Establishment of a Mouse Model of Acquired Aplastic Anemia Mediated by Cyclophosphamide Combined with Cyclosporine / 中国实验血液学杂志

OBJECTIVE@#To establish a stable mouse model of acquired aplastic anemia.@*METHODS@#Female BALB/C mice aged 6 months were intraperitoneally injected with cyclophosphamide and cyclosporine for 14 days. The number of peripheral blood cells, the concentration of hemoglobin, the number of bone marrow nucleated cells, bone marrow smear, bone marrow pathological sections and other indexes were observed.@*RESULTS@#In BALB/C mice injected intraperitoneally with cyclophosphamide and cyclosporine, the number of peripheral blood cells and the concentration of hemoglobin were significantly decreased, especially the white blood cells and platelets. Bone marrow smear showed a significant decrease in the number of nucleated cells and bone marrow hyperplasia. Bone marrow pathology showed decreased hematopoietic cells and increased non-hematopoietic cells such as adipocytes.@*CONCLUSION@#The mouse model with intraperitoneal injection of cyclophosphamide and cyclosporine can meet the diagnostic criteria of acquired aplastic anemia, which can be used as a mouse model for the study of the pathogenesis and treatment of acquired aplastic anemia.

Outcomes of haploidentical bone marrow transplantation in patients with severe aplastic anemia-II that progressed from non-severe acquired aplastic anemia / 医学前沿

Severe aplastic anemia II (SAA-II) progresses from non-severe aplastic anemia (NSAA). The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation (haplo-BMT) in patients lacking a human leukocyte antigen (HLA)-matched donor. This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II. Twenty-two patients were included and followed up, and FLU/BU/CY/ATG was used as conditioning regimen. Among these patients, 21 were successfully engrafted, 19 of whom survived after haplo-BMT. Four patients experienced grade II-IV aGvHD, including two with grade III-IV aGvHD. Six patients experienced chronic GvHD, among whom four were mild and two were moderate. Twelve patients experienced infections during BMT. One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease, and both recovered after rituximab infusion. Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4% ± 0.73% after a median follow-up of 42 months, indicating its effectiveness as a salvage therapy. These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.

Anemia aplásica en población pediátrica de Costa Rica: experiencia de 10 años / Aplastic anemia in Costa Rican pediatric population: a 10 year experience

Resumen Objetivo: La anemia aplásica es una enfermedad rara, potencialmente mortal sin diagnóstico y tratamiento temprano. El objetivo del estudio fue describir la epidemiología de la anemia aplásica en la población de 0 a 13 años a nivel nacional, atendida en el Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera", de la Caja Costarricense de Seguro Social, único centro del país disponible para la atención en hematología pediátrica. Métodos: Se realizó un estudio observacional retrospectivo de los pacientes atendidos en el Servicio de Hematología Pediátrica, con diagnóstico de anemia aplásica adquirida y las diversas formas de aplasias congénitas, en el periodo de enero 2006 a junio de 2016. Se registró el tipo de tratamiento recibido, su respuesta y la mortalidad asociada con la enfermedad, así como algunos datos epidemiológicos. Resultados: Se analizó un total de 27 casos, 23 con anemia aplásica adquirida y 4 con diversos tipos de anemias congénitas. La edad media al momento del diagnóstico fue de 81,7 meses, con una relación hombre: mujer de 1.1:1. De los 23 pacientes con anemia aplásica adquirida, 10 recibieron tratamiento con globulina antitimocito y presentaron respuesta a la globulina equina 2/5 pacientes como primera línea de tratamiento y 1 como segunda línea; con la globulina de conejo se obtuvo respuesta en 1/5 pacientes como primera línea y en 2 como segunda línea. Tres pacientes recibieron tratamiento con trasplante de médula ósea y presentaron una respuesta completa, sin evidenciar datos de enfermedad de injerto versus huésped u otras complicaciones al finalizar el estudio. No se logró demostrar diferencia significativa respecto al sexo, edad de diagnóstico, valores del hemograma, frecuencia de requerimiento de plaquetas o glóbulos rojos, grado de severidad ni mortalidad. Conclusión: Se confirmó la baja prevalencia de la anemia aplásica; la muestra obtenida durante el periodo analizado es pequeña y limita la observación de características relevantes ante referentes internacionales.

