Long-term outcomes of avascular necrosis in sickle cell disease using joint-specific patient-reported outcome measures: Results from a multicentre study.

Avascular necrosis (AVN) is a prevalent and progressive complication in young patients with sickle cell disease (SCD), but no study evaluated the long-term subjective and objective outcome measures. Oxford hip score (OHS) and Oxford shoulder scores (OSS) are validated joint-specific patient-reported outcome measures (PROMs). In this prospective multicentre study, 47 SCD patients with pre-existing diagnosis of AVN occurred at a median age of 35.9 (24.2-47.6) filled out the OHS and OSS at median follow-up of 9.4 years (4.5-12.9). No patient died after diagnosis of AVN. Hip AVN was present in 34 (72%) patients, with bilateral involvement in 25 (74%); 26 (59%) underwent total hip arthroplasty (THA) at a median age of 34.6 (22.6-49.5); and 4 (15%) required re-surgery. OHS revealed moderate to severe impairment both in patients underwent THA and no hip surgery. Shoulder AVN was present in 13 (6%) patients and OSS revealed mild to moderate impairment. A high rate of compromised joint function and pain was observed 10 years after diagnosis of AVN regardless of the type of treatment, outlying the need to improve the management of this sickle-related complication. OHS and OSS are validated joint-specific PROMs easy to use in all SCD centres.

Longitudinal prospective comparison of pancreatic iron by magnetic resonance in thalassemia patients transfusion-dependent since early childhood treated with combination deferiprone-desferrioxamine vs deferiprone or deferasirox monotherapy.

BACKGROUND: In transfusion-dependent thalassemia patients who started regular transfusions in early childhood, we prospectively and longitudinally evaluated the efficacy on pancreatic iron of a combined deferiprone (DFP) + desferrioxamine (DFO) regimen versus either oral iron chelator as monotherapy over a follow-up of 18 months. MATERIALS AND METHODS: We selected patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network who received a combined regimen of DFO+DFP (No.=28) or DFP (No.=61) or deferasirox (DFX) (No.=159) monotherapy between the two magnetic resonance imaging scans. Pancreatic iron overload was quantified by the T2* technique. RESULTS: At baseline no patient in the combined treatment group had a normal global pancreas T2* (≥26 ms). At follow-up the percentage of patients who maintained a normal pancreas T2* was comparable between the DFP and DFX groups (57.1 vs 70%; p=0.517).Among the patients with pancreatic iron overload at baseline, global pancreatic T2* values were significantly lower in the combined DFO+DFP group than in the DFP or DFX groups. Since changes in global pancreas T2* values were negatively correlated with baseline pancreas T2* values, the percent changes in global pancreas T2* values, normalized for the baseline values, were considered. The percent changes in global pancreas T2* values were significantly higher in the combined DFO+DFP group than in either the DFP (p=0.036) or DFX (p=0.030) groups. DISCUSSION: In transfusion-dependent patients who started regular transfusions in early childhood, combined DFP+DFO was significantly more effective in reducing pancreatic iron than was either DFP or DFX.

Impact of the COVID-19 Pandemic on Iron Overload Assessment by MRI in Patients with Hemoglobinopathies: The E-MIOT Network Experience.

BACKGROUND: The E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) project is an Italian Network assuring high-quality quantification of tissue iron overload by magnetic resonance imaging (MRI). We evaluated the impact of the COVID-19 pandemic on E-MIOT services. METHODS: The activity of the E-MIOT Network MRI centers in the year 2020 was compared with that of 2019. A survey evaluated whether the availability of MRI slots for patients with hemoglobinopathies was reduced and why. RESULTS: The total number of MRI scans was 656 in 2019 and 350 in 2020, with an overall decline of 46.4% (first MRI: 71.7%, follow-up MRI: 36.9%), a marked decline (86.9%) in the period March-June 2020, and a reduction in the gap between the two years in the period July-September. A new drop (41.4%) was recorded in the period October-December for two centers, due to the general reduction in the total amount of MRIs/day for sanitization procedures. In some centers, patients refused MRI scans for fear of getting COVID. Drops in the MRI services >80% were found for patients coming from a region without an active MRI site. CONCLUSIONS: The COVID-19 pandemic had a strong negative impact on MRI multi-organ iron quantification, with a worsening in the management of patients with hemoglobinopathies.

Overall and complication-free survival in a large cohort of patients with ß-thalassemia major followed over 50 years.

We report data on survival and complications for a longitudinal cohort of 709 transfusion-dependent ß-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 with 93.3% (95%CI: 88.6-98.3) in the youngest birth cohort (1985-1997) (p = 0.073). Females showed better survival than males (p = 0.022). There were a total of 93 deaths at a median age of 23.2 years with the most frequent disease-related causes being heart disease (n = 53), bone marrow transplant (BMT) complication (n = 10), infection (n = 8), liver disease (n = 4), cancer (n = 3), thromboembolism (n = 2) and severe anemia (n = 1). There was a steady decline in the number of deaths due to heart disease from the year 2000 onwards and no death from BMT was observed after the year 2010. A progressive decrease in the median age of BMT was observed in younger birth cohorts (p < 0.001). A total of 480 (67.7%) patients developed ≥1 complication. Patients in younger birth cohorts demonstrated better complication-free survival (p < 0.001) which was comparable between sexes (p = 0.230). Independent risk factors for death in multivariate analysis included heart disease (HR: 4.63, 95%CI: 1.78-12.1, p = 0.002), serum ferritin >1000 ng/mL (HR: 15.5, 95%CI: 3.52-68.2, p < 0.001), male sex (HR: 2.75, 95%CI: 0.89-8.45, p = 0.078), and splenectomy (HR: 6.97, 95%CI: 0.90-54.0, p < 0.063). Survival in patients with ß-thalassemia major continues to improve with adequate access to care, best practice sharing, continued research, and collaboration between centers.

