Neutropenia congénita de tipo IV: reporte de un caso / Congenital neutropenia type IV: case report

La neutropenia congénita grave (NCG) es una entidad heterogénea cuya característica común es un recuento absoluto de neutrófilos inferior a 0,5 x 10 9/l. Presenta gran heterogeneidad genética, las mutaciones más frecuentes son las del gen de la elastasa 2 (ELA 2). El tratamiento de primera elección es la administración de factor estimulador de colonias de granulocitos. Los pacientes con NCG presentan infecciones graves en etapas tempranas de la vida. Se presenta una paciente con NCG asociada a fenotipo peculiar con facies triangular, retromicrognatia, patrón venoso prominente en miembros inferiores, comunicación interauricular y mal progreso ponderal, en quien se diagnosticó déficit de la enzima glucosa 6 fosfato deshidrogenasa, subunidad catalítica 3 (G6PC3). A pesar de lo infrecuente de esta mutación como causa de NCG (2 %), su conocimiento cobra importancia porque la coexistencia del fenotipo característico con una NCG orienta en la solicitud del estudio genético que permite arribar al diagnóstico.

Severe congenital neutropenia (SCN) is a heterogeneous disease whose more common feature is an absolute neutrophil count less than 0.5 x 10 9/l. It presents great genetic heterogeneity. Autosomal dominant inherited mutations of the elastase 2 gene (ELA2) represent the most common etiology. The first choice treatment is the administration of granulocyte colony stimulating factor. Patients with SCN develop severe infections early in life. We present a patient who associated SCN to a peculiar phenotype, characterized by triangular facies, retromicrognathia, prominent venous pattern in the lower limbs, atrial septal defect and poor weight progress, in whom a deficiency of the enzyme glucose 6 phosphate dehydrogenase, a catalytic subunit 3 (G6PC3), was diagnosed. Despite the infrequency of this mutation as the origin of SCN (2%), its knowledge becomes important because the coexistence of the characteristic phenotype and SCN guides the request for the genetic study that allows reaching the diagnosis.

Técnicas e procedimentos de controle de infecções de cateteres venosos em onco-hematologia infantil: aspectos clínico-epidemiológicos e microbiológicos e prevalência de Corynebacterium spp. - Instituto Nacional de Câncer, RJ / Techniques and procedures central line infections control in childhood cancer patients: clinical and epidemiological aspects, microbiological and prevalence of Corynebacterium spp. - Instituto Nacional de Câncer, RJ

Estudo descritivo retrospectivo realizado no Instituto Nacional do Câncer José Alencar Gomes da Silva, HCI-Rio de Janeiro, Brasil, (INCA-HCI-RJ), no qual foram avaliadas infecções relacionadas aos acessos venosos para tratamento oncológico, nos setores Onco-Hematológicos pediátricos. A infecção representa uma importante complicação em pacientes oncológicos em tratamento. Devido ao tratamento oncológico que envolve: procedimentos cirúrgicos muitas vezes mutilantes, tratamento com quimioterápicos que ocasionam períodos de imunossupressão e neutropenia, e tratamento radioterápico com radiação e lise celular. O uso de dispositivos venosos associados a períodos de imunossupressão pode levar a infecção da corrente sanguínea e outras complicações (por exemplo trombose). No presente estudo foram investigados aspectos clínico-epidemiológicos das infecções e da susceptibilidade antimicrobiana em amostras clínicas obtidas de processos infecciosos associados ao uso de cateteres venosos de longa permanência no tratamento oncológico em pacientes do Hospital do Câncer José de Alencar Gomes da Silva, HCI/INCA, Rio de Janeiro Brasil. Foram avaliadas: a) prevalência das espécies diversas relacionadas aos quadros infecciosos identificados nestes pacientes oncológicos; b) prevalência de casos de complicações e outras infecções invasivas relacionadas ao uso de cateteres de longa permanência; c) perfis de susceptibilidade a antimicrobianos e ocorrência de multirresistência. O desenvolvimento deste projeto de pesquisa possibilitou a observação análise e validação da evolução dos processos envolvidos nos quadros de infecções nosocomiais em pacientes oncológicos pediátricos na prevenção de complicações que envolvem todo o sistema de saúde, além de contribuir na escolha de antimicrobianos e estratégias terapêuticas mais efetivas para o tratamento de infecções em cateteres por espécies multirresistentes de Corynebacterium.

Retrospective descriptive study conducted at the National Cancer Institute José Alencar Gomes da Silva, INCA / HCI-Rio de Janeiro, Brazil, (INCA-HCI-RJ). Infection represents an important complication in cancer patients. This group is more prone to infections due to the cancer treatment that involves: surgical procedures often mutilating, treatment with chemotherapy that cause periods of immunosuppression even with neutropenia, and radiotherapy treatment with radiation and cell lysis. The vascular devices associated with these periods can lead to bloodstream infection besides others complication as thrombosis. The number of reports of infections in hospitalized cancer patients increases morbidity and mortality rates. In the present study clinical and epidemiological aspects of infections were identified and antimicrobial susceptibility were investigated in clinical exams and samples from blood patients and venous catheter in children oncological patients at the José de Alencar Gomes da Silva, HCI / INCA, Rio de Janeiro Brazil. It was possible evaluate a) prevalence of various species infections in cancer patients; b) prevalence of cases of complications and other invasive infections related to the use of long-term catheters; c) antimicrobial susceptibility profiles and occurrence of multidrug resistance. The development of this research project in nosocomial infections in pediatric cancer patients was enabled analysis and validation of some process involved to prevent vascular complications that involve entire health system. In addition to contributing to the choice of antimicrobials and the most effective therapeutic strategies for the treatment of multi-resistant Corynebacterium sp.

