Vomiting after intrathecal chemotherapy under anesthesia in pediatric patients with hematologic cancers: A cohort study.

INTRODUCTION: Despite preventive strategies, vomiting is an adverse event affecting patients with cancer. However, literature on the incidence and risk factors for vomiting in pediatric patients with cancer are scarce. AIM: To assess the incidence and risk factors for vomiting within 24 h and goodness of fit for the Eberhart score in pediatric patients with hematologic cancers after receiving intrathecal chemotherapy under deep sedation. METHODS: This prospective cohort study included patients under 20 years of age with hematologic cancers who were scheduled to undergo intrathecal chemotherapy under anesthesia. The primary outcome was the occurrence of vomiting within 24 h after the end of anesthesia. Sociodemographic and procedure data and underlying diseases were collected. Patients were monitored during the procedure, in the postanesthesia care unit, and the day after (by phone call). RESULTS: A total of 139 patients were included, and the incidence of vomiting was 30.9% within 24 h after intrathecal chemotherapy under anesthesia, with 90.7% of vomiting prior to 6 h. Prophylactic ondansetron was administered prior to the procedure to 45.3% of patients. Risk factors for vomiting were female gender (hazard ratio: 2.47, 95% confidence interval: 1.35-4.53, p: .003), consolidation phase of treatment (hazard ratio: 2.16, 95% confidence interval: 1.10-4.24, p: .025), and history of kinetosis (hazard ratio: 2.49, 95% confidence interval: 1.31-4.70, p: .005). Incidence of vomit was higher than estimated by the Eberhart score distribution (observed incidence in patients with a score of zero: 33.3%; with a score of one: 28.8%; with a score of two: 60%). CONCLUSION: A high incidence of vomiting was observed within 24 h after intrathecal chemotherapy under propofol deep sedation. Risk factors for this outcome were established (being female, consolidation phase of treatment, and previous kinetosis), and evidence suggested that the Eberhart score was not suitable for the studied population.

The Infection Profile and Survival of Children and Adolescents With COVID-19 Undergoing Cancer Treatment: A Cohort Study.

OBJECTIVE: The objective of this study was to evaluate the clinical evolution of coronavirus disease 2019 (COVID-19) in children and adolescents with cancer. METHODS: Cohort involving patients undergoing cancer treatment, 19 years old and under, with the diagnosis of COVID-19 by real-time polymerase chain reaction, in a reference hospital, between March 2020 and November 2021. Data were collected from medical records and interviews with patients and/or guardians. The primary outcomes studied were severe/critical COVID-19 presentation, deaths from any cause and overall survival. The Cox proportional hazards multivariate regression analysis was performed to determine the risk of death. RESULTS: Sixty-two participants were included, most (67.7%) were male, with a median age of 6.8 years. Severe/critical forms of COVID-19, observed in 24.2%, seemed to indicate that the pediatric population undergoing cancer treatment has a higher morbidity rate than the general pediatric population (8-9.2%). During follow-up (4.5-18 months), 20 patients (32.3%) completed their cancer treatment and 18 died (29%)-6 during hospitalization and 12 after discharge. In total 61.1% of deaths occurred within 63 days of a detectable real-time polymerase chain reaction. Patients with a higher risk of death presented with severe/critical COVID-19 [adjusted hazard risk (aHR): 8.51; 95% confidence interval (CI): 2.91-24.80; P < 0.00] solid tumors (aHR: 3.99; 95% CI: 1.43-11.12; P = 0.008) and diarrhea as a symptom of COVID-19 (aHR: 3.9; 95% CI: 1.23-12.73; P = 0.021). CONCLUSIONS: These findings support the impact that severe acute respiratory syndrome-associated coronavirus 2 infection has on the population of children and adolescents with cancer, not only regarding immediate severity but also in their survival rate. Further studies evaluating long-term outcomes of COVID-19 in children and adolescents with cancer should be encouraged.

