Abstract Introduction Magnetic resonance imaging (MRI) T2* technique is used to assess iron overload in the heart, liver and pancreas of thalassaemic patients. Optimal iron chelation and expected tissue iron response rates remain under investigation. The objective of this study was to analyse serum ferritin and the iron concentration in the heart, liver and pancreas measured by MRI T2*/R2* during regular chelation therapy in a real-world cohort of patients with thalassemia. Methods We evaluated thalassaemic patients ≥ 7 years old undergoing chelation/transfusion therapy by MRI and assessed serum ferritin at baseline and follow-up from 2004-2011. Results We evaluated 136 patients, 92% major thalassaemic, with a median age of 18 years, and median baseline ferritin 2.033ng/ml (range: 59-14,123). Iron overload distribution was: liver (99%), pancreas (74%) and heart (36%). After a median of 1.2 years of follow-up, the iron overload in the myocardium reduced from 2,63 Fe mg/g to 2,05 (p 0.003). The optimal R2* pancreas cut-off was 148 Hertz, achieving 78% sensitivity and 73% specificity. However, when combining the R2* pancreas cut off ≤ 50 Hertz and a ferritin ≤ 1222 ng/ml, we could reach a negative predictive value (NPV) of 98% for cardiac siderosis. Only 28% were undergoing combined chelation at baseline assessment, which increased up to 50% on follow up evaluation. Conclusions Chelation therapy significantly reduced cardiac siderosis in thalassaemic patients. In patients with moderate/severe liver iron concentration undergoing chelation therapy, ferritin levels and myocardium iron improved earlier than the liver siderosis.

Abstract Introduction Knowing the information regarding the panorama of lymphoma diagnosis in patients treated in the Brazilian Public Unified Health System from the last 10 years is a challenge for Strategic Health Planning. Objective To characterize the Brazilian population with lymphoma treated in the Brazilian Public Unified Health System between 2008 and 2017 regarding staging, sex, residence site and mortality. Material and methods A descriptive, retrospective, and longitudinal trial with secondary data from DataSUS (SIA/SUS and SIM/SUS) obtained from patients with ICD-10 C81-85. Results There were 70,850 lymphoma cases between 2008 and 2017, of which 55% were male, the median age was 51 years, and 27% had Hodgkin Lymphoma. Most patients (56%) were treated outside the residence city. São Paulo State accounted for 25% of patients. Treatment initiation took more than 60 days in 27% of cases. A total of 45,601 deaths were due to lymphoma (12% Hodgkin Lymphoma and 88% Non-Hodgkin Lymphoma), with a median age 63 years, and were mainly males (55%). Staging data were inadequate in 23% of patients, and analysis was performed only on the valid records. Advanced disease was diagnosed in 58% of patients (60% male; 57% female) and was more common in Non-Hodgkin Lymphoma (62%) versus Hodgkin Lymphoma (49%). Discussion Late diagnosis interferes with mortality rates. Health promotion and cancer prevention campaigns, especially targeting the male public, and training for early diagnosis and early treatment are needed. Conclusion Effective measures for early diagnosis and treatment are urgently needed for lymphoma control.

ABSTRACT Introduction: It is important to know if patients with hemoglobinopathy could be more susceptible to COVID-19. Objective: Analyze SARS-CoV-2 infection in pediatric patients with hemoglobinopathy. Methods: Using the online platforms LILACS, PUBMED and EMBASE, on 17- JUL-2020 a search was made for the terms COVID-19 and SARS-CoV-2 associated with "sickle cell", "thalassemia" and "hemoglobinopathy". Results: There were 623 pediatric and adult patients with sickle cell disease (SCD) or beta thalassemia (BT) and COVID-19. Total mortality rate was 6.42%. No pediatric patient with BT has been described. So, our analysis focused on children and adolescents with SCD: there were 121 pediatric patients, one adolescent died, prophylactic anticoagulation was prescribed to six patients, 11.76% needed intensive care unit, blood transfusion was prescribed in 29.70%. Vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) were the main clinical manifestations in SCD. Discussion: Pediatric patients with SCD and COVID-19 have a low mortality rate when compared to adults, although is higher than the global pediatric population with COVID-19 (0−0.67%). The comorbidities associated with age and the long-term complications inherent to hemoglobinopathies may contribute to the increased mortality outside the pediatric age group. In SCD the clinical manifestations, both in children and adults, are VOC and ACS, and there was increase in blood requirement. Pediatric SCD patients with COVID-19 need more intensive care unit than the global pediatric population (3.30%). Conclusion: Despite pediatric population with SCD needs more intensive care, the outcome after infection by COVID-19 is favorable.

