HbS/ß+ thalassemia: Really a mild disease? A National survey from the AIEOP Sickle Cell Disease Study Group with genotype-phenotype correlation.

OBJECTIVES: HbS/ß+ patients' presence in Italy increased due to immigration; these patients are clinically heterogeneous, and specific guidelines are lacking. Our aim is to describe a cohort of HbS/ß+ patients, with genotype-phenotype correlation, in order to offer guidance for clinical management of such patients. METHODS: Retrospective cohort study of HbS/ß+ patients among 15 AIEOP Centres. RESULTS: A total of 41 molecularly confirmed S/ß+ patients were enrolled (1-55 years, median 10.9) and classified on ß+ mutation: IVS-I-110, IVS-I-6, promoter, and "others." Prediagnostic events included VOC 16/41 (39%), ACS 6/41 (14.6%), sepsis 3/41 (3.7%), and avascular necrosis 3/41 (7,3%). Postdiagnostic events were VOC 22/41 (53.6% %), sepsis 4/41 (9.7%), ACS 4/41 (9.7%), avascular necrosis 3/41 (7.3%), aplastic crisis 2/41 (4.8%), stroke 1/41 (2.4%), ACS 1/41 (2.4%), and skin ulcerations 1/41 (2.4%). The IVS-I-110 group presented the lowest median age at first SCD-related event (P = .02 vs promoter group) and the higher median number of severe events/year (0.26 events/patient/year) (P = .01 vs IVS-I-6 and promoter groups). Promoter group presented a specific skeletal phenotype. Treatment regimen applied was variable among the centers. CONCLUSIONS: HbS/ß+ is not always a mild disease. Patients with IVS-I-110 mutation could benefit from a standard of care like SS and S/ß° patients. Standardization of treatment is needed.

Total loss of GM3 synthase activity by a normally processed enzyme in a novel variant and in all ST3GAL5 variants reported to cause a distinct congenital disorder of glycosylation.

ST3GAL5-CDG is a rare syndrome which is caused by variant GM3 synthases, the enzyme involved in the biosynthesis of a-b-c-series gangliosides. Here we report a novel homozygous ST3GAL5 variant, p.Gly342Ser, in a patient suffering from failure to thrive, severe hearing, visual, motor, and cognitive impairment, and respiratory chain dysfunction. A GM3 synthase assay towards the natural acceptor substrate lactosylceramide was performed upon transfection in HEK-293T cells of expression plasmids carrying wild type and mutated ST3GAL5 cDNAs. The assay revealed a complete loss of enzyme activity. Identical results were obtained with the other four ST3GAL5 variants which have been reported to be pathogenic. HEK-293T clones permanently expressing HaloTag-ST3GAL5 carrying each of the five variants were assessed by quantitative PCR, flow cytometry, western blotting and confocal microscopy. The results indicated that transcription, translation, stability and intracellular localization of the tagged protein were identical to those of the wild type construct. Compared with the very mild phenotype of st3gal5 KO mouse models, the results suggest that unknown mechanisms, in addition to the lack of a-b-c-series gangliosides, contribute to the syndrome. Direct enzyme assay upon transfection in model cells appears to be an effective tool for characterizing variants of glycosyltransferases involved in glycosphingolipid biosynthesis.

Results of a multicenter universal newborn screening program for sickle cell disease in Italy: A call to action.

BACKGROUND: Sickle cell disease (SCD) is a chronic multisystem disorder requiring comprehensive care that includes newborn screening (NBS) as the first step of care. Italy still lacks a national SCD NBS program and policy on blood disorders. Pilot single-center screening programs and a regional targeted screening have been implemented so far, but more evidence is needed in order to impact health policies. POPULATION AND METHODS: NBS was offered to parents of newborns in gynecology clinics in Padova and Monza, tertiary care university hospitals in northern Italy. High-performance liquid chromatography (HPLC) was performed as the first test on samples collected on Guthrie cards. Molecular analysis of the beta-globin gene was performed on positive samples. RESULTS: A total of 5466 newborns were enrolled; for 5439, informed consents were obtained. A similar family origin was seen in the two centers (65% Italians, 9% mixed couples, 26% immigrants). Compared with SCD NBS programs in the United States and Europe, our results show a similar incidence of SCD patients and carriers. All SCD patients had a Sub-Saharan family background; HbS carriers were 15% Caucasians (Italian, Albanians) and 10% from other areas (North Africa-India-South America); carriers of other hemoglobin variants were mainly (47%) from other areas. CONCLUSIONS: Our results demonstrate the feasibility of a multicentric NBS program for SCD, give information on HbS epidemiology in two Northern Italian Areas, and support previous European recommendation for a universal NBS program for SCD in Italy: a high incidence of patients and carriers has been detected, with a high percentage of Caucasian carriers, impossible to identify in a targeted NBS.

