Abstract Objective: To assess the prevalence of chronic neutropenia (CN) and the clinical profile of patients with CN aged up to 18 years, followed in the pediatric hematology, rheumatology, or immunology outpatient clinic of a tertiary medical center from May 1, 2018, to 30 April 2019. Methods: Retrospective observational study carried out by collecting data from the patient’s medical charts. CN was defined as absolute neutrophil count (ANC) below 1.5 × 109/L lasting over three months. Autoimmune neutropenia (AIN) was defined by clinical criteria and an over twofold increase in ANC after glucocorticoid stimulation. AIN was considered secondary when associated with autoimmune or immunoregulatory disorders. Wilcoxon and Fisher’s exact tests were used to compare variables; the significance level was 5 %. Results: A total of 1,039 patients were evaluated; 217 (20 %) presented CN. Twenty-one (2 %) had AIN, classified as primary in 57 % of the cases. The average age at the onset of symptoms was 38.6 months. During follow-up, patients had 4.2 infections on average; frequency was higher among patients with secondary AIN (p = 003). Isolated neutropenia occurred in 43 % of the patients with AIN. Neutropenia resolved in eight (38 %) of the 21 patients with AIN within 19.6 months on average. Eight patients with secondary AIN met the criteria for Inborn Errors of Immunity. Conclusion: AIN prevalence was 2 %. Most cases were first evaluated by a pediatric immunologist or rheumatologist rather than a pediatric hematologist. This study highlights the need for a multidisciplinary approach involving a pediatric immunologist, rheumatologist, and hematologist. Objective (CN 1 years hematology rheumatology 2018 3 2019 Methods patient s charts (ANC 15 1. 109L L 109 (AIN stimulation disorders Fishers Fisher variables Results 1039 039 1,03 20 Twentyone Twenty one ( 386 38 6 38. followup, followup follow up, follow-up 42 4 4. p 003. 003 . 003) (3 196 19 19. Immunity Conclusion hematologist 201 10 103 03 1,0 00 0

RESUMO Objetivo: Avaliar a prevalência e descrever as principais manifestações clínicas, os exames complementares, o tratamento e a evolução de crianças com doenças neoplásicas atendidas inicialmente em um serviço terciário de reumatologia pediátrica. Métodos: Analisamos retrospectivamente o prontuário médico de pacientes com diagnóstico definitivo de neoplasia, identificados entre 250 casos novos atendidos no ambulatório de reumatologia pediátrica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto-USP, de julho de 2013 a julho de 2015. Resultados: Dos 250 pacientes, cinco (2%) tiveram diagnóstico de neoplasia. Desses, 80% apresentavam sintomas constitucionais, principalmente perda de peso e astenia e 60% artrite. Inicialmente, todos apresentavam pelo menos uma série alterada no hemograma, 80% aumento da desidrogenase lática (LDH) e 60% mielograma confirmatório. Dois pacientes necessitaram de biópsia, óssea e de intestino, para o diagnóstico final. Artrite idiopática juvenil foi o diagnóstico inicial mais frequente. Os diagnósticos definitivos foram leucemia linfoide aguda (dois casos), leucemia mieloide aguda-M3, neuroblastoma e linfoma (um caso cada). Dos pacientes estudados, três (60%) estão em remissão. Dois pacientes foram a óbito (40%), um deles com uso prévio de corticoide. Conclusão: Os sintomas constitucionais e musculoesqueléticos comuns às doenças reumáticas e neoplásicas podem retardar o diagnóstico e consequentemente agravar o prognóstico das neoplasias. O hemograma inicial, assim como o mielograma, podem estar normais no quadro inicial das neoplasias. Dessa forma, o seguimento clínico evolutivo desses casos torna-se imperativo e o tratamento, principalmente com corticoides, deve ser retardado até definição diagnóstica.

ABSTRACT Objective: To assess the prevalence and describe the clinical, laboratory and radiological findings, treatment and outcome of children with cancer initially referred to a tertiary outpatient pediatric rheumatology clinic. Methods: Retrospective analysis of medical records from patients identified in a list of 250 new patients attending the tertiary Pediatric Rheumatology Clinic, Ribeirão Preto Medical School hospital, University of São Paulo, from July 2013 to July 2015, whose final diagnosis was cancer. Results: Of 250 patients seen during the study period, 5 (2%) had a cancer diagnosis. Among them, 80% had constitutional symptoms, especially weight loss and asthenia, and 60% had arthritis. Initially, all patients had at least one alteration in their blood count, lactate dehydrogenase was increased in 80% and a bone marrow smear was conclusive in 60% of patients. Bone and intestine biopsies were necessary for the diagnosis in 2 patients. JIA was the most common initial diagnosis. The definitive diagnosis was acute lymphoblastic leukemia (2 patients), M3 acute myeloid leukemia, lymphoma, and neuroblastoma (one case each). Of 5 patients studied, 3 (60%) are in remission and 2 (40%) died, one of them with prior use of steroids. Conclusion: The constitutional and musculoskeletal symptoms common to rheumatic and neoplastic diseases can delay the diagnosis and consequently worsen the prognosis of neoplasms. Initial blood count and bone marrow smear may be normal in the initial framework of neoplasms. Thus, the clinical follow-up of these cases becomes imperative and the treatment, mainly with corticosteroids, should be delayed until diagnostic definition.