Colombian consensus on the diagnosis, treatment, and prevention of Candida Spp. disease in children and adults, / Consenso Colombiano Para el Diagnóstico, Tratamiento y Prevención de la Enfermedad por Candida Spp. en Niños y Adultos

Invasive Candidiasis (IC) and candidemia (as its most frequent manifestation) have become the main cause of opportunistic mycosis at hospital settings. This study, made by members of the Colombian Association of Infectious Diseases (ACIN), was aimed at providing a set of recommendations for the management, follow-up and prevention of IC / candidemia and mucous membrane candida infection in adult, pediatric and neonatal patients in a hospital setting, including the hemato-oncological and critical care units. All the data obtained through an exhaustive search were reviewed and analyzed in a comprehensive manner by all the members of the group, and the recommendations issued are being made after a careful review of the scientific literature available and the consensus of all specialists involved; the emergence of Candida Spp. problem is highlighted and a correct orientation to health professionals regarding the management of patients with candidiasis is provided in a rational and practical way, emphasizing patient evaluation, diagnostic strategies, prophylaxis, empirical treatment, directed treatment and preventative therapy.

La Candidiasis Invasora (CI) y la candidemia, como su manifestación más frecuente, se ha convertido en la principal causa de micosis oportunista a nivel hospitalario. Este manuscrito realizado por miembros de la Asociación Colombiana de Infectología (ACIN), tuvo como objetivo proporcionar un conjunto de recomendaciones para manejo, seguimiento y prevención de la CI/candidemia y de la infección candidiásica de mucosas, en población adulta, pediátrica y neonatal, en un entorno hospitalario, incluyendo las unidades hemato-oncológicas y unidades de cuidado crítico. Todos los datos obtenidos mediante una búsqueda exhaustiva, fueron revisados y analizados de manera amplia por todos los miembros del grupo, y las recomendaciones emitidas se elaboraron luego de la evaluación de la literatura científica disponible, y el consenso de todos los especialistas involucrados, reconociendo el problema de la emergencia de las infecciones por Candida Spp. y brindando una correcta orientación a los profesionales de la salud sobre el manejo de pacientes con enfermedad candidiásica, de una forma racional y práctica, enfatizando en la evaluación del paciente, estrategias de diagnóstico, profilaxis, tratamiento empírico, tratamiento dirigido y terapia preventiva.

Neutropenia febril asociada a la ingesta de metimazol: reporte de caso / Febrile neutropenia associated with methimazole ingestion: case report

La neutropenia se define como un recuento absoluto de neutrófilos menor a 1500 células /µL. Se debe a la disminución en la producción de granulocitos o al aumento en su destrucción, ya sea a nivel medular o periférico. Según la clasificación de la Organización Mundial de la Salud (OMS) los grados de neutropenia van de 0 a IV, de acuerdo a la magnitud de la disminución del recuento de neutrófilos. El grado IV es el de mayor riesgo y corresponde a recuentos por debajo de 500 células/µL. El impacto en la morbimortalidad asociada a la neutropenia no está vinculado con la disminución directa del recuento celular, sino con los procesos infecciosos asociados a los que son propensos los pacientes que la presentan. Existen diversas condiciones por las que se puede desarrollar neutropenia, entre las que se encuentran las infecciones, las malignidades y los fármacos. Estos últimos pueden generar eventos adversos por mecanismos dosis dependiente, como en el caso de la quimioterapia citotóxica o por una reacción idiosincrática. Se presenta el caso de una paciente femenina de 37 años de edad, con antecedentes de tirotoxicosis, tratada con propanolol y metimazol durante cuatro semanas, quien además de manifestaciones tóxicas, presentó neutropenia febril muy grave, que mejoró luego de suspensión del antitiroideo. Se pretende resaltar la asociación de neutropenia febril como complicación de uso de tionamidas y la importancia del seguimiento con exámenes de laboratorios para un diagnóstico oportuno(AU)

Neutropenia is defined as an absolute neutrophil count less than 1500 cells / μL. It is due to the decrease in the production of granulocytes or increase in their destruction, either at the medullary or peripheral level. According to the classification of the World Health Organization (WHO) the degrees of neutropenia range from 0 to IV, taking into account the magnitude of the decrease in the neutrophil count. Grade IV is the highest risk and corresponds to counts below 500 cells /μL. The impact on morbidity and mortality associated with neutropenia is not linked to the direct reduction of the cell count, but to the associated infectious processes to which patients who present it are prone. There are several conditions under which neutropenia can develop, including infections, malignancies and drugs. The latter can generate adverse effects by dose-dependent mechanisms, as in the case of cytotoxic chemotherapy or an idiosyncratic reaction. Next, the case of a female patient of thirty-seven years of age, with a history of thyrotoxicosis, treated with propanolol and methimazole for four weeks, who in addition to toxic manifestations, presents very severe febrile neutropenia that improves after suspension of the antithyroid. We aim to highlight the association of febrile neutropenia as a complication of thionamide use and the importance of follow-up with laboratory tests for an opportune diagnosis(AU)