Real-life experience with hydroxyurea in sickle cell disease: A multicenter study in a cohort of patients with heterogeneous descent.

We conducted the first nation-wide cohort study of sickle cell disease (SCD) in Italy, a Southern European country exposed to intense recent flux migration from endemic areas for SCD. We evaluate the impact of hydroxyurea on a total of 652 pediatric and adult patients from 33 Reference Centers for SCD (mean age 24.5±15years, 51.4% males). Hydroxyurea median treatment duration was 7years (range: <1year to 29years) at a mean therapeutic dose of 18±4.7mg/kg/day. Hydroxyurea was associated with a significant increase in mean total and fetal hemoglobin and a significant decrease in mean hemoglobin S, white blood and platelet counts, and lactate dehydrogenase levels. Hydroxyurea was associated with a significant reduction in the incidence of acute chest syndrome (-29.3%, p<0.001), vaso-occlusive crisis (-34.1%, p<0.001), hospitalization (-53.2%, p<0.001), and bone necrosis (-6.9%, p<0.001). New silent cerebral infarction (SCI) occurred during treatment (+42.4%, p<0.001) but not stroke (+0.5%, p=0.572). These observations were generally consistent upon stratification for age, descent (Caucasian or African), genotype (ßS/ßS, ßS/ß0 or ßS/ß+) and duration of treatment (< or ≥10years). There were no new safety concerns observed compared to those commonly reported in the literature. Our study, conducted on a large population of patients with different descent and compound state supports the benefits of hydroxyurea therapy as a treatment option. Registered at clinical trials.gov (NCT02709681).

Hydroxyurea prescription, availability and use for children with sickle cell disease in Italy: Results of a National Multicenter survey.

BACKGROUND: The number of patients with sickle cell disease (SCD) has increased in Italy in the past decade due to immigration. In spite of the established efficacy of hydroxyurea (HU) in childhood, population-based data regarding its prescription and effectiveness come mainly from studies performed in adults or outside Europe. POPULATION AND METHODS: The Hydroxyurea in SCD: A Large Nation-wide Cohort Study from Italy was a retrospective cohort study of adult and pediatric patients with SCD attending 32 centers. Pediatric data are analyzed separately. RESULTS: Out of 504 children followed in 11 centers, 206 (40%) were on HU (194 SS/Sß°, 12 SC/Sß+); 74% came from Sub-Saharian Africa and 18% from Europe. HU therapy indications for SS/Sß° patients were as follows: 57% painful vaso-occlusive crisis, acute chest syndrome or both, 24% anemia, 8% anemia, and other reasons (the majority had Hb ≤ 8-8.5 g/dl, revealing scarce acceptance of low Hb values by pediatric hematologist). Mean starting dose was 15.5 mg/kg, and dose at full regimen was 17.1 mg/kg. Mean age at HU therapy was 7.68 years, although it was lower for SS/Sß° patients. Only 10% started HU before 3 years. In 92%, 500 mg capsule was used; in 6%, the galenic was used; and in 2%, 100 mg tablet was used. Significant reduction of clinical events and inpatients admissions, with improvement in hematological parameters, was observed for SS/Sß° patients and a trend toward improvement for SC/Sß+ patients was also observed. CONCLUSIONS: HU effectiveness is demonstrated in a national cohort of children with SCD living in Italy, even at a lower dose than recommended, revealing good adherence to a treatment program by a socially vulnerable group of patients such as immigrants.

Successful utilization of an electronic pain diary in a multinational phase 3 interventional study of pediatric sickle cell anemia.

