RESUMEN
BACKGROUND: The complexity of Rh genetic variation among sickle cell disease (SCD) patients is high. Conventional molecular assays cannot identify all genetic variants already described for the RH locus as well as foresee novel alleles. Sequencing RHD and RHCE is indicated to broaden the search for Rh genetic variants. AIMS: To standardize the Next Generation Sequencing (NGS) strategy to assertively identify Rh genetic variants among SCD patients with serologic suspicion of Rh variants and evaluate if it can improve the transfusion support. METHODS: Thirty-five SCD patients with unexplained Rh antibodies were enrolled. A NGS-based strategy was developed to genotype RHD and RHCE using gene-specific primers. Genotype and serological data were compared. RESULTS: Data obtained from the NGS-based assay were gene-specific. Ten and 25 variant RHD and RHCE alleles were identified, respectively. Among all cases of unexplained Rh antibodies, 62% had been inaccurately classified by serological analysis and, of these, 73.1% were considered as relevant, as were associated with increased risk of hemolytic reactions and shortage of units suitable for transfusion. CONCLUSION: The NGS assay designed to genotype RH coding regions was effective and accurate in identifying variants. The proposed strategy clarified the Rh phenotype of most patients, improving transfusion support.
Asunto(s)
Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/genética , Variación Genética , Genotipo , Sistema del Grupo Sanguíneo Rh-Hr/genética , Alelos , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/terapia , Transfusión Sanguínea/métodos , Manejo de la Enfermedad , Pruebas Genéticas/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Fenotipo , Reproducibilidad de los ResultadosRESUMEN
Data on stem cell transplantation (SCT) for Diamond-Blackfan Anemia (DBA) is limited. We studied patients transplanted for DBA and registered in the EBMT database. Between 1985 and 2016, 106 DBA patients (median age, 6.8 years) underwent hematopoietic stem cell transplantation from matched-sibling donors (57%), unrelated donors (36%), or other related donors (7%), using marrow (68%), peripheral blood stem cells (20%), both marrow and peripheral blood stem cells (1%), or cord blood (11%). The cumulative incidence of engraftment was 86% (80% to 93%), and neutrophil recovery and platelet recovery were achieved on day +18 (range, 16 to 20) and +36 (range, 32 to 43), respectively. Three-year overall survival and event-free survival were 84% (77% to 91%) and 81% (74% to 89%), respectively. Older patients were significantly more likely to die (hazard ratio, 1.4; 95% confidence interval, 1.06 to 1.23; P < .001). Outcomes were similar between sibling compared to unrelated-donor transplants. The incidence of acute grades II to IV of graft-versus-host disease (GVHD) was 30% (21% to 39%), and the incidence of extensive chronic GVHD was 15% (7% to 22%). This study shows that SCT may represent an alternative therapeutic option for transfusion-dependent younger patients.
Asunto(s)
Anemia Aplásica , Anemia de Diamond-Blackfan , Trasplante de Células Madre Hematopoyéticas , Anemia Aplásica/terapia , Anemia de Diamond-Blackfan/terapia , Médula Ósea , Niño , Humanos , Estudios RetrospectivosRESUMEN
A match of HLA loci between patients and donors is critical for successful hematopoietic stem cell transplantation. However, the extreme polymorphism of HLA loci - an outcome of millions of years of natural selection - reduces the chances that two individuals will carry identical combinations of multilocus HLA genotypes. Further, HLA variability is not homogeneously distributed throughout the world: African populations on average have greater variability than non-Africans, reducing the chances that two unrelated African individuals are HLA identical. Here, we explore how self-identification (often equated with "ethnicity" or "race") and genetic ancestry are related to the chances of finding HLA compatible donors in a large sample from Brazil, a highly admixed country. We query REDOME, Brazil's Bone Marrow Registry, and investigate how different criteria for identifying ancestry influence the chances of finding a match. We find that individuals who self-identify as "Black" and "Mixed" on average have lower chances of finding matches than those who self-identify as "White" (up to 57% reduction). We next show that an individual's African genetic ancestry, estimated using molecular markers and quantified as the proportion of an individual's genome that traces its ancestry to Africa, is strongly associated with reduced chances of finding a match (up to 60% reduction). Finally, we document that the strongest reduction in chances of finding a match is associated with having an MHC region of exclusively African ancestry (up to 75% reduction). We apply our findings to a specific condition, for which there is a clinical indication for transplantation: sickle-cell disease. We show that the increased African ancestry in patients with this disease leads to reduced chances of finding a match, when compared to the remainder of the sample, without the condition. Our results underscore the influence of ancestry on chances of finding compatible HLA matches, and indicate that efforts guided to increasing the African component of registries are necessary.
