Comparative analysis between cytomorphology and flow cytometry methods in central nervous system infiltration assessment in oncohematological patients

ABSTRACT Introduction Oncohematological patients require the evaluation for possible infiltration of the central nervous system (CNS) by neoplastic cells at diagnosis and/or during the monitoring of the chemotherapeutic treatment. Morphological analysis using conventional microscopy is considered the method of choice to evaluate the cerebrospinal fluid (CSF) samples, despite technical limitations. Objective This study aimed to compare the performance of the cytomorphology and flow cytometric immunophenotyping (FC) in the detection of CNS infiltration. Method We evaluated 520 CSF samples collected from 287 oncohematological patients for whom the detection of neoplastic cells was simultaneously requested by cytomorphology and FC. Results Laboratory analyses revealed 435/520 (83.7%) conclusive results by the two methods evaluated, among which 385 (88.5%) were concordant. Discordance between the methods was observed in 50/435 (11.5%) samples, 45 (90%) being positive by FC. Furthermore, the FC defined the results in 69/72 (95.8%) inconclusive samples by cytomorphology. The positivity of FC was particularly higher among hypocellular samples. Among 431 samples with a cell count of < 5/μL, the FC identified neoplastic cells in 75 (17.4%), while the cytomorphology reported positive results in 26 (6%). Among the samples that presented adequate cell recovery for evaluation by both methods (506/520), the comparative analysis between FC and cytomorphology revealed a Kappa coefficient of 0.45 (CI: 0.37-0.52), interpreted as a moderate agreement. Conclusion The data showed that the CSF analysis by FC helps in the definition of CNS infiltration by neoplastic cells, particularly in the cases with dubious morphological analysis or in the evaluation of samples with low cellularity.

Cytogenetic abnormalities, WHO classification, and evolution of children and adolescents with acute myeloid leukemia

ABSTRACT Objectives: To describe cytogenetic and molecular abnormalities observed in children and adolescents with acute myeloid leukemia (AML), classify AML according to the World Health Organization (WHO) classifications from 2008 and 2016, and evaluate the prognosis according to clinical characteristics and cytogenetic abnormalities. Methods: A retrospective longitudinal study was performed on a population of 98 patients with AML, aged up to 16 years, seen in a single hospital from 2004 to 2015. Results: Among the 80 patients for whom it was possible to analyze the karyotype, 78.7% had chromosomal changes, the most frequent being t(15;17)(q22;q21). Of the 86 patients for whom we had cytogenetic or molecular data, making it possible to classify their AML according to the WHO classification, 52.3% belonged to the group with recurrent genetic abnormalities, 22% to the "AML not otherwise specified" group, 18.6% to the group with myelodysplasia-related cytogenetic changes, and 7% to the group with Down syndrome-related leukemia. Five-year overall survival (OS) for the whole group was 49.7% ± 5.2%. In the univariate and multivariate analyses, patients with myelodysplasia-related cytogenetic changes (OS 28.1% ± 12.2%) and those with "AML not otherwise specified" (OS 36.1% ± 11.2%) had an unfavorable prognosis when compared to patients with AML with recurrent genetic abnormalities (OS 71% ± 5.8%) and patients with Down syndrome-related AML (OS 83% ± 15.2%, p = 0.011). Conclusions: The results corroborate the importance of cytogenetic abnormalities as a prognostic factor and indicate the need for cooperative and prospective studies to evaluate the applicability of the WHO classification in the pediatric population.

Carcinoma adrenal em crianças: estudo longitudinal em minas gerais, brasil / Adrenal carcinoma in children: longitudinal study in minas gerais, brazil

RESUMO Objetivo: Analisar as características clínicas, laboratoriais e histopatológicas e o percurso até o estabelecimento do diagnóstico e do tratamento de pacientes com carcinoma de suprarrenal (CSR). Métodos: Estudo retrospectivo com 13 pacientes tratados no serviço de oncologia pediátrica do Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG) entre 2004 e 2015. Resultados: A idade ao diagnóstico variou de 1,0 a 14,8 anos (mediana: 2,0 anos). As manifestações de hipercortisolismo foram identificadas em todos os casos, e as de virilização, em todas as meninas. Todos os pacientes preencheram os critérios de Weiss para diagnóstico histopatológico de CSR. A imuno-histoquímica foi realizada em 61,5% dos casos. A maioria dos pacientes apresentou doença em estádio I (76,9%). Todos foram submetidos à ressecção tumoral total. Dois pacientes (estádios III e IV) receberam quimioterapia associada ao mitotano. O único óbito observado foi do paciente com doença em estádio IV. A probabilidade de sobrevida global para todo o grupo aos 5,0 anos foi de 92,3±7,4%. A mediana de tempo entre o início dos sintomas e o diagnóstico foi de 9,5 meses, e de 6,0 meses entre a primeira consulta e o início do tratamento. Conclusões: A baixa idade ao diagnóstico, o predomínio de casos com doença localizada e a ressecção tumoral completa - com apenas um caso de ruptura de cápsula tumoral - são possivelmente a explicação para a evolução favorável da população estudada. O longo percurso entre o início dos sintomas e o diagnóstico sugere a importância da capacitação dos pediatras para o reconhecimento precoce dos sinais e dos sintomas do CSR.

