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

Abstract 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.

Association of the clinical profile and overall survival of pediatric patients with acute lymphoblastic leukemia.

Introduction: The clarification of etiopathology, the improvement of chemotherapy regimens and their risk stratifications, and the improvement in treatment support have increased the survival of children and adolescents affected by Acute Lymphoblastic Leukemia (ALL) past few years. This study aimed to estimate overall survival (OS) and event-free survival (EFS) in an onco-hematology treatment center in Brazil, reports the main clinical-laboratory characteristics of patients at diagnosis, verify the frequency of treatment-related adverse effects and the main causes of death. Material and methods: Retrospective analysis involving patients diagnosed with ALL, treated with the protocol of the Brazilian Group for Treatment of Leukemias in Childhood (GBTLI), between 2010 and 2020 was carried out; the outcomes (relapse, deaths, development of new neoplasms) were analyzed SPSS® software was used for the statistical analyses, and the p-value was considered significant when less than 0.05 for all analyses. Results: 109 patients were included in the study; the median age was 5 years, with a slight predominance of males. Sixty-six patients were classified as high-risk (HR) group and 43 patients were classified as low-risk (LR) group. After 5 years of diagnosis, the OS was 71.5%, and the EFS was 65%. No statistical difference was found between the HR and LR groups for OS and EFS, while leukocyte counts were statistically associated with the outcome of death (p = 0.028). Among the patients, 28 (25.6%) died due to infection accounting 46.4% of death causes. Among the 34 patients with unfavorable outcomes (death and/or relapse), 32 had no research for the minimal residual disease at the end of remission induction, and 25 were not investigated for the presence of chromosomal abnormalities. The most reported complications and treatment-related adverse effects were increased liver transaminases (85.9%), airway infection (79.4%), oral mucositis (67.2%), febrile neutropenia (64.4%), and diarrhea (36.4%). Conclusions: The rates of OS and EFS obtained in this cohort are similar to those obtained in the few previous similar studies in Brazil and lower than those carried out in developed countries. The unavailability of prognostic tests may have hindered risk stratification and influenced the results obtained.

Therapy-related acute myeloid leukemia with KMT2A-SNX9 gene fusion associated with a hyperdiploid karyotype after hemophagocytic lymphohistiocytosis.

Therapy-related acute myeloid leukemia (t-AML) following treatment with topoisomerase-II inhibitors has been increasingly reported. These compounds (e.g. etoposide) promote DNA damage and are associated with KMT2A rearrangements. They are widely used as first-line treatment in hemophagocytic lymphohistiocytosis (HLH). Here we describe a newborn who developed t-AML after HLH treatment. We provide detailed clinical, cytogenetic, and molecular characteristics of this patient, including the identification of a novel gene fusion - KMT2A-SNX9 - in t-AML. Considering the dismal outcome of this case, we discuss the side-effects of etoposide administration during HLH treatment in infants.

Partnership of the Sociedade Brasileira de Oncologia Pediátrica and International Society of Pediatric Oncology to improve nutritional care for children with cancer in Brazil

Abstract The authors present a proposal of a partnership between the Sociedade Brasileira de Oncologia Pediátrica (SOBOPE) and the International Society of Pediatric Oncology (SIOP) to promote the standardization and improvement of nutritional care of kids under cancer treatment in Brazil. The results of the first meeting in Brazil as well as plans for future meetings are described.

Partnership of the Sociedade Brasileira de Oncologia Pediátrica and International Society of Pediatric Oncology to improve nutritional care for children with cancer in Brazil.

The authors present a proposal of a partnership between the Sociedade Brasileira de Oncologia Pediátrica (SOBOPE) and the International Society of Pediatric Oncology (SIOP) to promote the standardization and improvement of nutritional care of kids under cancer treatment in Brazil. The results of the first meeting in Brazil as well as plans for future meetings are described.

Identification of the MYST3-CREBBP fusion gene in infants with acute myeloid leukemia and hemophagocytosis

ABSTRACT Background: Acute myeloid leukemia presenting the MYST3-CREBBP fusion gene is a rare subgroup associated with hemophagocytosis in early infancy and monocytic differentiation. The aim of this study was to define the relevant molecular cytogenetic characteristics of a unique series of early infancy acute myeloid leukemia cases (≤24 months old), based on the presence of hemophagocytosis by blast cells at diagnosis. Methods: A series of 266 infant cases of acute myeloid leukemia was the reference cohort for the present analysis. Acute myeloid leukemia cases with hemophagocytosis by blast cells were reviewed to investigate the presence of the MYST3-CREBBP fusion gene by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. Results: Eleven cases with hemophagocytosis were identified with hemophagocytic lymphohistiocytosis being ruled out. Six cases were classified as myelomonocytic leukemia, three as AML-M7 and two as AML-M2. In five cases, the presence of the MYST3-CREBBP fusion gene identified by molecular cytogenetics was confirmed by fluorescence in situ hybridization. All patients received treatment according to the Berlin-Frankfürt-Münster acute myeloid leukemia protocols and only one out of the five patients with the MYST3-CREBBP fusion gene is still alive. Conclusions: Our findings demonstrate that the presence of hemophagocytosis in acute myeloid leukemia was not exclusively associated to the MYST3-CREBBP fusion gene. Improvements in molecular cytogenetics may help to elucidate more complex chromosomal rearrangements in infants with acute myeloid leukemia and hemophagocytosis.

