion requirement response in TDT are described, but the mechanisms of action, clinical predictors and markers of response, are unclear. In principle, ACE-011 may act on early and...
Article
β-thalassemia, a hereditary blood disorder caused by defective synthesis of hemoglobin β globin chains, leads to ineffective erythropoiesis and chronic anemia that may require blood transfusions. Sotatercept (ACE-011) acts as a ligand trap to inhibit negative regulators of late-stage erythropoiesis in the transforming growth factor β superfamily, c...
Article
Heart disease remains a leading cause of morbidity and mortality in transfusion-dependent thalassemia (TDT), which can be attributed to several factors but primarily develops in the setting of iron overload. This was a retrospective cohort study utilizing Webthal® patient data from five major centers across Italy. Patients without heart disease wer...