Health Education: Development and Validation of a Guideline for Oral Hygiene of Children Undergoing Cancer Treatment

Children with cancer commonly present oral health impairments due to lack of orientation about oral hygiene, which should be directed to caregivers since they are essential in this process. We developed and validated a guideline directed to caregivers for oral hygiene of children with cancer. This exploratory methodological study developed an educational guideline in three stages: analysis of oral health of children attended at the oncology service; literature review and development of the guideline for oral hygiene; semantic, appearance, and content validation by dentists, education professionals, and the target population. We used the Educational Content Validation Instrument in Health, and agreements of ≥ 80 % among evaluators were considered to maintain or modify the assessed items. Professionals and caregivers were mostly female; the latter were predominantly mothers with low educational level from inland areas of Pernambuco state (Brazil). Most professionals had more than ten years of experience in pediatric dentistry. Agreement was > 80 % in all items. The content of the guideline for oral hygiene was valid and relevant to be used in children with cancer.

Los niños con cáncer comúnmente presentan afecciones en la salud bucal por falta de orientación sobre la higiene bucal, la cual debe ser dirigida a los cuidadores ya que son fundamentales en este proceso. Desarrollamos y validamos una guía dirigida a cuidadores para la higiene bucal de niños con cáncer. Este estudio metodológico exploratorio desarrolló una directriz educativa en tres etapas: análisis de la salud bucal de los niños atendidos en el servicio de oncología; revisión de la literatura y desarrollo de la guía para la higiene oral; validación semántica, de apariencia y de contenido por parte de odontólogos, profesionales de la educación y población objetivo. Se utilizó el Instrumento de Validación de Contenido Educativo en Salud, y se consideraron acuerdos ≥ 80 % entre evaluadores para mantener o modificar los ítems evaluados. Los profesionales y cuidadores eran en su mayoría mujeres; estas últimas eran predominantemente madres con bajo nivel educativo del interior del estado de Pernambuco (Brasil). La mayoría de los profesionales tenían más de diez años de experiencia en odontopediatría. La concordancia fue > 80 % en todos los ítems. El contenido de la guía de higiene oral fue válido y pertinente para ser utilizado en niños con cáncer.

Excess Weight among Survivors of Acute Lymphoblastic Leukemia Survivors Treated at a Center in Northeast Brazil.

Therapeutic advances in the treatment of acute lymphoblastic leukemia (ALL) have increased the number of survivors but have promoted the development of long-term side effects, the best documented of which is obesity. The present retrospective case series analyzed data collected at diagnosis, end of treatment, and last follow-up visit of 210 ALL survivors treated between August 2005 and October 2014. Clinical and anthropometric data were collected from medical records. The nutritional diagnosis was based on z-scores of height-for-age (H/AZ) and body mass index-for-age (BMI/AZ) for males and females provided by the World Health Organization. H/AZ decreased and BMI/AZ increased between baseline and end of treatment, followed by H/AZ catch-up at follow-up. The prevalence of excess weight on the three occasions was 24.3%, 38.3, and 43.3%, respectively. Baseline excess weight (adjusted OR: 12.2; 95% CI: 5.5-27.0) and the ALL risk group (adjusted OR: 2.89; 95% CI: 1.1-7.6) were independently associated with excess weight at the end of treatment, whereas baseline excess weight (adjusted OR: 8.50; 95% CI: 3.93-18.40) and linear growth (adjusted OR: 2.02; 95% CI: 1.05-3.88) were independently associated with excess weight at follow-up. The frequency of excess weight had increased significantly by the end of treatment and persisted at follow-up. Baseline excess weight was the main factor associated with excess weight at the end of treatment and follow-up.

IKZF1 deletions associate with CRLF2 overexpression leading to a poor prognosis in B-cell precursor acute lymphoblastic leukaemia.