ABSTRACT Chimeric antigen receptor T (CAR-T) cell therapy is a novel therapeutic modality for acute lymphoblastic leukemia (ALL) with robust outcomes in patients with refractory or relapsed disease. At the same time, CAR-T cell therapy is associated with unique and potentially fatal toxicities, such as cytokine release syndrome (CRS) and neurological toxicities (ICANS). This manuscript aims to provide a consensus of specialists in the fields of Hema- tology Oncology and Cellular Therapy to make recommendations on the current scenario of the use of CAR-T cells in patients with ALL.

In the absence of an iron chelating agent, patients with beta-thalassemia on regular transfusions present complications of transfusion-related iron overload. Without iron chelation therapy, heart disease is the major cause of death; however, hepatic and endocrine complications also occur. Currently there are three iron chelating agents available for continuous use in patients with thalassemia on regular transfusions (desferrioxamine, deferiprone, and deferasirox) providing good results in reducing cardiac, hepatic and endocrine toxicity. These practice guidelines, prepared by the Scientific Committee of Associação Brasileira de Thalassemia (ABRASTA), presents a review of the literature regarding iron overload assessment (by imaging and laboratory exams) and the role of T2* magnetic resonance imaging (MRI) to control iron overload and iron chelation therapy, with evidence-based recommendations for each clinical situation. Based on this review, the authors propose an iron chelation protocol for patients with thalassemia under regular transfusions.

Objetivo: Avaliar o acúmulo de ferro em diferentes órgãos por meio da ressonância nuclear magnética T2* e correlacionar os resultados aos níveis de ferritina sérica, ferro plasmático lábil e outros órgãos envolvidos. Métodos: Foram avaliados retrospectivamente 115 pacientes talassêmicos (sendo 65 mulheres). A concentração hepática de ferro foi determinada em biópsia de 11 pacientes; os resultados foram comparados com os valores de T2* fígado. Resultados: a ferritina sérica média foi de 2.676,5 +/- 2.051,7 ng/mL. O ferro plasmático lábil foi anormal (> 0,6 Unidades/mL) em 48/83 pacientes (57%). A média dos valores de T2* no fígado foi 3,91 ± 3,95 ms, sugerindo siderose hepática em 92,1% pacientes. A média do T2* cardíaco foi de 24,96 ± 14,17 ms e 36% dos pacientes apresentavam siderose cardíaca (T2* < 20ms), dos quais 19% (22/115) já apresentavam sobrecarga cardíaca grave (T2* < 10 ms). A média de T2* no pâncreas foi de 11,12 ± 11,20 ms, perfazendo um total de 83,5% de pacientes com sobrecarga de ferro pancreático (T2* < 21 ms). Houve correlação significativa, curvilínea e inversa entre T2* fígado e a concentração de ferro hepática (r = −0,878; p <0,001) e correlação moderada entre T2* pâncreas e T2* miocárdio (r = 0,546; p <0,0001). Conclusão: Uma elevada taxa de acometimento hepático, pancreático e cardíaco por sobrecarga férrica foi demonstrada. Os níveis de ferritina não puderam prever sobrecarga de ferro hepático, cardíaco ou pancreáticos medidos por meio da ressonância nuclear magnética T2*. Não houve correlação entre a sobrecarga de ferro no fígado, pâncreas e miocárdio, nem entre a ferritina e os níveis plasmáticos de ferro sérico e os valores de T2* no fígado, coração e pâncreas.

