Barriers to medication adherence by caregivers of children with leukemia: an observational study / Barreiras de adesão medicamentosa por cuidadores de crianças com leucemia: um estudo observacional

ABSTRACT Objective: To identify barriers to adherence to home oral maintenance chemotherapy in children with leukemia treated at a specialized cancer center. Methods: We used the Brief Medication Questionnaire (BMQ) as a tool for screening barriers to adherence. The level of adherence was calculated considering at least one positive response in each BMQ domain, defined as Regimen Screen, Belief Screen, and Recall Screen. A positive screening for belief barriers (PSB) indicates that the caregiver reports not understanding the medication's mechanism of action and adverse effects. Results: Three important barriers to adherence were identified: beliefs, number of children of the caregiver, and age of the caregiver. The primary caregivers included 32 mothers (80%), four fathers (10%), three grandmothers (7.5%), and one unrelated caregiver (2.5 %). Most caregivers with a PSB were mothers. A PSB indicates that the caregiver reports not understanding the medication's mechanism of action and adverse effects. Caregivers with two or more children (median, three) had more barriers to adherence. Caregivers with potential non-adherence tended to be older than those with potential adherence, although without statistical significance (p=0.079, Mann-Whitney U test). Conclusions: The main barriers to adherence to home oral maintenance chemotherapy in children with leukemia identified through interviews with their caregivers, most often mothers, were lack of understanding of the treatment regimen, a greater number of children, and older age.

RESUMO Objetivo: Identificar barreiras de adesão ao tratamento de manutenção da quimioterapia via oral domiciliar, em uma amostra de crianças diagnosticadas com leucemia atendidas em um serviço especializado em oncologia. Métodos: O Brief Medication Questionnaire (BMQ) foi utilizado como instrumento de coleta para a identificação de barreiras de adesão. O nível de adesão foi calculado considerando-se pelo menos uma resposta positiva no domínio do BMQ, definido como regime, crença e recordação. Uma crença positiva mostra que o cuidador reporta não entender o mecanismo de ação e os efeitos adversos. Resultados: Três importantes barreiras de adesão foram identificadas, incluindo crença, o número de filhos do casal e a idade dos cuidadores. A mãe como principal responsável pelo tratamento da criança apresentou frequência maior entre as pessoas com rastreamento positivo para barreiras de crenças (BPC). Crença positiva significa que o cuidador relata não entender o mecanismo de ação dos medicamentos e os efeitos adversos. Quanto ao número de filhos, o estudo mostrou que quanto mais filhos (dois filhos ou mais, mediana=três) maior a barreira de adesão. Houve tendência de responsáveis com potencial não adesão serem mais velhos que os responsáveis com potencial adesão, embora sem significância estatística ao nível de significância de 5% (p=0,079, teste U de Mann-Whitney). Conclusões: As principais barreiras de adesão dos cuidadores de crianças com leucemia ao tratamento medicamentoso de manutenção foram dificuldades relatadas pelos cuidadores, na maioria das vezes as mães, que não entenderam como o medicamento funcionava, o número de filhos — quanto mais filhos menor a adesão — e a idade dos cuidadores. Cuidadores mais velhos aderiram menos ao tratamento prescrito.

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.

A sensitive and inexpensive high-resolution melting-based testing algorithm for diagnosis of transient abnormal myelopoiesis and myeloid leukemia of Down syndrome.

Patients with Down syndrome (DS) are commonly affected by a pre-leukemic disorder known as transient abnormal myelopoiesis (TAM). This condition usually undergoes spontaneous remission within the first 2 months after birth; however, in children under 5, 20%-30% of cases evolve to myeloid leukemia of Down syndrome (ML-DS). TAM and ML-DS are caused by co-operation between trisomy 21 and acquired mutations in the GATA1 gene. Currently, only next-generation sequencing (NGS)-based methodologies are sufficiently sensitive for diagnosis in samples with small GATA1 mutant clones (≤10% blasts). Alternatively, this study presents research on a new, fast, sensitive, and inexpensive high-resolution melting (HRM)-based diagnostic approach that allows the detection of most cases of GATA1 mutations, including silent TAM. The algorithm first uses flow cytometry for blast count, followed by HRM and Sanger sequencing to search for mutations on exons 2 and 3 of GATA1. We analyzed 138 samples of DS patients: 110 of asymptomatic neonates, 10 suspected of having TAM, and 18 suspected of having ML-DS. Our algorithm enabled the identification of 33 mutant samples, among them five cases of silent TAM (5/110) and seven cases of ML-DS (7/18) with blast count ≤10%, in which GATA1 alterations were easily detected by HRM. Depending on the type of genetic variation and its location, our methodology reached sensitivity similar to that obtained by NGS (0.3%) at a considerably reduced time and cost, thus making it accessible worldwide.