Cytokine Receptor-Like Factor 2 (CRLF2) overexpression occurs in 5-15% of B-cell precursor acute lymphoblastic leukaemia (B-ALL). In ∼50% of these cases, the mechanisms underlying this dysregulation are unknown. IKAROS Family Zinc Finger 1 (IKZF1) is a possible candidate to play a role in this dysregulation since it binds to the CRLF2 promoter region and suppresses its expression. We hypothesised that IKZF1 loss of function, caused by deletions or its short isoforms expression, could be associated with CRLF2 overexpression in B-ALL. A total of 131 paediatric and adult patients and 7 B-ALL cell lines were analysed to investigate the presence of IKZF1 deletions and its splicing isoforms expression levels, the presence of CRLF2 rearrangements or mutations, CRLF2 expression and JAK2 mutations. Overall survival analyses were performed according to the CRLF2 and IKZF1 subgroups. Our analyses showed that 25.2% of patients exhibited CRLF2 overexpression (CRLF2-high). CRLF2-high was associated with the presence of IKZF1 deletions (IKZF1del, p = 0.001), particularly with those resulting in dominant-negative isoforms (p = 0.006). Moreover, CRLF2 expression was higher in paediatric samples with high loads of the short isoform IK4 (p = 0.011). It was also associated with the occurrence of the IKZF1 plus subgroup (p = 0.004). Furthermore, patients with CRLF2-high/IKZF1del had a poorer prognosis in the RELLA05 protocol (p = 0.067, 36.1 months, 95%CI 0.0-85.9) and adult cohort (p = 0.094, 29.7 months, 95%CI 11.8-47.5). In this study, we show that IKZF1 status is associated with CRLF2-high and dismal outcomes in B-ALL patients regardless of age.

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.

COVID-19 cohort on children with cancer: delay in treatment and increased frequency of deaths / COVID-19 coorte de crianças com câncer: atraso no tratamento e aumento da frequência de óbitos

Abstract Objectives: to describe epidemiological characteristics and deaths in children with cancer and COVID-19 at a reference hospital in Recife, Brazil. Methods: cohort involving children under the age of 19 underwent cancer treatment during April to July 2020. During the pandemic, real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS -CoV-2) in nasal / oropharyngeal swab were collected in symptomatic patients or before hospitalization. Those with detectable results were included in this cohort study. The outcomes were delayed on cancer treatment and death. Descriptive analysis was performed and presented in preliminary results. Results: 48 children participated in the cohort, mostly with hematological neoplasms (66.6%.),69% were male, median age was 5.5 years. The most frequent symptoms were fever (58.3%) and coughing (27.7%);72.9% required hospitalization, 20% had support in ICU and 10.5% on invasive ventilatory assistance.66.6% of the patients had their oncological treatment postponed, 16.6% died within 60 days after confirmation of SARS-CoV-2 infection. Conclusions: COVID-19 led a delay in the oncological treatment for children with cancer and a higher mortality frequency when compared to the historical series of the service. It would be important to analyze the risk factors to determine the survival impact.

Resumo Objetivos: descrever características epidemiológicas e óbitos em crianças com câncer e a doença do novo coronavírus 2019 (COVID-19), em hospital de referência do nordeste brasileiro. Métodos: coorte envolvendo menores de 19 anos em tratamento de câncer, durante abril a julho de 2020. Pacientes sintomáticos ou antes de hospitalização foram submetidos a pesquisa do vírus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), por meio de reação em cadeia da polimerase com transcrição reversa em tempo real (RT-PCR), em swab naso/orofaríngeo. Foram incluídos aqueles com resultado detectável. Os desfechos foram atraso no tratamento oncológico e óbito. Realizada análise descritiva e apresentado os resultados preliminares. Resultados: 48 crianças, maioria com neoplasia hematológica (66,6%), sexo masculino (69%), mediana de idade 5,5 anos. os sintomas mais observados foram febre (58,3%) e tosse (27,7%); 72,9% necessitou internamento hospitalar, 20% suporte em unidade de terapia intensiva (UTI) e 10,5 % assistência ventilatória invasiva. O tratamento oncológico foi adiado em 66,6% dos pacientes, 16,6 % evoluiu para óbito até 60 dias após confirmação da infecção pelo SARS-CoV-2. Conclusões: COVID-19 determinou atraso no tratamento oncológico das crianças com câncer e aumento da frequência de óbitos quando comparada à série histórica do serviço. Será importante analisar os fatores de risco para determinar o impacto na sobrevida.

