Hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA) -matched donor is an effective option for severe aplastic anemia (SAA), but there is no standardized and recommended conditioning regimen. The occurrence of mixed chimerism after transplantation is associated with secondary graft failure and poor failure-free survival. Previous studies have shown that Fludarabine (Flu)/ Cyclophosphamide (Cy)/ antithymocyte globulin (antithymocyte globulin), ATG) and Cy/ATG conditioning regimens had higher rates of mixed chimerism and poorer failure-free survival. A small cohort study has suggested that adding busulfan to Flu/Cy/ATG or Cy/ATG can reduce the incidence of mixed chimerism and improve failure-free survival. This study was a prospective, multicenter, randomized controlled trial to compare the efficacy and safety of different conditioning regimens in the treatment of severe aplastic anemia (SAA) after hematopoietic stem cell transplantation (HSCT) from HLA-identical sibling or unrelated donor.

Inclusion Criteria:

1. Diagnosed as SAA/vSAA

2. Indication for hematopoietic stem cell transplantation

3. Available HLA matched sibling or unrelated donor

4. No active infection

5. No serious organ damage: liver and kidney function (ALT and AST < 2.5 times normal value, normal renal function, no cardiac insufficiency)

6. Signed informed consent

7. High risk factors of mixed chimerism, at least one of the following

   1. Age < 18 years old
   2. Ferritin level ≥2500ng/ml before transplantation

Exclusion Criteria:

1. Age > 50 years old
2. ECOG≥3
3. Active infections that were difficult to control
4. Severe liver and kidney dysfunction
5. Mental illness
6. Not signing the informed consent
7. pregnant or lactating women
8. Any condition considered by the investigators to be unsuitable for enrollment