La neutropenia: Una revisión narrativa / Neutropenia: A narrative review

Introducción: La Neutropenia constituye una de las complicaciones más comunes en pacientes que reciben tratamiento sistémico con quimioterapia, siendo esta una población heterogénea; por lo tanto su presentación clínica es inespecífica, pudiendo presentarse de manera asintomática o inclusive evidenciar cuadros muy severos con signos de sepsis grave. Ante lo referido, en la actualidad los grupos de trabajo requieren determinar de manera consistente los diferentes factores de riesgo que contribuyen a la presentación de neutropenia, con el objetivo de estratificar de manera óptima al paciente y así disminuir complicaciones. Puntos importantes: Este trabajo se enfatiza en analizar los factores de riesgo; tanto del paciente, la enfermedad y el tratamiento; de acuerdo a los sistemas de estratificación como MASCC, CISNE. Además se evaluaron los fundamentos clínicos y microbiológicos para categorizar al paciente e incluir medidas de soporte profiláctico a los grupos con mayor fragilidad, disminuyendo el alto riesgo de complicaciones severas. Conclusión: La neutropenia es un evento adverso indeseable en el manejo del tratamiento oncohematológico. Los sistemas de estratificación de riesgos MASCC y CISNE son herramientas útiles para seleccionar pacientes de bajo riesgo. Sin embargo, otros factores, como el tipo de tumor y el tipo de infección, pueden influir en la estratificación. Por lo tanto, es importante manejar a cada paciente de forma individualizada.El inicio de la profilaxis antimicrobiana y el uso de FECG pueden ayudar a reducir la morbimortalidad.

Introduction: Neutropenia is one of the most common complications in patients receiving systemic treatment with chemotherapy; this is a heterogeneous population; therefore, its clinical presentation is nonspecific, presenting asymptomatically or even showing very severe symptoms with signs of severe sepsis. Given those above, currently, the working groups need to consistently determine the different risk factors contributing to the presentation of neutropenia to stratify the patient and thus optimally reduce complications. Important points: This work emphasizes the analysis of risk factors, including the patient, the disease, and the treatment, according to stratification systems such as MASCC and CISNE. In addition, the clinical and microbiological foundations were evaluated to categorize the patient and include prophylactic support measures for the most frail groups, reducing the high risk of severe complications. Conclusion: Neutropenia is an undesirable adverse event in managing oncohaematological treatment. The MASCC and CISNE risk stratification systems are valuable tools for selecting low-risk patients. However, other factors, such as the type of tumor and infection, may influence the stratification. Therefore, it is essential to manage each patient individually. The initiation of antimicrobial prophylaxis and the use of FECG can help reduce morbidity and mortality.

Reações adversas medicamentosas em pacientes em quimioterapia e estratégias de intervenções / Adverse drug reactions in chemotherapy patients and intervention strategies / Reacciones adversas a medicamentos en pacientes quimioterápicos y estrategias de intervención

A quimioterapia do câncer pode ocasionar reações adversas medicamentosas (RAM), podendo resultar de interações medicamentosas (IM) e impactar na adesão. O presente estudo relatou as RAM apresentadas por pacientes em quimioterapia (QT) e propôs estratégias de intervenções. Este trabalho foi aprovado em comité de ética (5.160.503), sendo incluídos 23 pacientes em quimioterapia (oral- VO e/ou endovenosa- EV) e todos foram entrevistados. Recebiam apenas o QTEV, 20 pacientes e 2 QTEV e VO, a maioria em tratamento paliativo (50%), predomínio de estadiamento IV, sendo as doenças mais presentes de pâncreas (27,3%), estômago (22,7%) e mama (18,2%) e esquema mais usado foi Carboplatina + Paclitaxel. As principais comorbidades foram diabetes e hipertensão arterial. As interações medicamentosas foram classificadas em graves (45%), moderadas (55%) e intencional (75%), sendo necessário introdução de medicamentos de suporte (61%). Houve RAM de maior gravidade, neutropenia, sendo necessário a suspensão temporária, e de menor gravidade náuseas. Houve um óbito relacionado a evolução de doença e, talvez, o tratamento possa ter contribuído. Ao final, foram feitas as intervenções para cada caso e validado o formulário para a consulta farmacêutica a pacientes oncológicos.

Cancer chemotherapy can cause adverse drug reactions (ADRs), which can result from drug interactions (IM) and impact adherence. The present study reported the ADRs presented by patients undergoing chemotherapy (CT) and proposed intervention strategies. This work was approved by the ethics committee (5,160,503), and 23 patients on chemotherapy (oral-VO and/or intravenous-IV) were included and all were interviewed. Only received CTIV, 20 patients and 2 CTIV and VO, most in palliative treatment (50%), predominance of stage IV, being the most common diseases of pancreas (27.3%), stomach (22.7%) and breast (18.2%) and the most used regimen was Carboplatin + Paclitaxel. The main comorbidities were diabetes and arterial hypertension. Drug interactions were classified as severe (45%), moderate (55%) and intentional (75%), requiring the introduction of supportive drugs (61%). There were more severe ADRs, neutropenia, requiring temporary suspension, and less severe nausea. There was one death related to the evolution of the disease and, perhaps, the treatment may have contributed. At the end, interventions were made for each case and the form for the pharmaceutical consultation to cancer patients was validated.

La quimioterapia contra el cáncer puede causar reacciones adversas a los medicamentos (RAM), que pueden ser consecuencia de interacciones farmacológicas (IM) y repercutir en la adherencia. El presente estudio reportó las RAM presentadas por pacientes en quimioterapia (QT) y propuso estrategias de intervención. Este trabajo fue aprobado en comité de ética (5.160.503), se incluyeron 23 pacientes en quimioterapia (oral- VO y/o endovenosa-EV) y todos fueron entrevistados. Recibieron sólo QTEV, 20 pacientes y 2 QTEV y VO, la mayoría en tratamiento paliativo (50%), predominio de estadiaje IV, siendo las enfermedades más presentes las de páncreas (27,3%), estómago (22,7%) y mama (18,2%) y el esquema más utilizado fue Carboplatino + Paclitaxel. Las principales comorbilidades fueron la diabetes y la hipertensión arterial. Las interacciones farmacológicas se clasificaron como graves (45%), moderadas (55%) e intencionadas (75%), requiriendo la introducción de fármacos de apoyo (61%). La RAM más grave fue la neutropenia, que requirió la suspensión temporal, y la menos grave las náuseas. Hubo una muerte relacionada con la evolución de la enfermedad y, tal vez, el tratamiento pudo haber contribuido. Al final, se realizaron intervenciones para cada caso y se validó el formulario de consulta farmacéutica a pacientes oncológicos.

