Consensus of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) and the Brazilian Ministry of Health - General management of blood and blood products on the tests necessary for the release of exceptional medicines for sickle cell disease.

To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.

Extramedullary haematopoiesis in patients with thalassemia: a cross-sectional description of its prevalence, clinical features and survival.

INTRODUCTION: Despite knowledge advances on extramedullary haematopoiesis (EMH) in thalassemic patients, the real picture remains an open issue. OBJECTIVES: To assess EMH prevalence in patients with thalassemia major (TM) and intermedia (TI), to describe magnetic resonance imaging (MRI) findings and to explore clinical risk factors. METHODS: In this cross-sectional study, images and clinical records of 184 consecutive patients with thalassemia who underwent T2* MRI between 2004 and 2011 were reviewed. Association of EMH with survival was investigated for patients with available follow-up charts. RESULTS: EMH was detected in 16/168 (9.5%) patients with TM (aged 19-49 years) and in 3/16 (18.8%) with TI (aged 36-41 years). Most (88%) had paravertebral thoracic and/or abdominal masses. Age was significantly associated with EMH risk (hazard ratio, [HR] 1.10/year; confidence interval [CI]: 1.03-1.18; p-value < 0.001), while lower pancreatic iron content by T2*MRI (HR: 0.94/ms; CI: 0.89-0.99; p-value = 0.049) was a protective factor. Estimated survival rate was superior for EMH-positive (n = 19) when compared to EMH-negative patients (n = 75) (p-value = 0.013). CONCLUSIONS: The prevalence of EMH was 10.3% (19/184), presented mainly as tumoral masses of 3 to 10 cm. Age was a risk factor for EMH development, while lower pancreatic iron might be a protective factor in this cohort.

The impact of COVID-19 in children with Sickle Cell Disease: Results of a multicentric registry.

OBJECTIVE: To analyze the outcomes of children with sickle cell disease (SCD) and COVID-19. METHOD: A multicenter prospective study was conducted in five hematological centers from Central and Southeast Brazil, starting in April 2020. The variables recorded include clinical symptoms, diagnostic methods, therapeutic measures, and treatment sites. The clinical repercussions of the infection on the initial treatment and the overall prognosis were also evaluated. RESULTS: Twenty-five unvaccinated children, aged 4 to 17 years, with SCD and a positive SARS-CoV-2 RT-PCR result participated in this study. Patients were classified as SCD types SS (n = 20, 80%) and SC (n = 5, 20%). Clinical characteristics and evolution were similar in both groups (p>0.05), except for the fetal hemoglobin value which was higher among the SC patients (p = 0.025). The most frequent symptoms were hyperthermia (72%) and cough (40%). Three children were admitted to the intensive care unit, all of whom were overweight/obese (p = 0.078). No deaths were observed. CONCLUSIONS: Although SCD leads to specific complications, the results found in this sample suggest that COVID-19 does not seem to carry an increased mortality risk in pediatric patients with this disease.

Cardiac iron overload evaluation in thalassaemic patients using T2* magnetic resonance imaging following chelation therapy: a multicentre cross-sectional study

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.

Cardiac iron overload evaluation in thalassaemic patients using T2* magnetic resonance imaging following chelation therapy: a multicentre cross-sectional study.

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.

Blinatumomabe em pacientes pediátricos com leucemia linfoblástica aguda B em primeira recidiva de alto risco: um estudo de custo-efetividade / Blinatumomab in high-risk first relapse pediatric patients with acute lymphoblastic leukemia: a cost-effectiveness analysis