SARS-CoV-2 in children with cancer in Brazil: Results of a multicenter national registry.

BACKGROUND: Strategies to mitigate the impact of COVID-19 in special populations are complex and challenging. Few studies have addressed the impact of COVID-19 on pediatric patients with cancer in low- and middle-income countries. METHODS: Multicenter observational cohort study with prospective records and retrospective analyses starting in April 2020 in 21 pediatric oncology centers distributed throughout Brazil. PARTICIPANTS: Patients under 18 years of age who are infected by the SARS-CoV-2 virus (confirmed diagnosis through reverse transcriptase-polymerase chain reaction [RT-PCR]) while under treatment at pediatric oncology centers. The variables of interest included clinical symptoms, diagnostic and therapeutic measures. The repercussions of SARS-CoV-2 infection on cancer treatment and general prognosis were monitored. RESULTS: One hundred seventy-nine patients were included (median age 6 [4-13] years, 58% male). Of these, 55.9% had acute leukemia and 34.1% had solid tumors. The presence of SARS-CoV-2 was diagnosed by RT-PCR. Various laboratory markers were analyzed, but showed no correlation with outcome. Children with low or high BMI for age had lower overall survival (71.4% and 82.6%, respectively) than those with age-appropriate BMI (92.7%) (p = .007). The severity of presentation at diagnosis was significantly associated with outcome (p < .001). Overall mortality in the presence of infection was 12.3% (n = 22). CONCLUSION: In children with cancer and COVID-19, lower BMI was associated with worse prognosis. The mortality in this group of patients (12.3%) was significantly higher than that described in the pediatric population overall (∼1%).

Partição de Comprimidos Antineoplásicos Utilizados no Tratamento de Leucemias Agudas em Crianças e Adolescentes / Splitting of Antineoplastic Tablets Used in Acute Leukemias Treatment in Children and Adolescents / Partición de Comprimidos Antineoplásicos Empleados en el Tratamiento de Leucemias Agudas en Niños y Adolescentes

Introdução: A manipulação de antineoplásicos para ajuste de dose, como partição de comprimidos, é comum no tratamento de leucemias agudas de crianças e adolescentes. Objetivo: Identificar a frequência e descrever a prática da partição domiciliar de comprimidos antineoplásicos utilizados no tratamento oral de crianças e adolescentes com leucemias agudas na fase de manutenção. Método: Trata-se de um estudo transversal descritivo, realizado em um hospital pertencente à rede de saúde pública do Distrito Federal com assistência especializada em pediatria. Foram incluídos no estudo crianças e adolescentes entre 1 e 18 anos, diagnosticados com leucemias agudas e em fase de manutenção do tratamento no período de estudo. Foi aplicado um questionário semiestruturado ao responsável principal pela administração dos medicamentos quimioterápicos via oral, podendo ser o cuidador ou a própria criança/adolescente. Foram coletadas variáveis sociodemográficas dos pacientes e cuidadores e variáveis sobre a prática de partição de medicamentos antineoplásicos no domicílio. Resultados: Todos os 48 entrevistados no período do estudo relataram ter partido comprimidos antineoplásicos ao longo do tratamento de leucemias agudas, sendo estes mercaptopurina (n=45 [93,75%]) e tioguanina (n=3 [6,25%]). Conclusão: A partição de comprimidos antineoplásicos foi uma prática unânime em virtude da necessidade referida de ajuste de dose individual para o tratamento de leucemias agudas de crianças e adolescentes, considerando a indisponibilidade de formulações adequadas. Os resultados reforçam a necessidade de a partição ser uniformizada e realizada de maneira a minimizar os riscos e a garantir a segurança para as crianças e adolescentes e seus cuidadores.

