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Objective:To explore the values of peripheral blood neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR) in the differential diagnosis of cytopenic diseases.Methods:A retrospective case series study was conducted. The clinical data of 105 newly diagnosed patients with aplastic anemia (AA), myelodysplastic syndrome (MDS) or primary immune thrombocytopenia (ITP) who were admitted to Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from August 2017 to November 2020 were retrospectively analyzed. There were 42 patients with MDS (13 cases of hypoplastic MDS, 23 cases of non-hypoplastic MDS, 6 cases could not be classified), 42 patients with ITP, and 21 patients with AA. The peripheral blood lymphocyte count, neutrophil count, monocyte count, and platelet count of each untreated patient at the time of initial diagnosis were recorded, the NLR, MLR and PLR were calculated, and the differences of NLR, MLR and PLR among different diseases were compared; the differential diagnostic values of each index for AA, MDS and ITP were evaluated by using the receiver operating characteristic (ROC) curve.Results:The NLR [ M (IQR)] in ITP, AA and MDS groups was 3.08 (2.42), 0.57 (0.66) and 0.83 (1.27) ( χ2 = 56.84, P<0.001), the MLR was 0.26 (0.15), 0.13 (0.14) and 0.20 (0.33) ( χ2 = 18.71, P<0.001), and the PLR was 5.12 (9.97), 8.67 (14.21) and 49.32 (78.66) ( χ2 = 47.07, P<0.001). The best cut-off value of NLR for distinguishing ITP from MDS was 1.757, and the area under the curve (AUC) was 0.833 (95% CI: 0.811-0.955), while the sensitivity and specificity were 78.6% and 83.3%, respectively. The best cut-off value of NLR for distinguishing ITP from AA was 1.350, and the AUC was 0.993 (95% CI: 0.981-1.000), while the sensitivity and specificity were both 95.2%. The best cut-off value of PLR for distinguishing AA from MDS was 23.542, and the AUC was 0.841 (95% CI: 0.739-0.944), while the sensitivity and specificity were 85.7% and 73.8%, respectively. The best cut-off value of NLR for distinguishing AA from MDS was 0.764, and the AUC was 0.687 (95% CI: 0.556-0.891), while the sensitivity and specificity were 71.4% and 64.3%, respectively. The best cut-off value of MLR for distinguishing AA from MDS was 0.148, and the AUC was 0.736 (95% CI: 0.614-0.859), while the sensitivity and specificity were both 71.4%. Conclusions:The peripheral blood NLR, MLR and PLR have certain reference values for differential diagnosis of AA, MDS and ITP.
RESUMO
The level of minimal residual disease (MRD) is closely associated with prognosis in patients with acute lymphoblastic leukemia (ALL). Currently, 3 kinds of ALL-MRD detection methods commonly used at home and abroad include immunoglobulin heavy chain and T-cell receptor (IGH/TCR) gene rearrangement assessment, flow cytometry (FCM) and leukemia-associated fusion gene detection. IGH/TCR gene rearrangement assessment methods include real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and next-generation sequencing (NGS). RT-qPCR mainly detects the variable region of IGH/TCR rearrangement genes; it is about one log more sensitive than FCM, but microclones may be easily ignored leading to false negative results. NGS also detects the variable region of IGH/TCR rearrangement genes. The sensitivity of NGS-based MRD assays is higher than that of FCM and RT-qPCR, and its sensitivity is up to 10 -6, while small subclones causing recurrence can be tracked. The sensitivity of MRD was 10 -4 detected by using FCM, while FCM with ≥8-color can achieve 10 -6. However, such high level of sensitivity requires (2-5)×10 7 nucleated cells, which is rarely obtainable from remission marrows. FCM also requires substantial expertise on inspectors, and results may be easily affected by clonal evolution or phenotype shift. RT-qPCR can be used to detect fusion genes such as BCR-ABL, with a sensitivity of up to about 10 -5, but only few ALL patients carry specific gene fusions change that can be used as the monitoring of MRD. For Philadelphia chromosome-positive ALL patients, RT-qPCR is recommended to detect the level of MRD. For Philadelphia chromosome-negative ALL and T-cell ALL patients, FCM, RT-qPCR and NGS methods are all applicable.