Analysis Of The Correlation Between Late-onset Hemorrhagic Cystitis And Early Immune Reconstitution Post Allogeneic Hematopoietic Stem Cell Transplantation

Objective: It is to analyze the correlation between Late Onset Hemorrhagic Cystitis(LOHC)and early immune reconstruction post allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods: We study 110 patients,retrospectively,who underwent allo-HSCT in the department of hematology of our hospital from January 1,2014 to October 31,2016,and all the pretreatment schemes containing ATG/ ATG-f were selected.27 patients with LOHC are into the LOHC group and 54 cases in the control group are matched according patients' age sex match and disease state.The lymphocyte cells--CD3+,CD4+,initial CD4+,memory CD4+,CD8+,initial CD8+,memory CD8+,T regulatory,CD19+B,immature B,initial B and memory B cells--were detected at day 30,day 60 and day 90 post allo-HSCT.Meanwhile,we defined grade I-II LOHC as mild LOHC,and grade III-IV LOHC as severe LOHC.Statistical software spss 24.0 was used to analyze the measurement data((x±s).Non-parametric rank sum test was used to test the repeated measurement variance analysis.The counting data n(%)was analyzed by chi-square test and Logistic regression analysis.The test level P<0.05.Result: 1 The median time of LOHC onset in LOHC group was day 25.5(day 14-day 54)post allo-HSCT.2 The immune reconstruction in the LOHC group and control group 2.1 The subsets of T cell reconstructionThere was no significant difference between the LOHC group and the control group in T cell subsets restitution at day 30 and day 60 post allo-HSCT(P>0.05).The initial CD4+ and initial CD8+ cell counts of the LOHC group were lower than control group(0.55±0.47/ul vs 64.29±283.20/ul,P=0.040;156.09±142.51/ul vs 370.33±300.23/ul,P=0.016)at day +90 post allo-HSCT,while CD8+ and memory CD8+ were slightly higher than the control group(1228.18±1612.52/ul vs 880.48±337.25/ul,P=0.047;701.67±1096.51/ul vs 460.00±263.36/ul,P=0.052).2.2 The subsets of CD19+B cell reconstructionThe CD19+B and initial B cell counts of LOHC group were higher than control group(60.10±114.48/ul vs 31.09±54.69/ul,P=0.048;63.34±136.80/ul vs 26.56±51.07/ul,P=0.030)at day30 post allo-HSCT respectively.But CD19+B?initial B?memory B? immature B were significantly lower than the control group(43.96±52.91/ul vs 65.95±62.08/ul,P=0.004;41.11±54.49/ul vs 59.82±57.55/ul,P=0.003;4.35±5.63/ul vs 38.34±151.72/ul,P=0.022;0.54±0.72/ul vs 66.51±282.72/ul,P=0.003)respectively at day+90 post alloHSCT,while the immature B was lower firstly at day +60 post allo-HSCT.3 Immune reconstitution of mild and severe LOHC group 3.1 The subsets of T cell reconstructionThe overall level of CD3+,CD4+,memory CD4+,CD8+ and memory CD8+T cells of the early mild LOHC group were higher than the severe LOHC group and control group(P<0.05),and the initial CD8+T cells of severe LOHC group was lower than the mild LOHC group and control group(P<0.05).There were no significant difference among others(P>0.05).Notly,the Treg cells of the severe LOHC group were higher than the control group(33.26±82.87/ul vs 12.03±33.94/ul,P=0.049)at day +60 post allo-HSCT.While the CD3+,CD4+,memory CD4+,CD8+,initial CD8+ and memory CD8+ cell counts were lower than the mild LOHC group at day +90 post allo-HSCT.3.2 The subsets of CD19+B cell reconstructionThe CD19+B cell and initial B cell counts of the mild LOHC group were higher than the control group(123.34±184.82/ul vs 37.18±71.78/ul,P=0.021;132.80±202.20/ul vs 32.71±68.39/ul,P=0.019),respectively,at day 30 post allo-HSCT.The immature B cell level of the mild LOHC group was higher than the severe LOHC group(1.88±2.91/ul vs 0.19±0.16/ul,P=0.016)at day 30 post allo-HSCT.The memory B cell counts of the severe LOHC group were lower than the mild LOHC group(3.44±2.67/ul vs 5.72±8.88/ul,P=0.044),however,the level of CD19+B,initial B and immature B were significantly lower than the control group(P<0.01),and there was no statistical difference between the other groups at day 90 post allo-HSCT.Conclusion:1.The pathogenesis of LOHC post allo-HSCT may be related to the high level of initial B cells of CD19+B cells.LOHC may promote the early reconstruction of CD8+ and memory CD8+T lymphocytes cells,but delay the reconstruction of initial CD4+?initial CD8+ cells and CD19+B cell subsets,especially the subsets of initial CD4+ cells and CD19+B lymphocytes.2.The degree of LOHC affects the reconstruction of early immune cells.The Treg cells are involved in the immune regulation of severe LOHC,which may down-regulate the immune level of the T cell subsets.The high-intensity immunosuppressive drugs applied to control severe LOHC delay The high-intensity immunosuppressive drugs applied to control severe LOHC may delay early reconstruction of immune cells post allo-HSCT.