Introduction: Antineoplastic drug manipulation for dose adjustment, such as tablet splitting, is standard in acute leukemia treatment for children and adolescents. Objective: To identify the frequency and describe the practice of household splitting of antineoplastic tablet for oral treatment of children and adolescents with acute leukemias in the maintenance phase. Method: Cross-sectional descriptive study performed in a public health system hospital from Distrito Federal (Brazil) with specialized pediatric assistance. Children and teenagers between 1 and 18 years old, diagnosed with acute leukemia and in treatment maintenance phase during the study period were included. A semi-structured questionnaire was applied to the main responsible for administering oral chemotherapy drugs, which could be the caregiver or the child/adolescent themselves. Sociodemographic variables of patients and caregivers and variables on the practice of splitting antineoplastic drugs at home were collected. Results: All 48 interviewees in the study period reported having split antineoplastic tablets during the treatment for acute leukemias, such as mercaptopurine (n = 45 [93.75%]) and thioguanine (n = 3 [6.25%]). Conclusion: The splitting of antineoplastic tablets was a unanimous practice due to the reported need to adjust the individual dose for acute leukemia treatment in children and adolescents, considering the unavailability of adequate formulations. The results reinforce the need for splitting to be standardized and performed in a way that minimizes risks and ensures safety for patients and their caregivers

Introducción: La manipulación de fármacos antineoplásicos para el ajuste de dosis, como las particiones de comprimidos, es frecuente en el tratamiento de las leucemias agudas en niños y jóvenes. Objetivo: Identificar la frecuencia y describir la práctica de la división domiciliaria de medicamentos antineoplásicos utilizados en el tratamiento oral de niños y adolescentes con leucemias agudas en la fase de mantenimiento. Método: Se trata de un estudio transversal descriptivo realizado en un hospital de la red de salud pública del Distrito Federal (Brasil) con asistencia especializada en pediatría. El estudio incluyó a niños y jóvenes de entre 1 y 18 años de edad diagnosticados con leucemia aguda y en fase de mantenimiento del tratamiento en el período del estudio. Se aplicó un cuestionario semiestructurado a la persona principal responsable de la administración de fármacos quimioterapéuticos por vía oral, que puede ser el cuidador o el propio niño/joven. Fueron colectadas variables sociodemográficas de los pacientes y cuidadores y variables sobre la práctica de la división de los medicamentos antineoplásicos en domicílios. Resultados: Los 48 entrevistados en el período de estudio informaron haber roto las pastillas antineoplásicas durante el tratamiento de la leucemia aguda, siendo éstas mercaptopurina (n=45 [93,75%]) y tioguanina (n=3 [6,25%]). Conclusión: La partición de comprimidos antineoplásicos fue una práctica unánime debido a la necesidad mencionada de ajustar la dosis individual para el tratamiento de las leucemias agudas de niños y adolescentes, considerando la falta de formulaciones apropiadas. Los resultados refuerzan la necesidad de estandarizar y realizar la partición para minimizar los riesgos y garantizar la seguridad de los niños, jóvenes y sus cuidadores.

Novel mutations associated with pyruvate kinase deficiency in Brazil.

BACKGROUND: Pyruvate kinase deficiency is a hereditary disease that affects the glycolytic pathway of the red blood cell, causing nonspherocytic hemolytic anemia. The disease is transmitted as an autosomal recessive trait and shows a marked variability in clinical expression. This study reports on the molecular characterization of ten Brazilian pyruvate kinase-deficient patients and the genotype-phenotype correlations. METHOD: Sanger sequencing and in silico analysis were carried out to identify and characterize the genetic mutations. A non-affected group of Brazilian individuals were also screened for the most commonly reported variants (c.1456C>T and c.1529G>A). RESULTS: Ten different variants were identified in the PKLR gene, of which three are reported here for the first time: p.Leu61Gln, p.Ala137Val and p.Ala428Thr. All the three missense variants involve conserved amino acids, providing a rationale for the observed enzyme deficiency. The allelic frequency of c.1456C>T was 0.1% and the 1529G>A variant was not found. CONCLUSION: This is the first comprehensive report on molecular characterization of pyruvate kinase deficiency from South America. The results allowed us to correlate the severity of the clinical phenotype with the identified variants.