Estudo da variação neutropênica pelo sulfato de vincristina em cães com tvt tratados em um hospital veterinário do noroeste paulista / Neutropenic variation by vincristine sulfate in tvt dogs treated in a veterinary hospital in northwestern são paulo / Estudio de la variación neutropénica por sulfato de vincristina en perros con tvt tratados en el hospital veterinario del noroeste paulista

O presente estudo avaliou dados epidemiológicos de neutropenia induzida por sulfato vincristina em cães com Tumor Venéreo Transmissível (TVT), num Hospital Veterinário do Noroeste paulista. Para tanto, trata-se de um estudo do tipo retrospectivo de protocolos eletrônicos e formulários manuais de dados digitalizados de 51 casos de TVT. O atendimento ambulatorial e de internação desses animais foi realizado no período de setembro de 2006 a dezembro de 2009. Dentre os resultados, destaca-se que 51 animais foram diagnosticados com TVT, sendo 37 fêmeas (73%) e 14 (27%) machos; 46 animais (90,2%) foram tratados exclusivamente com sulfato de vincristina. Os cães Sem Raça Definida-SRD (n=28) foram os maiores acometidos com 54,9%; seguidos pelos Poodles com quatro cães (7,84%). Os animais com idade entre 37 e 84 meses obtiveram a maior porcentagem de acometimento pelo TVT com 20 casos (39,22%). Em doze animais (23,52%) foi observada neutropenia (valores entre 390 a 1927 cél/µL). Conclusão: a possível toxicidade medular induzida pela vincristina foi verificada pela descrição da neutropenia. Dessa forma, a identificação de quadros neutropênicos, por meio da realização de hemogramas semanais, é considerada obrigatória e de extrema relevância devido à prevalência de mielotoxicidade secundária à utilização deste quimioterápico.

The present study aims to assess epidemiological data on neutropenia induced by vincristine sulfate among dogs with Canine Transmissible Venereal Tumor (CTVT) at a veterinary hospital in the Northwestern region in the São Paulo State. Methodology: This is a retrospective study of electronic protocols and digitalized data from manually filled form from 51 CTVT cases. These animals were treated in an outpatient care clinic and hospitalization took place from September 2006 to December 2009. Results: 51 animals were diagnosed with CTVT; among these, 37 were female (73%) and 14 were male (27%). From these, 46 animals (90.2%) were treated exclusively with vincristine sulfate. Among them, mongrels (n=28) were the most common, with 54.9%, followed by Poodles, with 4 dogs (7.84%). Animals aged from 37 and 84 months were the largest age group, with 20 cases (39.22 %). Neutropenia (390 to 1927 cells/µL) was observed in 12 animals. Conclusion: possible vincristine-induced marrow toxicity was verified by the description of neutropenia. Thus, neutropenia identification through weekly blood count cells is considered extremely important and mandatory due to the prevalence of myelotoxicity following treatment with this chemotherapeutic drug.

Este estudio busca evaluar datos epidemiológicos de neutropenia inducida por sulfato vincristina en perros con Tumor Venéreo Transmisible (TVT), en un Hospital Veterinario del Noroeste Paulista. Es un estudio del tipo retrospectivo de protocolos electrónicos y formularios manuales de datos digitalizados de 51 casos de TVT. El atendimiento de ambulatorio y de internación de esos animales se realizó en el período de septiembre de 2006 a diciembre de 2009. Entre los resultados, se destaca que 51 animales fueron diagnosticados con TVT, siendo 37 hembras (73%) y 14 (27%) machos; 46 animales (90,2%) fueron tratados exclusivamente con sulfato de vincristina. Los perros Sin Raza Definida ? SRD (n=28) fueron los más acometidos con 54,9%; seguidos por los Poodles con cuatro perros (7,84%). Los animales con edad entre 37 y 84 meses obtuvieron mayor porcentaje de acometimiento por TVT, con 20 casos (39,22%). En doce animales (23,52%0 se ha observado neutropenia (valores entre 390 a 1927 cél/µL). Conclusión: la posible toxicidad medular inducida por vincristina se ha verificado por la descripción de la neutropenia. Así, la identificación de cuadros neutropénicos por medio de realización de hemogramas semanales, es considerada obligatoria y de extrema relevancia debido a la prevalencia de mielotoxicidad secundaria a la utilización de este quimioterápico.