Asunto(s)
Anemia de Células Falciformes/genética , Población Negra/genética , Médula Ósea/cirugía , Trasplante de Médula Ósea/métodos , Brasil , Etnicidad/genética , Frecuencia de los Genes/genética , Genotipo , Antígenos HLA/genética , Trasplante de Células Madre Hematopoyéticas/métodos , Prueba de Histocompatibilidad/métodos , Humanos , Polimorfismo Genético/genética , Sistema de Registros , Donante no Emparentado , Población Blanca/genéticaRESUMEN
Lymphoblasts from 186 consecutive untreated children <18 years were analysed by flow cytometry in Brazil. Socio-economic status was defined by family income; undernourishment by height and weight for age standardised z scores below -1.28. The observed frequencies were precursor-B (pre-B) CD10 positive acute lymphoblastic leukaemia (ALL) (CD10+) 65%, pre-B CD10 negative (CD10-) 13%, and T-ALL 18%. The typical incidence peak at age 2-5 years was observed among the CD10 positive cases. Nutritional variables were not associated with immunophenotypes. Low monthly per capita income was associated with T-immunophenotype (P=0.024). In conclusion, a direct association between unfavourable socio-economic status and the T-phenotype indicates a potential role of socio-economic factors on the genesis of ALL in children, thus confirming indirect data of the international literature.
Asunto(s)
Leucemia-Linfoma de Células T del Adulto/epidemiología , Linfocitos/patología , Clase Social , Adolescente , Estatura , Peso Corporal , Brasil/epidemiología , Niño , Preescolar , Femenino , Citometría de Flujo , Humanos , Incidencia , Lactante , Leucemia-Linfoma de Células T del Adulto/metabolismo , Masculino , Neprilisina/metabolismo , Fenómenos Fisiológicos de la Nutrición , Leucemia-Linfoma Linfoblástico de Células Precursoras B/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismoAsunto(s)
Enfermedades Endémicas , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Toxoplasma , Toxoplasmosis , Adulto , Anciano , Aloinjertos , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Toxoplasmosis/diagnóstico , Toxoplasmosis/etiología , Toxoplasmosis/terapiaRESUMEN
O presente trabalho relata o caso de paciente de 38 anos, feminina, portadora de Leucemia Mieloblástica Aguda, que desenvolveu febre näo responsiva à antibioticoterapia de largo espectro durante o período de aplasia medular. Logo após a recuperaçäo medular, persistia com febre, tosse e hemoptise. O exame de escarro mostrou hifas septadas e cultura positiva para Aspergillus sp. A radiografia de tórax demonstrou a presença de dois nódulos nos lobos superior direito e esquerdo respectivamente, sendo tais achados confirmados pela tomografia computadorizada. É discutida a correlaçäo patológico-radiológica da Aspergilose Pulmonar Invasiva no paciente imunossuprimido e o progresso na obtençäo do diagnóstico precoce com consequente melhora do pronóstico destes pacientes.
Asunto(s)
Humanos , Femenino , Adulto , Aspergilosis/diagnóstico , Leucemia Mieloide Aguda/complicaciones , Agranulocitosis , Terapia de Inmunosupresión , Enfermedades Pulmonares Fúngicas/diagnóstico , Brasil , PronósticoRESUMEN
Foram estudados retrospectivamente 99 pacientes adultos portadores de leucemia mielóide aguda diagnosticados e tratados no Hospital das Clínicas - Universidade Federal de Minas Gerais. Foram analisadas taxa de remissäo completa, sobrevida global e sobrevida em remissäo completa. Näo foram excluídos pacientes que tenham recebido apenas tratamentos suportivo, nem pacientes com leucemia secundária à mielodisplasia, ou secundária à quimioterapia. A idade do grupo foi 38 anos. A associaçäo de citosina arabinosídeo e daunoblastina ou mitoxantrone (7+3) foi utilizada em 78 casos na induçäo da remissäo. A terapia pós-remissäo consistiu de altas doses de Citosina arabinosídeo em 19 pacientes e manutençäo em 22. O tempo mínimo de seguimento em Remissäo Completa foi de 12 meses. A taxa de Remissäo Completa foi de 41,4 por cento. A Sobrevida Global estimada aos 3 anos Ú de 11 por cento + 4,0 por cento. A idade abaixo de 40 anos foi o fator mais favorável para a Sobrevida Global e Remissäo Completa (p = 0,023 e p= 0,0009, respectivamente). A Sobrevida em Remissäo Completa estimada aos 3 anos foi de 18,5 por cento + 7,0 por cento. A alta taxa de morte na induçäo foi o principal fator negativo, para remissäo completa e sobrevida global. O uso de Altas doses de Citosina Arabinosídeo foi o principal fator favorável para a sobrevida em remissäo completa (p=0,022). Para os pacientes que usaram Altas doses de Citosina Arabinosídeo, a sobrevida em Remissäo Completa estimada aos 24 meses foi de 32,5 por cento + 11,4 por cento.