Novel mutations associated with pyruvate kinase deficiency in Brazil

Abstract Background: Pyruvate kinase deficiency is a hereditary disease that affects the glycolytic pathway of the red blood cell, causing nonspherocytic hemolytic anemia. The disease is transmitted as an autosomal recessive trait and shows a marked variability in clinical expression. This study reports on the molecular characterization of ten Brazilian pyruvate kinase-deficient patients and the genotype-phenotype correlations. Method: Sanger sequencing and in silico analysis were carried out to identify and characterize the genetic mutations. A non-affected group of Brazilian individuals were also screened for the most commonly reported variants (c.1456C>T and c.1529G>A). Results: Ten different variants were identified in the PKLR gene, of which three are reported here for the first time: p.Leu61Gln, p.Ala137Val and p.Ala428Thr. All the three missense variants involve conserved amino acids, providing a rationale for the observed enzyme deficiency. The allelic frequency of c.1456C>T was 0.1% and the 1529G>A variant was not found. Conclusion: This is the first comprehensive report on molecular characterization of pyruvate kinase deficiency from South America. The results allowed us to correlate the severity of the clinical phenotype with the identified variants.

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.

Frequency of copy number abnormalities in common genes associated with B-cell precursor acute lymphoblastic leukemia cytogenetic subtypes in Brazilian children.

Copy number alterations (CNAs) in genes committed to B-cell precursors have been associated with poor survival in subgroups of patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). We investigated submicroscopic alterations in a series of 274 Brazilian children with BCP-ALL by multiplex ligation-dependent probe amplification and evaluated their correlation with clinical and laboratory features. The relevance of overlapping CNA abnormalities was also explored. Deletions/amplifications in at least one gene were identified in 83% of the total series. In children older than 2 years, there was a predominance of CNAs involving deletions in IKZF1, CDKN2A, and CDKN2B, whereas the pseudoautosomal region 1 (PAR1) had deletions that were found more frequently in infants (P <0.05). Based on the cytogenetic subgroups, favorable cytogenetic subgroups showed more deletions than other subgroups that occurred simultaneously, specifically ETV6 deletions (P <0.05). TCF3-PBX1 was frequently deleted in RB1, and an absence of deletions was observed in IKZF1 and genes localized to the PAR1 region. The results corroborate with previous genome-wide studies and aggregate new markers for risk stratification of BCP-ALL in Brazil.

Clinical and molecular epidemiology of neonatal leukemia in Brazil.

The clinical and molecular findings of 77 cases of neonatal leukemia (NL) and 380 of infant leukemia (IL) were selected to distinguish features between NL and IL. Somatic gene mutations associated with acute leukemia including FLT3, RAS and PTPN11 were revisited. There were 42 cases of congenital leukemia associated with Down syndrome (DS) and 39 of these cases presented features of acute myeloid leukemia (AML)-M7. Twenty-seven of the DS cases underwent spontaneous remission and were reclassified as a transient myeloproliferative disorder. GATA1 mutations were found in 70% of these cases. In non-DS, frequent abnormalities were MLL rearrangements, mainly MLL-AFF1 in acute lymphoblastic leukemia and MLL-MLLT3 in AML. The FLT3 mutation was not found, while RAS (n = 4) and PTPN11 (n = 2) mutations were identified and reported for the first time in NL. There was substantial evidence to support that somatic abnormalities occur in utero. Thus, congenital leukemia is a good model for understanding leukemogenesis.

NQO1 rs1800566 (C609T), PON1 rs662 (Q192R), and PON1 rs854560 (L55M) polymorphisms segregate the risk of childhood acute leukemias according to age range distribution.

PURPOSE: The risk of developing childhood leukemia has been associated with gene polymorphisms that decrease the activity of detoxifying metabolic enzymes and enzymes involved in systemic oxidative stress. We investigated the NQO1 and PON1 polymorphisms for associations with susceptibility to childhood leukemia. METHODS: Samples from 1,027 Brazilian children (519 acute lymphoblastic leukemia, ALL; 107 acute myeloid leukemia, AML; 401 controls) were analyzed. TaqMAN real-time assays were used to determine the NQO1 rs1800566 (C609T), PON1 rs662 (Q192R), and PON1 rs854560 (L55M) frequencies. Logistic regression was used to evaluate the association of polymorphisms with cases and controls, with age and somatic fusion genes (MLL-r and ETV6-RUNX1) as covariables. RESULTS: Children with at least one NQO1 variant allele were at lower risk for developing infant AML (odds ratio (OR) 0.26, 95 % confidence interval (CI) 0.10-0.68); no association was detected for ALL. PON1 rs854560 (L55M) was associated with an increased risk of developing childhood leukemia (LM + MM, OR 1.93, 95 % CI 1.32-2.81). The PON1 rs662 R192R genotype had a statistically significant decreased frequency in ALL (OR 0.64, 95 % CI 0.43-0.93). Infant ALL cases were more likely to harbor homozygous PON1 rs854560 alleles than controls (OR 1.72, 95 % CI 1.03-2.89); at least one M allele was associated with an increased risk of ALL in children older than 1 year (OR 1.99, 95 % CI 1.17-3.3). CONCLUSIONS: The NQO1 rs1800566 (C609T), PON1 rs854560 (L55M), and PON1 rs662 (Q192R) polymorphisms modified risk depending on leukemia subtype (decreased in AML, increased and decreased in ALL, respectively), age strata, and variant genotype combinations.