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.

Prevalencia de gérmenes con multi resistencia antibiótica en bacteriemia asociada a neutropenia febril en pacientes oncológicos hospitalizados. Un estudio de centro único / Prevalence of germs with multi antibiotic resistance in bacteremia associated with febrile neutropenia in hospitalized cancer patients. A single-center study

Introducción: El cáncer en el año 2020 provoco 1,4 millones de muertes, el 47% en personas menores de 65 años de edad,la neutropenia febril en el paciente oncológico aumenta los casos de infecciones graves, incrementando la morbimortalidad cuando no se ha empezado un tratamiento de oportuno. El objetivo del presente estudio fue describir una población con esta patología en un centro de referencia regional. Metodología: Este estudio transversal, se realizó en el Instituto Oncológico Nacional "Dr. Juan Tanca Marengo", Sociedad de Lucha contra el Cáncer, Solca Guayaquil, período enero 2020-junio 2021, con una muestra no probabilística, de pacientes con neoplasias, neutropenias y cultivos positivos. Se registraron variables demográficas, clínicas, de laboratorio. Se utiliza estadística descriptiva invariada. Resultados: Se analizan 126casos, de edad promedio 55 años, el 50.8% fue de sexo femenino; el 88.1 % ingresó con neutropenia febril; la estancia hospitalaria promedio fue de 7 días. La Escherichia coli fue el microorganismo más frecuente con el 17.5 %, seguido por Klebsiella neumonía en el 9.5 %, Enterobacteria aerógenas y Pseudomonas eruginosa en el 4.8 %. El 70.2 % de las bacterias aisladas presentó resistencia bacteriana, el 47 % fueron bacterias betalactamasa de espectro ampliado (BLEA), el 40 % fue betalactamasa de espectro extendido (BLEE), y el 5 % productor de carbapenémicas (KPC), el 57.5 % con resistencia bacteriana tuvo una estancia hospitalaria mayor a 7 días Conclusión: El principal microorganismo fue Escherichia coli y la resistencia mayormente la tuvieron las bacterias betalactamasa de espectro ampliado positiva; permitiendo conocer la epidemiología local del perfil microbiológico y su relación con los pacientes oncológicos con neutropenia febril

In troduction:Cancer in 2020 caused 1.4 million deaths, 47% in people under 65 years of age, febrile neu-tropenia in cancer patientsincreases cases of serious infections, increasing morbidity and mortality when Timely treatment has not been started. The objective of the present study was to describe a pop-ulation with this pathology in a regional reference center.Met hodology: This cross-sectional study was conducted at the National Oncology Institute "Dr. Juan Tanca Marengo," Society for the Fight Against Cancer, Solca-Guayaquil, period January 2020-June 2021, with a non-probabilistic sample of patients with neoplasms, neutropenia, and positive cultures. Demo-graphic, clinical, and laboratory variables were recorded. Univariate descriptive statistics are used.R esults: 126 cases were analyzed, with an average age of 55 years; 50.8% were female; 88.1% were admitted with febrile neutropenia; the average hospital stay was seven days. Escherichia coli was the most frequent microorganism with 17.5%, followed by Klebsiella pneumoniae in 9.5%, Enterobacter aerogenes, and Pseudomonas aureginosa in 4.8%. 70.2% of the isolated bacteria presented bacterial resistance, 47% were extendedspectrum beta-lactamase bacteria (ESBL), 40% were extended-spectrum betalactamase (ESBL), and 5% produced carbapenemases (KPC), 57.5% with bacterial resistance had a hospital stay greater than seven days.C o nclusion: The main microorganism was Escherichia coli, and resistance was primarily found in ex-tended-spectrum beta-lactamase-positive bacteria, allowing us to know the local epidemiology of the microbiological profile and its relationship with cancer patients with febrile neutropenia

Neutropenia al diagnóstico de lupus eritematoso sistémico: prevalencia y correlaciones clínicas y serológicas. Nuestra cohorte / Neutropenia at diagnosis of systemic lupus erythematosus: prevalence and clinical and serological correlations. Our cohort

Introducción: las manifestaciones hematológicas en el lupus eritematoso sistémico (LES) son frecuentes. La leucopenia se presenta del 50 al 60% de los casos, pero solo el 17% tiene un recuento leucocitario <1.000/mm3. La neutropenia en pacientes con leucopenia ocurre entre un 20-40% (según el valor de corte del laboratorio). Los mecanismos posibles de neutropenia descriptos son: aumento en la destrucción de granulocitos periféricos por anticuerpos antineutrófilos, opsonización y destrucción por monocitos; cambios en el pool esplénico y marginal; y disminución en la producción medular. La formación de trampas extracelulares de neutrófilos (neutrophil extracellular traps, NETs) contribuye en la producción de interferón tipo 1 (IFN-1) a partir de plasmocitos y células dendríticas causando daño endotelial y cambios protrombóticos. La NETosis y el clearence anormal de material apoptótico promueven mayor liberación de antígenos y la consiguiente formación de autoanticuerpos. Las consecuencias infecciosas de la neutropenia al diagnóstico de LES se desconocen. Los objetivos del presente estudio fueron conocer la prevalencia de la neutropenia al diagnóstico de LES, determinar su correlación con otras variables de la patología, y estudiar su relación con una mayor probabilidad de actividad, daño, infecciones y mortalidad. Materiales y métodos: estudio descriptivo, retrospectivo. Se incluyeron pacientes con diagnóstico de LES (Systemic Lupus International Collaborating Clinics, SLICC 2012) de la cohorte del Sanatorio, desde enero de 2010 a diciembre de 2020. Se consignaron variables demográficas y asociadas a la enfermedad (criterios clínicos y de laboratorio). Escala de actividad: Systemic Lupus Erythematosus Disease Activity Index 2k (SLEDAI-2k). Se dividieron en dos grupos según la presencia de neutropenia (<1.500/mm3). Se definió un subgrupo de neutropenia severa: <500/mm3. En pacientes con neutropenia se evaluó la presencia de infección viral, bacteriana y tratamiento con factor de crecimiento de colonias de granulocitos y monocitos (GM-GSF). Análisis estadístico: los datos descriptivos se presentaron como medias y sus desvíos estándar (±DS) (variables continuas) y porcentajes (variables categóricas). Se compararon variables independientes de acuerdo con su distribución con test Mann Whitney. Se utilizó prueba t de Student para comparación de medias, y chi cuadrado (X2) para variables cualitativas. Se consideró como estadísticamente una p≤0,05. Resultados: se incluyeron 70 pacientes. Mujeres 59 (84%), edad media 38,6 años (18-72). Leucopenia 24 (34%), linfopenia 30 (42,8%), neutropenia 12 (17%), neutropenia severa 2 (2,8%) y plaquetopenia 7 (10%). Grupo con neutropenia (n=12): Sicca 12 (100%). Media índice neutrófilo/linfocito (INL) 1,33 (DS 0,69), infecciones: virus de Epstein-Barr (VEB) IgM (+) uno, parvovirus y CMV solicitados y negativos dos. PAMO realizada una: normal. Pacientes en tratamiento con GM-GSF: dos, sin eventos adversos. Dos infecciones urinarias. Conclusiones: en nuestro estudio se observó correlación entre neutropenia con síntomas Sicca, leucopenia y linfopenia, y un INL menor. Se desconoce si se relacionó a peor evolución. La presencia de infección fue baja (16%). Dos pacientes requirieron GM-GSF (con neutropenia severa), sin haber presentado eventos adversos.

