Effects and Predictive Factors of Immunosuppressive Therapy Combined with Umbilical Cord Blood Infusion in Patients with Severe Aplastic Anemia

Abstract

Purpose: To investigate the efficacy and safety of umbilical cord blood (UCB) infusion (UCBI) plus immunosuppressive therapy (IST) treatment in comparison to IST treatment, as well as predictive factors for clinical responses, in severe aplastic anemia (SAA) patients.

Materials and methods: Totally, 93 patients with SAA were enrolled in this cohort study. In the IST group, rabbit antithymocyte globulin (r-ATG) combined with cyclosporine A (CsA) was administered, while in the IST+UBCI group, r-ATG, CsA, and UCB were used.

Results: After 6 months of treatment, UCBI+IST achieved a higher complete response (CR) rate (p=0.002) and an elevated overall response rate (ORR) (p=0.004), compared to IST. Regarding hematopoietic recovery at month 6, platelet responses in the UCBI+IST group were better than those in the IST group (p=0.002), and UCBI+IST treatment facilitated increasing trends in absolute neutrophil count (ANC) response (p=0.056). Kaplan-Meier curves illuminated UCBI+IST achieved faster ANC response (p<0.001) and platelet response (p<0.001), compared with IST therapy. There was no difference in overall survival (OS) between the two groups (p=0.620). Furthermore, logistic regression analysis demonstrated that UCBI+IST was an independent predicting factor for both CR (p=0.001) and ORR (p<0.001), compared to IST; meanwhile, very severe aplastic anemia (VSAA) and ANC could predict clinical responses as well. However, Cox proportional hazard regression indicated that VSAA (p=0.003), but not UCBI+IST, affected OS. Safety profiles showed that UCBI+IST therapy did not elevate adverse events, compared with IST treatment.

Conclusion: UCBI+IST achieved better clinical responses and hematopoietic recovery than IST, and was well tolerated in SAA patients.

Keywords: Effect; immunosuppressive therapy (IST); predictive factors; severe aplastic anemia (SAA); umbilical cord blood infusion (UCBI).

Fig. 1. Comparison of treatment responses between UCBI+IST and IST treatments at 6 months. Both CR and ORR were higher in the UCBI+IST group than the IST group. Differences between groups were detected by chi-square test. p<0.05 was considered significant. IST, immunosuppressive therapy; UCBI, umbilical cord blood infusion; ORR, overall response rate; CR, complete response; PR, partial response; NR, no remission.

Fig. 2. K-M curves analysis for days to ANC, platelet, and hemoglobin responses in the UCBI+IST and IST groups. K-M curves revealed that patients in the UCBI+IST group achieved faster ANC (A) and platelet (B) responses, compared to the IST group. While no difference was discovered in hemoglobin response (C). Differences between groups were detected by K-M curves and log-rank test. p<0.05 was considered significant. K-M, Kaplan-Meier; ANC, absolute neutrophil count; IST, immunosuppressive therapy; UCBI, umbilical cord blood infusion.

Fig. 3. Accumulating OS rates of patients in UCBI+IST and IST groups. No difference in accumulating OS rates between the two groups was found. Differences between groups were detected by Kaplan-Meier curve and log-rank test. p<0.05 was considered significant. OS, overall survival; IST, immunosuppressive therapy; UCBI, umbilical cord blood infusion.

Fig. 4. Comparison of adverse events between IST and UCBI+IST treatments. No differences were observed in infection, fever, hemorrhage, ATG-related serum diseases, and rush between IST and UCBI+IST groups. Differences between groups were evaluated by chi-square test. p<0.05 was considered significant. IST, immunosuppressive therapy; UCBI, umbilical cord blood infusion; ATG, antithymocyte globulin.