Flow Cytometric Analysis of Peripheral Blood Neutrophil Myeloperoxidase Expression for Ruling Out Myelodysplastic Syndromes: Protocol for a Diagnostic Accuracy Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 400
- 试验地点
- 8
- 主要终点
- Area under the receiver operating characteristic (ROC) curve
研究概览
简要总结
Myelodysplastic syndromes (MDS) are clonal bone marrow neoplasms characterized by dysplasia and ineffective hematopoiesis leading to peripheral blood cytopenias, with an increased risk of progression to acute myeloid leukemia. The conventional diagnostic work-up of MDS relies on cytomorphological evaluation of bone marrow, which may be complemented by conventional cytogenetic, flow cytometry, and molecular analysis by next generation sequencing techniques.
Suspicion of MDS is the commonest reason for bone marrow aspirate in older patients with unexplained peripheral blood cytopenias. Yet many patients are exposed to unnecessary bone marrow aspiration-related discomfort and harms, because of the limited prevalence of disease among subjects referred for suspected MDS. In this context, a valid and reliable assay based on peripheral blood sample that accurately discriminates MDS from other cytopenia etiologies without requiring invasive bone marrow aspiration is warranted.
The accuracy of peripheral blood neutrophil myeloperoxidase expression quantified by flow cytometric analysis for the diagnosis of MDS is supported by three primary studies totaling 211 individuals. An intra-individual robust coefficient of variation (RCV) value for neutrophil myeloperoxidase expression lower than 30.0% accurately ruled out MDS, with both sensitivity and negative predictive value point estimates of 100%, in consecutive patients with suspected disease. This biomarker might obviate the need for cytomorphological evaluation of bone marrow aspirate for up to 35% of patients referred for suspected MDS. Although promising, these preliminary results require replication in an independent external validation sample.
The broad aim of the multicenter MPO-MDS-Valid study project is to prospectively validate the diagnostic accuracy of intra-individual RCV for peripheral blood neutrophil myeloperoxidase expression quantified by flow cytometric analysis among consecutive patients referred for suspected MDS.
详细描述
The primary objective of the MPO-MDS-Valid study is to estimate the discriminative accuracy (i.e., area under the ROC curve point estimate along with 95% confidence interval [CI]) of the intra-individual RCV for neutrophil myeloperoxidase expression in peripheral blood for the diagnosis of MDS in consecutive patients.
The secondary objectives are:
- To estimate the negative predictive value of the intra-individual RCV for neutrophil myeloperoxidase expression in peripheral blood (with a prespecified threshold of 30.0%) for ruling out MDS in consecutive patients.
- To estimate the prevalence of alternate diagnoses established by bone marrow cytomorphology among true negative patients (i.e., patients with intra-individual RCV value lower than 30.0% and for whom MDS was ruled out by the reference method).
Study design: The MPO-MDS-Valid study project is a multicenter diagnostic accuracy study of an index test by comparison with a reference standard in unselected consecutive patients. An institutional review board (Comité de Protection des Personnes Nord Ouest III) reviewed and approved the study protocol and the information form, prior to study initiation. No specific intervention is assigned to participants. All diagnostic testing, procedures, and medication ordering are performed at the discretion of attending physicians. The index test result will have no impact on patient management.
Screening: All consecutive patients referred for suspicion of MDS to the immuno-hematology lab at the study sites will be screened for eligibility. A lab physician will review inclusion and exclusion criteria, using computerized medical and laboratory records.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age at enrollment ≥18 years
- •Referral for suspicion of myelodysplastic syndrome
- •Indication for bone marrow examination
- •≥1 peripheral blood cytopenia defined by hemoglobin concentration <12 g/dL for female and <13g/dL for male patients, platelet count <150 x109/L, absolute neutrophil count <1.8 x109/L
- •Inpatient or outpatient care
排除标准
- •Refusal to participate
- •History of or active documented MDS or CMML
- •Enrollment in intensive or critical care unit
- •Incarcerated or individuals protected by French regulation (Article L1121.5 and following, Code de la Santé Publique)
- •Not affiliated with social security system
- •Previous enrollment in the study
结局指标
主要结局
Area under the receiver operating characteristic (ROC) curve
时间窗: Baseline
The area under the ROC curve point estimate along with 95% confidence interval will quantify the accuracy of the index test (i.e., intra-individual RCV for neutrophil myeloperoxidase expression in peripheral blood) for the diagnosis of myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). The reference diagnosis will be established by cytomorphological evaluation of bone marrow aspirate performed by independent experienced hematopathologists blinded to the index test results. Morphologic assessment may be complemented by bone marrow flow cytometric score, karyotype, and molecular profiling, where relevant.
次要结局
- Negative predictive value(Baseline)
- Prevalence of alternate diagnoses for true negative cases(Baseline)