Abstract Objective: Aplastic anemia is a rare and life-threatening disease without diagnosis and early treatment. The objective of this study was to describe the epidemiological characters of patients with aplastic anemia and 0-13 years old in Costa Rica, to treat in the Hospital Nacional de Niños Dr.Carlos Sáenz Herrera, CajaCostarricense de Seguro Social; only there offers Pediatric Hematology service. Methods: We performed an observational retrospective study, there including the patients diagnosed with both acquired aplastic anemia and inherited bone marrow failure syndromes from January 2006 to June 2016, regardless of sex or ethnicity. We evaluated the treatment received, the response to each treatment, and mortality associated with the disease. Results: An overall of 27 patients were included, 23 diagnosed with acquired aplastic anemia and, 4 with bone marrow failure syndrome. The mean age of diagnosis was 81.7 months, with a male to female ratio of 1.1:1. Of the 23 patients diagnosed with acquired aplastic anemia, 10 received immunosuppressive therapy with antithymocite globulin, with a response to horse globulin as a first line treatment in 2/5 patients, and 1 as a second line treatment. Patients with rabbit globulin showed to response in 1/5 cases when used as a first line treatment, and a response as a second line treatment after a no response treatment with horse globulin in 2/3 patients. Three patients treated with a matched related donor bone marrow transplant and showed complete response, without complications including graft versus host disease by the end of the study period. There was no statistical difference regarding sex, age of diagnosis, blood cell counts, frequency of blood product transfusions, degree of severity associated or, mortality. Conclusions: Our results confirm the low incidence of aplastic anemia, it's a little study population and has limited results of relevant characteristics and can´t compare with international studies.

The latest treatment advances of severe acquired aplastic anemia / 中华实用儿科临床杂志

Acquired aplastic anemia is a refractory blood disease for children,and severe acquired aplastic anemia can be a great threaten for life.China is a high incidengce area,children at a period during which this disease can mostly occur.In China,except some congenital aplastic anemia,most children who have this diease is acquired aplastic anemia.In 2009,the Britain society of hematology recommended Guidelines for the diagnosis and management of aplastic anaemia,which represented the latest diagnosis and treatment principle and mainstream view of the clinical methodology about aplastic anemia.They make it clear that the main treatment for the disease are allogeneic hematopoietic stem cell transplantation(allo-HSCT) and immunosuppressive therapy(IST).This article collects the documents in recent 5 years,and provides a overview about the latest advance of the allo-HSCT and IST in the word.

POT1 Gene Expression in Patients of Acquired Aplastic Anemia with Different TCM Syndromes and Correlation Study / 中国中医药信息杂志

Objective To observe the mRNA expression levels of POT1 in peripheral blood mononuclear cells of acquired aplastic anemia patients with different syndrome, and explore its relationship with acquired aplastic anemia and its TCM syndrome. Methods Peripheral blood mononuclear cells of 52 cases with acquired aplastic anemia and 20 cases as control group were collected to detect mRNA expression of POT1 by using real-time quantitative polymerase chain reaction (RT-qPCR), and its relation with TCM syndrome was analyzed. Results The expression levels of POT1 mRNA in patients with acquired aplastic anemia were lower significantly than control group (P<0.05). The expression levels of POT1 mRNA in patients with deficiency of kidney-yin were lower than patients with deficiency of kidney-yang, and it was lowest in patients with kidney deficiency of both yin and yang. There was significant correlation between the expression levels of POT1 mRNA and age (r=0.374, P=0.038). Conclusion The changes in expression levels of POT1 play a role in the pathogenesis of acquired aplastic anemia. There is correlation between mRNA expression level of POT1 in peripheral blood mononuclear cells and TCM syndrome.

Genetic polymorphisms of glutathione s-transferase mu1 and theta1 in patients with acquired aplastic anemia: a Brazilian experience

The causes of acquired aplastic anemia (AAA) include immunologic mechanisms and oxidative DNA damage. Glutathione S-transferase (GST) plays an important role in detoxification. In humans, GST genes encode four main clones: alpha (A), mu (M), pi (P) and theta (T). Among GST genes, GST M1 and T1 have null genotypes that result in a lack of activity. The aim of this study was to investigate polymorphisms of the GSTM1 and GSTT1 enzyme in Brazilian patients with AAA. The null allele of GSTM1 was observed in 3 (16.6 percent) patients and the GSTT1 null genotype was observed in only one (5.5 percent) patient. This study did not find any association between genetic polymorphisms of the GSTM1/GSTT1 detoxifying enzymes and the pathogenesis of AAA.

As causas de anemia aplástica adquirida (AAA) incluem mecanismos imunológicos e oxidativos de lesão ao DNA. Glutathiona S-transferase (GST) é fundamental na detoxicação celular. Em humanos, os genes da GST são codificados por quatro clones: alpha (A), mu (M), pi (P) e theta (T). Entre os genes da GST, GST M1 e T1 possuem um genótipo nulo que resulta em ausência de atividade enzimática. O objetivo deste estudo foi investigar os polimorfismos das enzimas GSTM1 e GSTT1 em pacientes brasileiros portadores de AAA. O alelo nulo da GSTM1 foi observado em três (16.6 por cento) pacientes e o GSTT1 nulo foi observado somente em um (5.5 por cento) paciente. Este estudo não encontrou associação entre os polimorfismos genéticos das enzimas de detoxicação GSTM1/ GSTT1 e a patogênese da AAA.