The Role Of Lymphocyte Subsets In The Prognosis Of Myeloid Malignant Diseases

Part 1: Clinical significance of detecting lymphocyte subsets in malignant lymphoid diseaseObjective: To analyzed the expression levels of lymphocyte subsets associated antigens of peripheral blood in malignant lymphoid disease(MLD), and evaluate the role of cellular immune function on the prognosis.Methods: From Jan,2014 to Apr,2016, total of one hundred and fifteen patients with MLD and 20 heallty controls(NC) of similar age were enrolled in this study, including 18 patients with acute lymphocyte leukemia(ALL), 52 non-Hodgkin lymophoma(NHL) patients and 45 multiple myeloma(MM) patients. The expression levels of CD3+,CD4+,CD8+,CD4+/CD8+、NK cell in peripheral blood were detected by Flow cytometery(FCM).Results: 1) Compared with the healthy controls(NC),the expression levels of CD4+,CD4+/CD8+ and NK cell of peripheral blood in MLD patients were decreased, while the CD8+ cell was increased(P<0.01);2) Compared with effective group, the expression levels of CD4+, CD4+/CD8+ and NK cell in refractory group were decreased before chemotherapy, while the CD8+ was increased(P<0.01);3) The expression levels of CD4+,CD4+/CD8+ and NK cell in CR group after chemotherapy were higher than those before chemotherapy, while the CD8 was opposited(P<0.01), and were closed to the levels of NC(P>0.05); 4) The expression levels of CD4+,CD4+/CD8+ and NK cell in CR group after chemotherapy were higher than those in PR group, while the CD8+ was opposited(P<0.05); 5) The expression levels of CD3+,CD4+,CD8+in refractory group after chemotherapy were lower than those before chemotherap(P<0.05); 6) With ann arbor stages increasing, the expression levels of CD4+,CD4+/CD8+ and NK cell in Ⅲ- Ⅳstage before chemotherapywere lower than those inⅠ-Ⅱstage, while the CD8+ was opposited(P<0.05);7) There was negative correlation betweent CD4+/CD8+ and IPI score, β2-MG, ISS stages and lymphocytes percentage in bone marrow(P<0.05).Conclusion: MLD in early stage existe lymphocyte subsets imbalance,and only perform cellular immune dysfunction. with disease progressing, the immune function was suppressed obviously. The cellular immune dysfunction are closely associated with poor response at the beginning, and lapse to refractory easily, which suggests that the cellular immune function status has a important reference value in disease prognosis. Effective treatment can correct immune dysfunction and promote the immune system to maintain steady.Part 2: The changes and implication of follicular helper T cells and its associated molecules in patients with malignant lymphoid diseaseObjective : To investigate the changes of follicular helper T cells and associated molecules in the peripheral blood(PB) of patients with malignant lymphoid disease(MLD) dynamically and explore the role on pathogenesis of the disease.Methods: From Jun,2014 to Jun,2016, total of fifty-five patients with MLD and 10 heallty controls(NC) of similar age were enrolled in this study, including 9 patients with acute lymphocyte leukemia(ALL), 30 non-Hodgkin lymophoma(NHL) patients and 16 multiple myeloma(MM) patients. The percentages of CD4+CXCR5+ and expression of ICOS+, PD1+ among the T cells were detected by Flow cytometery(FCM), while the level of IL-21 in plasma was detected by ELISA tests.Results: 1)The percentages of Tfh cells and expression of ICOS and/or PD1 in PB of all untreated patients were significantly higher than those of NC(P<0.01), and MM group<ALL group<NHL group;2) The levals of Tfh cells, ICOS and PD1 were presented a declining trend overall at the end of 2th, 4th, 6th chemotherapy courses(P<0.05). More so, the level might be close to even lower than the normal after the 6th course; 3)The percentages of Tfh cells, ICOS and PD1 in those pts who achieved PD at the end of 2th course were close to even higher than before treatment; While at the end of 6th course the percentages who received CR were closer to those of NC(P>0.05), and apparently lower than those who achieved PR(P<0.05); 4) The percentages of Tfh cells in patients of T-ALL and T-NHL were higher than B-ALL and B-NHL(P>0.05), and much higher than NC(P<0.01); 5) The percentages of IL-21 in pts were much higher than that of NC(P<0.01), and MM group<ALL group<NHL group; 6) Multiple liner regression analysis showed that there was positive correlation between the number of Tfh cells and LDH, IPI score, ann arbor staging system, ISS staging system, β2-MG and lymphocytes percentage in Bone marrow(P<0.05).Conclusion : The hyper-activation of Tfh cells might be associated with the immunopathogenesis of MLD caused by excessive expression of ICOS,PD-1 and IL-21. Test the Tfh cells dynamically could be used to estimate the state and the remedial effect. Tfh cells and their realted molecules could be potiential therapeutic targets for MLD.