Efficacy And Prognosis Assessment Of V/SAA Patients Based On The Standard Immunosuppressive Regimen

Objective:To evaluate the efficacy and safety of eltrombopag(EPAG)added to standard immunosuppressive therapy(IST)regimen in Chinese newly diagnosed V/SAA patients.Method:We retrospectively analyzed the clinical data of 37 newly diagnosed V/SAA patients(EPAG group)between October 2019 and March 2021 who received EPAG and standard IST.In previously diagnosed V/SAA patients who received standard IST,according to age and disease severity,in a ratio of 1:2,randomly matched 74 patients(IST group)for efficacy and survival analysis.The patients in EPAG group who started using EPAG before ATG were included in the pre-ATG group;those who started using EPAG after ATG were included in the post-ATG group.Results:1.In EPAG group,21/37(56.8%)patients achieved hematologic response(HR)at 3 months after treatment,and 27/37(73%)patients achieved HR at 6 months,which were both higher than those of IST group[36/74(48.6%)at 3 months and 43/74(58.1%)at 6 months](P values were 0.420 and 0.126 respectively).2.7/37(18.9%)patients in EPAG group achieved complete hematologic response(CR)at 3 months and 10/37(27.1%)patients achieved CR at 6 months,both were significantly higher than those of IST group[2/74(2.7%)and 8/74(10.8%),P values were 0.006 and 0.029].3.For patients in EPAG group,the median time reached HR[59(15～193)d vs 70(25～1650)d,P=0.052]and CR[90(45～364)d vs 360(90～1178)d,P<0.001]were both shorter than those of IST group.4.The Kaplan-Meier survival curve showed that EPAG group had fewer early deaths than that of IST group(0%vs 6.8%,P=0.153).The 2-year OS rate(85.5%vs 87.6%,P=0.575)of EPAG group was not different from that of IST group.But the 2-year EFS rate of EPAG group(73.0%vs 53.5%,P=0.076)was higher than that of IST group.5.In EPAG group,62.2%patients had adverse effects,among them 95.7%patients showed slight and tolerable adverse effects and did not need a dose titration.6.In EPAG group,the baseline ANC,ARC,and PLT of patients who obtained HR at 6 months were higher than those of patients without HR(P values were 0.021,0.001,and 0.005,respectively);the patients who achieved CR at 6 months had higher ANC and ARC at baseline than patients without CR(P values were 0.038 and 0.014,respectively).Logistic multivariate analysis showed that ARC(P=0.018)at baseline was the only independent prognostic factor for 6-month CR in EPAG group.7.In post-ATG group,the 3-month HR rate(68.4%vs 44.5%,P=0.141)and CR rate(31.6%vs 5.6%,P=0.090),and 6-month HR rate(78.9%vs 66.6%,P=0.476)and CR rate(42.1%vs 11.1%,P=0.062)were higher than those of pre-ATG group.8.The serum ferritin(SF)levels of patients in EPAG group at 3 months and 6 months after treatment were not different from that at baseline(P values were 0.886 and 0.153,respectively);the SF levels of patients in IST group at 3 months and 6 months were significantly higher than that at baseline(P values were 0.004 and 0.029,respectively).Conclusion:EPAG added to standard IST regimen(EPAG+ATG+CsA)had a better,faster response in Chinese V/SAA patients,and the hematologic response rate was much higher.This new regimen was safe,and the adverse effects were mostly slight and tolerable.The factors affecting the prognosis of patients in EPAG group were still parameters reflecting residual hematopoiesis of bone marrow.Early administration of EPAG before ATG without adequate immunosuppressive therapy did not result in a higher hematologic response rate.Objective:To reassess the predictors for 6-month response in V/SAA patients who failed to respond to immunosuppressive therapy(IST)at 3 months.Methods:We retrospectively analyzed the clinical data of 173 V/SAA patients who received IST and were classified as non-responders at 3 months.Univariate and multivariate logistic regression analysis were used to evaluate factors that could predict the response at 6months.Results:1.A total of 173 patients without hematologic responses at 3 months after IST were included in this study,including 90 males and 83 females;the median age was 30(672)years old;90 SAA patients and 83 VSAA patients;33 cases were treated with rATG,and 140 cases were treated with p-ATG.2.58 cases(33.5%)obtained hematologic response at 6 months after IST,including 3 cases of CR and 55 cases of PR;115 cases without hematologic responses at 6 months after IST,including 107 cases of NR;3 cases lost of follow-up;1 patient underwent allo-HSCT;3 patients died due to infection and 1 patient due to cerebral hemorrhage.3.Univariate analysis showed that 3-month HGB(P=0.017),PLT(P=0.005),ARC(P<0.001),CsA-CO(P=0.042),sTfR(P=0.003),ARC△(P<0.001),and sTfR△(P<0.001)were related to 6-month response.4.The results of multivariate analysis showed that PLT(P=0.020)and ARC△(P<0.001)were independent prognostic factors predicting the 6-month response.If ARC△less than 6.9×109/L,the 6-month hematologic response rate was low regardless of patient’s PLT count.5.Survival analysis showed that both the 3-year OS(P=0.002 and 3-year EFS(P<0.001)of the non-responders at 6 months were significantly lower than those of the response group.Conclusion:Residual hematopoietic indicators at 3 months after IST are prognostic parameters.The improved value of reticulocyte count could reflect whether the bone marrow hematopoiesis was recovering and the degree of recovery.A second treatment could be performed as soon as possible for patients with very low ARC△.