Estudo da variação neutropênica pelo sulfato de vincristina em cães com tvt tratados em um hospital veterinário do Noroeste Paulista / Neutropenic variation by vincristine sulfate in tvt dogs treated in a veterinary hospital in northwestern São Paulo / Estudio de la variación neutropénica por sulfato de vincristina en perros con tvt tratados en el hospital veterinario del Noroeste Paulista

O presente estudo avaliou dados epidemiológicos de neutropenia induzida por sulfato vincristina em cães com Tumor Venéreo Transmissível (TVT), num Hospital Veterinário do Noroeste paulista. Para tanto, trata-se de um estudo do tipo retrospectivo de protocolos eletrônicos e formulários manuais de dados digitalizados de 51 casos de TVT. O atendimento ambulatorial e de internação desses animais foi realizado no período de setembro de 2006 a dezembro de 2009. Dentre os resultados, destaca-se que 51 animais foram diagnosticados com TVT, sendo 37 fêmeas (73%) e 14 (27%) machos; 46 animais (90,2%) foram tratados exclusivamente com sulfato de vincristina. Os cães Sem Raça Definida-SRD (n=28) foram os maiores acometidos com 54,9%; seguidos pelos Poodles com quatro cães (7,84%). Os animais com idade entre 37 e 84 meses obtiveram a maior porcentagem de acometimento pelo TVT com 20 casos (39,22%). Em doze animais (23,52%) foi observada neutropenia (valores entre 390 a 1927 cél/µL). Conclusão: a possível toxicidade medular induzida pela vincristina foi verificada pela descrição da neutropenia. Dessa forma, a identificação de quadros neutropênicos, por meio da realização de hemogramas semanais, é considerada obrigatória e de extrema relevância devido à prevalência de mielotoxicidade secundária à utilização deste quimioterápico...

The present study aims to assess epidemiological data on neutropenia induced by vincristine sulfate among dogs with Canine Transmissible Venereal Tumor (CTVT) at a veterinary hospital in the Northwestern region in the São Paulo State. Methodology: This is a retrospective study of electronic protocols and digitalized data from manually filled form from 51 CTVT cases. These animals were treated in an outpatient care clinic and hospitalization took place from September 2006 to December 2009. Results: 51 animals were diagnosed with CTVT; among these, 37 were female (73%) and 14 were male (27%). From these, 46 animals (90.2%) were treated exclusively with vincristine sulfate. Among them, mongrels (n=28) were the most common, with 54.9%, followed by Poodles, with 4 dogs (7.84%). Animals aged from 37 and 84 months were the largest age group, with 20 cases (39.22 %). Neutropenia (390 to 1927 cells/µL) was observed in 12 animals. Conclusion: possible vincristine-induced marrow toxicity was verified by the description of neutropenia. Thus, neutropenia identification through weekly blood count cells is considered extremely important and mandatory due to the prevalence of myelotoxicity following treatment with this chemotherapeutic drug...

Este estudio busca evaluar datos epidemiológicos de neutropenia inducida por sulfato vincristina en perros con Tumor Venéreo Transmisible (TVT), en un Hospital Veterinario del Noroeste Paulista. Es un estudio del tipo retrospectivo de protocolos electrónicos y formularios manuales de datos digitalizados de 51 casos de TVT. El atendimiento de ambulatorio y de internación de esos animales se realizó en el período de septiembre de 2006 a diciembre de 2009. Entre los resultados, se destaca que 51 animales fueron diagnosticados con TVT, siendo 37 hembras (73%) y 14 (27%) machos; 46 animales (90,2%) fueron tratados exclusivamente con sulfato de vincristina. Los perros Sin Raza Definida – SRD (n=28) fueron los más acometidos con 54,9%; seguidos por los Poodles con cuatro perros (7,84%). Los animales con edad entre 37 y 84 meses obtuvieron mayor porcentaje de acometimiento por TVT, con 20 casos (39,22%). En doce animales (23,52%0 se ha observado neutropenia (valores entre 390 a 1927 cél/µL). Conclusión: la posible toxicidad medular inducida por vincristina se há verificado por la descripción de la neutropenia. Así, la identificación de cuadros neutropénicos por medio de realización de hemogramas semanales, es considerada obligatoria y de extrema relevancia debido a la prevalencia de mielotoxicidad secundaria a la utilización de este quimioterápico...

Neutropenia febril / Febrile neutropenia

A Neutropenia Febril (NF) deve ser considerada uma emergência médica, cujo diagnóstico precoce e tratamento antimicrobiano empírico são fundamentais para o bom desfecho dos casos. Este trabalho serve como um guia para acadêmicos e médicos, no qual abordaremos diagnóstico, estratificação de risco e terapias antimicrobianas da Neutropenia Febril.

Febrile Neutropenia (FN) should be considered a medical emergency in which an early diagnoses and empiric antibiotic therapy are essential for a successful outcome. This paper serves as a guide for medical students and physicians, in which we will report diagnoses, risk stratification and antimicrobial therapies.