BACKGROUND/AIMS: Patients with sickle cell anemia can experience recurrent pain episodes, which affect quality of life. The reported prevalence of pain is higher in studies using patient diaries than in healthcare facility utilization data. Determining Effects of Platelet Inhibition on Vaso-Occlusive Events was a multinational study that assessed the efficacy and safety of prasugrel in reducing the rate of vaso-occlusive events in children with sickle cell anemia (NCT01794000) and included an electronic patient-reported outcome diary to record pain occurrence. We aimed to capture diary completion rates and compliance in children who used the electronic patient-reported outcome diary during the Determining Effects of Platelet Inhibition on Vaso-Occlusive Events study and examine factors contributing to diary completion rates and compliance. METHODS: Daily electronic patient-reported outcome diary data were collected for up to 9 months in Determining Effects of Platelet Inhibition on Vaso-Occlusive Events participants aged 4 to <18 years in Africa, the Americas, Europe, and the Middle East. The questionnaires were available in 11 languages/dialects for collecting subjective (pain intensity, activity interference) and objective (study drug use, analgesic use, school attendance) data. Pain intensity was measured using the Faces Pain Scale-Revised. Data were entered by participants or caregivers and transferred wirelessly each day to a central database. Diary completion rates were the number of daily diary entries divided by the total number of expected daily diary entries. Percentages of participants who were compliant with the diary (≥80% diary completion) were calculated. RESULTS: A total of 311 participants received a diary; 268 provided diary data through Month 9. Diary completion rates and compliance were high throughout the collection period and across all groups and regions, despite no games being included on the device. For subjective data, the overall completion rate was 94.4%, and 92.6% of participants were compliant. For objective data, the overall completion rate was 93.3%, and 89.7% of participants were compliant. Completion rates and compliance differed significantly by age and region and were higher for 4 to <12 year olds and very much higher for participants from Africa and the Middle East. Caregivers almost always entered data for participants <6 years and rarely entered data for participants ≥12 years. Comparing participant-entered and caregiver-entered data, pain intensity score data were more consistent for 4 to <12 year olds than older children, but pain intensity scores for older children were higher when entered by caregivers. CONCLUSION: With appropriate design, participant training, and sufficient monitoring, an electronic patient-reported outcome diary can capture daily sickle cell-related pain data in large multinational studies. Providing a mechanism for caregiver reporting is particularly valuable for participants <6 years and may also facilitate compliance in older children who experience high levels of pain.

Thyroid Function Tests in Children and Adolescents With Trisomy 21: Definition of Syndrome-Specific Reference Ranges.

CONTEXT: The lack of syndrome-specific reference ranges for thyroid function tests (TFT) among pediatric patients with Down syndrome (DS) results in an overestimation of the occurrence of hypothyroidism in this population. OBJECTIVE: To (a) outline the age-dependent distribution of TFT among pediatric patients with DS; (b) describe the intraindividual variability of TFT over time; and (c) assess the role of elevated thyrotropin (TSH) in predicting the future onset of overt hypothyroidism. METHODS: In this retrospective, monocentric, observational analysis, we included 548 patients with DS (0-18 years) longitudinally assessed between 1992 and 2022. Exclusion criteria were abnormal thyroid anatomy, treatments affecting TFT, and positive thyroid autoantibodies. RESULTS: We determined the age-dependent distribution of TSH, FT3, and FT4 and outlined the relative nomograms for children with DS. Compared with non-syndromic patients, median TSH levels were statistically greater at any age (P < .001). Median FT3 and FT4 levels were statistically lower than controls (P < .001) only in specific age classes (0-11 for FT3, 11-18 years for FT4). TSH levels showed a remarkable fluctuation over time, with a poor (23%-53%) agreement between the TSH centile classes at 2 sequential assessments. Finally, the 75th centile was the threshold above which TSH values predicted future evolution into overt hypothyroidism with the best statistical accuracy, with a satisfactory negative predictive value (0.91), but poor positive predictive value (0.15). CONCLUSION: By longitudinally assessing TFT in a wide pediatric DS population, we outlined the syndrome-specific reference nomograms for TSH, FT3, and FT4 and demonstrated a persistent upward shift of TSH compared to non-syndromic children.

Environmental Factors in Northern Italy and Sickle Cell Disease Acute Complications: A Multicentric Study.