ABSTRACT Objective: To analyze clinical, laboratory and histopathological features and the path to diagnosis establishment and treatment of patients with adrenal carcinoma (AC). Methods: Retrospective study with 13 patients assisted at the pediatric oncology service of Hospital das Clínicas, Universidade Federal de Minas Gerais, Brazil, between 2004 and 2015. Results: Age at diagnosis ranged from 1.0 to 14.8 years (median: 2.0 years). Manifestations of hypercortisolism were identified in all cases and virilization in all girls. All patients met the Weiss criteria to AC histopathological diagnosis. Immunohistochemistry was performed in 61.5% of the cases. Most patients had stage I disease (76.9%). All subjects were submitted to total tumor resection. Two patients (stages III and IV disease) received chemotherapy associated to mitotane. The only death case was that of a patient with stage IV disease. The probability of overall survival for the entire group up to 5.0 years was 92.3±7.4%. The median time between the onset of symptoms and diagnosis was 9.5 months, and 6.0 months between first visit and start of treatment. Conclusions: Low age at diagnosis, predominance of cases with localized disease and complete tumor resection - with only one case of tumor capsule rupture - can possibly explain the favorable evolution of the studied population. The long period between onset of symptoms and diagnosis highlights the importance of training pediatricians for early recognition of AC signs and symptoms.

Análise de sobrevida de pacientes portadores de tumores do sistema nervoso central / Survival analysis of patients with central nervous tumor

Objetivos: analisar a sobrevida de pacientes com diagnóstico de tumores do sistema nervoso central (SNC) em um serviço de referência em Oncologia Pediátrica, sua apresentação clínica, evolução e influência de fatores prognósticos. Métodos: estudo de coorte histórica. Foram estudados pacientes menores de 19 anos, no período de março de 2003 a dezembro de 2009. O método de Kaplan-Meier foi utilizado para estimar a probabilidade de sobrevida global (SGLO). O teste de log rank e o modelo de regressão de Cox foram usados nas análises univariada e multivariada. Resultados: foram incluídos 159 pacientes, com mediana de tempo de seguimento de 13 meses. O intervalo entre o início dos sintomas e o diagnóstico teve mediana de 1,9 mês; 52% eram do gênero masculino. A mediana de idade ao diagnóstico foi de 7,2 anos. Os diagnósticos histológicos mais frequentes foram glioma de baixo grau (27%), meduloblastoma (19,5%) e tumor de tronco encefálico (17,6%). Cefaleia foi o sintoma mais frequente ao diagnóstico. A localização primária mais comum dos tumores foi a infratentorial (55,3%). A SGLO aos cinco anos foi de 42% (IC 95, 33 a 53%). Na análise univariada, foi observada associação significativa entre tempo de surgimento dos sintomas e o diagnóstico (p=0,046) e diagnóstico histológico (p<0,001). Na análise multivariada, esses fatores mantiveram-se e foram acrescidos da localização primária do tumor. Discussão: a SGLO observada neste estudo foi claramente inferior às descritas na literatura internacional, porém semelhante à de dois outros centros de referência nacionais. Estudos multicêntricos em nível nacional são necessários para confirmação desses resultados.

Objetives: To evaluate outcome of patients with the diagnosis of Central Nervous System tumors at a local reference pediatric oncology service, their clinical presentation, evolution and influence of prognostic factors. Methods: Patients enrolled in this retrospective study between March,2003 and December,2009, were less than nineteen years old at the time of the diagnosis. Kaplan-Meier method was used to estimate the overall survival (OS). Log rank test and Cox?s method were used in the statistical analysis. Results: Study population consisted of 159 patients with median follow up period of 13 months. Median of the time between onset of symptoms and diagnosis was 1,9 months. Boys comprised 52% of the studied population. Median age at diagnosis was 7,2 years. Most common diagnostic subtypes were low grade glioma (27%), medulloblastoma (19,5%) and brain stem tumors (17,6%). Headache was the most frequent symptom (57%) and infratentorial tumors correspond to 55,3% of the cases. An estimated OS of 42% (CI 95%, 33% to 53%) was observed for the role group. An association between outcome and the following variables was observed: interval between the time of onset of symptoms and diagnosis (p=0,046)and histological classification of the tumors (p<0,001). In the multivariate analysis, these variables were sustained, added of the primary location of the tumor in the Central Nervous System. Discussion: Overall survival detected in this study was clearly worse when compared with international centers rates, although were similar to other Brazilian studies. It?s important to develop multicentric studies to confirm data showed in this study

Óxido nitroso a 50% em oxigênio para procedimentos dolorosos pediátricos realizados por não anestesiologistas: uma revisão sistemática da literatura / Nitrous oxide 50% in oxygen for painful pediatric procedures used by non-anestesiologists: a systematic review of the literature

