RESUMO
AML is stratified into risk-categories based on cytogenetic and molecular features that prognosticate survival and facilitate treatment algorithms, though there is still significant heterogeneity within risk groupings with regard to risk of relapse and prognosis. The ambiguity regarding prognosis is due in large part to the relatively outdated criteria used to determine response to therapy. Whereas risk assessment has evolved to adopt cytogenetic and molecular profiling, response criteria are still largely determined by bone marrow morphologic assessment and peripheral cell count recovery. Minimal residual disease refers to the detection of a persistent population of leukemic cells below the threshold for morphologic CR determination. MRD assessment represents standard of care for ALL and PML, but concerns over prognostic capability and standardization have limited its use in AML. However, recent advancements in MRD assessment and research supporting the use of MRD assessment in AML require the reconsideration and review of this clinical tool in this disease entity. This review article will first compare and contrast the major modalities used to assess MRD in AML, such as RQ-PCR and flow cytometry, as well as touching upon newer technologies such as next-generation sequencing and digital droplet PCR. The majority of the article will discuss the evidence supporting the use of MRD assessment to prognosticate disease at various time points during treatment, and review the limited number of studies that have incorporated MRD assessment into novel treatment algorithms for AML. The article concludes by discussing the current major limitations to the implementation of MRD assessment in this disease. The manuscript is bookended by a clinical vignette that highlights the need for further research and refinement of this clinical tool.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Leucemia Mieloide Aguda/tratamento farmacológico , Proteínas de Fusão Oncogênica/sangue , Adulto , Biópsia , Medula Óssea/patologia , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Gerenciamento Clínico , Feminino , Citometria de Fluxo , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Neoplasia Residual , Proteínas de Fusão Oncogênica/genética , Reação em Cadeia da Polimerase/métodos , Prognóstico , Proteína 1 Parceira de Translocação de RUNX1/genética , Medição de Risco , Análise de Sequência de DNAAssuntos
Amiloidose/tratamento farmacológico , Antineoplásicos Alquilantes/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Hospitalização/tendências , Melfalan/uso terapêutico , Condicionamento Pré-Transplante/métodos , Antineoplásicos Alquilantes/administração & dosagem , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina , Melfalan/administração & dosagem , Estudos RetrospectivosRESUMO
In this study we tested whether the quantitative matching of developing neuronal populations may depend on the size of the afferent supply. Partial deafferentation of the middle division of the parabigeminal nucleus (PBm) was produced before the period of naturally occurring cell death, by reducing the neuronal population of the superior colliculus following partial lesions or eye removal. The number of neurons surviving cell death in the PBm was linearly related to the number of its afferent neurons. This result supports the hypothesis that neurotrophic control by the afferent supply during the period of natural neuronal death is a major determinant of the number of neurons in the developing brain.
