The Comparison Of Clinical Outcomes Between Matched Sibling Stem Cell Transplantation and Immunosuppressive Treatment As a First-Line Treatment For Adult Patients With Severe Aplastic Anemia

Allogeneic stem cell transplantation (SCT) from matched-sibling donor (MSD) and immunosuppressive treatment (IST) are the most widely used first-line treatments for patients with severe aplastic anemia (SAA). Overall long-term survival rates are comparable between the two groups. However, patients with age of over 40 have not been generally considered as candidates of SCT from MSD (MSD-SCT) due to higher transplant-related mortality. Recent improvements in MSD-SCT such as less intensive fludarabine-based conditioning, and use of rabbit anti-thymocyte globuline (ATG) instead of horse ATG as first-line IST may change these results. Therefore, we compared the clinical outcomes between MSD-SCT with fludarabine-based conditioning and IST with rabbit ATG and cyclosporine A (CsA).

We analyzed the clinical results of 54 adult SAA patients who were treated with MSD-SCT and 93 with IST as a first-line treatment from March 2006 to May 2012 at Seoul St. Mary’s Hospital, Seoul, Korea. The patients who were treated with MSD-SCT received conditioning with fludarabine (30 mg/m²/day × 6 days), cyclophosphamide (50 mg/kg/day × 2 days), and rabbit ATG (Thymoglobulin^®, 2.5 mg/kg/day × 4 days). Those who were treated with IST received rabbit ATG (2.5 mg/kg/day × 5 days) with CsA.

The median ages were not significantly different between the MSD-SCT group and IST group (38.5 years vs. 43.0 years; P=0.103). Other baseline characteristics were comparable except the interval from diagnosis to treatment (100 days vs. 40 days; P=0.013), absolute lymphocyte count (0.68 × 10⁹/L vs. 0.93 × 10⁹/L; P=0.013), and platelet count (10.0 × 10⁹/L vs. 11.0 × 10⁹/L; P=0.035). In the IST group, overall response and complete response rates at 1 year were 44.1% (95% CI, 33.8-54.8) and 10.8% (95% CI, 5.3-18.9). Treatment failure developed in 55 (59.1%) patients due to non-response in 34 (36.6%), relapse in 5 (5.4%), clonal evolution in 3 (3.2%), and treatment-related mortality in 13 (14.0%) patients. After treatment failure, 17 (18.3%) patients received SCT from MSD or unrelated donor. In the MSD-SCT group, 10 (18.5%) patients experienced treatment failure due to secondary graft failure in 5 (9.3%), clonal evolution in 1 (1.9%), and treatment-related mortality in 4 (7.4%) patients. Among the patients who experienced secondary graft failure, 4 (7.4%) patients received secondary SCT, which resulted in sustained graft function. Consequently, overall survival (OS) at 3 years in the MSD-SCT group was not significantly different compared to that in the IST group (90.7% vs. 81.0%; P=0.139). However, the MSD-SCT group showed significantly higher failure-free survival (FFS) at 3 years compared to the IST group (80.2% vs. 46.6%; P<0.001). When we analyzed the patients with age of over 40 years, OS at 3 years in the MSD-SCT group was not significantly different compared to that in the IST group (87.5% vs. 74.7%; P=0.251), whereas FFS at 3 years in the MSD-SCT group was significantly higher compared to that in the IST group (84.0% vs. 43.0%; P=0.001).

Our data suggest that MSD-SCT is more favorable than IST as a first-line treatment, considering the curative nature of MSD-SCT even in patients over 40 years of age.

No relevant conflicts of interest to declare.