Objetivo: revisar trabalhos publicados relacionados à utilização do óxido nitroso a 50% em oxigênio da dor durante realização de procedimentos em crianças. Método: revisão sistemática dos últimos 43 anos indexados nas bases de dados: MEDLINE (PubMed), Cochrane BVS, SciELO e LILACS. Resultados: foram identificados 399 artigos. Os motivos de exclusão de artigos potencialmente relevantes foram: não utilizar o óxido nitroso em concentração fixa a 50% em oxigênio, não ser ensaio clínico aleatório,estudo sem método específico de avaliação da dor, estudo avaliando outro método analgésico, além da mistura equimolar, associado no mesmo grupo de tratamento. Apenas dois estudos apresentaram qualidade metodológica adequada. Pesquisa avaliou a dor durante injeção intramuscular de Palivizumab, comparando mistura equimolar de óxido nitroso em oxigênio com o anestésico tópico EMLA® isolado e um terceiro grupo com as duas medidas analgésicas associadas. Neste estudo, mistura equimolar mostrou-se eficaz na redução da dor leve a moderada durante a injeção intramuscular. Outro comparou morfina ao óxido nitroso a 50% em oxigênio durante retirada de dreno de tórax em crianças, demonstrando que a mistura equimolar, quando utilizada em um procedimento que causa dor intensa, não teve resultados superiores à morfina. Conclusão: esta revisão mostrou insuficiência de ensaios clínicos com metodologia adequada para avaliação da eficácia da mistura de óxido nitroso em oxigênio a 50%. São necessários novos estudos, realizados em procedimentos que causam dor de diferentes intensidades, para que conclusões mais precisas sejam obtidas.

Objective: To revise published papers on the use of Nitro Oxide of up to 50% in Oxygen used to decrease pain intensity during procedures on children. Method: systematic revision of indexed data bases from the last 43 years: MEDLINE (PubMed), Cochrane BVS, SciELO and LILACS. Results: Initially, 399 articles were identified. The main reasons for the exclusion of potentially relevant articles were: not using nitro oxide at a fixed concentration of 50% in oxygen; not being a randomly clinic essay; being a study without a specific method of pain assessment; a study with assessment of another analgesic method; as well as the equimolar mixture associated in the same treatment group. After analysis, only two studies presented adequate quality methodology. One study evaluated pain during the intramuscular injection of Palivizumab, comparing the equimolar mixture of nitro oxide in oxygen with the topical anesthetic EMLA and in an isolated third group with the two associated analgesic measurements. In this study, the equimolar mixtures demonstrated an efficient reduction in slight to moderate pain during the intramuscular injection. The other study compared morphine to Nitro oxide at 50% in oxygen during the removal of Thorax drainer in children, showing that the equimolar mixture, when used in a procedure that causes intense pain, didn?t present better results than morphine. Conclusion: This revision has shown an insufficiency of clinical trials with adequate methodology to evaluate the efficiency of the mixture of Nitro oxide in oxygen at 50%. Further studies with procedures that cause different pain intensity are necessary so that more precise conclusions can be obtained

Hemophagocytic lymphohistiocytosis: a case series of a Brazilian institution

Objective: To describe the clinical and laboratory presentation of hemophagocytic lymphohistiocytosis in children treated at a referral institution. Methods: A retrospective descriptive study was carried out of seven children diagnosed with hemophagocytic lymphohistiocytosis between 2010 and 2012. The criteria for diagnosis were those proposed by the Histiocyte Society. When indicated, immunochemotherapy was prescribed according to the HLH94 and HLH2004 protocols of the Histiocyte Society. Results: The patients' ages at diagnosis ranged from one month to nine years. All patients had splenomegaly, fever, anemia, thrombocytopenia, hyperferritinemia and hypertriglyceridemia. Bone marrow hemophagocytosis was detected in six patients. In six cases, infectious diseases triggered the syndrome. In two cases, associated with visceral leishmaniasis, remission was achieved after treatment of the underlying infection. Three patients, who had Epstein–Barr-related hemophagocytic lymphohistiocytosis, required treatment with immunochemotherapy. They are alive and in remission; one patient had symptoms of juvenile rheumatoid arthritis and another, who was suspected of having primary hemophagocytic lymphohistiocytosis, entered into remission after bone marrow transplantation. Two deaths (28.6%) occurred in patients with suspected primary hemophagocytic lymphohistiocytosis; one whose clinical picture was triggered by cytomegalovirus infection did not respond to immunochemotherapy and the other died before any specific treatment was provided. Conclusion: As reported before, hemophagocytic lymphohistiocytosis has a multifaceted presentation with nonspecific signs and symptoms. In secondary forms, remission may be achieved by treating the underlying disease. In the primary forms, remission may be achieved with immunochemotherapy, but bone marrow transplantation is required for cure...

