Efficacy Of Intensive Immunosuppressive Regimen In The Treatment Of 78 Cases Of Severe Aplastic Anemia

Objective:To explore the short-term efficacy,long-term prognosis and survival of 78 patients with severe aplastic anemia(SAA)treated with intensive immunosuppressive regimen,and analyze the relevant factors affecting the efficacy and prognosis.Methods:The clinical characteristics and therapeutic effects of 78 patients with severe aplastic anemia who received antithymocyte globulin(ATG)combined with cyclosporine A(CSA)immunotherapy in the Hematology Department of the tumor center of the first hospital of Jilin University from May 2010 to June 2018 were analyzed retrospectively.Long-term follow-up was performed to obtain long-term prognosis and survival,and the factors that may affect the efficacy and prognosis were analyzed.The follow-up date is until April 2019.SPSS 21.0 statistical software was used to complete the data statistical analysis,and P < 0.05 was statistically significant.Results:1.In this group of SAA cases,the male to female ratio is 1.05: 1,and the median age is 26 years old(6 ~ 61 years old).2.Of the 78 patients with severe aplastic anemia,a total of 60 patients were effective,of which 11 patients(14.10%)achieved complete treatment response(CR)and 28 patients(35.90%)achieved partial treatment response(PR)within 3 months,the effective rate is 50.00%;6 months CR 22 cases(28.57%),36 cases(46.75%),with an effective rate of 75.32%;9 months of CR(33.33%),33 cases of PR(44.00%),an effective rate of 77.33%;32-year CR(44.44%),23 cases of PR(31.94%),the effective rate was 76.39%.Three patients were lost to follow-up,two patients had not yet reached the one-year efficacy evaluation time,and one patient died of unknown cause after obtaining PR.3.The results of univariate analysis showed that the severity of the disease,infection within 1 month of treatment,baseline absolute neutrophil count,reticulocyte absolute value and lymphocyte absolute value were related to the efficacy of immunosuppressive therapy(P < 0.05),and gender,age,and infection before ATG treatment Condition,PNH clone before treatment,gene mutation,chromosomal abnormality,presence of HLA-DR15 gene,history of infectious disease,diagnosis to treatment interval,baseline iron load,hemoglobin,and platelet were not related to the efficacy of immunosuppressive therapy(P > 0.05).Multivariate Logistic regression results showed that the severity of the disease(OR = 0.205,95%CI 0.062 ~ 0.676,P = 0.009)and infection within 1 month of ATG treatment(OR = 5.891,95%CI 1.463 ~ 23.719,P = 0.013)Independent factors influencing hematologic response within 1 year after treatment.4.The 1-year,2-year,3-year,4-year,and 5-year survival rates of the patients in this study were 86.8%,83.2%,82.3%,80.1%,and 74.9%,respectively.5.The results of univariate analysis showed that the severity of the disease,the absolute value of baseline neutrophils,and the absolute value of baseline reticulocyte were related to the prognosis;multivariate analysis showed that the severity of the disease was an independent factor affecting the prognosis of SAA patients(P = 0.001),Compared with SAA patients,non-very severe aplastic anemia(VSAA)patients had a higher risk of death than SAA patients,HR = 6.786(95%CI: 2.180-21.129).6.Among the 78 patients,the median event-free survival time was 36.5 months.Four patients had chromosomal abnormal karyotypes at follow-up of 24 months,40 months,54 months,and 66 months,respectively.One patient also had PTPN11 Gene mutations;2 patients were converted to myelodysplastic syndromes(MDS)at 54 and 66 months of follow-up,respectively,and subsequently converted to acute myeloid leukemia(AML)and chronic myelomonocytic leukemia(CMML);7 patients were followed up at 18 months,Recurrence of aplastic anemia occurred at 24 months(2 persons),50 months,97 months,104 months,and 125 months.Conclusions:1.Intensive immunosuppressive regimens for SAA have good efficacy and high long-term survival rate.2.The severity of the disease and infection within 1 month of ATG treatment are independent factors influencing hematological response within 1 year after treatment,while the severity of the disease is an independent factor affecting the prognosis of SAA patients.Actively preventing and treating infections early may improve the efficacy after IST.3.After immunosuppressive therapy,a few patients have recurrence or clonal progression.Of the 78 patients,4 had abnormal chromosome karyotypes,of which 1 patient has a mutation in the PTPN11 gene at the same time;2 patients are converted to MDS,and then to AML and CMML;7 patients have recurrent aplastic anemia.