ABSTRACT Objectives: To evaluate the use of magnetic resonance imaging in patients with β-thalassemia and to compare T2* magnetic resonance imaging results with serum ferritin levels and the redox active fraction of labile plasma iron. Methods: We have retrospectively evaluated 115 chronically transfused patients (65 women). We tested serum ferritin with chemiluminescence, fraction of labile plasma iron by cellular fluorescence and used T2* MRI to assess iron content in the heart, liver, and pancreas. Hepatic iron concentration was determined in liver biopsies of 11 patients and the results were compared with liver T2* magnetic resonance imaging. Results: The mean serum ferritin was 2,676.5 +/- 2,051.7 ng/mL. A fraction of labile plasma iron was abnormal (> 0,6 Units/mL) in 48/83 patients (57%). The mean liver T2* value was 3.91 ± 3.95 ms, suggesting liver siderosis in most patients (92.1%). The mean myocardial T2* value was 24.96 ± 14.17 ms and the incidence of cardiac siderosis (T2* < 20 ms) was 36%, of which 19% (22/115) were severe cases (T2* < 10 ms). The mean pancreas T2* value was 11.12 ± 11.20 ms, and 83.5% of patients had pancreatic iron deposition (T2* < 21 ms). There was significant curvilinear and inverse correlation between liver T2* magnetic resonance imaging and hepatic iron concentration (r= −0.878; p < 0.001) and moderate correlation between pancreas and myocardial T2* MRI (r = 0.546; p < 0.0001). Conclusion: A high rate of hepatic, pancreatic and cardiac impairment by iron overload was demonstrated. Ferritin levels could not predict liver, heart or pancreas iron overload as measured by T2* magnetic resonance imaging. There was no correlation between liver, pancreas, liver and myocardial iron overload, neither between ferritin and fraction of labile plasma iron with liver, heart and pancreas T2* values

CONTEXTO E OBJETIVO: A anemia aplástica e a agranulocitose são doenças raras, entretanto freqüentemente letais. Muitas vezes são causadas por medicações e outras exposições ambientais. A incidência dessas doenças parece variar consideravelmente entre diferentes regiões geográficas, e poucos dados sobre a incidência são disponíveis para os países da América Latina. O objetivo deste trabalho é determinar a incidência de anemia aplástica e agranulocitose no Brasil. TIPO DE ESTUDO E LOCAL: Estudo de incidência. Sete centros participaram da fase piloto do estudo representando as cinco regiões brasileiras. MÉTODOS: Cada centro realizou busca ativa por novos casos em uma região definida, por meio de contatos regulares com todos os hematologistas, principais laboratórios clínicos e clínicos de hospitais de sua região. RESULTADOS: Foram identificados 74 casos de anemia aplástica e 16 casos de agranulocitose. A mediana de idade dos pacientes com agranulocitose foi de 31 anos (intervalo inter-quartil - IIQ 12,5 - 48,2), 32,2% eram do sexo masculino e 81,2% eram da raça branca. A mediana de idade dos pacientes com anemia aplástica foi de 21 anos (IIQ 15,0-35,2), 62,2% eram do sexo masculino, 50,0% da raça branca e 39,2% da raça parda. A incidência de agranulocitose foi estimada em 0,5 casos/milhão de habitantes/ano, variando de 0,0 a 1,1 caso/milhão de habitantes/ano entre as diferentes regiões brasileiras. A incidência de anemia aplástica foi de 2,7 casos/milhão de habitantes/ano, variando de 1,1 a 7,1 casos/milhão de habitantes/ano entre as diferentes regiões. CONCLUSÕES: A anemia aplástica e a agranulocitose são doenças raras no Brasil. Entretanto existe considerável variabilidade na incidência destas doenças entre as diferentes regiões brasileiras.

CONTEXT AND OBJECTIVE: Aplastic anemia and agranulocytosis are rare but life-threatening disorders, often caused by drugs and other environmental exposures. Reported incidence of these diseases seems to vary between different geographic regions, and few data on their incidence are available for Latin American countries. The aim of this work is to determine the incidence of agranulocytosis and aplastic anemia in Brazil. DESIGN AND SETTING: Incidence study. Seven centers took part in the pilot phase, so as to represent all Brazilian regions. METHODS: Each center conducted an active search for new cases in a defined region by means of regular contacts with all hematologists, main clinical laboratories and clinicians in hospitals of the region. RESULTS: 74 patients with aplastic anemia and 16 with agranulocytosis were identified. Patients with agranulocytosis had a median age of 31 years (interquartile range, IQR: 12.5-48.2); 32.2% were male and 81.2% were white. The median age of aplastic anemia patients was 21 years (IQR 15.0-35.2); 62.2% were male, 50.0% were white and 39.2% mulatto. The incidence of agranulocytosis was estimated to be 0.5 cases per million individuals per year, ranging from 0.0 to 1.1 cases per million per year between regions. The incidence of aplastic anemia was 2.7 cases per million per year, ranging from 1.1 to 7.1 cases per million per year between regions. CONCLUSIONS: Aplastic anemia and agranulocytosis are rare diseases in Brazil. However, there is considerable variability in their incidences between different regions.