Introduction: hematological manifestations are frequent in systemic erythematosus lupus (SLE). Leukopenia is seen in between 50 to 60% of cases, but only 17% has a leukocyte count <1,000/mm3. Neutropenia in patients with leukopenia occurs between 20-40% of cases, depending on the cut-off value used. Possible described mechanisms for neutropenia are: an increase in destruction of granulocytes by anti-neutrophil antibodies, opsonization and destruction by monocytes; change in the splenic and marginal neutrophil pool; a diminished production in the bone marrow. The formation of NETs contributes to the production of INF-1 from plasmocytes and dendritic cells, causing endothelial damage and pro-thrombotic changes. NETosis and apoptotic abnormal clearence promote the formation of antigens and subsequent autoantibodies. Infectious consequences of neutropenia in SLE are still unknown. The objectives of this article were to know the prevalence of neutropenia at diagnosis of SLE in our hospital, and secondly to determine its correlation with other variables of the disease and to investigate whether it's related with a greater probability of infections. Materials and methods: descriptive, retrospective study. Patients with diagnosis of SLE (SLICC 2012) from our cohort were included. Demographic and related to disease variables were stated. Activity scale: SLEDAI-2k. Patients were divided into two groups according to the presence or absence of neutropenia (<1.500/mm3 ) and multivariate analysis was performed to clinical and analytical variables. A subgroup with severe neutropenia (<500/mm3) was evaluated. Multivariate analysis was performed to detect correlations between a diminished neutrophil count and clinical manifestations, disease severity, autoantibodies profile, infections, and associated diseases. In neutropenic patients, the presence of viral or bacterial infection and the use of GM-GSF were evaluated. Statistical analysis was performed as mean +/-SD for continuous variables and percentage for categorical variables. T-Test or Mann-Whitney were used to compare independent variables according to distribution. Student's T and Chi-Square for qualitative variables. Statistical significance: p<0.05. Results: 70 patients were included. Female 59 (84%), mean age 38.6 years (18- 72). Leukopenia 24 (34%), lymphopenia 30 (42.8%), neutropenia 12 (17%), severe 2 (2.8%), thrombocytopenia 7 (10%). Neutropenic group: Sicca 12 (100%), neutrophil/lymphocyte index (NLI) 1.33 (DS 0.69), infections: EBV IgM+1/12, parvovirus and CMV negative 2/12. BMA 1/12, without pathologic findings. GM-GSF 2/12. Infections: 2/12 (urinary). Conclusions: we observed a correlation between Sicca symptoms, leuko and lymphopenia, and a lower NLI. The clinical significance of these findings was uncertain. The presence of infection was low (16%). Two required GM-GSF, having not presented adverse events.

Riesgo de infección en pacientes oncológicos colonizados por bacterias productoras de p-lactamasas de espectro extendido y enterobacterias productoras de carbapenemasas / Risk of infection in cancer patients colonized by extended expectrum p-lactamases and carbapenem producing Enterobacteriaceae

INTRODUCCIÓN: La prevalencia de microorganismos multirresistentes es un problema de salud pública que continúa creciendo a lo largo del mundo. Existe una población principalmente susceptible de ser colonizada y posteriormente infectarse, son los pacientes oncológicos. OBJETIVO: Identificar las características clínicas y patológicas de los pacientes oncológicos y su relación con la infección con microorganismos productores de BLEE y EPC. PACIENTES Y MÉTODOS: Se condujo un estudio retrospectivo y de carácter analítico entre el primero de enero de 2019 y el 30 de junio de 2020 en tres unidades hemato-oncológicas. RESULTADOS: Incluyó a 3.315 pacientes, de los cuales 217 (6,5%) se encontraban colonizados por microorganismos productores de BLEE y EPC; de éstos, 106/217 (48,8%) presentaron al menos un episodio de infección. El microorganismo más frecuentemente aislado fue Klebsiella pneumoniae, en 29/106 (27,4%). De los infectados, 18/106 (17%) presentaron infección por el mismo microorganismo colonizador. La mucositis (p = 0,002), edad mayor a 65 años (p = 0,041), hipoalbuminemia (p < 0,01), neutropenia (p < 0,01) y la presencia dispositivos invasivos (p < 0,01) demostraron una relación con el desarrollo de infección. CONCLUSIÓN: La presencia de hipoalbuminemia (OR 3,3, IC 1,5-7,1, p < 0,01), dispositivos invasivos (OR 5,8, IC 3.0-11,4, p < 0,01) y neutropenia (OR 4,1, IC 1,5-11,4, p < 0,01) predicen el desarrollo de infecciones.

BACKGROUND: The prevalence of multi-resistant microorganisms is a public health problem that continues to grow globally. There is a population that is mainly susceptible to being colonized and subsequently infected, and these are cancer patients. AIM: To identify the clinical and pathological characteristics of cancer patients and their relationship with infection with ESBL and CPE producing microorganisms. METHODS: A retrospective and analytical study was conducted between January 1, 2019 and June 30, 2020 in three hematooncological units. RESULTS: We included 3315 patients of which 217 (6.5%) were colonized by microorganisms producing ESBL and CPE. Of these, 106/217 (48.8%) had at least one episode of infection. The most frequently isolated microorganism was Klebsiella pneumoniae 29/106 (27.4%). Of those infected, 18/106 (17%) presented infection by the same colonizing microorganism. Mucositis (p = 0.002), age over 65 years (p = 0.041), hypoalbuminemia (p < 0.01), neutropenia (p < 0.01) and the presence of invasive devices (p < 0.01) demonstrated a relationship with development of infection. The presence of hypoalbuminemia (OR 3.3, CI 1.5-7.1, P < 0.01), invasive devices (OR 5.8, CI 3.0-11.4, p < 0.01) and neutropenia (OR 4.1, CI 1.5-11.4, p < 0.01) predict the development of infections.