Palliative care in pediatric hematological oncology patients: experience of a tertiary hospital

Objective: To evaluate the approach to palliative care for hematological oncology patients in the pediatric ward of a tertiary hospital. Methods: This was a retrospective, descriptive study of 29 hematological oncology patients who died between 2009 and 2011. Data regarding the approach and prevalence of pain, prevalence of other symptoms, multidisciplinary team participation, communication between staff and family and limited invasive therapy were collected from the medical records. Results: Twenty-seven (93.1%) patients displayed disease progression unresponsive to curative treatment. The median age at death was ten years old. Pain was the most prevalent symptom with all patients who reported pain receiving analgesic medications. The majority took weak (55.2%) and/or strong (65.5%) opioids. The patients were followed by pediatricians and a pediatric hematologist/oncologist. Participation of other professionals was also documented: 86.2% were followed by social services and 69% by psychologists, among others. There were explicit descriptions of limitation of invasive therapy in the medical records of 26 patients who died with disease progression. All these decisions were shared with the families. Conclusion: Although the hospital where this study was conducted does not have a specialized team in pediatric palliative care, it meets all the requirements for developing a specific program. The importance of approaching pain and other prevalent symptoms in children with cancer involving a comprehensive multidisciplinary team is evident. Discussions were had with most of the families on limiting invasive therapy, but no record of a well-defined and coordinated treatment plan for palliative care was found...

Cuidados paliativos em pediatria: uma revisão / Los cuidados paliativos en pediatría: una revisión / Palliative care in pediatrics: a review

A expansão tecnológica das últimas décadas modificou o perfil dos pacientes na pediatria, tornando cada vez mais frequente a assistência a crianças com doenças crônicas e ameaçadoras à vida. Cuidados paliativos envolvem a assistência ativa e total prestada a essas crianças, nas dimensões de seu corpo, mente e espírito, bem como o suporte oferecido a sua família. O presente estudo revisa aspectos relevantes na abordagem paliativa: a prevalência e abordagem dos sintomas, a participação de equipe multiprofissional, a comunicação com a família, os cuidados ao final da vida e a limitação de terapêuticas invasivas. A despeito do reconhecimento da importância da medicina paliativa, nossas universidades ainda priorizam a medicina curativa. Instituir esse tema no processo de formação do médico é uma necessidade real e absoluta, visando proporcionar vida e morte dignas aos nossos pacientes.

La expansión tecnológica de las últimas décadas ha cambiado el perfil de los pacientes de pediatría, volviendo cada vez más frecuente la asistencia a los niños con enfermedades crónicas y potencialmente mortales. Cuidados paliativos involucran la asistencia activa y total prestada a estos niños y niñas, en el ámbito de su cuerpo, mente y espíritu, así como el apoyo ofrecido a toda su familia. Este estudio proporciona un análisis de los aspectos relevantes en el enfoque paliativo: la prevalencia y abordaje de los síntomas, la participación de un equipo multidisciplinario, la comunicación con la familia, la atención al final de la vida y la limitación de las terapias invasivas. A pesar del reconocimiento de la importancia de la medicina paliativa, nuestras universidades siguen dando prioridad a la medicina curativa. Establecer ese tema en el proceso de la educación médica es una necesidad real y absoluta, con el objetivo de proporcionar una vida y una muerte dignas a nuestros pacientes.

The technological expansion in recent decades changed the profile of the patients in pediatrics, with assistance to children with chronic and life-threatening conditions more frequent each time. Palliative care involves an active and full assistance provided to these children, in the context of their body, mind and spirit as well as the support offered to their entire family. This study provides a review of relevant aspects in palliative approach: the prevalence and approach of symptoms, the participation of a multidisciplinary team, communication with family, care at end of life and limitation of invasive therapies. Despite recognition of the importance of palliative medicine, our universities still give priority to curative medicine. Introducing this theme in the process of medical education is a real and absolute need, aiming to provide dignified life and death to our patients.

Gene rearrangement study for minimal residual disease monitoring in children with acute lymphocytic leukemia

OBJECTIVE To detect markers for minimal residual disease monitoring based on conventional polymerase chain reaction for immunoglobulin, T-cell receptor rearrangements and the Sil-Tal1 deletion in patients with acute lymphocytic leukemia. METHODS Fifty-nine children with acute lymphocytic leukemia from three institutions in Minas Gerais, Brazil, were prospectively studied. Clonal rearrangements were detected by polymerase chain reaction followed by homo/heteroduplex clonality analysis in DNA samples from diagnostic bone marrow. Follow-up samples were collected on Days 14 and 28-35 of the induction phase. The Kaplan-Meier and multivariate Cox methods were used for survival analysis. RESULTS Immunoglobulin/T-cell receptor rearrangements were not detected in 5/55 children screened (9.0%). For precursor-B acute lymphocytic leukemia, the most frequent rearrangement was IgH (72.7%), then TCRG (61.4%), and TCRD and IgK (47.7%); for T-acute lymphocytic leukemia, TCRG (80.0%), and TCRD and Sil-Tal deletion (20.0%) were the most common. Minimal residual disease was detected in 35% of the cases on Day 14 and in 22.5% on Day 28-35. Minimal residual disease on Day 28-35, T-acute lymphocytic leukemia, and leukocyte count above 50 x 109/L at diagnosis were bad prognostic factors for leukemia-free survival in univariate analysis. Relapse risk for minimal residual disease positive relative to minimal residual disease negative children was 8.5 times higher (95% confidence interval: 1.02-70.7). CONCLUSION Immunoglobulin/T-cell receptor rearrangement frequencies were similar to those reported before. Minimal residual disease is an independent prognostic factor for leukemia-free survival, even when based on a non-quantitative technique, but longer follow-ups are needed.

