Influence of different asparaginase formulations in the prognosis of children with acute lymphocytic leukaemia in Brazil: a multicentre, retrospective controlled study.

Our group recently showed that the (ASNase) formulation available in Brazil from 2017 to 2018 when used at the same dose and frequency as the formulation provided previously did not reach the activity considered therapeutic. Based on these, our goal was to assess the impact of these facts on the prognosis of children with ALL at different oncology centers. A multicentre retrospective observational study followed by a prospective follow-up. Patients aged >1 and <18 years in first-line treatment followed up at 10 referral centres, between 2014 and 2018 who received the formulation Leuginase® were identified (Group B). For each patient, the centre registered 2 patients who received ASNase in the presentation of Aginasa® exclusively (Group A). Data collection was registered using (Redcap® ). A total of 419 patients were included; 282 in Group A and 137 in B. Group A had a 3-year OS and EFS of 91·8% and 84·8% respectively, while Group B had a 3-year OS of 83·8% (P = 0·003) and EFS of 76·1% (P = 0·008). There was an impact on 3-year OS and EFS of children who received a formulation. This result highlights the importance of evaluating ASNase and monitoring its activity.

Penetrance of the TP53 R337H Mutation and Pediatric Adrenocortical Carcinoma Incidence Associated with Environmental Influences in a 12-Year Observational Cohort in Southern Brazil.

The TP53 R337H mutation is associated with increased incidence of pediatric adrenocortical tumor (ACT). The different environmental conditions where R337H carriers live have not been systematically analyzed. Here, the R337H frequencies, ACT incidences, and R337H penetrance for ACT were calculated using the 2006 cohort with 4165 R337H carriers living in Paraná state (PR) subregions. The effectiveness of a second surveillance for R337H probands selected from 42,438 tested newborns in PR (2016 cohort) was tested to detect early stage I tumor among educated families without periodical exams. Estimation of R337H frequencies and ACT incidence in Santa Catarina state (SC) used data from 50,115 tested newborns without surveillance, ACT cases from a SC hospital, and a public cancer registry. R337H carrier frequencies in the population were 0.245% (SC) and 0.306% (PR), and 87% and 95% in ACTs, respectively. The ACT incidence was calculated as ~6.4/million children younger than 10 years per year in PR (95% CI: 5.28; 7.65) and 4.15/million in SC (CI 95%: 2.95; 5.67). The ACT penetrance in PR for probands followed from birth to 12 years was 3.9%. R337H carriers living in an agricultural subregion (C1) had a lower risk of developing pediatric ACT than those living in industrial and large urban subregion (relative risk = 2.4). One small ACT (21g) without recurrence (1/112) was detected by the parents in the 2016 cohort. ACT incidence follows R337H frequency in each population, but remarkably environmental factors modify these rates.

Tissue expression of retinoic acid receptor alpha and CRABP2 in metastatic nephroblastomas.

BACKGROUND: Nephroblastoma or Wilms tumor is the most frequent kidney cancer in children and accounts for 98% of kidney tumors in this age group. Despite favorable prognosis, a subgroup of these patients progresses to recurrence and death. The retinoic acid (RA) pathway plays a role in the chemoprevention and treatment of tumors due to its effects on cell differentiation and its antiproliferative, anti-oxidant, and pro-apoptotic activities. Reports describe abnormal cellular retinoic acid-binding protein 2 (CRABP2) expression in neoplasms and its correlation with prognostic factors and clinical and pathological characteristics. The aim of this study was to evaluate the immunohistochemical expression of retinoic acid receptor alpha (RARA) and CRABP2 in paraffin-embedded samples of nephroblastomas via semiquantitative and quantitative analyses and to correlate this expression with prognostic factors. METHODS: Seventy-seven cases of nephroblastomas were selected from pediatric oncology services. The respective medical records and surgical specimens were reviewed. Three representative tumor samples and one non-tumor renal tissue sample were selected for the preparation of tissue microarrays (TMA). The Allred scoring system was used for semiquantitative immunohistochemical analyses, whereas a morphometric analysis of the stained area was employed for quantitative evaluation. The nonparametric Mann-Whitney test was used for comparisons between two groups, while the nonparametric Kruskal-Wallis test was used to compare three or more groups. RESULTS: Immunopositivity for RARA and CRABP2 was observed in both the nucleus and cytoplasm. All histological components of the nephroblastoma (blastema, epithelium, and stroma) were positive for both markers. RARA, based on semiquantitative analyses, and CRABP2, bases on quantitative analyses, exhibited increased immunohistochemical expression in patients with metastasis, with p values of 0.0247 and 0.0128, respectively. These findings were similar to the results of the quantitative analysis of RARA expression, showing greater immunopositivity in tumor samples of patients subjected to pre-surgical chemotherapy. No significant correlation was found with the other variables studied, such as disease stage, anaplasia, risk group, histological type, nodal involvement, and clinical evolution. CONCLUSIONS: Semiquantitative and quantitative analyses of the markers RARA and CRABP2 indicate their potential as biomarkers for tumor progression and their participation in nephroblastoma tumorigenesis.

Linfoma de Burkitt: estudo de oito casos e revisão de literatura / Burkitt's lymphoma: report of eight cases and review of literature

O linfoma de Burkitt envolve principalmente sítios extra-nodais. Pode ser classificado como endêmico, relacionado ao HIV e esporádico, estando a última forma relacionada à crianças e adultos jovens. No relato em questão, estudou-se oito casos de linfoma de Burkitt da variante esporádica durante os anos de 1998 e 2001. Os dados clínicos foram obtidos mediante revisão das lâminas histológicas . A relação masculino:feminino foi de 5:3, e a idade média, no momento dodiagnóstico, foi de 5 anos e 5 meses. Em cico pacientes, o tumor primário encontrava-se no abdômen, enquanto que nos tres restantes, na região cervical. Três pacientes apresentaram metástases para sistema nervoso central. A mortalidade de 62,5 por cento registrada em 9 meses foi devido ao diagnóstico tardio da doença e a agressividade biológica deste tipo de linfoma

Estudo retrospectivo de 20 crianças com histiocitose das celulas de Langerhans / Retrospective study of 20 children with Langerhans cell histiocytosis

As histicitoses das celulas de Langerhans (HCL) sao doencas raras, que podem variar de simples lesoes osseas com resolucoes espontaneas ate doencas sistemicas potencialmente...

Sindrome hemofagocitica secundaria / Secondary hemophagocytic syndrome

Embora consideradas doencas raras, as sindromes hemofagociticas representam verdadeiros desafios para o diagnostico, bem como para o tratamento. Os autores relatam o caso de uma crianca de 7 anos de idade, que desenvolveu a doenca apos uma meningite por Haemophilus influenzae e discutem os aspectos fisiopatologicos, clinicos e terapeuticos das sindromes hemofagociticas

O uso de eritropoetina em crianças com tumores cerebrais em tratamento intensivo com quimioterapia / Use of erythropoietin in children with brain tumors in intensive treatment with chemotherapy

Foram analisadas cinco crianças portadoras de tumores cerebrais malignos em vigencia de quimioterapia intensiva, com a finalidade de estudar a eficacia da eritropoetina recombinante humana (rHuEPO), em diminuir as necessidades de transfusöes de concentrados de hemacias. Duas crianças testemunhas de Jeova receberam rHuEPO. Nenhuma diferença foi observada nos requerimentos de concentrados de hemacias, comparando-se com o grupo de pacientes que näo receberam rHuEPO