Estudio de Infecciones diseminadas por candida en pacientes con neutropenia febril asociada a enfermedades hemato-oncológicas / Study disseminated Candida infections in patients with febrile neutropenia associated with hemato-oncological diseases

Mundialmente, en las últimas dos décadas se ha observado un incremento en la frecuencia de las infecciones micóticas diseminadas, con alta morbi-mortalidad, particularmente importante en las infecciones por Candida. El objetivo es determinar la frecuencia de candidiasis diseminada, en pacientes con enfermedades hemato-oncológicas o aplasia medular que ingresaron a los servicios de medicina interna del hospital universitario de caracas, con fiebre y neutropenia, entre enero y septiembre de 2010, realizándose evaluación exhaustiva y tomándose muestras de sangre, además de otras muestras en caso de presencia de lesiones, para el diagnóstico micológico. Se evaluaron 48 pacientes en el período del estudio, diagnósticandose 21 casos (43,75%) de micosis diseminadas, catalogadas como infecciones probadas en 13 y probables en 8 casos. De las infecciones probadas 8 (38%) correspondieron a infecciones por Candida: en uno se aisló Candida albicans y en 7, Candida no albicans: 2 pacientes con candida tropicalis, 2 con candida glabatra y uno con candida guillermondii. Dos cepas fueron informadas como candida spp, y 5 por otros hongos. Las infecciones micóticas diseminadas contribuyen sustancialmente a la morbimortalidad de los pacientes con neutropenia, por lo tanto es fundamental la sospecha y diagnóstico temprano de estas entidades en los pacientes con cáncer de origen hematológico y aplasia medular.

Wordwide, there has been an increase in the incidence of disseminated fungal diseases during the last two decades, with high morbidity and mortality particularly importante in Candida infections. To determine the frequency of disseminated candidiasis in patients with hemato-oncological diseases or bone marrow aplasia and febrile neutropenia. A descriptive, prospective and analytical study was conducted. Patients with hemato-oncological diseases or bone marrow aplasia who were hospitalized at the internal medicine service of the hospital universitrio de caracas, with fever and neutropenia, between january and september, 2010 were included, making torough assessment and taking blook samples as well as other clinical specimen when other lesions were present, for mycological diagnosis. During the study period, 48 patients were evaluated. Twenty one cases were diagnosed (43.75%) as disseminated fungal disease. They were classified as proven in 13 cases and probable in 8. From the proven diseases, 8 (38%) corresponded to Candida infections: in one, Candida albicans was isolated and in 7, Candida non-albicans: 2 patients with Candida tropicalis were found, 2 with Candida glabrata and one with Candida guillermondii. Two were reported as Candida spp. In 5 patients other fungi were found. Dissemiated fungal infections substantially contribute to morbidity and mortality in neutropenic patients. For this reason, awareness and early diagnosis of this disease are crucial are crucial in patients with hematological cancer and bone marrow aplasis.

Evidence-Based Guidelines for Empirical Therapy of Neutropenic Fever in Korea

Neutrophils play an important role in immunological function. Neutropenic patients are vulnerable to infection, and except fever is present, inflammatory reactions are scarce in many cases. Additionally, because infections can worsen rapidly, early evaluation and treatments are especially important in febrile neutropenic patients. In cases in which febrile neutropenia is anticipated due to anticancer chemotherapy, antibiotic prophylaxis can be used, based on the risk of infection. Antifungal prophylaxis may also be considered if long-term neutropenia or mucosal damage is expected. When fever is observed in patients suspected to have neutropenia, an adequate physical examination and blood and sputum cultures should be performed. Initial antibiotics should be chosen by considering the risk of complications following the infection; if the risk is low, oral antibiotics can be used. For initial intravenous antibiotics, monotherapy with a broad-spectrum antibiotic or combination therapy with two antibiotics is recommended. At 3-5 days after beginning the initial antibiotic therapy, the condition of the patient is assessed again to determine whether the fever has subsided or symptoms have worsened. If the patient's condition has improved, intravenous antibiotics can be replaced with oral antibiotics; if the condition has deteriorated, a change of antibiotics or addition of antifungal agents should be considered. If the causative microorganism is identified, initial antimicrobial or antifungal agents should be changed accordingly. When the cause is not detected, the initial agents should continue to be used until the neutrophil count recovers.

Cardiac and renal malformations in a patient with sepsis and severe congenital neutropenia

G6BC3 deficiency is a new neutropenic syndrome, which is characterized by severe persistent neutropenia, early onset infections and additional organ involvement, especially cardiac and urogenital malformations. In this report, we present the clinical details of a recently known case of severe congenital neutropenia [SCN] with G6PC3 mutation, who experienced the first episode of infections at birth. Repeated absolute neutrophil count of less than 500/micro l was detected during work-up of sepsis in the first month of life. SCN was diagnosed and granulocyte colony-stimulating factor [GCSF] administration initiated. Bone marrow examination revealed maturation arrest in myeloid series at promyelocyte-myelocyte stage. Diarrhea, bronchiolitis, and urinary tract infection were other infectious complications, while hydronephrosis, atrial septal defect, and patent ductus arteriosus were other manifestations. Prompt and accurate diagnosis of neutropenic patients and appropriate treatment can prevent further complications and improve the quality of life of the affected patients

Late-onset Neutropenia Following Rituximab Therapy as a Treatment of Diffuse Large B-cell Lymphoma: A Single Institution Study / 대한진단검사의학회지

