Flow Cytometric Analysis of Peripheral Blood Neutrophil Myeloperoxidase Expression for Ruling Out Myelodysplastic Syndromes: A Pilot Diagnostic Accuracy Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Area under the Receiver Operating Characteristic (ROC) curve of neutrophil myeloperoxidase expression in peripheral blood
研究概览
简要总结
Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal bone marrow neoplasms that predominate in the elderly, with a median age at diagnosis of 70 years. MDS are characterized by peripheral blood cytopenia and morphologic dysplasia for one or more hematopoietic cell lineage, reflecting ineffective hematopoiesis.
The diagnostic work-up of MDS includes a bone marrow aspirate and biopsy, which is an invasive procedure, for cytomorphologic and cytogenetic evaluations. Because the prevalence of disease is lower than 20% in subjects referred for suspected MDS, many patients are exposed to unnecessary bone marrow aspiration-related discomfort and harms.
An objective assay is highly desirable for accurately ruling out MDS based on peripheral blood samples, which may obviate the need for invasive bone marrow aspiration and biopsy in patients with negative results.
Few studies have investigated the value of peripheral blood flow cytometric analysis for the diagnosis of MDS and/or chronic myelomonocytic leukemia (CMML). Although promising, these studies lacked replication of their results, used a case-control design, which was prone to spectrum bias, or yielded imprecise diagnostic accuracy estimates due to relatively limited sample sizes.
Anecdotal evidence supports the potential of flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression for the diagnosis of MDS and CMML. Myeloperoxidase is an enzyme synthetized during myeloid differentiation that constitutes the major component of neutrophil azurophilic granules. Myeloperoxidase expression may reflect neutrophil hypogranulation, which is a classical although subjective dysplastic feature of MDS. Flow cytometric analysis of myeloperoxidase expression in bone marrow neutrophil granulocytes has been used for discriminating low versus high grade MDS. Yet a study reporting on the accuracy of flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression for the diagnosis of MDS is still lacking, to our knowledge.
In this study, the investigators hypothesize that flow cytometric analysis of neutrophil myeloperoxidase expression in peripheral blood may accurately rule out MDS and obviate the need for bone marrow aspiration and biopsy, with sensitivity approaching 100%, in routine practice.
In this observational diagnostic accuracy study, burden will be null for recruited patients. No specific intervention is assigned to participants. All diagnostic testing, procedures, and medication ordering are performed at the discretion of attending physicians. Flow cytometry analysis of peripheral blood neutrophil myeloperoxidase expression will not require additional blood sample. A test result will have no impact on patient management. No follow-up visits are planned in this cross-sectional study.
详细描述
The primary objective of MPO-MDS-pilot study is to estimate the accuracy of flow cytometric analysis of neutrophil myeloperoxidase expression in peripheral blood for the diagnosis of myelodysplastic syndromes (MDS) and/or chronic myelomonocytic leukemia (CMML).
The secondary objectives are:
- to provide accuracy estimates for prespecified thresholds of neutrophil myeloperoxidase expression in peripheral blood in ruling out MDS and/or CMML.
- to estimate the prevalence of alternate diagnosis established by bone marrow cytomorphology.
The MPO-MDS-pilot project is a multicenter, phase II, cross-sectional, diagnostic accuracy study of consecutive unselected patients referred for suspected MDS or CMML.
Screening: All consecutive patients referred to the immuno-hematology lab at the study sites for suspicion of MDS 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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥50 years;
- •Clinical suspicion of myelodysplastic syndromes (MDS) and / or chronic myelomonocytic leukemia (CMML);
- •Peripheral blood cytopenia defined by hemoglobin concentration <10 g/dL, platelet count <100 x109/L, and/or absolute neutrophil count <1.8 x109/L.
排除标准
- •History of or active documented MDS or CMML;
- •Admission to the intensive care unit;
- •Suspicion of hematological disease other than MDS requiring bone marrow aspirate and/or biopsy (i.e., acute leukemia,...);
- •Absolute neutrophil count <0.5 x109/L;
- •Not affiliated with a social security system;
- •Homelessness;
- •Incarcerated;
- •Inability to understand research information and/or to provide non-opposition, because of language restriction, dementia, or altered mental status;
- •Refusal to participate;
- •Previous enrollment in the study.
结局指标
主要结局
Area under the Receiver Operating Characteristic (ROC) curve of neutrophil myeloperoxidase expression in peripheral blood
时间窗: Baseline
The primary outcome is the discrimination of the index test (i.e., flow cytometry analysis of neutrophil myeloperoxidase expression in peripheral blood) for the diagnosis of myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMLL) quantified by the area under the ROC curve point estimate along with its 95% confidence interval.
次要结局
- Sensitivity point estimates (along with 95% confidence interval) of neutrophil myeloperoxidase expression in peripheral blood for the diagnosis of MDS or CMML(Baseline)
- Specificity point estimates (along with 95% confidence interval) of neutrophil myeloperoxidase expression in peripheral blood for the diagnosis of MDS or CMML(Baseline)
- Negative predictive value point estimates (along with 95% confidence interval) of neutrophil myeloperoxidase expression in peripheral blood for the diagnosis of MDS or CMML(Baseline)
- Positive predictive value point estimates (along with 95% confidence interval) of neutrophil myeloperoxidase expression in peripheral blood for the diagnosis of MDS or CMML(Baseline)
- Prevalence point estimate (along with 95% confidence interval) for alternate diagnosis established by bone marrow cytomorphology.(Baseline)