Enterocolitis neutropénica en el paciente oncológico pediátrico / Neutropenic enterocolitis in the pediatric cancer patient

Resumen La enterocolitis neutropénica (ECN) es una enfermedad heterogénea de foco digestivo, pero afectación sistémica, que corresponde a una condición clínica grave que amenaza la vida de pacientes inmunocomprometidos, particularmente oncológicos pediátricos. De patogenia aún poco definida y aunque de causa multifactorial, la ECN se asocia a los efectos citotóxicos de la quimioterapia empleada y se caracteriza por la triada clásica que incluye fiebre, neutropenia y dolor abdominal, donde la principal injuria se localiza en la mucosa intestinal, provocando su alteración como barrera y facilitando la invasión bacteriana intramural. La ECN constituye un reto diagnóstico para el equipo tratante, que requiere ser oportuno y contar con apoyo de un óptimo laboratorio general e imagenológico, para iniciar un completo manejo multidisciplinario en unidades y centros de alta complejidad. Se presenta una revisión actualizada del tema incorporando aspectos epidemiológicos, factores de riesgo, elementos de apoyo diagnóstico, consideraciones terapéuticas y medidas de prevención a fin de aportar en el conocimiento de esta patología, y reducir morbimortalidad en estos pacientes.

Abstract Neutropenic enterocolitis (NEC) is a heterogeneous disease of the gastrointestinal tract with systemic response, that corresponds to a severe and life-threatening clinical condition in immunocompromised patients, especially in childhood cancer. The pathologic features are poorly understood, although its multifactorial cause of NEC is well established and it is associated with the cytotoxic effects of the chemotherapy agents used and recognized by the classic triad of fever, neutropenia, and abdominal pain, secondary to gastrointestinal injuries that alters mucosal permeability and helps intramural bacterial invasion. NEC is truly a clinical challenge that requires an early diagnosis and a multidisciplinary approach including basic laboratory and imagological tests in high complexity centers. We present a current review, adding epidemiological aspects, risks factors, diagnostic support elements, therapeutic considerations, and preventive measures in order to provide knowledge of this disease and help to reduce morbidity and mortality associated with it.

Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study / 中华血液学杂志

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

Analysis of the Efficacy of Pemetrexed Maintenance Therapy in Patients with Malignant Pleural Mesothelioma / 中国肺癌杂志

BACKGROUND@#Malignant pleural mesothelioma (MPM) is a highly aggressive disease arising from pleural mesothelial cells. Advanced pleural mesothelioma has a poor prognosis, with a median survival of no more than 15 months. First line standard chemotherapy regimen recommended is Pemetrexed based chemotherapy regimen, with or without bevacizumab. There is no consensus on whether patients who have received first-line standard chemotherapy can benefit from pemetrexed maintenance chemotherapy. The study aimed to investigate the efficacy and safety of pemetrexed maintenance therapy (PMT) after treatment with a pemetrexed and platinum regimen for patients with MPM.@*METHODS@#A total of 40 MPM patients were collected from Cancer Hospital Chinese Academy of Medical Sciences from January 2013 to January 2018, eligible patients were unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum, including pemetrexed maintenance therapy group (22 cases) and observation group (18 cases). The last follow-up was conducted in January 2020. The primary endpoint were progression free survival (PFS), and the secondary end points were overall survival (OS), the efficacy, adverse reactions of PMT.@*RESULTS@#The median PFS in the PMT arm was longer than that in the observation arm (8.5 mon vs 3 mon, P=0.008), but there was no significant difference in median OS (26.4 mon vs 15.7 mon, P=0.177). Objective response rate (ORR) of two group were 22.7% and 0%, respectively. The grade 3-4 toxicity in PMT group included grade 4 neutropenia in 1 patient (4.5%), grade 3 neutropenia in 1 patient (4.5%), grade 4 anemia in 1 patient (4.5%) and grade 3 nausea and anorexia in 1 patient (4.5%).@*CONCLUSIONS@#Pemetrexed maintenance therapy following initial pemetrexed and platinum chemotherapy improve PFS in patients with MPM, and is well tolerated.

Effect of Age on the Time of Neutropenia after Initial Induction Therapy for Patients with Newly Diagnosed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of age on the time of neutropenia after initial induction therapy for newly diagnosed acute myeloid leukemia (AML) patients.@*METHODS@#Data of 18-65 years old AML patients treated in our hospital from Junuary 2015 to July 2020 were retrospectively analyzed. The clinical characteristics, time of neutropenia after initial induction treatment, early responses, and related influencing factors for the time of neutropenia were analyzed and compared between 18-40 years old group and 41-65 years old group.@*RESULTS@#There were 112 patients enrolled in this study, including 66 (58.9%) males, and their median age was 46 years old. Compared with 18-40 years old group, the incidence of FLT3-ITD gene mutation increased (P=0.039) but core binding factor (CBF) decreased (P=0.003) significantly in 41-65 years old group. The incidence of neutropenia was 97.3%, and the average time was (18.70±1.192) days. The time of neutropenia was (21.43±1.736) days in 41-65 years old group, which was longer than (14.91±1.356) days in 18-40 years old group (P=0.006). The time of neutropenia in CBF positive group was shorter than that in negative group (P=0.012), as well as in patients with remission (CR+CRi) (≤ 2 courses) than those with non-remission (NR) (P=0.024), while in high-risk group was longer than that in low-risk group (P=0.040). Multivariate analysis showed that age, FLT3-ITD gene mutation positive, and non-remission (NR) after two courses of treatment were independent risk factors for the time of neutropenia.@*CONCLUSION@#In non-elderly patients with newly diagnosed AML, age is an influencing factor for the time of neutropenia. Key words　　;

Síndrome de Evans y desregulación inmune: complejidades moleculares y etiopatogénicas / Evans syndrome and immune dysregulation: molecular and etiopathogenic complexities