Avaliação e tratamento da dor em oncologia pediatrica / Pain assessment and treatment in children with oncological diseases

Nos últimos anos ocorreu considerável melhora na sobrevida das crianças com câncer. Nos últimos anos ocorreu considerável melhora na sobrevida das crianças com câncer. Entretanto, apesar da crescente conscientização sobre as causas e tratamento da dor, estudos mostram que essas crianças continuam a experimentar diariamente sintomas angustiantes, físicos e emocionais causados pela doença e seu tratamento. O objetivo deste trabalho foi revisar a literatura a respeito das particularidades associadas à dor infantil relacionada ao câncer, salientando as suas principais causas assim como as possibilidades terapêuticas disponíveis. Foram revisados artigos referentes ao tema proposto, publicados nos últimos 20 anos, entre janeiro de 1990 e novembro de 2010, utilizando as bases Scientific Eletronic Library Online (SCIELO) e National Library Of Medicine ­ PubMed (MEDLINE). A chave para o controle da dor é a obtenção de uma avaliação detalhada por equipe multidisciplinar para o desenvolvimento de um plano de tratamento específico para cada criança, com frequentes reavaliações. Apesar de algumas limitações, a escada analgésica da Organização Mundial de Saúde serve como pilar para o tratamento desses pacientes, contribuindo para o alívio da dor oncológica em todo o mundo. Para melhor abordagem, terapias combinadas (farmacológicas e não farmacológicas) devem ser utilizadas adaptando-se às necessidades individuais, com o objetivo de minimizar a dor e os efeitos adversos do tratamento. (AU)

In recent years there has been a considerable improvement in survival of children with cancer. However, despite growing awareness about the causes and treatment of pain, studies show that these children continue to experience daily physical and emotional distressing symptoms caused by the disease and its treatment. The aim of this study was to review the literature regarding the particularities associated with children pain related to cancer, highlighting their main causes and therapeutic possibilities available. We reviewed articles relating to the proposed theme published from the last 20 years, between January 1990 and November 2010 using the bases Scientific Electronic Library Online (SciELO), National Library Of Medicine ­ PubMed (MEDLINE). The key to pain control is to obtain a detailed evaluation by a multidisciplinary team to develop a specific treatment plan for each child, with frequent reassessments. Despite some limitations, the analgesic ladder of the World Health Organization serves as a pillar to treat these patients, providing pain relief worldwide. For a better pain management, combined therapies (pharmacological and nonpharmacological) should be used adapted to individual needs, in order to minimize pain and side effects of treatment.(AU)

Isolated relapse in the oral cavity of a child with t-lineage acute lymphoblastic leukemia

Despite high cure rates, approximately 20% of patients with acute lymphoblastic leukemia (ALL) have disease relapse. Isolated recurrence in oral cavity is extremely unusual. The aim of this paper is to report a case of an isolated relapse occurred in a child with T-lineage ALL. Clinical picture included swelling and pain in the right upper gingiva of the oral cavity, with no other clinical or hematological alterations. Diagnosis was confirmed by biopsy and immunohistochemical staining. Bone marrow aspiration was normal. Five months later leukemic infiltration of the bone marrow was detected and systemic chemotherapy was reintroduced. This case report highlights the relevance of dental care during and after chemotherapy, not only to treat lesions in the oral cavity resulting from the disease itself or from treatment side effects, but also to detect unusual sites of ALL relapse.

Apesar dos altos índices de cura, cerca de 20% dos pacientes com leucemia linfóide aguda (LLA) apresentam recidiva da doença. Recidiva isolada na cavidade oral é extremamente incomum. O objetivo deste trabalho é relatar um caso de recidiva isolada em criança com LLA de linhagem T. A apresentação clínica foi quadro de edema e dor na cavidade oral, na região superior da gengiva à direita, sem outras alterações clínicas ou hematológicas. O diagnóstico foi confirmado por meio de biópsia e imuno-histoquímica. O mielograma era normal. Cinco meses após a manifestação inicial na cavidade oral, foi detectada infiltração leucêmica na medula óssea. O tratamento com quimioterapia sistêmica foi reintroduzido. Este relato de caso ressalta a importância do acompanhamento clínico e odontológico durante e após o tratamento quimioterápico, não somente com o objetivo de tratar as alterações na cavidade oral decorrentes da própria doença ou dos efeitos adversos do tratamento, mas para que sejam detectadas apresentações incomuns de recidiva na LLA.

Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

BACKGROUND: Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. METHODS: This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. RESULTS: The estimated probabilities of overall survival and event free survival at 5 years were 69.5% ( 3.6%) and 58.8% ( 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis > 50 x 10(9)/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count < 50 x 10(9)/L (p-value = 0.0008). There was no difference in cumulative central nervous system relapse (isolated or combined) for the other analyzed variables: immunophenotype, traumatic lumbar puncture, interval between diagnosis and first lumbar puncture and place where the procedure was performed. CONCLUSIONS: These results suggest that a leukocyte count > 50 x 10(9)/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.