Reduced-dose intensity therapy for pediatric lymphoblastic leukemia: long-term results of the Recife RELLA05 pilot study.

Treatment-related mortality is common among children with acute lymphoblastic leukemia (ALL) treated in poor-resource settings. We applied a simplified flow cytometric assay to identify patients with precursor B-cell ALL (B-ALL) at very low risk (VLR) of relapse and treated them with a reduced-intensity treatment plan (RELLA05). VLR criteria include favorable presenting features (age ≥ 1 and < 10 years), white blood cell count of <50 ×109/L, lack of extramedullary leukemia, and minimal residual disease level of <0.01% on remission induction day 19. Except for 2 doses of daunorubicin, treatment of patients with VLR B-ALL consisted of a combination of agents with relatively low myelotoxicity profiles, including corticosteroids, vincristine, L-asparaginase, methotrexate, and 6-mercaptopurine. Cyclophosphamide, systemic cytarabine, and central nervous system radiotherapy were not used. Of 454 patients with ALL treated at the Instituto de Medicina Integral Professor Fernando Figueira in Recife, Brazil, between December 2005 and June 2015, 101 were classified as having VLR B-ALL. There were no cases of death resulting from toxicity or treatment abandonment during remission induction. At a median follow-up of 6.6 years, there were 8 major adverse events: 6 relapses, 1 treatment-related death (from septicemia) during remission, and 1 secondary myeloid leukemia. The estimated 5-year event-free and overall survival rates were 92.0% ± 3.9% and 96.0% ± 2.8%, respectively. The 5-year cumulative risk of relapse was 4.24% ± 2.0%. The treatment was well tolerated. Episodes of neutropenia were of short duration. Patients with B-ALL selected by a combination of presenting features and degree of early response can be successfully treated with a mildly myelosuppressive chemotherapy regimen.

Survival and risk factors for mortality in pediatric patients with acute myeloid leukemia in a single reference center in low-middle-income country.

Despite advances in therapy and care for children with acute myeloid leukemia (AML), survival rates for children in low- and middle-income countries (LMICs) remain poor. We studied risk factors for mortality and survival in children with AML in a LMIC to develop strategies to improve survival for AML children in these countries. This retrospective cohort (2000-2014) analyzed newly diagnosed AML patients (age < 19 years) at a reference center in Brazil. Demographic and clinical variables were reviewed by AML subtype: acute promyelocytic leukemia (APL), AML with Down syndrome (AML-DS), and other AML subtypes. Cumulative hazard risk for early death (ED) until 6 weeks of treatment and risk factors for mortality were determined by the multivariate Cox hazard models. Survival was assessed for each AML subtypes. A total of 220 patients were diagnosed: APL 50 (22.7%), AML-DS 16 (7.3%), and other AML subtypes 154 (70.0%). The cumulative hazard function values for ED for all patients with AML were 12.5% (95% CI 8.5-18.4%); for each AML patients subtypes: APL, 21.7% (95% CI 11.7-40.5%); AML-DS, 6.2% (95% CI 0.9-44.4%); and other AML subtypes, 10.2% (95% CI 6.2-17.0%). White blood cell count (cutoff 10 × 109/L for APL and 100 × 109/L for other AML subtypes) and Afro-descendance were significant risk factors for mortality in APL and other AML subtypes, respectively. Overall survival for patients with APL, AML-DS, and other AML subtypes was 66.8%, 62.5%, and 38.0%, respectively. APL patients had the highest incidence of ED and those with other subtypes had increased relapse risk. We also observed high rates of death in complete remission mainly due to infection. Better risk classification and identification of risk factors for infection may improve the survival of these patients.

