Rosario Di Maggio

In the long-term follow up study (de-LIGHT), the magnitude of transfusion burden was significantly and incrementally associated with morbidity development in transfusion-dependent patients achieving target hemoglobin thresholds.

Summary: Evidence on the impact of anaemia and iron control on morbidity and mortality in β‐thalassaemia is limited to short‐term studies assessing spot measures. We conducted a retrospective longitudinal cohort study of 557 patients with β‐thalassaemia followed from diagnosis for a median of 38 years. There was a significant association between the lifetime proportion spent on transfusion and thalassaemia‐related mortality (adjusted hazard ratios (HR) 0.987 for each 1‐percent increase, p = 0.014). In both patients with non‐transfusion‐dependent β‐thalassaemia (NTDT) and transfusion‐dependent β‐thalassaemia (TDT) (lifetime proportion on transfusion ≤70% and >70%, respectively), there was a significant association between a lifetime anaemia and iron control index (LAICI) and mortality (NTDT: adjusted HR 0.916 for each 1‐point increase, p = 0.017; TDT: adjusted HR 0.672, p = 0.027). Survival was significantly lower in patients with suboptimal than optimal LAICI, defined based on international NTDT and TDT guidelines for anaemia and iron overload management (NTDT: adjusted HR 0.395, p = 0.046; TDT: adjusted HR 0.205, p = 0.020 for optimal vs. suboptimal LAICI). Patients with optimal LAICI had significantly lower odds of cardiac (NTDT, TDT), vascular (TDT), hepatic (NTDT), endocrine morbidity (NTDT, TDT) and osteoporosis (NTDT). Optimal anaemia and iron control throughout the entire disease course are essential to reduce morbidity and mortality in patients with β‐thalassaemia.

Background: Liver disease is common in patients with β‐thalassemia, but data on lifetime incidence and risk factors are limited.Methods: We conducted a retrospective cohort study of 557 patients with β‐thalassemia followed from diagnosis for a median of 38 years. Predictive, survival, and regression analyses were used to determine the association between liver disease and potential risk factors.Results: The crude incidence of liver disease was 26.4% (fibrosis/cirrhosis 24.2%, median age 34.4 years; hepatocellular carcinoma 2.3%, median age 45.4 years, 38.5% not preceded by cirrhosis). Among evaluated risk factors, only hepatitis C virus (HCV) infection (adjusted hazard ratio [HR]: 2.195, p < 0.001) and lifetime serum ferritin level (adjusted HR per 100‐ng/mL increase: 1.030, p < 0.001) were significantly associated with liver disease, with a lifetime serum ferritin level > 1500 ng/mL being the best predictor (p = 0.001). Liver disease‐free survival was significantly shorter in patients who had both versus either or neither risk factor (p < 0.001). Mostly severe and persistent but not mild–moderate or temporary/fluctuating elevation in liver enzymes was associated with liver disease development.Conclusion: Patients with β‐thalassemia have a considerably increased lifetime risk of liver disease that is primarily driven by HCV infection and/or uncontrolled iron overload, especially in the 4th–5th decades of life.

Background: Hereditary hemoglobin disorders are the most common globally distributed monogenic red cell diseases. The rights of women with thalassemia or sickle cell disease (SCD) to motherhood need to be protected by creating a roadmap to guide her, and her family network, along all the phases of the event. In fact, pregnancy in these vulnerable patients requires special attention and guidelines from the counseling stage (giving information about the special requirement and risks posed by their pregnancy with respect to the general population) the pre-conception stage, the early and mid-late pregnancy stage, to labor and lactation. The biocomplexity of these diseases requires a multidisciplinary team synergizing with gynecologists and obstetricians. In addition, the presence of a multicultural scenario requires healthcare workers to overcome stereotypes and adopt appropriate anthropological tools that might help them integrate the different cultural models of disease and motherhood. Methods: The Management Committee of the Society for Thalassemia and Hemoglobinopathies (SITE) selected and brought together a multidisciplinary and multiprofessional group made up of experts in hemoglobinopathies and experts in anthropology, flanked along with by experts with methodological and organizational expertise in order to create recommendations based on the integration of available scientific evidence together with expert opinion. Results: The panelists critically analyzed the literature, combining in a single document practices developed over several years of managing young women with hemoglobinopathies in a sensitive phase of their lives. Conclusions: This good practice document is the result of a collegial effort by Italian experts on hemoglobinopathies who are members of SITE. (SITE).

Allogeneic stem cell transplantation remains the only therapy for congenital, severe haemoglobinopathies that is able to reverse the pathological phenotype. In the severe form of thalassemia, regular transfusions are needed early in life. This population of patients could benefit from allo-SCT. However, the great efficacy of transplantation must be counterbalanced by the mortality and morbidity related to the procedure. In this short review, we reviewed the most recent data in the field of transplantation in transfusion-dependent thalassemia (TDT), highlighting the factors that have a major impact on outcomes.

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 first event of VTE.

In sickle cell disease (SCD), hydroxyurea (HU) treatment decreases the number of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) by increasing fetal hemoglobin (HbF). Data are lacking regarding the frequency of HU dose modification or whether sub-therapeutic doses (p < 0.0001). This improvement was observed in all SCD phenotypes. The white blood cell (WBC) counts were found to be lower, and HbF increased in both HU groups (p = 0.004, 0.001). The maximal HbF response to HU in HbS/β⁺-thalassemia was 20%, similar to those observed for HbSS (19%) and HbS/β⁰-thalassemia (22%). HbS/β⁺-thalassemia could have a similar disease severity as HbSS or HbS/β⁰-thalassemia. Patients with HbS/β⁰-thalassemia or HbS/β⁺-thalassemia phenotypes responded to HU.

Objectives: The liver remains the primary site of iron storage, with liver iron concentration (LIC) being a strong surrogate of total body iron. MRI‐R2 can accurately measure LIC. The LICNET (Liver Iron Cutino Network) was established to diagnostics of liver iron overload by MRI‐R2 subjects with hemochromatosis in hematological disorders. The aims of the study were to look at variation in LIC measurements during time across different chelation regimens.Methods: This was a cross‐sectional study of 130 patients attending 9 Italian centers participating in the LICNET. LIC comparisons over time (T₀ and T₁) were made using t test and/or Wilcoxon test.Results: LIC significantly decreased from MRI1 to MRI2 although at high variance (median change −0.8 mg Fe/g dw, range: −29.0 to 33.0; P = .011) and 7.7% of patients shifted from LIC values of high risk (>15 mg Fe/g dw) to an intermediate‐risk category (7‐15 mg Fe/g dw). Median change in LIC and correlation with serum ferritin levels (SF), during different chelation regimens, is reported.Conclusions: These findings suggest as longitudinal variation in the LIC is possible, across all chelation regimens. It confirms as SF levels not always can be used for estimating changes in LIC.