The effect of pretreatment with fludarabine and antithymocyte globulin and cyclophosphamide before hematopoietic stem cell transplantation on the treatment of severe aplastic anemia

Objective To investigate the efficacy and safety use of the FCA regimen consisting of fludarabine (Flu),low-dose cyclophosphamide (CTX) and antithymocyte globulin (ATG) in allogeneic hematopoietic stem cell transplantation for severe aplastic anemia (SAA). Methods FCA transplantation pre-treatment regimen was performed for SAA-Ⅰ(n=2) and SAA-Ⅱ(n=2) patients. Combination of bone marrow and peripheral blood stem cell from low-resolution HLA matching (6/6 loci) sibling donors (n=3) were transplanted for three patients, while high-resolution HLA (10/10 loci) of unrelated donor peripheral blood hematopoietic stem cell transplantation for one patient. Conditioning regimen consisted of fludarabine 30 mg·m-2d-1×5 d, CTX 50～60 mg·kg-1d-1×5 d and ATG 3 mg·kg-1d-1×3 d was used for sibling donor transplantation, while CTX 20 mg·kg-1d-1×2 d, ATG 5 mg·kg-1d-1×3 d and fludarabine 30 mg·m-2 d-1×4 d was used for unrelated transplantation. Low-dose of cyclosporine A (CsA) combined with low-dose of short-term-methotrexate (MTX) and enzyme mofetil (MMF) 0.5 g bid (+1 d～+28 d) was used for prophylaxis of graft-versus-host disease(GVHD) in the unrelated transplantation.The transplantation complication, volume of blood transfusion,hematopoietic reconstitution, state of chimerism and survivorship were observed. Results Four patients successfully achieved stem cells engraftment. The time for the patient achieving the absolute count of neutrophil (ANC) 0.5×109/L and of PLT20×109/L post-transplant was ranged between 10 d to 15 d and 10 d to 20 d,respectively. The transfused volume of red blood cells and platelets after transplantation were 3 U to 6 U and 4 U to 10 U, respectively. Followed up for 7 to 42 months,all patients achieved full donor chimerismed hematological complete remission. Case 1 was complicated with extensive cGVHD and died of multiple organ failure,other three cases remained disease-free survival.Case 4 of unrelated transplantation was complicated with mild localized chronic graft-versus-host disease and cytomegalovirus viremia, but was controlled quickly. Conclusion The FCA conditioning regimen of fludarabine, low-dose CTX and ATG in allogeneic hematopoietic stem cell transplantation for SAA patient is effective and enhance immune tolerance in patients and worth promoting.