非清髓性异基因造血干细胞移植预处理方案的毒性比较

Toxicity of fluadarabine versus antithymocyteglobulin in conditioning regimen of non-myeloablative allogeneic hematopoietic stem cell transplantation

背景:选择高效低毒的预处理方案是提高造血干细胞移植成功率的关键。氟达拉滨和抗胸腺细胞球蛋白,均属于强效免疫抑制剂,常用于非清髓性造血干细胞移植预处理中。目的:对采用氟达拉滨或抗胸腺细胞球蛋白为基础的非清髓性异基因造血干细胞移植预处理方案患者,在预处理中及移植后早期毒性进行比较。方法:32例血液系统恶性肿瘤患者中,按照非清髓性预处理方案中的免疫抑制剂分成两组即氟达拉滨组和抗胸腺细胞球蛋白组,预处理方案均为氟达拉滨或抗胸腺细胞球蛋白联合减低化疗强度的白消安/环磷酰胺,或者马法兰。抗胸腺细胞球蛋白组在形成混合性嵌合体后进行供者淋巴细胞输注。对两组患者预处理中出现的器官毒性进行统计学分析,毒性分级参照Bearman等制订的预处理相关毒性(RRT)分级标准。结果与结论:两组无因预处理相关毒性而死亡。氟达拉滨组转氨酶发生率、腹泻发生率与和抗胸腺细胞球蛋白组比较差异均无显著性意义(P>0.05);氟达拉滨组肝脏毒性发生率、黏膜炎发生率均显著低于抗胸腺细胞球蛋白组(P<0.05);血液学毒性方面,氟达拉滨组白细胞达最低值、血小板≥50×109L-1的时间、输注红细胞量、输注血小板的量均低于抗胸腺细胞球蛋白组(P<0.05)。

BACKGROUND： The highly-effective conditioning regirnens of proper dose and low-toxicity are the key to the successful hematopoietic stem cell transplantation. Fludarabine and antithymocyteglobulin are intensive immunosuppressants, and are usually used in conditioning regimen of non-myeloabiative hematopoietic stem cell transplantation. OBJECTIVE： To compare the toxicity of fluadarabine versus antithymocyteglobulin in the conditioning regimen of non-myeloablative aUogeneic hematopoietic stem cell transplantation. METHODS： Thirty-two patients with malignant hematologic diseases were divided into fludarabine group and antithymocyteglobulin group according to the difference of immunosuppressants in conditioning regimen.Conditioning regimen consisted of fluadarabine or antithymocyteglobulin combined with the reduced-dose busulfan and cyclophosphamide or L-Sarcolysinum. The donor lymphocyte infusion was performed after the formation of mixed chimerism in antithymocyteglobulin group. The toxicity in the two groups was statistically analyzed, and the regimen-related toxicity was scored using the criteria of Bearman. RESULTS AND CONCLUSION： No one died of regimen-related toxicity in two groups. There were no significant differences in the incidence of transaminase and diarrhea between fluadarabine and antithymocyteglobulin groups （P 〉 0.05）; while the incidence of liver toxicity and mucositis in fluadarabine group was lower than that in the antithymocyteglobulin group （P 〈 0.05）. About hemotologic toxicity, the time for white blood call count reaching the lowest value and platelets≥50×10^9/L, the volume of infused red cells and the volume of infused platelets in the fluadarabine group were lower than those in the antithymocyteglobulin group （P 〈 0.05）.