The European Myeloma Network (EMN) organized two flow cytometry workshops. The first aimed to identify specific indications for flow cytometry in patients with monoclonal gammopathies, and consensus technical approaches through a questionnaire-based review of current practice in participating laboratories. The second aimed to resolve outstanding technical issues and develop a consensus approach to analysis of plasma cells. The primary clinical applications identified were: differential diagnosis of neoplastic plasma cell disorders from reactive plasmacytosis; identifying risk of progression in patients with MGUS and detecting minimal residual disease. A range of technical recommendations were identified, including: 1) CD38, CD138 and CD45 should all be included in at least one tube for plasma cell identification and enumeration. The primary gate should be based on CD38 vs. CD138 expression; 2) after treatment, clonality assessment is only likely to be informative when combined with immunophenotype to detect abnormal cells. Flow cytometry is suitable for demonstrating a stringent complete remission; 3) for detection of abnormal plasma cells, a minimal panel should include CD19 and CD56. A preferred panel would also include CD20, CD117, CD28 and CD27; 4) discrepancies between the percentage of plasma cells detected by flow cytometry and morphology are primarily related to sample quality and it is, therefore, important to determine that marrow elements are present in follow-up samples, particularly normal plasma cells in MRD negative cases.
Summary Flow cytometric immunophenotyping is considered an indispensable tool for the diagnosis, classification and monitoring of disease in monoclonal gammopathies. The clinical sensitivity of flow cytometry is comparable with advanced molecular methods. Clinical application of flow cytometry in monoclonal gammopathies has various dimensions, such as differential diagnosis of malignant plasma cell disorder from reactive plasmacytosis, identifying the progression risk in monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic multiple myeloma (MM), and minimal residual disease detection. Flow cytometry‐based clonality assessment with immunophenotyping encourages and enables the most stringent method of diagnosis and follow‐up. The objective of this review is to update the malignant plasma cells phenotypic profile of MGUS and MM. The most comprehensive antigens, such as CD19, CD27, CD28, CD45, CD56 and CD117, play a significant role in the characterization of normal and malignant plasma cells. Several research groups described the putative phenotype of myeloma cell progenitors, but no remarkable suggestion could be made because of disparity. This review also focuses on the association of malignant phenotypic markers and chromosomal aberrations that identify the specific prognostic features in monoclonal gammopathies.
Background/Aims: High rates of cognitive impairment (CI) are an alarming problem in patients undergoing chronic hemodialysis (HD). Its pathophysiology remains unclear and there are indications that brain ischemia might be one of the key causes. Cerebral tissue oxygenation, as measured by near-infrared spectroscopy, is known to be decreased in HD patients. However, it is unknown whether CI is associated or not associated with lower cerebral oxygenation in these patients. The primary aim of our study was to probe this possible association. Our secondary aim was to assess other factors possibly related to cerebral ischemia and CI. Methods: Thirty-nine patients treated by chronic HD were included in this cross-sectional study. All measurements were performed before the initiation of an HD session. The Montreal Cognitive Assessment (MoCA) was administered according to published recommendations. Regional saturation of oxygen (rSO2) of the left frontal lobe was measured using the INVOS 5100C device. Basic medical history and laboratory data were recorded, and handgrip strength was analyzed. We used the unpaired t test to compare the rSO2 and other variables between cognitively normal patients (MoCA score ≥26) and those who displayed CI (MoCA score <26). Multiple linear regression analysis was used to adjust for principal confounders. Results: Cognitively impaired patients had lower brain rSO2 values compared to cognitively normal patients (48 ± 9 vs. 57 ± 10%, p = 0.01). Among other variables, higher red cell distribution width (15.8 ± 1.9 vs. 13.8 ± 1.6%, p = 0.01) and lower hand grip strength (49.2 ± 23.3 vs. 99.3 ± 31.4 lbs, p < 0.001) also displayed a significant association with CI. The relation between rSO2 and MoCA score was significant after adjustment for age and gender (p = 0.007). Conclusion: Decreased brain oxygenation is associated with weaker cognitive performance in patients undergoing chronic HD. Further understanding the causes of cerebral ischemia in HD patients could lead to the prevention of cognitive decline in this population.
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