供者淋巴细胞输注与免疫抑制剂减停反转重型地中海贫血移植后嵌合率有效性及安全性的比较

Safety and priority comparison between donor lymphocyte infusion and immunosuppressant reduction in converting incomplete post-transplant chimerism for patients with Thalassemia major

目的探讨减停免疫抑制剂(IDR)与供者淋巴细胞输注(DLI)在治疗重型地中海贫血(TM)移植后出现供受者细胞混合嵌合状态(MC)的疗效比较。方法将本中心2009年1月—2018年12月期间78例移植后出现MC的患者分组。供者细胞在90%~95%和75%~89%的分别定为MC1和MC2组。比较IDR组与DLI组在移植后不同时间(早期:≤90 d,中期:91 d~179 d,晚期:≥180 d)MC的纠正率及移植物抗宿主病(GVHD)的发生率,分析DLI组剂量及方法。结果DLI组MC纠正率高于IDR组;但DLI组GVHD发生率明显高于IDR组。发生在中期的MC1患者,DLI组GVHD发生率高于IDR组。IDR组内早、中、晚期DLI者,GVHD发生率分别为54%,29%和5%(P=0.001)。结论MC1无论发生哪期,建议先行逐渐减停免疫抑制剂。晚期发生的MC2患者建议直接DLI治疗。DLI治疗后GVHD与DLI应用时间相关,DLI越早越易发生GVHD。

Objective To compare immunosuppressive drugs reduction(IDR)and donor lymphocyte infusion(DLI)in the correction of MC after TM transplant.Methods Seventy-eight patients with MC after transplant in our center from January 2009 to December 2018 were divided in to groups.90%-95%and 75%-89%of donor cells were assigned to MC1 and MC2 groups,respectively.The IDR and DLI groups were compared at different times after transplant(early-stage:≤90 days,intermediate-stage:91-179 days,late-stage:≥180 days).The incidence of MC correction and the graft versus host disease(GVHD)occurrence and the dose and application of DLI were analyzed.Results The correction rate of MC in DLI group was higher than that in IDR group.However,the incidence of GVHD in DLI group was significantly higher than that in IDR group.For MC1 patients occurred in intermediate stage,the incidence of GVHD in DLI group was higher than that in IDR group.In IDR group,the incidence of GVHD was 54%,29%and 5%for early-stage,intermediate-stage,and late-stage patients,respectively(P=0.001).Conclusions No matter what stage of MC1 occurs,it is recommended to stop immunosuppressant gradually first.For MC2 patients occurred in late-stage,direct DLI treatment is recommended.After DLI,GVHD is correlated with DLI time.The earlier DLI time,the higher GVHD occurred.