Introducción: El síndrome de Evans se define como la presencia de citopenias inmunes que afectan dos o más líneas celulares simultánea o secuencialmente. Generalmente se refiere a la combinación de anemia hemolítica autoinmune con trombocitopenia inmune primaria, pero puede incluir también neutropenia autoinmune. Su etiología se atribuye a la producción de autoanticuerpos patológicos contra las células sanguíneas pero su causa real se desconoce. Objetivo: Explicar la relación del síndrome de Evans con la desregulación del sistema inmune. Método: Se realizó una revisión de la literatura en inglés y español a través del sitio web PubMed y el motor de búsqueda Google académico, de artículos publicados sobre el tema. El 69,73 por ciento correspondieron a los últimos 5 años. Conclusiones: La inmunopatología del síndrome de Evans se puede atribuir a una alteración en el desarrollo o la función de los linfocitos, de manera que el equilibrio inmunológico se inclina hacia la autorreactividad(AU)

Introduction: Evans syndrome is defined as the presence of autoimmune cytopenias affecting two or more blood cell lines, either simultaneously or sequentially. Most often, this refers to the combination of autoimmune hemolytic anemia and immune thrombocytopenia but can include autoimmune neutropenia as well. The etiology of Evans syndrome has been attributed to pathologic autoantibody production against the blood cells, but the true underlying cause remaining unknown. Objective: to explain the relationship of Evans syndrome with dysregulation of the immune system. Method: a review of the literature in English and Spanish was carried out through the PubMed website and the academic Google search engine for articles published on the subject. 69,73 percent corresponded to the last 5 years. Conclusions: the immunopathology of Evans syndrome can be attributed to an alteration in the development or function of lymphocytes, such that the immune balance is inclined towards self-reactivity(AU)

Duffy phenotyping and FY*B-67T/C genotyping as screening test for benign constitutional neutropenia

ABSTRACT Objective: Low levels of neutrophils can be an intrinsic condition, with no clinical consequences or immunity impairment. This condition is the benign constitutional neutropenia (BCN), defined as an absolute neutrophils count (ANC) ≤2000 cells/mm. Diagnosis of BCN is of exclusion where patients are submitted to blood tests and possibly to invasive diagnostic search until secondary causes of neutropenia are ruled out. The natural history of the disease suggests benign evolution and Brazilian study showed an overall frequency of 2.59%. The main mechanisms include reduced neutrophil production, increased marginalization, extravasation to the tissues and immune destruction. Genetic studies showed strong association between the single nucleotide variant rs2814778 located on chromosome 1q23.2 in the promoter region of the atypical chemokine receptor 1 (Duffy blood group system) gene (ACKR1, also termed DARC) and BCN. The aim of this study is to evaluate FY phenotypes and genotypes including the analysis of the rs2814778 SNP in Brazilian patients with BCN in order to determine an effective diagnostic tool, allowing reassurance of the patient and cost reduction in their care. Methods: Case control study, with 94 individuals (18 patients and 76 controls). Phenotyping was performed by gel test and genotyping was performed by PCR-RFLP. Results: White blood cell (WBC) and absolute neutrophils (AN) counts showed lower levels in patients compared to controls. In the patient group 83.3% were genotyped as FY*B/FY*B. The SNP rs2814778 (-67T > C) was identified in 77.8% of the patients genotyped as FY*B-67C/FY*B-67C. In the control group, 72.7% were homozygous for the wild type and 23.3% were heterozygous. Conclusion: This study reinforces that FY phenotyping and genotyping can be used to detect most people with BCN, avoiding excessive diagnostic investigation. Besides, this procedure may reduce health costs and be reproductible in clinical practice.

Características clínicas y microbiológicas de infecciones del torrente sanguíneo en pacientes adultos neutropénicos / Clinical and microbiological characteristics of bloodstream infections in adult neutropenic patients

RESUMEN Las infecciones del torrente sanguíneo (IS) en pacientes oncológicos neutropénicos constituyen una patología de relevancia y se asocian a un aumento de la morbimortalidad. El objetivo de este estudio fue determinar las características epidemiológicas y microbiológicas de los episodios de IS en pacientes adultos neutropénicos con neoplasias hematológicas (NH) y neoplasias sólidas (NS). Se realizó un estudio retrospectivo en dos hospitales de tercer nivel entre 2009 y 2016. Se incluyeron todos los pacientes neutropénicos mayores de 18años con NH y NS que presentaron episodios de IS. Se excluyeron aquellos con neoplasias dermatológicas no melanoma. Se identificaron 143 episodios de IS, de los cuales el 80,4% fueron en personas con NH. El 97,9% de los pacientes tuvieron neutropenia de alto riesgo, sin diferencia entre los grupos NH y NS. Los orígenes más frecuentes de IS fueron bacteriemia primaria (46,9%) e infección asociada a catéter (21%), sin diferencias significativas entre grupos. El 74,1% de los aislamientos fueron bacilos gram negativos yEscherichiacolifue el microorganismo más frecuente (32,1%). El coco gram positivo más frecuentemente aislado fueStaphylococcusaureus(28,1%), seguido del grupo de los estafilococos coagulasa negativos (ECN), sin diferencias entre ambos tipos de neoplasias. El 67,5% de los ECN fueron multirresistentes; solo el 11,1% de los aislamientos deS. aureusfue resistente a la meticilina. El 17,6% de los aislamientos deE. coliy el 27,6% de los deKlebsiellapneumoniaefueron multirresistentes. No hubo diferencias en la frecuencia de aislamientos multirresistentes al comparar entre ambos tipos de neoplasia. Como conclusión, las IS en pacientes neutropénicos fueron más frecuentes en pacientes con NH y las causaron, principalmente, bacilos gram negativos. Se observó una elevada mortalidad en los pacientes neutropénicos con IS.

ABSTRACT Bloodstream infections (BI) are relevant in neutropenic patients because they are associated with an increased number of complications and death. The objective was determinate the epidemiologic and microbiologic features of the BI in neutropenic patients with solid neoplasm (SN) and hematologic neoplasm (HN). Retrospective study in two third level hospitals between 2009 and 2016. They were included all the patients older than 18 years-old with active oncologic disease and neutropenia, who had BI. Patients with dermatologic cancer other than melanoma where excluded. A total of 143 BI in neutropenic were observed, of which 80.4% occurred in HN. Around 97.9% of the patients had a high-risk neutropenia without differences between both groups. The most frequent site of BI was primary bacteremia (46.9%) and catheter-associated infection (21%), without significant differences between the two groups. The gram negatives bacilli (GNB) predominated over the gram positive cocci (GPC) and they represented 74.1% of the isolated bacteria, beingEscherichia colithe most frequent (32.8%). Among the gram positive cocci,Staphylococcus aureus(28.1%) was the most frequent isolated, followed by coagulase-negativeStaphylococci(CNS). There were no differences in microbiological isolates between both groups. With regard to the antimicrobial susceptibility 67.5% of the CNS, 17.6% of theE. coliand 27.6% of theKlebsiella pneumoniaewere multiresistant with no differences between both groups. Only 11.1% of S. aureus isolates were methicillin resistant. In conclusion BI of the neutropenic patients where most frequents within patients with HN, GNB were the main microbiological isolates. High mortality was observed in neutropenic patients with BI.