Real-life experience with liver iron concentration R2 MRI measurement in patients with hemoglobinopathies: baseline data from LICNET.

BACKGROUND: Real-life data on the use of R2 MRI for the assessment of liver iron concentration (LIC) remain limited. METHODS: We conducted a cross-sectional analysis on 363 patients (mean age 35.6 yr, 44.1% men) with hemoglobinopathies (204 ß-thalassemia major [TM], 102 ß-thalassemia intermedia [TI], and 57 sickle cell disease [SCD]) that were evaluated with R2 MRI as part of LICNET, an MRI network of 13 Italian treatment centers. RESULTS: The mean LIC was 7.8 mg/g (median: 4.0), with high LIC (>7 mg/g) noted in both transfused (TM, TI 37%; SCD 38%) and non-transfused (TI 20%) patients. Ferritin levels correlated with LIC in both transfused (TM, TI, SCD) and non-transfused (TI) patients (P < 0.001), although lower values predicted high LIC in non-transfused patients (1900 vs. 650 ng/mL in TM vs. non-transfused TI). A correlation between LIC and ALT levels was only noted in HCV-negative patients (rs = 0.316, P < 0.001). The proportion of patients with high LIC was significantly different between iron chelators used (P = 0.023), with the lowest proportion in deferasirox (30%) and highest in deferiprone (53%)-treated patients. CONCLUSIONS: High LIC values persist in subgroups of patients with hemoglobinopathy, warranting closer monitoring and management optimization, even for non-transfused patients with relatively low ferritin levels.

Erythrocytapheresis is a valid and safe therapeutic option in dysmetabolic iron overload syndrome.

Dysmetabolic iron overload syndrome is a rare event causing hepatic impairment with serious long-term side effects. Here, we describe a case of metabolic syndrome-related hepatic iron overload that showed a rapid, effective, and safe response to erythrocytapheresis. J. Clin. Apheresis 31:443-447, 2016. © 2015 Wiley Periodicals, Inc.

Extramedullary hematopoiesis is associated with lower cardiac iron loading in chronically transfused thalassemia patients.

The aim of this study was to evaluate, in a large cohort of chronically transfused patients, whether the presence of extramedullary hematopoiesis (EMH) accounts for the typical patterns of cardiac iron distribution and/or cardiac function parameters. We retrospectively selected 1,266 thalassemia major patients who had undergone regular transfusions (611 men and 655 women; mean age: 31.3 ± 8.9 years, range: 4.2-66.6 years) and were consecutively enrolled within the Myocardial Iron Overload in Thalassemia network. The presence of EMH was evaluated based on steady-state free precession sequences; cardiac and liver iron overloads were quantified using a multiecho T2* approach; cardiac function parameters and pulmonary diameter were quantified using the steady-state free precession sequences; and myocardial fibrosis was evaluated using the late gadolinium enhancement technique. EMH was detected in 167 (13.2%) patients. The EMH+ patients had significantly lower cardiac iron overload than that of the EMH- patients (P = 0.003). The patterns of cardiac iron distribution were significantly different in the EMH+ and EMH- patients (P < 0.0001), with a higher prevalence of patients with no myocardial iron overload and heterogeneous myocardial iron overload and no significant global heart iron in the EMH+ group EMH+ patients had a significantly higher left ventricle mass index (P = 0.001) and a significantly higher pulmonary artery diameter (P = 0.002). In conclusion, in regularly transfused thalassemia patients, EMH was common and was associated with a thalassemia intermedia-like pattern of cardiac iron deposition despite regular transfusion therapy.

Acute Chest Syndrome: the role of erythro-exchange in patients with sickle cell disease in Sicily.

Acute Chest Syndrome (ACS) describes a syndrome characterized by the presence of a new pulmonary infiltrate on a chest X-ray, fever, and respiratory symptoms and is the leading cause of death and hospitalization in sickle cell disease (SCD). We studied 21 patients affected by SCD (13 HbSbeta+, 4 HbS beta(o), 4 HbSS, mean age 38.2 years). Six out of the 21 patients developed one episode of ACS (two patients had positive blood cultures, for Mycoplasma pneumoniae and Haemophilus influenzae respectively). The aim of our study was to evaluate the therapeutic efficacy of red cell-exchange during ACS. This procedure decreases HbS levels. The patients who underwent erythro-exchange showed a dramatic clinical and radiographic improvement with stabilized HbS levels between 20% and 30%. During follow up (14-32 months), none of the 6 patients developed viral complications related to transfusion therapy, alloimmunization or recurrence of ACS. In conclusion, in regard to the pre- and post-red cell-exchange clinical and laboratory data, we can say that red cell-exchange provides a dramatic resolution of the episode of ACS, minimizes the development of iron overload, and rapidly decreases HbS and hematocrit levels. In light of our results, we hypothesize that ACS episodes are secondary to pulmonary damage and to a gradual worsening related to age, and that there is some evidence that individuals affected by SCD in the third to fourth decade of life are more susceptible to ACS and/or other severe disease-related complications, needing repeated and strict clinical follow up.