Langerhans cell histiocytosis: 37 cases in a single Brazilian institution

OBJECTIVES: To improve the level of 'definitive' diagnosis of Langerhans cell histiocytosis by immunohistochemical investigation of the CD1a surface antigen and to compare outcomes in respect to age, gender, stage of the disease, treatment response and level of diagnostic accuracy. METHODS: A retrospective study was carried out of 37 children and adolescents with possible Langerhans cell histiocytosis between 1988 and 2008. The diagnoses were revisited using immunohistochemical investigations for CD1a, S-100 and CD68 in an attempt to reach definitive diagnoses for all cases. RESULTS: Before the study, only 13 of 37 patients (35.1 percent) had a 'definitive' diagnosis; by the end of the study, this number rose to 25 patients (67.6 percent). All reviewed cases were positive for the CD1a antigen. Overall survival was 88.5 percent. Multisystem disease (Stage 2; n=19) and absence of response at the 6th week of therapy (n=5) were associated to significantly lower overall survival (p-value = 0.04 and 0.0001, respectively). All deaths occurred in patients with multisystem disease and organ dysfunction at diagnosis. Other potential prognostic factors were not significant. Reactivation episodes occurred in 75 percent of the patients with multisystem disease. Diabetes insipidus was the most common sequel (21.6 percent). CONCLUSION: The level of diagnostic accuracy was increased through immunohistochemistry. The overall survival rate was similar to international multicentric studies. Multisystem disease and absence of response at six weeks of treatment were the most important unfavorable prognostic factors. The frequency of reactivation for patients with multisystem disease was higher than described in the literature, probably because maintenance chemotherapy was used only in two cases.

A perspectiva dos pais sobre a obtenção do diagnóstico de leucemia linfóide aguda em crianças e adolescentes: uma experiência no Brasil / The parents' perspective on receiving a diagnosis of acute lymphoid leukemia in children and adolescents: a Brazilian experiment

OBJETIVOS: conhecer a percepção dos pais para o diagnóstico de leucemia em seus filhos. MÉTODOS: pesquisa qualitativa tendo como referencial a teoria das representações sociais ancorada na tradição da sociologia compreensiva. Utilizou-se entrevista semi estruturada para a coleta de dados. Foram entrevistados 20 pais de crianças e adolescentes com diagnóstico de leucemia linfóide aguda (LLA). Para análise dos dados empregou-se a técnica de análise do conteúdo. As diretrizes de humanização da assistência e princípios bioéticos foram os eixos norteadores da análise dos dados. RESULTADOS: os pais recordaram-se claramente da progressão dos sintomas da doença até o diagnóstico. A palavra leucemia foi associada ao câncer e à morte. Dificuldades relacionadas à escuta dos sintomas, a particularidades clínicas da leucemia e ao encaminhamento no sistema de saúde foram os principais motivos para a demora do diagnóstico definitivo. Destacam-se as peregrinações por diferentes locais, perda da resolubilidade, gastos desnecessários, desgaste emocional e atraso nas ações de saúde. CONCLUSÕES: o câncer envolve valores culturais sobre a morte, cuja carga simbólica é maior no caso da criança. A busca do diagnóstico da leucemia pelos pais é exemplo emblemático do tortuoso caminho percorrido quando o mal que acomete a criança não se enquadra no rótulo das doenças comuns.

OBJECTIVES: to investigate how parents perceive a diagnosis of lymphoid leukemia in their children. METHODS: qualitative research based on the sociological theory of social representations was used. Data was gathered by way of semi-structured interviews. Twenty parents of children diagnosed as having acute lymphoid leukemia (ALL). The content analysis technique was used to analyze data. Data analysis was guided by the principles of bioethics and humane care. RESULTS: the parents clearly recalled the progression of symptoms up to diagnosis. The word leukemia was associated with cancer and death. Difficulties related to listening to the symptoms, the specific clinical features of leukemia and the referral system were the main reasons for delay in arriving at a final diagnosis. The parents highlighted the need to move about a lot from one place to another, the lack of resolution, unnecessary costs, emotional strain and the slowness of the health services. CONCLUSIONS: cancer brings with out cultural values concerning death and these bear greater weight when a child is involved. The search for a diagnosis of leukemia by parents is a good example of the tortuous path they have to tread when what is wrong with their children is not something that bears the label of a common disease.

Apresentação cutânea inicial de linfomas na infância / Initial cutaneous manifestation of lymphomas in children

Os linfomas cutâneos compreendem um grupo heterogêneo de desordens linfoproliferativas que envolvem a pele e são classificados como um subgrupo dos linfomas não Hodgkin. No período de 1981 a 2007, 100 casos de linfomas em crianças foram admitidos no Serviço de Hematologia, do Hospital das Clínicas da Universidade Federal de Minas Gerais, sendo que nove apresentaram manifestação cutânea inicial. Três pacientes foram classificados como linfoma cutâneo primário e seis como sistêmicos. Sete pacientes apresentaram linfoma de células T, um, linfoma linfoblástico B e um, imunofenótipo indefinido. Nenhum óbito ocorreu nos pacientes com linfoma cutâneo primário.