Eficacia y seguridad del tratamiento empírico con piperacilina/tazobactan como monoterapia en episodios de neutropenia y fiebre en niños con cáncer: revisión sistemática y meta-análisis / Efficacy and safety of empirical treatment with piperacillin/tazobactan as monotherapy in episodes of neutropenia and fever in children with cancer: systematic review and meta-analysis

INTRODUCCIÓN: La neutropenia febril en niños con patología oncohematològica requiere un tratamiento empírico precoz y adecuado. Esta revisión sistemática se realizó para evaluar si piperacilina/tazobactam (PTZ) monoterapia es más efectiva y segura que los comparadores, en niños con episodios de neutropenia febril de causa oncológica. MATERIAL Y MÉTODOS: Se realizó una búsqueda bibliográfica en Embase, MEDLINE utilizando los términos de búsqueda (('febrile neutropenia' OR hemato oncology OR haemato oncology OR 'immunocompromised host' OR 'immunocompromised patient' OR 'chemotherapy-induced febrile neutropenia') AND (piperacillin OR tazobactam OR 'piperacillin plus tazobactam' OR 'piperacillin/tazobactam' OR 'piperacillin-tazobactam' OR tazocin OR 'piperacillin-tazobactam drug combination')). El criterio de valoración de eficacia fue la incidencia de fracaso terapéutico. El punto final de seguridad fue la ausencia de cualquier efecto adverso (EA). RESULTADOS: Se identificaron 1.388 estudios, de los cuales se incluyeron 11 que cumplían los criterios de elegibilidad. Los estudios presentaron notable homogeneidad ( I 2 0%) y no se detectó sesgo de publicación (p 0,36). El riesgo de fracaso terapéutico de PTZ no fue mayor que en los comparadores (RR global: 0,94; IC95% 0,83 a 1,07) como tampoco lo fue, la incidencia de EA. CONCLUSIONES: El riesgo de fracaso terapéutico no fue superior para la PTZ como monoterapia frente a los comparadores

BACKGROUND: Febrile neutropenia in children with onco-hematological diseases is an important cause of morbidity and mortality and requires early and adequate empirical treatment. This systematic review was conducted to evaluate if piperacillin/ tazobactan (PTZ) monotherapy leads to a lower incidence of therapeutic failures than comparators. METHODS: A literature search was carried out in Embase, and MEDLINE databases using the search terms ('febrile neutropenia' OR hemato oncology OR haemato oncology OR 'immunocompromised host' OR 'immunocompromised patient' OR 'chemotherapy-induced febrile neutropenia') AND (piperacillin OR tazobactam OR 'piperacillin plus tazobactam' OR 'piperacillin/tazobactam' OR 'piperacillin-tazobactam' OR tazocin OR 'piperacillin-tazobactam drug combination')), Efficacy endpoint was treatment failure rate. The safety end-point was absence of any adverse effects (AE). RESULTS: Eleven studies were included. No heterogeneity was detected ( I 2 0%). The risk of failure was not superior for piperacillin/tazobactan to comparators (Global RR: 0.94; IC95% 0.83 a 1.07). Rates of adverse events were similar among studies. No publication bias was detected (p 0.36). CONCLUSIONS: This systematic review and meta-analysis showed that treating episodes of febrile neutropenia in oncology pediatric patients, the risk of failure for PTZ was not superior to comparators. Adverse events were similar to the comparators.

Association between UGT1A1*28 gene polymorphism and severe neutropenia due to colorectal cancer treatment with irinotecan: evidence based on meta-analysis / Associação entre o polimorfismo do gene UGT1A1*28 e a neutropenia severa decorrente do tratamento do câncer colorretal com irinotecano: evidências baseadas em meta-análise

Abstract Objective The present study aimed to evaluate the relationship between UGT1A1*28 gene polymorphism and the prevalence of neutropenia in patients with colorectal cancer treated with irinotecan. Method Thirteen studies were included. These papers were selected from the Virtual Health Library, Scientific Electronic Library Online, International Health Sciences Literature and PubMed, and their data were collected and evaluated using the BioEstat 5.3 software (BioEstat, Belém, PA, Brazil). Results Three genotypes were analyzed, namely 6/6 (wild type), 6/7, and 7/7. In total, 2,146 patients were included in the present study; of these, 55.6% (n=1,193) had 6/6 genotype, 37.3% (n=801) were heterozygous (6/7), and 7.1% (n=152) had the 7/7 genotype. A total of 1,672 (77.9%) patients displayed mild neutropenia, whereas 474 (22.1%) had severe neutropenia. When contrasting the 6/7 and 7/7 genotypes with the 6/6 genotype using statistical tests for meta-analysis, patients with the 7 allele, either Conclusion The analysis of the UGT1A1*28 gene polymorphism can aid the choice of treatment for patients with colorectal cancer in personalized medicine, increasing the chances of therapeutic success.

Resumo Objetivo Avaliar a relação do polimorfismo do gene UGT1A1*28 com a prevalência de neutropenia em pacientes com câncer colorretal submetidos a tratamento com o irinotecano. Método Foram incluídos 13 estudos sobre o tema proposto, selecionados nas bases de dados da Biblioteca Virtual de Saúde, Scientific Electronic Library Online, International Health Sciences Literature e PubMed.Os dados foramcoletados dos artigos científicos selecionados e avaliados com o auxílio do software BioEstat 5.3 (BioEstat, Belém, PA, Brasil). Resultados Osgenótipos analisados foram6/6 (tipo selvagem), 6/7 e 7/7. Foramincluídos 2.146 pacientes. Destes, 55,6% (n=1.193) apresentaram genótipo 6/6, 37,3% (n=801) eramheterozigotos (6/7) e 7,1%(n=152) tinhamo genótipo 7/7.Umtotal de 1.672 (77,9%) pacientes apresentou neutropenia leve e 474 (22,1%) neutropenia severa. Ao contrastar os genótipos 6/7 e 7/7 como 6/6, percebeu-se, coma execução dos testes estatísticos demetaanálise, que os pacientes como alelo 7, emhomozigose ou heterozigose, tinhammaior risco de desenvolver neutropenia severa que pacientes com o genótipo 6/6 (razão de chances =1,559; intervalo de confiança de 95%=1,163-2,090; p=0,003). Conclusão A análise do polimorfismo do gene UGT1A1*28 pode auxiliar na escolha do tratamento do paciente comcâncer colorretal, no contexto da medicina personalizada, ampliando, assim, as chances de sucesso terapêutico.

