Anti-thymocyte globulin (ATG) has been used in severe aplastic anemia as a part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective in preventing graft versus host disease (GVHD) and rejection of organ transplants. As the fludarabine based conditioning regimens without total body irradiation have been reported to be promising for transplantation from alternative donors in SAA, thymoglobulin was added to fludarabine and cyclophosphamide conditioning to reduce GVHD and to allow good engraftment in unrelated donor transplantation. Our previous phase II study of fludarabine, cyclophosphamide plus thymoglobulin conditioning resulted in good engraftment (100%) and survival rate (74%). But grade III/IV toxicities occurred in 25% of patients and all events were treatment related mortalities. As cyclophosphamide is more toxic agent than fludarabine, we plan a new phase II study re; 'reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated donor transplantation in severe aplastic anemia' by reducing dosage of cyclophosphamide and increasing dosage of fludarabine.

Inclusion Criteria:

1. Diagnosis of severe aplastic anemia defined by any two or three peripheral blood criteria and either marrow criterion.

   • Peripheral blood

     1. Neutrophils < 0.5 x 109/l
     2. Platelets < 20 x 109/l
     3. Corrected reticulocytes < 1%

   • Bone marrow

     1. Severe hypocellularity (< 25%)
     2. Moderate hypocellularity (25-30%) with hematopoietic cells representing < 30% of residual cells

2. No prior hematopoietic stem cell transplantation.

3. Age: no limits.

4. Performance status: ECOG 0-2.

5. Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases:

   • Heart: a shortening fraction > 30% and ejection fraction > 45%.
   • Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper
   • Kidney: creatinine <2 × normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2.

6. Patients must lack any active viral infections or active fungal infection.

7. Appropriate donor is available: Matched in 6/6 of A, B, DR loci.

8. Patients (or one of parents if patients age < 19) should sign informed consent.

Exclusion Criteria:

1. Pregnant or nursing women.
2. Malignant or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
3. Psychiatric disorder that would preclude compliance.
4. Congenital aplastic anemia including Fanconi anemia.
5. Manipulated bone marrow.