减低剂量环磷酰胺的预处理方案对重型再生障碍性贫血同胞全相合外周血造血干细胞移植疗效的影响

Improved outcome by optimized conditioning regimens with an increased dose of cyclophosphamide in allogeneic peripheral blood stem cell transplantation for severe aplastic anemia

目的分析减量环磷酰胺（cy）的联合预处理方案对接受同胞全相合外周血造血干细胞移植（MSD—PBSCT）的重型再生障碍性贫血（SAA）患者疗效的影响。方法51例获得性SAA患者接受MSD—PBSCT，预处理方案含两种减量Cy（150mg／kg或120mg／kg）联合氟达拉滨（Flu）和抗胸腺细胞球蛋白（ATG）。比较两组患者生存率、植入情况、移植物抗宿主病（GVHD）和感染发生率问的差异。结果预处理含150mg／kgCy组（Cyl50组）患者与含120mg／kgCy组（Cyl20组）比较，5年总生存与无失败生存率相近（93．5％对90．0％，x2=0．170，P=-0．680；90．3％对85．0％，x2=0．285，P=0．594）。但是多因素分析结果显示，Cyl20组急性GVHD（HR=3．89，95％CI1．21～12．53，P=-0．023）及慢性GVHD（HR=4．48，95％CI1．40～14．32，P=0．011）发生风险均显著高于Cyl50组。而两组间的机会性感染发生率及移植排斥率差异均无统计学意义。结论与120mg／kg相比，150mg／kg的cy联合Flu和ATG的预处理方案更能改善接受MSD．PBSCT治疗的获得性SAA患者的总体疗效。

Objective To respectively analyze the impact of conditioning regimens with a dose- decreased cyclophosphamide （Cy） on the outcome in fully matched sibling donor （MSD） peripheral blood stem cell transplantation （PBSCT） for severe aplastic anemia （SAA）. Methods Two conditioning regimens with different doses of Cy （150 mg/kg or 120 mg/kg） in combination with fludarabine （Flu） and antithymocyte globulin （ATG） for MSD-PBSCT were investigated in 51 patients with acquired SAA. Results Overall survival and failure-free survival in patients received 150 mg/kg of Cy （Cy150 cohort） or 120 mg/kg （Cyl20 cohort） were 93.5% vs 90.0% （x2-0.170, P=0.680） and 90.3% vs 85.0% （x=0.285, P- 0.594） respectively. However, either acute or chronic graft-versus-host disease risks were higher in Cyl20 cohort than in Cyl50 cohort （HR-3.89, 95% CI 1.21-12.53, p=0.023; HR=4.48, 95% C1 1.40-14.32, P=- 0.011, respectively）. No difference was found for opportunistic infections or graft failure between two cohorts. Conclusion Cy at a dose of 150 mg/kg, in combination with Flu and ATG, was more effective than that of 120 mg/kg Cy to produce improved clinical outcome in the setting of acquired SAA patients after MSD-PBSCT.