Profilaxis antifúngica primaria en pacientes oncohematológicos: ¿a quiénes, cuándo y con qué? / Primary antifungal prophylaxis in oncohematological patients: who, when, and with what?

Resumen Las infecciones fúngicas invasoras (IFI) constituyen una de las principales complicaciones infecciosas en pacientes oncohematológicos y con trasplante de células progenitoras hematopoyéticas (TCPH), ocasionando alta morbimortalidad e incrementando significativamente los costos de atención y la estadía hos pitalaria. La epidemiología de las IFI ha cambiado en las últimas décadas, siendo los hongos filamentosos, particularmente Aspergillus spp., los principales agentes etiológicos. Existen múltiples factores de riesgo para una IFI; pero la neutropenia profunda y prolongada, y la inmunodeficiencia celular severa siguen siendo los más importantes. Por este motivo, la población de mayor riesgo la constituyen los pacientes con leucemias agudas, mielodisplasias y TCPH alogénicos con enfermedad injerto contra huésped (EICH), en tratamiento con corticoides. Numerosos ensayos clínicos aleatorizados y metaanálisis han demostrado que la profilaxis antifúngica primaria (PAF) reduce significativamente la incidencia de IFI, tanto de aquellas causadas por Candida spp. como por Aspergillus spp., la mortalidad relacionada a IFI y la mortalidad global en algunos grupos de pacientes. Asimismo, en enfermos de alto riesgo, en donde se espera una incidencia de IFI elevada, es una estrategia costo-efectiva. Varios antifúngicos han demostrado beneficio clínico y pueden utilizarse como estrategia de PAF en diferentes escenarios, presentando ventajas y desventajas que deben ser tenidas en cuenta al momento de indicar una PAF. Para esto, sociedades científicas nacionales e internacionales, han emitido recomendaciones de indicación de PAF. Se analizan los aspectos relacionados con la eficacia clínica de los diferentes antifúngicos según la población de riesgo, las potenciales desventajas, momento y forma de administración.

Abstract Invasive fungal infections (IFI) are among the main infectious complications in patients with hema tological malignancies and with hematopoietic stem cell transplant (HSCT), causing high morbidity and mortality and significantly increasing the healthcare cost and hospital stay. The epidemiology of IFIs has changed in recent decades, with filamentous fungi, particularly Aspergillus spp., being the main etiological agents. There are multiple risk factors for having an IFI; however, the most important are profound and prolonged neutropenia and severe cellular immunodeficiency. For this reason, the population at greatest risk is made up of patients with acute leukemias, myelodysplasias and allogeneic HSCT with graft-versus-host disease (GVHD) treated with cortico steroids. Numerous randomized clinical trials and meta-analyses have shown that primary antifungal prophylaxis (AFP) significantly reduces the incidence of IFI, particularly those caused by Candida spp. and Aspergillus spp., IFI-related mortality, and overall mortality in some group of patients. Likewise, in high-risk patients, where a high incidence of IFI is expected, it is a cost-effective strategy. Several antifungals have demonstrated clinical benefit. They can be used as a AFP strategy in different settings, presenting advantages and disadvantages that must be taken into account in each case. For this, national and international scientific societies have issued recom mendations for the indication of AFP. Aspects related to the different antifungals' clinical efficacy are analyzed considering the population at risk, the potential disadvantages, timing, and form of administration.

Etiología bacteriana y susceptibilidad antibiótica en adultos con leucemias agudas y neutropenia febril con factores de alto riesgo / Bacterial etiology and antibiotic susceptibility in adults with acute leukemias and febrile neutropenia with high-risk factors

Introducción: La neutropenia febril es una complicación que predispone a infecciones bacterianas de etiología diversa y aumenta la mortalidad en los pacientes con leucemia. El objetivo general del presente trabajo determinó la frecuencia de la etiología bacteriana, en los objetivos específicos se cuantificó en porcentaje los tipos de bacterias encontradas, se identificó la susceptibilidad y la resistencia antimicrobiana, además de sus infecciones, se estableció los factores de alto riesgo de mal pronóstico más frecuentes. Métodos: En el presente descriptivo de tipo transversal se revisaron historias clínicas del servicio de oncología clínica del Instituto Oncológico Nacional "Dr. Juan Tanca Marengo" Solca_Guayquil. El período estudio fue del 1ro de enero del 2013 al 31 de diciembre del 2014. El cálculo muestral fue probabilístico de 60 casos. Se incluyeron pacientes con leucemia en curso de quimioterapia y que evolucionaron con leucopenia febril, adicionalmente se incluyeron los pacientes con focos infecciosos evidentes y cultivos positivos. Las variables fueron demográficas características clínicas de la leucemia, estudio bacteriológico, tratamiento antibiótico y comorbilidades. Se utiliza estadística descriptiva. Resultados: Ingresaron al estudio 58 pacientes, fueron 30/58 mujeres (51%). La mayoría con edades de 17 a 20 años 15/58 casos (25.9%). 35/58 casos (60%) correspondieron a leucemias linfobásticas y 23/58 casos (40%) a miloides. El foco infeccioso más frecuentemente fue gastrointestinal 18 %(n=27), la piel y tejidos blandos con un 17 %(n=26). Se realizaron 98 cultivos, con el 52% de culti-vos positivos, 25 % BLEE, 4% BLAC. La etiología fue E. Coli 26% aislada de sangre. La sensibilidad fue 100 % amikacina, 100 %, imipenem ,100 meropenem, 100 % tigeciclina, 90 % piperazilina tazobactam, 18 %, cefepime, 50% clindamicina y 50% oxacilina. El máximo tiempo de neutropenia fue 30 días, con una mediana de neutrófilos 230 u/ul, con un promedio de 3 días de fiebre. Los factores de riesgo fueron 17% desnutrición ,15% hepatopatías %, 6% hipertensión y diabetes. Conclusiones: La etiología bacteriana más frecuente fue E. Coli. Existe una sensibilidad antibiótica baja para los gram negativos en todas las cefalosporinas de primera hasta cuarta generación en los antibiogramas del estudio. Hay un perfil de baja resistencia a los antibióticos carbapenémicos junto a amikacina con piperacilina tazobactam. La vancomicina y el linezolid no tienen resistencia bacteriana la presentación etológica para gram positivos, el más prevalente fue el estafilococo aureus meticilino resistente tipo BLAC.