Incidence and survival of childhood leukemia in Recife, Brazil: A population-based analysis.

BACKGROUND: Leukemia is the most common pediatric cancer with incidence rates of around 48 per million for children under 15 years of age. The median age-adjusted incidence rate (AAIR) in children aged 0-14 years in Brazil is 53.3 per million. While overall survival rates for children with leukemia have improved significantly, data for incidence, trends, and relative survival among children and adolescents with leukemia in Recife, Brazil, remain incomplete, which hampers our analyses and provision of the best healthcare. The objective of this report is to provide that data. METHODS: Data from the Population-Based Cancer Registry of Recife were analyzed from 1998 to 2007. Our analyses included frequencies and AAIR, together with age-specific incidence rates for all leukemias, acute lymphoblastic leukemia, and acute myeloid leukemia. To evaluate incidence trends, joinpoint regression, including annual average percent change, were analyzed. Relative survival was calculated using the life-table method. RESULTS: One hundred seventy-five cases were identified, 51% in females. The review reduced the not otherwise specified (NOS) leukemia category by 50% and diagnosis by death certificate only from 5.7% to 1.1%. The AAIR for leukemia was 41.1 per million, with a peak among children aged 1-4 (78.3 per million). Incidence trends during the period were stable. The five-year relative survival rate was 69.8%. CONCLUSIONS: These data represent the incidence rate and survival of childhood leukemia in Recife, located in the northeast region of Brazil, using a high-quality database.

Estado nutricional de crianças e adolescentes sobreviventes de leucemia linfoide aguda tratados em um Centro de Referência da Região Nordeste do Brasil / Nutritional status of children and adolescents survivors of acute lymphocytic leukemia treated at a reference center in Northeastern Brazil

OBJETIVO: Avaliar o estado nutricional e os fatores clínicos, laboratoriais e comportamentais associados ao excesso de peso em crianças e adolescentes sobreviventes de leucemia linfoide aguda, tratados em um centro de referência da Região Nordeste do Brasil. MÉTODOS: Estudo de série de casos com 30 sobreviventes de leucemia linfoide aguda. Entre os meses de março e setembro de 2011, foram coletados dados clínicos, comportamentais e laboratoriais. O diagnóstico antropométrico foi realizado em três ocasiões distintas: no momento do diagnóstico, no término do tratamento, e no período pós-tratamento, a partir dos índices altura/idade e índice de massa corporal/idade, segundo a Organização Mundial de Saúde. RESULTADOS: A amostra tinha idade média de 10,2 anos (DP=3,2). Observou-se que 33,3% dos sobreviventes tinham excesso de peso no início e no término do tratamento. No período pós-tratamento, encontrou-se aumento significante do escore-Z de índice de massa corporal/idade, e uma frequência de 43,3% de excesso de peso, além de 16,6% e 35,5% de obesidade abdominal por meio da circunferência da cintura e razão cintura/estatura respectivamente. O crescimento linear foi significativamente diminuído quando comparado os escores-Z de altura/idade no início e no término do tratamento. Na análise dos dados laboratoriais, obtiveram-se 52,1% com colesterol total acima do recomendado. Entretanto, 58,3%, 66,7% e 79,2% evidenciaram, respectivamente, Lipoproteína de Alta Densidade e Lipoproteína de Baixa Densidade-colesterol e triglicerídeo na faixa considerada desejável. CONCLUSÃO: Os sobreviventes de leucemia linfoide aguda analisados apresentaram maior risco para o desenvolvimento de doenças crônicas não transmissíveis uma vez que apresentam frequência importante de excesso de peso, obesidade abdominal e colesterol total elevado.