Prevenção de câncer de colo uterino:desafios de uma década / Cervical cancer prevention: challenges in a decade

O objetivo deste estudo foi identificar no ambulatório de ginecologia oncológica, dentro de um serviço terciário no Hospital Regional da Asa Norte da Secretaria de Estado de Saúde do Distrito Federal, quais fatores estariam contribuindo para o insucesso do programa de prevenção do câncer de colo uterino em especial aqueles relacionados aos formulários,ao cadastro de resultados no SISCOLO e ao acompanhamento das pacientes com alterações na colpocitologia oncótica.

The objective of this study was to identify at the oncological gynecology unit, within a tertiary care service at the North Wing Regional Hospital of the Federal District State Secretariat of Health, which factors would be contributing for the uterine cancer prevention program lack of success, particularly those related to forms, to results registry in the SISCOLO, and patients’ follow up with oncotic colpocytology.

Auditory-evoked response analysis in Brazilian patients with sickle cell disease.

The objective of the present study was to evaluate the integrity of the peripheral and central auditory systems of sickle cell disease (SCD) patients, through electrophysiological evaluation utilizing auditory evoked potentials, and comparing the results obtained in SCD patients with individuals without SCD. A total of 80 individuals were evaluated: 40 SCD patients; and 40 healthy age- and sex-matched controls. Brainstem auditory evoked response (BAER) was used to check neural integrity and electrophysiological thresholds, and cognitive potential (P300) to analyse the auditory selective attention. Despite the exclusion of individuals with comorbidities typical of SCD, the predominance of hearing loss among the patients was detected in 16 ears (20%). The absolute latencies of the BAER were within the expected range but the SCD group showed a small but statistically significant reduction of the interpeaks I-V, indicative of cochlear alteration. P300 latency and amplitude were adequate for both groups suggesting the absence of central auditory system abnormalities. The present findings suggest that SCD causes variable degree of cochlear abnormalities without evidence of neural problems.

ETV6-RUNX1 fusion gene and additional genetic changes in infant leukemia: a genome-wide analysis.

Acute lymphoblastic leukemia (ALL) in infants is characterized by a high frequency of MLL gene rearrangements. By contrast, the t(12;21) ETV6-RUNX1 fusion gene is typically detected in children older than 2 years. In a series of Brazilian infant leukemia cases, however, four younger cases harbored ETV6-RUNX1, at ages 2, 3, 5, and 7 months. This finding could represent a unique model for delineating the additional genomic hits required to accelerate the emergence of a frank leukemia in these t(12;21)-positive cases. We applied a whole-genome copy number analysis with single-nucleotide polymorphism (SNP) arrays, comparing t(12;21) infants with older pediatric age groups. Recurrent deletions, including 9p21.3 (CDKN2A, CKDN2B, and MTAP), 11p13 (CD44), 12p13.2 (ETV6), and patient-specific abnormalities were identified. Although infant cases with t(12;21) did not display specific genetic abnormalities explaining the short latency to overt leukemia, the frequency of copy number abnormalities increased proportionally with age. This novel SNP array analysis in an extremely rare series of cases opens new ideas about the etiology of ETV6-RUNX1-positive ALL.

Detection of mutations in GATA1 gene using automated denaturing high-performance liquid chromatography and direct sequencing in children with Down syndrome.

