Clinical analysis of allogeneic hematopoietic stem cell transplantation with high-dose cyclophosphamide-induced immune tolerance for severe aplastic anemia

Objective The study was aimed to explore the efficacy and safety of allogeneic stem cell transplantation (allo-HSCT) with high-dose cyclophosphamide-induced immune tolerance in the treatment of severe aplastic anemia(SAA). Method 20 cases with SAA received reducing the intensity conditioning allo-HSCT from 2012 August to 2014 August, it is a new method for post-transplantation with high-dose cyclophosphamide-induced immune tolerance, including 12 males and 8 females, the age ranged from 6 to 37 years old, and the average age of 17.8 years old, all are HLA-mismatched transplantation and received CsA therapy, eleven of them received ATG intensive immune therapy.The donors accepted mobilization with cell colony stimulating factor from both peripheral blood and bone marrow. The improved Preconditioning regimen was reduced strength of fludarabine combined with Busulfex and cytarabine、cyclophosphamide. Cyclophosphamide (50mg/Kg/d) induced immune tolerance on the + 3 days after transplantation, combined immunosuppressive agents were used for graft-versus-host disease(GVHD) prophylaxis, including CsA, Amethopterin, tacrolimus, etc..and observed toxicity、GVHD and disease-free survival in patients after transplantation. Result 17 cases of hematopoietic reconstitution and the other three cases implants after the second transplantion, the average time were 17.4 d and 21.3 d respectively with neutrophils≥0.5×109/L and platelets≥20×109/L.Implantation was confirmed by the evidence of 100% of donor hematopoiesis and T lymphocyte subsets counts increased significantly before and after the transplantation. Follow-up to 2015 April, With the median follow-up duration of 17.7 months (6~32 months), 3 cases died of complication and the other 17 patients remained disease-free survival, disease-free survival rate was 85% and the longest disease-free survival time up to 32 months. Conclusion Reduced intensity allogeneic hematopoietic stem cell transplantation with high-dose cyclophosphamide-induced immune tolerance treatment is the safe and effective method for severe aplastic anemia. Key words: Severe aplastic anemia; Hematopoietic stem cell transplantation; Cyclophosphamide; Immune tolerance