BACKGROUND: Late-onset neutropenia (LON) following rituximab therapy has been reported in recent years. However, its incidence has not been reported in Korea. The aim of this study is to investigate the incidence of LON after rituximab therapy in Korean patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Ninety-eight cases of DLBCL treated with rituximab between 2004 and 2008 were evaluated. We identified LON as defined by the neutrophil count of <1.5x10(9)/L without apparent cause after the recovery of neutrophil count following rituximab therapy. Bone marrow aspiration and biopsy specimens at the time of neutropenia were available for retrospective review in only 5 of the patients. RESULTS: LON was observed in 15 (15.3%) of the 98 patients. In the bone marrow specimens of the 5 patients, promyelocytes were relatively increased and the maturation index of the granulopoiesis was 2:1-3:1, which reflects maturation arrest. CONCLUSIONS: The incidence of LON following rituximab therapy was 15.3% in Korean patients with DLBCL. Although there are several hypotheses about the causative mechanisms of LON, we suggest that maturation arrest at the promyelocyte stage of granulopoiesis may be one of the mechanisms involved in the development of LON.

Ausencia del receptor CD16b en neutrófilos / Neutrophils without CD16b receptors

Se presentan dos pacientes (mujeres de 41 y 15 años de edad) con ausencia del receptor para el fragmento Fc de IgG, CD16b en neutrófilos (fenotipo "null"). El caso 1 fue referida al laboratorio con diagnóstico de hemoglobinuria nocturna paroxística y el caso 2) con diagnóstico presuntivo de neutropenia inmune. En ambos casos se comprobó por citometría de flujo la ausencia de expresión de CD16b, sin deficiencias en la expresión de otras moléculas del sistema de alloantígenos propios de neutrófilos ni defectos en el anclaje a membrana por glicosil fosfatidil inositol (GPI). Las manifestaciones clínicas en ambas pacientes: anemia en el caso 1 y leucopenia en el caso 2 no pueden ser atribuidas exclusivamente a la carencia de CD16b, ya que otros receptores para Fc de IgG (CD32 y CD64) podrían suplir la función de CD16b. Sin embargo, es importante tener en cuenta esta rara deficiencia (b y neutropenia isoinmune natal transitoria en niños nacidos de mujeres con fenotipo "null".

Occurrence of the rare CD16b deficiency ("null" phenotype) in neutrophils from two female patients (41 and 15 years old) is reported. The first case was referred with a diagnosis of anemia related to paroxistic nocturnal hemoglobinuria and the second case, with presumptive diagnosis of immune neutropenia. In both cases, absence of CD16b expression was determined by flow cytometry without deficiencies of other neutrophil alloantigens or defects of membrane anchorage through glycosil phosphatydil inositol (GPI) linkage. Clinical manifestations in both patients could not be attributed exclusively to the absence of CD16b, as other receptors for the IgG Fc fragment (CD32 and CD64) could compensate this deficiency that occurs in < 1% of the caucasic population. Nevertheless, it is important to take this rare deficiency into account in order to prevent isoantibody formation after eventual blood transfusions, or transient neonatal immune neutropenia in children born to women with the "null" phenotype.

Intoxicação experimental aguda por samambaia (Pteridium aquilinum) em bovinos / Experimental acute poisoning by bracken fern (Pteridium aquilinum) in cattle

Este experimento foi delineado para investigar os seguintes pontos em relação à intoxicação aguda por samambaia (Pteridium aquilinum) em bovinos: 1) a intensidade da trombocitopenia em diferentes momentos da intoxicação e sua relação com possíveis déficits na hemostasia secundária, 2) a relação da neutropenia com as manifestações morfológicas de septicemia ocasionalmente observadas na necropsia, e 3) o mecanismo da anemia e sua relação com a perda de sangue, a vida média eritróide e a evolução da doença. As hastes superiores mais verdes de P. aquilinum foram administradas a quatro bovinos sem raça definida, com idade média de 1,5 ano e pesos entre 190-215 kg. Um bovino de idade e peso semelhantes foi usado como controle e, exceto por não ter recebido P. aquilinum, foi mantido nas mesmas condições que os outros quatro. Os quatro bovinos que receberam a planta morreram com quadro característico da intoxicação aguda por samambaia após receberem durante 53-58 dias, doses diárias de 8,0, 8,6, 10,2 e 10,6g/kg de peso corporal, que totalizaram, ao final do experimento, respectivamente, 112,7, 107,6, 85,7, 90,15 kg da planta, o que corresponde, respectivamente, a 59,3 por cento, 63,3 por cento, 47,4 por cento, 47,5 por cento da planta em relação ao peso dos bovinos. A doença caracterizou-se por febre de até 42,5 graus C e diversos graus de hemorragias observadas clinicamente, na necropsia e na histopatologia. A morte ocorria 6-7 dias após o início do quadro febril. As alterações hematológicas revelaram trombocitopenia e neutropenia acentuadas. Em dois dos quatro bovinos havia anemia leve. Não houve variações significativas nos tempos de coagulação dos bovinos intoxicados, quando avaliados os fatores de coagulação (secundária), excluindo-se assim a possibilidade da participação de distúrbios da hemostasia secundária na patogênese das hemorragias nessa intoxicação. A determinação dos produtos da degradação da fibrina no soro revelou dados conflitantes...