Denaturing high-performance liquid chromatography (dHPLC) was developed to screen DNA variations by separating heteroduplex and homoduplex DNA fragments by ion-pair reverse-phase liquid chromatography. In this study, we have evaluated the dHPLC screening method and direct sequencing for the detection of GATA1 mutations in peripheral blood and bone marrow aspirates samples from children with Down syndrome (DS). Cases were ascertained consecutively as part of an epidemiological study of DS and hematological disorders in Brazil. A total of 130 samples corresponding to 115 children with DS were analysed using dHPLC and direct sequencing methods to detect mutations in GATA1 exons 2, 3 and 4 gene sequences. The overall detection rate of sequencing and dHPLC screening methods was similar. Twenty mutations were detected in exon 2 and one mutation in exon 3 (c.231_232 dupGT) sequences of acute megakaryoblastic leukemia and transient leukemia samples. Four GATA1 mutations were newly described [c.155C > G; c.156_178 del23 bp; c.29_30 del GG; c.182C > A and c.151A > T,c.153_162 del 10 bp). Out of four, three had single nucleotide change. In conclusion, our results indicate that dHPLC is an efficient and valuable tool for GATA1 mutational analysis.

[Prevalence of sickle cell trait and sickle cell anemia among newborns in the Federal District, Brazil, 2004 to 2006]. / Prevalência do traço e da anemia falciforme em recém-nascidos do Distrito Federal, Brasil, 2004 a 2006.

To determine the prevalence of sickle cell trait and sickle cell anemia among newborns in the Federal District, Brazil, a cross-sectional prevalence study covering the years 2004 to 2006 was conducted. Test results reported from the Neonatal Screening Program in the Federal District Health Department from 2004 to 2006 were analyzed, and prevalence rates were calculated. Neonatal blood samples were tested by isoelectric focalization. From January 2004 to December 2006, 116,271 newborns were tested for hemoglobinopathies, corresponding to 85% of all live births from mothers residing in the Federal District. The study identified 3,760 newborns with sickle cell trait (Hb AS) and 109 with sickle cell anemia (Hb SS). The prevalence rates were 323 (Hb AS) and 9 (Hb SS) per 10,000 live births. The high prevalence of sickle cell trait highlights the importance of neonatal screening in the Federal District to support work by health managers and professionals for planning educational measures and reducing the morbidity associated with sickle cell disease.

Prevalência do traço e da anemia falciforme em recém-nascidos do Distrito Federal, Brasil, 2004 a 2006 / Prevalence of sickle cell trait and sickle cell anemia among newborns in the Federal District, Brazil, 2004 to 2006

Para determinar a prevalência da anemia e traço falciforme em recém-nascidos no Distrito Federal, Brasil, no período de 2004 a 2006, foi realizado um estudo seccional de prevalência. Foram utilizados os registros dos resultados de testes realizados de 2004 a 2006 pelo Programa de Triagem Neonatal da Secretaria de Estado de Saúde do Distrito Federal, e calculados os coeficientes de prevalência. As amostras de sangue dos recém-nascidos foram analisadas pela técnica de focalização isoelétrica. No período de 1º de janeiro de 2004 a 31 de dezembro de 2006, foram realizados 116.271 testes de triagem neonatal para hemoglobinopatias, correspondendo a 85 por cento do número de nascidos vivos de mães residentes no Distrito Federal. Foram identificados, nos três anos, 3.760 recém-nascidos, com traço falciforme (Hb AS) e 109 com anemia falciforme (Hb SS). Os coeficientes de prevalência foram, respectivamente, 323 (Hb AS) e 9 (Hb SS) por 10 mil nascidos vivos. A elevada prevalência do traço falciforme evidencia a importância da triagem neonatal no Distrito Federal para atuação de gestores e profissionais da saúde no planejamento de ações educativas e na redução da morbidade associada às doenças falciformes.

To determine the prevalence of sickle cell trait and sickle cell anemia among newborns in the Federal District, Brazil, a cross-sectional prevalence study covering the years 2004 to 2006 was conducted. Test results reported from the Neonatal Screening Program in the Federal District Health Department from 2004 to 2006 were analyzed, and prevalence rates were calculated. Neonatal blood samples were tested by isoelectric focalization. From January 2004 to December 2006, 116,271 newborns were tested for hemoglobinopathies, corresponding to 85 percent of all live births from mothers residing in the Federal District. The study identified 3,760 newborns with sickle cell trait (Hb AS) and 109 with sickle cell anemia (Hb SS). The prevalence rates were 323 (Hb AS) and 9 (Hb SS) per 10,000 live births. The high prevalence of sickle cell trait highlights the importance of neonatal screening in the Federal District to support work by health managers and professionals for planning educational measures and reducing the morbidity associated with sickle cell disease.