BACKGROUND: Environmental factors seem to influence clinical manifestations of sickle cell disease (SCD), but few studies have shown consistent findings. We conducted a retrospective multicentric observational study to investigate the influence of environmental parameters on hospitalization for vaso-occlusive crises (VOC) or acute chest syndrome (ACS) in children with SCD. METHODS: Hospital admissions were correlated with daily meteorological and air-quality data obtained from Environmental Regional Agencies in the period 2011-2015. The effect of different parameters was assessed on the day preceding the crisis up to ten days before. Statistical analysis was performed using a quasi-likelihood Poisson regression in a generalized linear model. RESULTS: The risk of hospitalization was increased for low maximum temperature, low minimum relative humidity, and low atmospheric pressure and weakly for mean wind speed. The diurnal temperature range and temperature difference between two consecutive days were determined to be important causes of hospitalization. For air quality parameters, we found a correlation only for high levels of ozone and for low values at the tail corresponding to the lowest concentration of this pollutant. CONCLUSIONS: Temperature, atmospheric pressure, humidity and ozone levels influence acute complications of SCD. Patients' education and the knowledge of the modes of actions of these factors could reduce hospitalizations.

Transfusional Approach in Multi-Ethnic Sickle Cell Patients: Real-World Practice Data From a Multicenter Survey in Italy.

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 patients (median age 23 years; 802 males/777 females), referring to 34 comprehensive Italian centers for hemoglobinopathies. Although we observed a similar proportion of Caucasian (47.9%) and African (48.7%) patients, Italian SCD patients clustered into two distinct overall groups: children of African descent and adults of Caucasian descent. We found a subset of SCD patients requiring more intensive therapy with a combination of HC plus chronic transfusion regimen, due to partial failure of HC treatment alone in preventing or reducing sickle cell-related acute manifestations. Notably, we observed a higher use of acute transfusion approaches for SCD patients of African descent when compared to Caucasian subjects. This might be related to (i) age of starting HC treatment; (ii) patients' low social status; (iii) patients' limited access to family practitioners; or (iv) discrimination. In our cohort, alloimmunization was documented in 135 patients (8.5%) and was more common in Caucasians (10.3%) than in Africans (6.6%). Alloimmunization was similar in male and female and more frequent in adults than in children. Our study reinforces the importance of donor-recipient exact matching for ABO, Rhesus, and Kell antigen systems for RBC compatibility as a winning strategy to avoid or limit alloimmunization events that negatively impact the clinical management of SCD-related severe complications. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03397017.

Precocious puberty and empty sella syndrome in a girl cured of acute lymphoblastic leukemia.

We describe a case of precocious puberty in a girl treated with chemoradiotherapy according to the Italian Association of Pediatric Hematology and Oncology ALL 9503 protocol for acute lymphoblastic leukemia (ALL) from the age of 15 months until the age of 3 years and 4 months. The patient was treated with chemotherapy and cranial irradiation (18 Gy in 12 fractions). At 7 years of age, during topical estrogenic treatment for congenital adhesions of the labia minora, she showed bilateral breast development that evolved into precocious puberty. A magnetic resonance imaging of the brain showed an "empty sella" (ES); the etiology of the ES, and the consequent precocious puberty, being presumably iatrogenic. Children treated with cranial radiotherapy should be carefully checked for signs of precocious puberty and the exogenous administration of estrogens should be avoided, as far as possible, because these could act as a trigger factor in a population at higher risk of precocious puberty.

GH deficiency in adult B-thalassemia major patients and its relationship with IGF-1 production.

Endocrine complications in Β-thalassemia represent a prominent cause of morbidity. Above all, dysfunction of GH-IGF-1 axis is of a major concern because of its pathogenic role on cardiac and bone disease, frequently described in this clinical setting. The aim of this paper is to analyze GH-IGF-1 axis in a cohort of 25 adult patients affected by Β-thalassemia. We found that GH deficiency was present in only 8% of our patients if diagnosis was based on GH peak below 9µg/L to two GH provocative tests instead of only one, and was mainly related to iron overload. On the contrary, IGF-1 production was impaired in a higher percentage of patients (72%), without significant correlation with iron burden. Of note, patients with hepatitis C virus infection showed lower IGF-1 concentrations than uninfected subjects despite a normal GH reserve, suggesting that partial GH insensitivity at the post-receptor level may play a key role in IGF-1 deficiency described in thalassemic patients.

Dexamethasone Stimulation Test in the Diagnostic Work-Up of Growth Hormone Deficiency in Childhood: Clinical Value and Comparison With Insulin-Induced Hypoglycemia.