This experiment was design to address the following points in relation to the acute poisoning by bracken fern (Pteridium aquilinum) in cattle: 1) the severity of the thrombocytopenia in different stages of the intoxication and its relationship to possible deficits in the secondary hemostasis, 2) the relationship between neutropenia and the morphological signs of septicemia occasionally found at necropsy, and 3) the mechanism of anemia and its relationship with blood loss, medium life of erythrocytes and the progress of the disease. The fresh green upper parts of P. aquilinum were fed to four mixed breed calves with average age of 18 months and weights ranging from 190 to 215 kg. A calf of similar age and weight was kept together with the other four under the same conditions, except for the ingestion of P. aquilinum. The four fern-fed calves died with typical features of acute bracken fern poisoning after being fed with the plant for 53-58 days daily doses of 8.0, 8.6, 10.2, and 10.6g/kg body weight totaling at the end of the experiment, respectively, 59.3 percent, 63.3 percent, 47.4 percent, and 47.5 percent of bracken fern in relation to their body weight. The disease was characterized by fever up to 42.5 grades C and varying degrees of hemorrhages observed clinically, at necropsy and on histological examination. Death occurred 6-7 days after the onset of fever. The hematological changes consisted mainly of marked thrombocytopenia and neutropenia. Two of the four affected calves had mild anemia. The deficits in secondary hemostasis were mild in each case. There were no significant changes thus permitting to rule out the role of secondary hemostasis in the pathogenesis of the hemorrhages in the bracken fern poisoning. The measurement of fibrin degradation products in the serum showed conflicting results and did no allow for a solid conclusion regarding the role of disseminated intravascular coagulation in the pathogenesis of the hemorrhages...

White blood cell counts in healthy Jamaican adults / Conteo de glóbulos blancos en adultos jamaicanos sanos

The investigation of presumed neutropenia places a burden on the health services, especially those of developing countries, including Jamaica. This may be because the normal ranges used in the laboratory are based on the values generated from the Caucasian population. Previous studies looking at African and Afro-Caribbean groups have found lower counts for these populations compared with Caucasians. To address this issue, 195 healthy adults donating blood at the National Public Health Laboratory and the University Hospital of the West Indies blood banks in Kingston, Jamaica, were screened for complete blood count (CBC) differentials between June 2001 and June 2006. The geometric means for the neutrophil counts were found to be 2.4 x 10(9)/L for men and 2.7 x 10(9)/L for women, with 95% confidence intervals of 2.2-2.8 x 10(9)/L and 2.5-3.1 x 10(9)/L respectively. Values for the Jamaican population were similar to those of other Afro-Caribbean groups. Based on this distribution, 14% of healthy Jamaicans would fall below the normal ranges derived from Caucasians and therefore presumed to have neutropenia. We recommend that the lower reference ranges obtained for Afro-Caribbean adults be adopted for that population.

La investigación de una neutropenia presunta, representa una carga para los servicios de salud, sobre todo en los países en vías de desarrollo, incluyendo Jamaica. La razón de ello puede estribar en que los rangos normales usados en el laboratorio, se basan en valores generados a partir de la población caucásica. Estudios previos sobre los grupos africanos y afro-caribeños, han hallado conteos más bajos para estas poblaciones, en comparación con las caucásicas. A fin de abordar este problema, 195 adultos sanos que donaron sangre al Laboratorio Nacional de Salud Pública y a los bancos de sangre del Hospital Universitario de West Indies en Kingston, Jamaica, fueron tamizados en busca de diferenciales en conteos completos de sangre (CCS), entre junio de 2001 y Junio de 2006. Para los conteos de neutrófilos, se halló que las medias geométricas fueron 2.4 x 10(9)/L para los hombres y 2.7 x 10(9)/L para las mujeres, con intervalos de confianza del 95% equivalentes a 2.2-2.8 x 10(9)/L y 2.5-3.1 x 10(9)/L respectivamente. Los valores para la población jamaicana fueron similares a los de otros grupos afro-caribeños. Sobre la base de esta distribución, el 14% de los jamaicanos saludables caerían por debajo de los rangos normales derivados a partir de los caucásicos, y por consiguiente se presumiría que tienen neutropenia. Nosotros recomendamos que los rangos de referencia más bajos obtenidos para los adultos afro-caribeños sean adoptados para esa población.

