The Efficacy And Safety Of Modified Immunosuppressive Therapy In Patients With Severe Aplastic Anemia And Transfusion-Dependent Non-Severe Aplastic Anemia: A Retrospective Cohort Study

This study aimed to evaluate the efficacy and safety of combined immunosuppressive therapy (IST) plus mesenchymal stromal cell infusion (MSCI) and/or umbilical cord blood infusion (UCBI) in severe aplastic anemia (SAA) or transfusion-dependent non-severe aplastic anemia (TD-NSAA) patients. A total of 79 patients with SAA or TD-NSAA were recruited as the study cohort and divided into the IST group (n=30), the IST+UCBI group (n=28), or the IST+UCBI+MSCI group (n=21) according to the treatment each patient underwent. The patients in the three groups were treated with intravenous rabbit antithymocyte globulin for 5 days and oral cyclosporine A (CsA). The patients in the IST+UCBI and IST+UCBI+MSCI groups were treated with an additional unrelated UCBI and/or MSCI. At 6 months post treatment, the overall response rate (ORR) in the IST+UCBI+MSCI group was higher compared with the ORR in the IST group (81.0% vs 50%, P=0.039). The IST+UCBI and IST+UCBI+MSCI groups achieved shorter median times to response (TTR) than the IST group did (84.2 days vs 145.5 days, P=0.010; 84.3 days vs 145.5 days, P=0.008, respectively). There were no significant differences in the incidences of relapse, serum sickness, Epstein-Barr virus (EBV) reactivation, cytomegalovirus (CMV) reactivation, or serious infection in the three groups. The estimated 5-year overall survival (OS) and failure-free survival (FFS) did not differ in the three groups. A logistic regression analysis revealed that IST+UCBI+MSCI and very SAA (VSAA) can predict ORR. However, only the response to IST was found to be predictive of improved OS and FFS. These data suggest that IST+UCBI+MSCI achieves a higher ORR and a shorter TTR than IST and are well tolerated in SAA and TD-NSAA patients.