To analyze the efficacy and prognosis of FC/ATG pretreatment combined with cyclosporine delayed oral regimen for haploid stem cell transplantation (HSCT) in patients with severe aplastic anemia (SAA).

A total of 106 SAA patients who underwent HSCT in the Third Hospital of Shanxi Medical University from December 2011 to September 2021 were analyzed. The efficacy of FC/ATG and Bucy/ATG pretreatment regimens, delayed oral administration of cyclosporine and normal oral administration regimens were compared. The evaluation indicators included adverse reactions related to pretreatment, hematopoietic reconstitution, chimerism of donor and recipient stem cells, monitoring of cyclosporine plasma concentration, incidence of graft versus host disease (GVHD), and the survival and prognosis of patients were analysed. The measurement data with normal distribution were compared by group t test, and the measurement data with non-normal distribution were compared by Mann-Whitney U test. Enumeration data were compared by Fisher exact probability method. Gray test was used to calculate the cumulative incidence of acute and chronic GVHD. The overall survival rate was calculated by Kaplan-Meier method and compared by log-rank test. Cox proportional hazards model was used to analyze the risk factors of acute GVHD after HSCT in SAA patients. P< 0.05 was considered statistically significant.

There were 34 patients in Bucy/ATG pretreatment group and 72 patients in FC/ATG pretreatment group; 36 patients chose the normal oral regimen of cyclosporine (after gastrointestinal symptoms disappeared), and 62 patients chose the delayed oral regimen of cyclosporine (maintained intravenous infusion for + 50 d and then changed to oral administration). Neutrophils and platelets were successfully implanted in both pretreatment schemes. The incidences of grades Ⅲ-Ⅳ oral ulcer and diarrhea in Bucy/ATG group (61.8% and 44.1%) were higher than those in FC/ATG group (16.7% and 18.1%), and the differences were statistically significant (all P<0.05). Severe infection caused 5 deaths (14.7%) in Bucy/ATG group and 3 deaths (4.2%) in FC/ATG group during pretreatment, and the difference in mortality was statistically significant (P<0.05). There were significant differences in the blood concentration of cyclosporine between the normal oral group and the delayed oral group at + 30 d, + 40 d and + 50 d, and the blood concentration of cyclosporine in the delayed oral group was more stable (t=-4.322, -5.751 and -9.773, all P<0.05). The cumulative incidence of acute GVHD (52.8%) and moderate to severe chronic GVHD (55.6%) in the cyclosporine normal oral regimen group were higher than those in the cyclosporine delayed oral regimen group (24.2% and 22.6%, all P<0.05). HLA mismatch (RR=0.476, 95%CI: 0.932-1.679, P<0.05) and cyclosporine normal oral regimen (RR=0.329, 95%CI: 1.331-1.843, P<0.05) were risk factors for acute GVHD. The median follow-up time of 106 recipients was 37.6 months (11-93 months), and a total of 21 patients died. The 2-year survival rates after HSCT in Bucy/ATG group and FC/ATG group were 66.3% and 87.9%, respectively (χ²=7.355, P<0.05).

FC/ATG pretreatment combined with cyclosporine delayed oral regimen may be a safe and effective regimen for HSCT in the treatment of SAA.