Identification of the MYST3-CREBBP fusion gene in infants with acute myeloid leukemia and hemophagocytosis.

BACKGROUND: Acute myeloid leukemia presenting the MYST3-CREBBP fusion gene is a rare subgroup associated with hemophagocytosis in early infancy and monocytic differentiation. The aim of this study was to define the relevant molecular cytogenetic characteristics of a unique series of early infancy acute myeloid leukemia cases (≤24months old), based on the presence of hemophagocytosis by blast cells at diagnosis. METHODS: A series of 266 infant cases of acute myeloid leukemia was the reference cohort for the present analysis. Acute myeloid leukemia cases with hemophagocytosis by blast cells were reviewed to investigate the presence of the MYST3-CREBBP fusion gene by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. RESULTS: Eleven cases with hemophagocytosis were identified with hemophagocytic lymphohistiocytosis being ruled out. Six cases were classified as myelomonocytic leukemia, three as AML-M7 and two as AML-M2. In five cases, the presence of the MYST3-CREBBP fusion gene identified by molecular cytogenetics was confirmed by fluorescence in situ hybridization. All patients received treatment according to the Berlin-Frankfürt-Münster acute myeloid leukemia protocols and only one out of the five patients with the MYST3-CREBBP fusion gene is still alive. CONCLUSIONS: Our findings demonstrate that the presence of hemophagocytosis in acute myeloid leukemia was not exclusively associated to the MYST3-CREBBP fusion gene. Improvements in molecular cytogenetics may help to elucidate more complex chromosomal rearrangements in infants with acute myeloid leukemia and hemophagocytosis.

[Severe aplastic anemia in children]. / Anemia aplástica severa: análise dos pacientes pediátricos atendidos pelo serviço de transplante de medula óssea do Hospital de Clínicas de Curitiba no período de 1979-1993.

UNLABELLED: A Severe Aplastic Anemia is a rare disease that happens in the entire world. Because the rarity, it is difficult to characterize the features of the patients that have this disease, and to find their possible etiological factors. PURPOSE: To report all cases of severe aplastic anemia in young people who were attended in the hospital and characterize some variables like age, sex, geographic area of residence, etiologies and socioeconomic status. METHODS: It was done a descriptive analyze of all pediatric patient's features (below 18 years) who came to the hospital in 1979-1993 with severe aplastic anemia based on the classification proposed for Camitta et al. The data were obtained from the hospital records in 134 children, and the investigator in 79 families performed interviews. RESULTS: The age ranged from 2-18 years (mean 10.89 years). The male to female ratio was 64:70. Most of the patients came from urban zone of south Brazil. We did not identify any etiologic agents in 34% of the cases. Prior exposure to the agricultural pesticides and benzene derivative was the most common etiologic factors that were related. The household income of 83.5% of the families was < $ 65 U.S./capita, and 70.9% of the patient's mother did not finish the primary school CONCLUSION. In this group, severe aplastic anemia is more frequent in 11 years old girls. Most of them are the in urban zone of south Brazil, with low socioeconomic status, and related prior exposure agricultural pesticides and benzene derivative.

Anemia aplástica severa: análise dos pacientes pediátricos atendidos pelo serviço de transplante de medula óssea do Hospital de Clínicas de Curitiba no período de 1979-1993 / Severe aplastic anemia in children

A anemia aplástica severa é uma doença rara que acomete pessoas de todas as regiöes do mundo. Devido a sua raridade, existem dificuldades em se caracterizar o perfil dos pacientes acometidos pela doença, assim como identificar possíveis fatores implicados na sua etiologia. OBJETIVO: Descrever o perfil dos pacientes pediátricos atendidos com anemia aplástica severa, analisando variáveis como distribuiçäo de idade, sexo, local de habitaçäo, etiologia e nível socioeconômico. MÉTODOS: FOI realizada uma análise descritiva das características encontradas em todos os pacientes com idade inferior a 18 anos, encaminhados no período de 1979-1993 com diagnóstico da doença, conforme classificaçäo proposta por Camitta et al. As informaçöes foram obtidas através do prontuário médico e de um questionário aplicado pela pesquisadora em 79 das 134 famílias. RESULTADOS: A média das idades foi de 10,89 anos. Houve leve predominância do sexo feminino. A maioria dos pacientes residia na zona urbana da regiäo sul do país. 34 por cento das famílias näo identificaram um fator causal. Os pesticidas agrícolas e os derivados de benzeno foram os fatores causais mais relatados no questionário. Das 79 famílias que responderam ao questionário, 83,5 por cento tinham renda familiar inferior a 1 salário mínimo " per capita" e 70,9 por cento das mäes tinham nível de escolaridade inferior o primeiro grau completo. CONCLUSÄO: O perfil da populaçäo pediátrica com anemia aplástica severa atendida no Serviço de Transplante de Medula Ossea de Curitiba é formado predominantemente por crianças de 11 anos, do sexo feminino, provenientes da zona urbana da regiäo sul do país, com baixo nível socioeconômico, que relataram os pesticidas agrícolas e derivados de benzeno como possíveis fatores etiológicos