OBJECTIVE: This study evaluated the nutritional status and clinical, laboratory, and behavioral factors associated with overweight among children and adolescents survivors of acute lymphocytic leukemia treated at a reference center in Northeastern Brazil. METHODS: A case-series study was carried out with 30 survivors of acute lymphocytic leukemia. Clinical, behavioral and laboratory data were collected between March and September 2011. The anthropometric variables height-for-age and body mass index-for-age were determined on three different occasions (time of diagnosis, end of treatment, and post-treatment period), using the reference standards of the World Health Organization. RESULTS: The mean age and standard deviation of the sample was 10.2±3.2 years. A total of 33.3% of the survivors were overweight at the beginning and end of treatment. In the post-treatment period, a significant increase was found in the body mass index-for-age Z-score. The frequency of excess weight was 43.3%. The frequency of abdominal obesity was 16.6% and 35.5% based on the waist circumference and waist-to-height ratio, respectively. The comparison of body mass index-for-age Z-scores before and after treatment revealed significantly stunted linear growth. The laboratory tests showed that total cholesterol was 52.1% above the upper limit. However, 58.3%, 66.7%, and 79.2% of the sample had high-density lipoprotein and low-density lipoprotein cholesterol, and triglyceride levels, respectively, within the recommended ranges. CONCLUSION: Based on the frequency of excess weight, abdominal obesity, and high total cholesterol, the study survivors of acute lymphocytic leukemia were at greater risk of developing chronic, non-communicable diseases.

Delayed diagnosis of leukemia and association with morbid-mortality in children in Pernambuco, Brazil.

The objectives of this study were to describe the interval between symptom onset and diagnosis of acute leukemia, to assess risk factors for delayed diagnosis, and its effect on early morbid-mortality and event-free survival (EFS). Records of children aged 1 month to 18 years diagnosed with acute leukemia were reviewed for clinical, demographic, and health care provider factors, and for time to diagnosis. Of 288 patients diagnosed, 55% had a delay in diagnosis. The median time to diagnosis was 31 days. There were significant associations between the diagnostic delay and the distance from the tertiary care hospital (P=0.04), initial consultation in an outpatient clinic (P=0.04), presenting symptoms of bone/joint pain (P=0.04), family with more than 3 children (P=0.02), birth order of third or greater (P=0.009), paternal age <30 years (P=0.03), and paternal education <8 years (P=0.008). There was no association between delayed diagnosis and early morbid-mortality or EFS at 5 years. Initial consultation in an outpatient setting, presenting symptoms of bone/joint pain, and birth order of third or greater remained statistically significant in multivariate analyses, but the delay did not have an impact on early morbid-mortality or EFS. Education of primary care providers in atypical presentations of acute leukemia may decrease the diagnostic delay.

Molecular findings in childhood leukemia in Brazil: high frequency of MLL-ENL Fusion/t(11;19) in infant leukemia.

Translocations involving chromosome 11q23 are frequently found in pediatric leukemia, especially in infants. The mixed lineage leukemia (MLL)-AF4 fusion/t(4;11) is mostly found in acute lymphoblastic leukemia (ALL) and MLL-AF9 fusion/t(9;11) in acute myeloid leukemia (AML). We study 441 consecutive new cases of childhood leukemia diagnosed in Brazil. Chromosomal translocation was determined solely by conventional polymerase chain reaction (PCR) in 72 out of 265 ALL and in 43 out of 103 AML. MLL-AF4 fusion/t(4;11) was detected in 3 out of 265 ALL and MLL-AF9 fusion/t(9;11) in 4 out of 103 of AML. MLL-rearrangements were presented in 7 out of 23 infant leukemia, whose 5 were MLL-ENL fusion/t(11;19). No fusion MLL-AF4 fusion/t(4;11) was found. Other translocation frequencies differed from that reported for an American population suggesting interethnic differences on chromosomal translocations frequencies in acute leukemia.