Context: dexamethasone has been demonstrated to elicit GH secretion in adults, but few data are available about its effectiveness as a provocative stimulus in the diagnostic work-up of GH deficiency (GHD) in childhood. Objective: to assess the clinical value of dexamethasone stimulation test (DST) as a diagnostic tool for pediatric GHD. Design and setting: retrospective single-center analysis. The study population included 166 patients with a pathological response to arginine stimulation test (AST, first-line test) and subsequently tested with either insulin tolerance test (ITT) or DST as a second-line investigation between 2008 and 2019. Main outcome measures: comparison between GH peaks and secretory curves induced by ITT and DST; degree of agreement between DST and AST versus ITT and AST. Results: the pathological response to AST (GH peak < 8 ng/mL) was confirmed by an ITT in 80.2% (89/111) of patients and by a DST in 76.4% (42/55), with no statistical difference between the two groups (p value 0.69). Mean GH peaks achieved after ITT and DST were entirely comparable (6.59 ± 3.59 versus 6.50 ± 4.09 ng/ml, respectively, p 0.97) and statistically higher than those elicited by arginine (p < 0.01 for both), irrespectively of the average GH peaks recorded for each patient (Bland-Altman method). Dexamethasone elicited a longer lasting and later secretory response than AST and ITT. No side effects were recorded after DST. Conclusions: DST and ITT confirmed GHD in a superimposable percentage of patients with a pathological first-line test. DST and ITT share a similar secretagogue potency, overall greater than AST.

The Potential Synergic Effect of a Complex Pattern of Multiple Inherited Genetic Variants as a Pathogenic Factor for Ovarian Dysgenesis: A Case Report.

Non-syndromic primary ovarian insufficiency due to ovarian dysgenesis in 46,XX patients is an uncommon finding in the general population, even though several monogenic variants have been reported as causative factors. Here, we describe a 15-year-old patient diagnosed with gonadal dysgenesis possibly due to the interaction of three potentially pathogenic variants of genes involved in ovarian maturation, namely factor in the germline alpha (FIGLA), newborn ovary homeobox-encoding (NOBOX) and nuclear receptor subfamily 5 group A member 1 (NR5A1). We also describe a different degree of residual ovarian function within the proband's family, whose female members carry one to three demonstrated variations in the aforementioned genes in a clinical spectrum potentially dependent on the number of alleles involved. Our results support the hypothesis that the severity of the clinical picture of the proband, resulting in complete ovarian dysgenesis, may be due to a synergic detrimental effect of inherited genetic variants.

Evaluation of Technical Issues in a Pilot Multicenter Newborn Screening Program for Sickle Cell Disease.

A multicenter pilot program for universal newborn screening of Sickle cell disease (SCD) was conducted in two centres of Northern Italy (Padova and Monza). High Performance Liquid Chromatography (HPLC) was performed as the first test on samples collected on Guthrie cards and molecular analysis of the ß-globin gene (HBB) was the confirmatory test performed on the HPLC-positive or indeterminate samples. 5466 samples of newborns were evaluated. Of these, 5439/5466 were submitted to HPLC analysis and the molecular analysis always confirmed in all the alteration detected in HPLC (62/5439 newborns); 4/5439 (0.07%) were SCD affected, 37/5439 (0.68%) were HbAS carriers and 21/5439 (0.40%) showed other hemoglobinopathies. Stored dried blood spots were adequate for HPLC and ß-globin gene molecular analysis. Samples were suitable for analysis until sixteen months old. A cut-off of A1 percentage, in order to avoid false negative or unnecessary confirmation tests, was identified. Our experience showed that several technical issues need to be addressed and resolved while developing a multicenter NBS program for SCD in a country where there is no national neonatal screening (NBS) program for SCD and NBS programs occur on a regional basis.

Intrabone hematopoietic stem cell gene therapy for adult and pediatric patients affected by transfusion-dependent ß-thalassemia.

ß-thalassemia is caused by ß-globin gene mutations resulting in reduced (ß+) or absent (ß0) hemoglobin production. Patient life expectancy has recently increased, but the need for chronic transfusions in transfusion-dependent thalassemia (TDT) and iron chelation impairs quality of life1. Allogeneic hematopoietic stem cell (HSC) transplantation represents the curative treatment, with thalassemia-free survival exceeding 80%. However, it is available to a minority of patients and is associated with morbidity, rejection and graft-versus-host disease2. Gene therapy with autologous HSCs modified to express ß-globin represents a potential therapeutic option. We treated three adults and six children with ß0 or severe ß+ mutations in a phase 1/2 trial ( NCT02453477 ) with an intrabone administration of HSCs transduced with the lentiviral vector GLOBE. Rapid hematopoietic recovery with polyclonal multilineage engraftment of vector-marked cells was achieved, with a median of 37.5% (range 12.6-76.4%) in hematopoietic progenitors and a vector copy number per cell (VCN) of 0.58 (range 0.10-1.97) in erythroid precursors at 1 year, in absence of clonal dominance. Transfusion requirement was reduced in the adults. Three out of four evaluable pediatric participants discontinued transfusions after gene therapy and were transfusion independent at the last follow-up. Younger age and persistence of higher VCN in the repopulating hematopoietic cells are associated with better outcome.

