Clinical analysis of FCA as a conditioning regimen for the allogeneic hematopoietic stem cell transplantation in 27 patients with severe aplastic anemia
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摘要: 目的:评价FCA(氟达拉滨+减量环磷酰胺+抗胸腺细胞球蛋白)作为重型再生障碍性贫血(SAA)患者异基因造血干细胞移植(allo-HSCT)预处理方案的疗效及安全性。方法:对2014年11月—2020年5月在徐州医科大学附属医院骨髓移植中心接受allo-HSCT治疗的27例SAA患者进行回顾性研究,其中男13例(48.1%),女14例(51.9%);中位年龄23(3~48)岁;骨髓联合外周血造血干细胞移植23例(85.2%),脐血联合外周血造血干细胞移植2例(7.4%),外周血造血干细胞移植2例(7.4%);HLA全合同胞供者(MSD)15例(55.6%),HLA单倍体相合亲缘供者(HFD)12例(44.4%)。预处理方案:氟达拉滨120 mg/m2,-5~-2 d;环磷酰胺120 mg/kg,-5~-2 d;抗胸腺细胞球蛋白(兔抗人)10 mg/kg,-5~-2 d。采用环孢素A+短程甲氨蝶呤+霉酚酸酯方案预防移植物抗宿主病(GVHD)。结果:27例患者中性粒细胞、血小板中位植入时间分别为13(10~25) d、15(11~111) d。3例(11.1%)患者发生Ⅲ~Ⅳ度急性GVHD,1例(3.7%)患者发生广泛型慢性GVHD。27例患者中7例死亡,生存的20例患者均获得造血重建,并在移植后不同时间点检测STR-PCR结果均为完全供者嵌合。移植过程中17例(63.0%)患者发生CMV血症;20例(74.1%)发生EBV血症,其中1例(3.7%)进展为EBV相关移植后淋巴细胞增殖性疾病;10例(37.0%)患者在骨髓抑制期发生败血症;3例(11.1%)发生肺部感染;1例(3.7%)发生中枢神经系统感染;1例(3.7%)发生肛周感染。存活患者的中位随访时间39.1(3.5~70.2)个月,预期5年总生存率及无失败生存率均为73.3%。MSD组及HFD组的5年总生存率及无失败生存率差异均无统计学意义(均为86.2%和57.1%;χ2=2.962,P=0.085)。结论:氟达拉滨联合减量环磷酰胺及抗胸腺细胞球蛋白预处理方案行HLA同胞全相合及亲缘单倍体相合allo-HSCT治疗SAA均安全有效。Abstract: Objective: To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation(allo-HSCT) for severe aplastic anemia(SAA) with pre-transplant conditioning using FCA(fludarabine+reduced-dose cyclophosphamide+anti-thymocyte globulin).Methods: The clinical data of 27 SAA patients(male 13, female 14) who received allo-HSCT from November 2014 to May 2020 in the bone marrow transplantation center of Affiliated Hospital of Xuzhou Medical University were analyzed retrospectively. Among them, 23 patients(85.2%) received bone marrow combined mobilized peripheral blood stem cells transplantation, 2 patients(7.4%) received cord blood combined mobilized peripheral blood stem cells transplantation and 2 patients(7.4%) underwent mobilized peripheral blood stem cells transplantation. Fifteen patients(55.6%) received MSD-HSCT and 12 patients(44.4%) received HFD-HSCT. The conditioning regimen was consisted of fludarabine 120 mg/m2,-5 to-2 d, cyclophosphamide 120 mg/kg,-5 to-2 d; ATG 10 mg/kg,-5 to-2 d. GVHD prophylaxis was performed by cyclosporine +short-term course methotrexate+mycophenolate mofetil.Results: The median durations of myeloid engraftment were 13(10 to 25) days and 15(11 to 111) days for platelets. Three patients(11.1%) had grade III to IV aGVHD. Only 1 patient(3.7%) had extensive cGVHD during the follow-up period. Seven cases of the 27 patients were died. All the 20 surviving patients achieved hematopoietic reconstitution. And the results of STR-PCR detection during the 20 surviving patients at different time points after transplantation were complete donor chimerism. During the transplantation process, 17 patients(63.0%) developed CMV viremia, 20 patients(74.1%) with EBV viremia, 1 patient(3.7%) with EBV progressed post-transplant lymphoproliferative disorders; 10 patients(37.0%) with septicemia during bone marrow suppression; 3 patients(11.1%) with pulmonary infection; 1 patient(3.7%) with central nervous systems infections; 1 patient(3.7%) with perianal infection. The median follow-up time of survival patients was 39.1(3.5 to 70.2) months. Both the expected 5-year overall survival rate and failure-free survival rate were 73.3%. There was no significant difference in 5-year overall survival rate and failure-free survival rate between MSD group and HFD group(86.2% and 57.1%; χ2=2.962, P=0.085).Conclusion: For both MSD-HSCT and HFD-HSCT, fludarabine combined with reduced-dose cyclophosphamide and anti-thymocyte globulin pretreatment regimen is safe and effective in the treatment of SAA.
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