Cutaneous lymphomas comprise a heterogeneous group of lymphoproliferative disorders with skin involvement and are classified as a subgroup of non-Hodgkin lymphomas. From 1981 to 2007, 100 children with non-Hodgkin lymphomas were admitted to the Hematology Unit of the Federal University of Minas Gerais Teaching Hospital. In nine of these children, the skin was involved at the onset of the disease. Three patients were classified as having primary cutaneous lymphoma, while in six the disease was systemic with cutaneous involvement. In seven patients, the immunophenotype was T-cell, in one it was B-cell, and in the remaining case the immunophenotype was indefinable. No deaths occurred in any of the children with primary cutaneous lymphoma.

Compliance with a protocol for acute lymphoblastic leukemia in childhood

BACKGROUND: Remission rates achieved after the initial treatment of acute lymphoblastic leukemia may be similar in both developed and developing countries, but relapse rates are much higher in the latter. Thus, other reasons are needed, in addition to biological characteristics of the leukemic cells themselves, to explain the unfavorable evolution of patients living in unfavorable socioeconomic and cultural conditions. OBJECTIVE: The aim of this study was to retrospectively evaluate compliance to an acute lymphoblastic leukemia treatment protocol. .... The median white blood cell count was higher when compared with the protocol recommendations; the median 6-MP dose was lower than the standard recommended dose. The estimated probability of event-free survival was higher for patients with lower median leukocyte counts and close to those predetermined by the protocol. Event-free survival was also higher for children with a higher percentage of days without chemotherapy due to bone marrow or liver toxicity excluding undue interruptions. In multivariate analysis, both factors remained statistically significant. These results suggest that the intensity of maintenance chemotherapy may not have been enough in some children, to achieve adequate myelosuppression, hence the observation of higher leukocyte counts and none or rare episodes of therapy interruption. CONCLUSIONS: Compliance to the therapeutic protocol by both doctors and patients should always be considered in the evaluation of therapeutic failure in acute lymphoblastic leukemia; strict adherence to treatment protocols contributes to better treatment results in acute lymphoblastic leukemia children.

Aspectos da qualidade de vida relacionada à saúde em oncologia pediátrica / Issues of health related quality of life in pediatric oncology

Nas últimas décadas, houve aumento significativo nos índices de sobrevida das crianças e adolescentes com diagnóstico de neoplasias malignas. Essa acentuada melhora levanta questionamentos não só em relação à quantidade ou duração da sobrevida, mas também quanto à qualidade de vida. A mortalidade não é mais o ponto final apropriado quando se está considerando a eficácia de uma intervenção médica. As crianças e seus cuidadores experimentam significativo comprometimento da qualidade de vida nos meses que se seguem ao diagnóstico do câncer. Dessa forma, tanto as decisões clínicas quanto a condução de pesquisas só deveriam ser realizadas juntamente com o desenvolvimento de boas medidas de avaliação da qualidade de vida. Objetivo: alertar o pediatra a respeito da importância da avaliação da qualidade de vida relacionada à saúde de crianças e adolescentes com câncer.Métodos: foram selecionadas 39 referências em pesquisa realizada nas bases de dados Medline e no LILACS, utilizando-se as palavras-chave qualidade de vida, sobrevida, neoplasia. (AU)

There has been in the last decades a significant increase in the survival rate of children and adolescents with cancer diagnosis. This impressive improvement raises issues related not only to the amount of gained survival years but also to the quality of such survival. Mortality is no longer the more the appropriate end point to evaluate the efficacy of a medical intervention. Children and their parents suffer a remarkable decline in their quality of life during several months after the cancer diagnosis. Thus it would be highly appropriate that the evaluation of the quality of life was also an integral part of the clinical decisions and research in this area. Objective: to alert pediatricians to the importance of evaluating health related quality of life in children and adolescents with cancer. Methods: 39 references were selected from Medline and LILACS databases using the key words quality of life, survival and neoplasm. (AU)

Condições da cavidade bucal e acompanhamento odontológico de crianças com leucemia linfocítica aguda / Conditions of the oral cavity and of dental attendance of children with acute lymphocytic Leukemia

Objetivos: avaliar as condições da cavidade bucal de crianças com leucemia linfocítica aguda (LLA) e as complicações decorrente da quimioterapia e, verificar se um acompanhamento odontológico promove melhoria nas condições bucais. Métodos: estudo clínico, prospectivo, envolvendo 31 crianças, com idade entre 2 e 14 anos, com diagnóstico de LLA, tratadas em um hospital universitário de Belo Horizonte (MG). O plano de tratamento odontológico consistiu de avaliação inicial e urgência, adaptação comportamental e adequação do meio bucal, tratamento reabilitador e manutenção preventiva. Resultados: a mediana do período de acompanhamento foi de 11 meses. Das 31 crianças, 20 não haviam recebido atendimento odontológico prévio. Na avaliação odontológica inicial, 21 (67,7%) pacientes apresentavam atividade de cárie, 18 tinham necessidade de abordagem odontológica invasiva e 19 tinham gengivite. O índice de necessidades invasivas (INI) variou de 0% a 22,5% e 13 pacientes tinham INI=0. Dezoito apresentaram algum tipo de lesão em mucosa, sendo as mais freqüentes, úlceras, herpes labial e mucosite. Na avaliação odontológica final, 25 (80,6%) estavam sem atividade de cárie, três apresentavam necessidade de abordagem odontológica invasiva e 13 tinham gengivite. O INI variou de 0% a 4,3% e 28 pacientes tinham INI = 0. As medidas do índice de placa visível e INI iniciais foram significativamente maiores do que as finais (p<0,001). Conclusão: um programa de atendimento odontológico durante o tratamento quimioterápico favoreceu o equilíbrio e a manutenção da saúde bucal dessas crianças.

