以FCA预处理的造血干细胞移植治疗SAA的临床研究

目的探讨以氟达拉滨（Flu）、低剂量环磷酰胺（CTX）和抗胸腺细胞球蛋白（ATG）为预处理的FCA方案异基因造血干细胞移植治疗重型再生障碍性贫血（SAA）的疗效及安全性。方法用FCA预处理方案预处理移植治疗SAA-Ⅰ型和SAA-Ⅱ型患者各2例,其中同胞供者人类白细胞抗原（HLA）低分辨配型（6/6位点）全相合的骨髓联合外周血造血干细胞移植3例、非血缘关系高分辨HLA配型（10/10位点）全相合的外周血造血干细胞移植1例。同胞供者的预处理方案：Flu30mg·m-2d-1×5d,CTX50～60mg·kg-1d-1×5d,ATG3mg·kg-1d-1×3d。非血缘关系的预处理方案：CTX20mg·kg-1d-1×2d,ATG5mg·kg-1d-1×3d,Flu30mg·m-2d-1×4d。移植物抗宿主病（GVHD）的预防：均采用低剂量环孢素A（CsA）联合低剂量短程甲氨蝶呤（MTX）,非血缘关系移植加用霉酚酸酯（MMF）0.5gbid,＋1d～＋28d。观察移植并发症、输血量、造血重建、嵌合体和生存状态。结果 4例患者均获得造血干细胞的成功植入,移植后中性粒细胞绝对值（ANC）〉0.5×109/L的时间为＋10d～＋15d,血小板（PLT）〉20×109/L的时间为＋10d～＋20d,移植后输注红细胞3～6U,血小板4～10U,随访7～42个月,完全供者嵌合体,血液学完全缓解;患者1出现广泛型慢性移植物抗宿主病（cGVHD）,死于多脏器功能衰竭,其余3例无病生存,其中非血缘关系移植的患者4发生轻度局限型cGVHD和巨细胞病毒血症,经过治疗很快控制。结论 Flu、低剂量CTX和ATG的FCA预处理方案的异基因造血干细胞移植治疗SAA的疗效肯定,患者耐受性好,值得推广。

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.