Objetivo: Estimar a custo-efetividade do blinatumomabe como novo padrão no tratamento de consolidação de pacientes pediátricos com leucemia linfoblástica aguda de células precursoras B (LLA-B) em primeira recidiva de alto risco. Métodos: Um modelo de sobrevida particionado com horizonte lifetime e ciclo de quatro semanas foi construído na perspectiva do Sistema Único de Saúde (SUS). Sobrevida livre de eventos e sobrevida global foram extrapoladas com base no ensaio clínico 20120215, usando funções paramétricas. A taxa de desconto foi de 5%. O impacto de variações em pressupostos foi explorado em análises de cenário. Resultados: O custo lifetime com desconto para o caso base foi de R$ 351.615 para blinatumomabe contra R$ 97.770 para HC3 (grupo controle de quimioterapia-padrão), com ganho de 9,96 e 6,74 anos de vida ajustados para qualidade (QALYs), respectivamente. A razão de custo-efetividade incremental (RCEI) foi de R$ 78.873/QALY. Considerando um cenário sem descontos, a RCEI foi de R$ 33.731/QALY ganho. Os outros cenários com maior impacto na RCEI foram a exclusão do desperdício de blinatumomabe (isto é, considerando que a sobra em frasco-ampola de um paciente seria reaproveitada para outro paciente: R$ 35.751) e a alteração do tempo de infusão (troca de bolsa em 48 ou 96 horas em vez de 24 horas: R$ 35.515). A probabilidade de o blinatumomabe ser custo-efetivo foi de 65,7% na análise probabilística, considerando um limiar de R$ 95.501. Conclusões: Blinatumomabe é custo-efetivo para pacientes pediátricos com LLA-B derivada em primeira recidiva de alto risco na perspectiva do SUS.

Objective: To estimate the cost-effectiveness of blinatumomab as the new standard treatment of consolidation in high-risk first relapse pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL). Methods: A partitioned survival model with a lifetime horizon and a 4-week cycle was developed from the Brazilian public healthcare payer's perspective (SUS). Event-free survival and overall survival were extrapolated based on data from the 20120215 clinical trial using parametric functions. A 5% discount rate was used, and the impact of variations in model parameters and assumptions were explored in scenario analyses. Results: The discounted base case lifetime cost was R$ 351,615 for blinatumomab vs. R$ 97,770 for standard chemotherapy control group (HC3), with 9.96 QALYs gained with blinatumomab vs. 6.74 QALYs gained with HC3. The incremental costeffectiveness ratio (ICER) was R$ 78,873/QALY. Considering an undiscounted scenario, the ICER was.

Overview of lymphoma diagnosis in Brazilian public health system patients: Open data analysis for health care planning

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.

Overview of lymphoma diagnosis in Brazilian public health system patients: Open data analysis for health care planning.

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.

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. II: CAR-T cell therapy for patients with CD19+ acute lymphoblastic leukemia.

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 Hematology Oncology and Cellular Therapy to make recommendations on the current scenario of the use of CAR-T cells in patients with ALL.

Hemoglobinopathy and pediatrics in the time of COVID-19

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.

Hemoglobinopathy and pediatrics in the time of COVID-19.

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.

Helicobacter pylori infection & immune thrombocytopenic purpura in children and adolescents: A randomized controlled trial.

Helicobacter pylori and immune thrombocytopenic purpura (ITP) association is not well established in chronic ITP (cITP) in children, although the cure of thrombocytopenia in approximately half of H. pylori eradicated adult patients has been described. The aim of this study was to investigate the effect of H. pylori eradication on platelet (PLT) recovery in cITP children and adolescents through a randomized, controlled trial. A total of 85 children (mean age 11.4 years) with cITP were prospectively enrolled. Diagnosis of H. pylori was established by two locally validated tests, (13)C-urea breath test and monoclonal stool antigen test. Twenty-two infected patients were identified, and randomly allocated into two groups: H. pylori treatment group (n = 11) and the non-intervention control group (n = 11). The control group was offered treatment if the thrombocytopenia persisted after the follow-up. At baseline, there were no differences regarding age, sex, duration of disease, and PLT count between groups. Sixty three of 85 patients were uninfected. PLT response was classified as complete response: PLT > 150 × 10(9 )l(-1); partial response: PLT 50-150 × 10(9 )l(-1), or an increase of 20-30 × 10(9 )l(-1); no response: PLT < 50 × 10(9 )l(-1) or an increase of <20 × 10(9 )l(-1) after at least 6 months of follow-up. Complete response was observed in 60.0% (6/10, one excluded) H. pylori eradicated patients vs. 18.2% (2/11) in non-eradicated patients (p = 0.08; OR = 6.75) after 6-9 months of follow-up. Among uninfected patients, only 13.8% (8/58) presented complete response. Two non-treated controls were treated after 6-12 months of follow-up, and PLT response was observed in 61.5% (8/13) of H. pylori eradicated patients, and in 19.0% (11/58) of uninfected patients (p = 0.004). Cytotoxin associated gene A and vacuolating cytotoxin gene A IgG antibodies were present in almost all infected patients. Therefore, the study suggests that H. pylori eradication plays a role in the management of H. pylori infected cITP children and adolescents.