CONTEXTO: Neurofibromatose tipo 1 (NF-1) é a doença genética autossômica dominante mais prevalente no ser humano. A doença de moyamoya é uma vasculopatia cerebral que raramente se encontra associada à NF-1, particularmente na faixa etária pediátrica. Este estudo descreve a ocorrência desta associação em um lactente. RELATO DE CASO: Paciente feminina, aos oito meses de idade, apresentou quadro de crise convulsiva com movimentos clônicos. Evoluiu com acidente vascular encefálico isquêmico e com hemiparesia à direita. Ressonância nuclear magnética mostrou achados compatíveis com a doença de moyamoya. O diagnóstico de NF-1 foi realizado aos 20 meses de vida. CONCLUSÃO: Apesar da raridade desta associação na faixa etária infantil, crianças com sintomas neurológicos focais e diagnóstico de NF-1 merecem ser investigadas para síndrome de moyamoya.

CONTEXT: Neurofibromatosis type 1 (NF-1) is the most prevalent autosomal dominant genetic disorder among humans. Moyamoya disease is a cerebral vasculopathy that is only rarely observed in association with NF-1, particularly in the pediatric age range. The present study reports an occurrence of this association in an infant. CASE REPORT: An eight-month-old female presented convulsive seizures with clonic movements. The patient suffered an ischemic stroke with hemiparesis. Magnetic resonance imaging revealed radiological findings compatible with moyamoya disease. The diagnosis of NF-1 was made at the age of 20 months. CONCLUSION: Despite the rarity of this association in childhood, children with focal neurological symptoms and a diagnosis of NF-1 deserve to be investigated for moyamoya syndrome.

CONTEXTO: Apesar dos avanços nos índices de cura da leucemia linfoblástica aguda (LLA) aproximadamente 25% das crianças sofrem recaídas da doença. A expressão dos genes de resistência múltipla a drogas (MDR-1), genes relacionados à proteína de resistência múltipla a drogas (MRP) e genes da proteína de resistência pulmonar (LRP) podem conferir o fenótipo de resistência ao tratamento das neoplasias. OBJETIVO: Analisar a expressão dos genes de resistência MDR-1, MRP e LRP em crianças diagnosticadas com LLA por meio da técnica da reação em cadeia da polimerase da transcriptase reversa (RT-PCR) semiquantitativa, associando estas expressões à sobrevida livre de eventos (SLE) e a variáveis clínico-laboratoriais. TIPO DE ESTUDO: Estudo clínico retrospectivo. LOCAL: Laboratório de Oncologia Pediátrica do Departamento de Puericultura e Pediatria da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo, Brasil. MÉTODOS: Amostras de medula óssea de 30 crianças com o diagnóstico de leucemia linfoblástica aguda foram avaliadas quanto à expressão do RNA-mensageiro para os genes MDR-1, MRP e LRP, pela reação em cadeia da RT-PCR semiquantitativa. RESULTADOS: Dos três genes estudados, somente a expressão aumentada de LRP esteve relacionada a uma pior SLE (p = 0.005). A presença do antígeno para leucemia linfoblástica aguda comum (CALLA) se correlacionou à expressão aumentada de LRP (p = 0.009) e a risco aumentado de ocorrência de recaída ou óbito (p = 0.05). O risco relativo de ocorrência de recaída ou óbito é seis vezes maior em crianças com alta expressão de LRP ao diagnóstico (p = 0.05), o que se confirma na análise multivariada dos três genes estudados (p = 0.035). DISCUSSÃO: A resistência celular a drogas é um determinante de resposta ao tratamento oncológico e sua avaliação por RT-PCR pode ser de importância. CONCLUSÕES: A avaliação da expressão dos genes de resistência a drogas antineoplásicas na leucemia linfoblástica aguda da criança ao diagnóstico, particularmente do gene LRP, pode ser de relevância clínica e deve ser objeto de estudos prospectivos.

CONTEXT: Despite the advances in the cure rate for acute lymphoblastic leukemia, approximately 25% of affected children suffer relapses. Expression of genes for the multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP), and lung resistance protein (LRP) may confer the phenotype of resistance to the treatment of neoplasias. OBJECTIVE: To analyze the expression of the MDR-1, MRP and LRP genes in children with a diagnosis of acute lymphoblastic leukemia via the semiquantitative reverse transcription polymerase chain reaction (RT-PCR), and to determine the correlation between expression and event-free survival and clinical and laboratory variables. DESIGN: A retrospective clinical study. SETTING: Laboratory of Pediatric Oncology, Department of Pediatrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil. METHODS: Bone marrow aspirates from 30 children with a diagnosis of acute lymphoblastic leukemia were assessed for the expression of messenger RNA for the MDR-1, MRP and LRP genes by semi-quantitative RT-PCR. RESULTS: In the three groups studied, only the increased expression of LRP was related to worsened event-free survival (p = 0.005). The presence of the common acute lymphoblastic leukemia antigen (CALLA) was correlated with increased LRP expression (p = 0.009) and increased risk of relapse or death (p = 0.05). The relative risk of relapse or death was six times higher among children with high LRP expression upon diagnosis (p = 0.05), as confirmed by multivariate analysis of the three genes studied (p = 0.035). DISCUSSION: Cell resistance to drugs is a determinant of the response to chemotherapy and its detection via RT-PCR may be of clinical importance. CONCLUSIONS: Evaluation of the expression of genes for resistance to antineoplastic drugs in childhood acute lymphoblastic leukemia upon diagnosis, and particularly the expression of the LRP gene, may be of clinical relevance, and should be the object of prospective studies.