Objectives: To evaluate the conditions of the oral cavity of children with acute lymphocytic leukemia (ALL) and the current oral complications of the chemotherapy and, to verify whether the introduction of the dental attendance promotes an improvement in the oral conditions. Methods: It was a clinical, prospective study, involving 31 children, with age between 2 and 14 years, with diagnosis of LLA, treated in a university hospital. The dental treatment consisted of initial evaluation and urgency, behavioral adjustment and adaptation of the oral environment, rehabilitator treatment and preventive maintenance. Results: The medium one of the period of attendance was of 11 months. From the 31 children, 20 had not received any previous dental service. At the initial dental evaluation, 21 (67.7%) patients had decay activity of caries, 18 had necessity of invasive dental approach and 19 they had gingivitis. The index of invasive needs (INI) varied of 0% to 22.5% and 13 patients had IN equal zero. Eighteen had some type of lesion an the mucosa, having been the most frequent, ulcers, herpes labial and mucosite. In the final dental evaluation, 25 (80.6%) were without decay activity, three presented necessity of invasive dental approach and 13 had gingivitis. The INI varied of 0% to 4.3% and 28 patients had INI equal zero. The measures of the index of initial visible plaque and INI were significantly higher than the final ones (p<0.001). Conclusion: In accordance with the results of this study, can be concluded that the establishment of a dental service program during the chemotherapic treatment favored the balance and the maintenance of those children's oral health.

Recidiva da leucemia linfoblástica na criança: experiência do Serviço de Hematologia do Hospital das Clínicas da UFMG (1988-2005) / Relapse of acute lymphoblastic leukemia in child: experience of the Division of Hematology: Hospital das Clínicas da UFMG(1988-2005)

Objetivos: Analisar a evolução de crianças com primeira recidiva da leucemia linfoblástica (LLA) e identificar fatores prognósticos para segunda recidiva ou óbito. Métodos: Análise retrospectiva de 95 pacientes com recidiva da LLA tratados no Hospital das Clínicas, Universidade Federal de Minas Gerais, Brasil, entre 1988 e 2005. Resultados: A idade ao diagnostico inicial variou de 3 meses a 15,2 anos (mediana de 6 anos); 53 crianças eram do sexo masculino. A recaída medular isolada ou combinada ocorreu em 81% dos casos e a recaída extramedular isolada em 19%. Sessenta crianças alcançaram a segunda remissão. Todas foram submetidas ao tratamento com drogas citostáticas e em nenhuma criança com LLA em segunda remissão foi feito transplante de medula óssea. A probabilidade estimada de sobrevida global em 10 anos para todo o grupo foi de 16,1% (IC 95%: 9,3% - 24,6%). O óbito ocorreu em 77 crianças e a doença em atividade foi a principal causa. Os pacientes foram estratificados em 3 subgrupos: recidiva muito precoce (primeiros 18 meses desde o diagnóstico inicial), recidiva precoce (entre 18 e 30 meses) e recidiva tardia (mais de 30 meses após a data do diagnóstico inicial). A probabilidade estimada de sobrevida livre de eventos em 10 anos para cada um desses grupos foram, respectivamente, 2,2% (IC 95%: 0,2%-10%), 12,5% (IC 95%: 3,1%-28,7%) e 32,5% (IC 95%: 14,6%-51,9%; p< 0001). Conclusões: A duração da primeira remissão foi a única variável estatisticamente significativa que influenciou o prognóstico das crianças com recidiva da LLA.

Objectives: To follow up children in first relapse of acute lymphoblastic leukemia (ALL) and to identify prognostic factors for a second relapse or death. Methods: Retrospective analysis of 95 patients with relapse of ALL followed at Hospital das Clínicas, Universidade Federal de Minas Gerais, Brazil, between 1988 and 2005. Results: The age at initial diagnosis varied from 3 months to 15.2 years (median 6 y); 53 were male. Isolated or combined marrow relapse occurred in 81% of cases and isolated extramedullary relapse in 19%. Sixty children reached the second remission. They all were given cytostatic drugs and no ALL children in second remission were transplanted. The estimated probability of overall survival at 10 years from relapse was 16.1% (95% CI: 9.3% - 24%) for all 95 children. 77 children died and most of them were again in relapse. Patients were stratified into 3 subgroups according to time to first relapse: very early (within 18 months from initial diagnosis), early (from 18 to 30 months), and late relapsing children (later than 30 months). The estimated probability of event-free survival at 10 years for these 3 subgroups were 2.2% (95% CI: 0.2%-10%), 12.5% (95% CI: 3.1%-28.7%), and 32.5% (95% CI: 14.6%- 51.9%), respectively (p < 0.0001). Conclusions: The duration of first remission remained the only statistically significant variant to predict the prognosis of relapsed children with ALL.