Mucositis oral en pacientes pediátricos con cáncer: relación con la neutropenia y protocolo de tratamiento / Oral mucositis in pediatric patients with cancer: relation to neutropenia and treatment protocol

Las mucositis es la complicación oral más común inducida por la quimioterapia; es el resultado de interacciones complejas entre múltiples factores, entre los que resaltan los estadíos de neutropenia y el protocolo de tratamiento. El propósito de este estudio fue determinar la relación entre la mucositis oral, la neutropenia y el protocolo de tratamiento en pacientes pediátricos con enfermedades neoplásicas del Servicio de Oncohematología de la Fundación Hospital de Especialidades Pediátricas de Maracaibo. Se realizó una investigación retrospectiva entre los años 2000 y 2005. Se incluyeron en el estudio historias clínicas de pacientes con cáncer en edades de 0 a 18 años, que recibieron quimioterapia y/o radioterapia. De los 77 pacientes evaluados, 42 (54,54 por ciento) desarrollaron mucositis, de los cuales 28 (66,66 por ciento) correspondieron al sexo masculino y 14 (33,34 por ciento) al femenino. El mayor porcentaje (35,71 por ciento) de mucositis se observó en el grupo de 0 a 5 años de edad. El tipo de protocolo de tratamiento donde se evidenció mayores casos de mucositis fue el Protocolo Total XV, con 16 pacientes (38,11 por ciento). Se observó una correlación significativa entre la mucositis y la neutropenia (r)= 0,9734, p<0,0001. Existe una relación de la mucositis y los estadios de neutropenia, especialmente durante la administración del Protocolo Total XV.

Laryngitis and neutropenia from parvovirus-B19.

Parvovirus-B19 has been reported a rare cause of acute laryngitis. Here, we described an 11-month-old girl who had prolonged acute laryngitis and neutropenia associated with parvovirus-B19 infection. Intravenous immunoglobulin therapy resulted in resolution of her symptoms, except neutropenia. We concluded that parvovirus-B19 can cause prolonged laryngitis and intravenous immunoglobulin treatment should be considered.

Novas diretrizes na abordagem clínica da neutropenia febril e da sepse em oncologia pediátrica / New guidelines for the clinical management of febrile neutropenia and sepsis in pediatric oncology patients

OBJETIVOS: Fornecer subsídios à abordagem diagnóstica, profilática e terapêutica da neutropenia febril e da sepse em criança com doença oncológica, dando especial atenção aos novos protocolos e diretrizes. FONTES DE DADOS: Revisão de literatura científica utilizando uma busca bibliográfica eletrônica nas páginas do MEDLINE, Medscape, SciELO, Google, Cochrane e PubMED com as palavras-chave febrile, neutropenic, cancer, children, sepse, intensive, care. Foram selecionados artigos publicados entre 1987 e 2007, preferencialmente artigos de revisão, protocolos, revisões sistemáticas, estudos epidemiológicos, recomendações de força-tarefa e ensaios clínicos fase III. Foram revistos os consensos publicados pela Infectious Diseases Society of America, Center for Diseases Control e Infectious Diseases Working Party da German Society of Hematology and Oncology, além de recomendações da World Federation of Pediatric Intensive and Critical Care Societies e da Society of Critical Care Medicine. SíNTESE DOS DADOS: A utilização de esquemas quimioterápicos agressivos, transplante de medula óssea e recursos de terapia intensiva aumentaram a sobrevida nas crianças com câncer e também a morbidade infecciosa, sendo as complicações sépticas a principal causa de mortalidade. Diversos fatores de risco têm sido identificados, como neutropenia, tipo oncológico, sinais clínicos e marcadores de resposta inflamatória (reação em cadeia da polimerase, procalcitonina), assim como a maior resistência aos antimicrobianos e antifúngicos. Protocolos de classificação de risco, de diagnóstico e tratamento devem ser estabelecidos em cada serviço, respeitando a flora microbiológica da população estudada. A terapia intensiva pediátrica tem aumentado a sobrevida a curto e longo prazo nestes pacientes. CONCLUSÕES: Pacientes oncológicos são particularmente vulneráveis a complicações infecciosas. A identificação e o tratamento precoce são fundamentais para a melhora da sobrevida.

OBJECTIVES: To provide a foundation for the diagnostic, prophylactic and therapeutic management of febrile neutropenia and sepsis in children with oncological diseases, with special attention to new protocols and guidelines. SOURCES: A review of the scientific literature utilizing an electronic bibliographic search on MEDLINE, Medscape, SciELO, Google, Cochrane and PubMED using the keywords febrile, neutropenic, cancer, children, sepsis, intensive, care. Articles published between 1987 and 2007 were selected, with preference given to review articles, protocols, systematic reviews, epidemiological studies, task force recommendations and phase III clinical trials. Consensus documents published by the Infectious Diseases Society of America, the Center for Diseases Control and the Infectious Diseases Working Party of the German Society of Hematology and Oncology, in addition to the recommendations of the World Federation of Pediatric Intensive and Critical Care Societies and Society of Critical Care Medicine, were also reviewed. SUMMARY OF THE FINDINGS: The use of aggressive chemotherapy regimens, bone marrow transplantation and intensive care resources have increased the survival rates of children with cancer and also their infectious morbidity, with septic complications as the principal cause of mortality. Several risk factors have been identified, such as neutropenia, oncology type, clinical signs and inflammatory response markers (polymerase chain reaction, procalcitonin) and also increased resistance to antimicrobials and antifungal agents. Protocols for risk classification, diagnosis and treatment should be established at each service, taking into account the microbiological flora of each population. Pediatric intensive care has increased the short and long-term survival of these patients. CONCLUSIONS: Oncology patients are particularly vulnerable to infectious complications. Early identification and treatment are fundamental to improving...