Introduction: Febrile neutropenia is a complication that predisposes to bacterial infections of diverse etiology and increases mortality in patients with leukemia. The general objective of this work determined the frequency of bacterial etiology, in the specific objectives the types of bacteria found were quantified in percentage, susceptibility and antimicrobial resistance were identified, in addition to their infections, factors were established high risk of poor prognosis more frequent. Methods: In this descriptive cross-sectional type, clinical records of the clinical oncology service of the National Oncological Institute "Dr. Juan Tanca Marengo "Solca_Guayquil. The study period was from January 1, 2013 to December 31, 2014. The sample calculation was probabilistic of 60 cases. Patients with leukemia undergoing chemotherapy and who evolved with febrile leukopenia were included, additionally patients with obvious infectious foci and positive cultures were included. The variables were demographic, clinical characteristics of the leukemia, bacteriological study, antibiotic treatment, and comorbidities. Descriptive statistics are used. Results: 58 patients entered the study, 30/58 were women (51%). The majority aged 17 to 20 years 15/58 cases (25.9%). 35/58 cases (60%) corresponded to lymphoblastic leukemias and 23/58 cases (40%) to myloids. The most frequent infectious focus was gastrointestinal 18% (n = 27), skin and soft tissues with 17% (n = 26). 98 cultures were performed, with 52% positive cultures, 25% ESBL, 4% BLAC. The etiology was E. Coli 26% isolated from blood. The sensitivity was 100% amika-cin, 100%, imipenem, 100 meropenem, 100% tigecycline, 90% tazobactam piperazilin, 18%, ce-fepime, 50% clindamycin, and 50% oxacillin. The maximum time of neutropenia was 30 days, with a neutrophil average of 230 u / ul, with an average of 3 days of fever. The risk factors were 17% malnutrition, 15% liver disease, 6% hypertension and diabetes. Conclusions: The most frequent bacterial etiology was E. Coli. There is a low antibiotic sensitivity for gram negatives in all first through fourth generation cephalosporins in the study antibiograms. There is a profile of low resistance to carbapenemic antibiotics together with amikacin with piperacillin tazobactam. Vancomycin and linezolid do not have bacterial resistance in the ethological presentation for gram positives, the most prevalent was methicillin-resistant staphylococcus aureus BLAC type.

Manejo em longo prazo de glicogenose tipo 1b: experiência de um centro terciário brasileiro / Long term management of glycogen storage disease type 1b: a brazilian tertiary center experience

ABSTRACT BACKGROUND Glycogen storage disease (GSD) type 1b is a multisystemic disease in which immune and infectious complications are present, in addition to the well-known metabolic manifestations of GSD. Treatment with granulocyte-colony stimulating factor (G-CSF) is often indicated in the management of neutropenia and inflammatory bowel disease. OBJECTIVE To report on the demographics, genotype, clinical presentation, management, and complications of pediatric patients with glycogen storage disease type 1b (GSD 1b), with special attention to immune-related complications. METHODS Retrospective case series of seven patients with GSD 1b diagnosed and followed at a tertiary university hospital in Brazil, from July/2000 until July/2016. RESULTS Mean age at referral was fourteen months. Diagnosis of GSD 1b was based on clinical and laboratory findings and supported by genetic studies in five cases. All patients presented suffered from neutropenia, managed with G-CSF - specifically Filgrastim. Hospitalizations for infections were frequent. Two patients developed inflammatory bowel disease. Six patients remained alive, one died at age 14 years and 9 months. The mean age at the end of the follow-up was 11.5 years. Compliance to treatment was suboptimal: poor compliance to medications, starch and dietetic management of GSD were documented, and outpatient appointments were frequently missed. CONCLUSION Managing GSD 1b is challenging not only for the chronic and multisystemic nature of this disease, but also for the additional demands related dietary restrictions, use of multiple medications and the need for frequent follow-up visits; furthermore in Brazil, the difficulties are increased in a scenario where we frequently care for patients with unfavorable socioeconomic status and with irregular supply of medications in the public health system.

RESUMO CONTEXTO Glicogenose (GSD) tipo 1b é uma doença multissistêmica em que complicações imunológicas e infecciosas estão presentes, além das manifestações metabólicas bem conhecidas da GSD. O tratamento com fator estimulador de colônias de granulócitos (G-CSF) é frequentemente indicado no tratamento da neutropenia e doença inflamatória intestinal. OBJETIVO Relatar sobre a dados demográficos, genótipo, apresentação clínica, manejo e complicações de pacientes pediátricos com GSD tipo 1b (GSD 1b), com atenção especial às complicações relacionadas ao sistema imunológico. MÉTODOS Série de casos retrospectiva de sete pacientes com GSD 1b diagnosticados e acompanhados em um hospital universitário terciário no Brasil, de julho/2000 a julho/2016. RESULTADOS A idade média no encaminhamento foi de 14 meses. O diagnóstico de GSD 1b foi baseado em achados clínicos e laboratoriais e apoiado por estudos genéticos em cinco casos. Todos os pacientes apresentaram neutropenia, tratada com G-CSF - especificamente Filgrastim. As hospitalizações por infecções foram frequentes. Dois pacientes desenvolveram doença inflamatória intestinal. Seis pacientes permanecem vivos, um morreu aos 14 anos e 9 meses de idade. A média de idade ao final do acompanhamento foi de 11,5 anos. A adesão ao tratamento foi sub-ótima: má adesão aos medicamentos, amido e manejo dietético de GSD foram documentados, e consultas ambulatoriais foram frequentemente perdidas. CONCLUSÃO O manejo da GSD 1b é um desafio, não apenas pela natureza crônica e multissistêmica desta doença, mas também pelas demandas adicionais relacionadas a restrições dietéticas, uso de múltiplos medicamentos e a necessidade de consultas de acompanhamento frequentes; no Brasil, isso ainda é dificultado em um cenário em que frequentemente atendemos pacientes com situação socioeconômica desfavorável e com oferta irregular de medicamentos no sistema público de saúde.