Adrenal axis function after high-dose steroid therapy for childhood acute lymphoblastic leukemia.

BACKGROUND: A 4-week course of high-dose glucocorticoids may cause prolonged adrenal suppression even after a 9-day tapering phase. In this study, adrenal function and signs and symptoms of adrenal insufficiency were prospectively assessed in children with acute lymphoblastic leukemia (ALL) after induction treatment including high-dose prednisone (PDN) or dexamethasone (DXM). PROCEDURES: Sixty-four children with ALL, treated according to the AIEOP ALL 2000 Study protocol, underwent low dose ACTH (LD-ACTH) stimulation 24 hr after the last tapered steroid dose. In those with impaired cortisol response, additional LD ACTH tests were performed every 1-2 weeks until cortisol levels normalized. Signs and symptoms of adrenal insufficiency were recorded during the observation period. RESULTS: All patients had normal basal cortisol values at diagnosis. Twenty-four hours after last glucocorticoid dose, morning cortisol was reduced in 40/64 (62.5%) patients. LD-ACTH testing showed adrenal suppression in 52/64 (81.5%) patients. At the following ACTH test 7-14 days later, morning cortisol values were reduced in 8/52 (15.4%) patients and response to the test was impaired in 12/52 (23%). Adrenal function completely recovered in all patients within 10 weeks. No difference was found between patients treated with PDN or DXM. Almost 35% of children with impaired cortisol values at the first test developed signs or symptoms of adrenal insufficiency. One child developed a severe adrenal crisis during adrenal suppression. CONCLUSIONS: High-dose glucocorticoid therapy in ALL children may cause prolonged adrenal suppression and related clinical symptoms. Laboratory monitoring of cortisol levels and steroid coverage during stress episodes may be indicated.

Periodic erythroexchange is an effective strategy for high risk paediatric patients with sickle-cell disease.

We performed an 11 year retrospective study on 34 sickle-cell paediatric patients, focusing on efficacy, safety and costs of an exchange transfusion program in 13 high risk patients. A good clinical control with improvement in patients' quality of life, no disease related complications, no significant iron overload and no procedure related side effects were observed during periodic erythroexchange. Costs of periodic erythroexchange versus chronic transfusion regimen were comparable. Periodic erythroexchange appeared a good alternative to chronic transfusion regimen for controlling the most severe forms of disease, particularly in patients who do not tolerate or do not respond to hydroxyurea.

Diagnosis and management of newly diagnosed childhood autoimmune haemolytic anaemia. Recommendations from the Red Cell Study Group of the Paediatric Haemato-Oncology Italian Association.

Autoimmune haemolytic anaemia is an uncommon disorder to which paediatric haematology centres take a variety of diagnostic and therapeutic approaches. The Red Cell Working Group of the Italian Association of Paediatric Onco-haematology (Associazione Italiana di Ematologia ed Oncologia Pediatrica, AIEOP) developed this document in order to collate expert opinions on the management of newly diagnosed childhood autoimmune haemolytic anaemia.The diagnostic process includes the direct and indirect antiglobulin tests; recommendations are given regarding further diagnostic tests, specifically in the cases that the direct and indirect antiglobulin tests are negative. Clear-cut definitions of clinical response are stated. Specific recommendations for treatment include: dosage of steroid therapy and tapering modality for warm autoimmune haemolytic anaemia; the choice of rituximab as first-line therapy for the rare primary transfusion-dependent cold autoimmune haemolytic anaemia; the indications for supportive therapy; the need for switching to second-line therapy. Each statement is provided with a score expressing the level of appropriateness and the agreement among participants.

Successful recovery of acute hemosiderotic heart failure in beta-thalassemia major treated with a combined regimen of desferrioxamine and deferiprone.

We report the case of a 25-years-old male with beta-thalassemia major who developed acute heart failure, with severe systolic dysfunction, resulting from iron overload. Combined iron chelation with desferrioxamine and deferiprone together with standard cardiological treatment induced prompt and complete restoration of the cardiac function.