同种异基因造血干细胞移植后基于血细胞嵌合状态的个体化免疫治疗  

Individualized immunotherapy based on blood cell chimerism after allogeneic hematopoietic stem cell transplantation

作　　者：万理萍[1] 王椿[1] 蒋瑛[1] 颜式可[1] 姜杰玲[1] 杨隽[1] 蔡宇[1] 秦尤文[1] 王小蕊[1] 

机构地区：[1]上海交通大学附属第一人民医院血液科,上海200080

出　　处：《诊断学理论与实践》2010年第1期25-30,共6页Journal of Diagnostics Concepts & Practice

摘　　要：目的:研究同种异基因造血干细胞移植(allo-HSCT)后血细胞嵌合率变化与复发的关系;观察根据血细胞嵌合率变化给予个体化免疫抑制剂治疗和供者淋巴细胞输注(DLI)的疗效。方法:106例供者细胞顺利植入的allo-HSCT患者,采用聚合酶链反应(PCR)扩增短串联重复序列的方法,动态检测移植后T淋巴细胞、B淋巴细胞、自然杀伤(NK)细胞的嵌合率。根据血细胞嵌合率的变化调整免疫抑制剂剂量和DLI的使用。结果:6例患者在移植后2个月,供者T细胞嵌合状态一直为混合嵌合(MC),将免疫抑制剂减量后均达到完全供者嵌合(FDC)。12例患者在移植后1～5个月,发生供者T细胞嵌合率下降,予免疫抑制剂减量后转为FDC。24例患者血液学复发或髓外复发(进展),有6例在复发前共发生10例次血细胞嵌合率下降,经免疫抑制剂减量或停药后一度回升至FDC,但最终血液学或髓外复发。12例患者在复发或疾病进展后停用免疫抑制剂,共给予DLI23例次,其中8例在DLI前或后给予化疗,最终5例再次达到完全缓解,其余患者最终均因疾病复发死亡。Ⅱ度及Ⅱ度以上急性移植物抗宿主病(GVHD)发生率为28.3%。慢性GVHD发生率为55.7%。中位随访期为17(1.5～90.0)个月,无病生存65例,死亡41例。67例标危患者预期3年生存率为59.0%;39例高危患者预期3年生存率为44.7%。结论:T淋巴细胞、NK细胞和B淋巴细胞的嵌合状态可作为血液恶性肿瘤复发的预测指标;基于血细胞嵌合率的个体化免疫治疗可以推迟甚至避免临床复发,且不增加急性GVHD的发生。Objective To investigate the relationship between blood cell chimerism and relapse after allogeneic hematopoietic stem cell transplantation （allo-HSCT）,and to evaluate the efficacy of individualized immunosuppressant therapy and donor lymphocyte infusion based on the changes of blood cell chimerism.Methods T lymphocyte,B lymphocyte and NK cell chimerism were determined by PCR amplification of short tandem repeat sequences in 106 successfully engrafted patients with allo-HSCT.Individualized immunosuppressant therapy and donor lymphocyte infusion were administrated to patients based on the change of blood cell chimerism.Results T lymphocytes of 6 patients achieved full donor chimerism from mixed chimerism with the reduction of immunosuppressant dose.T lymphocytes of 12 patients achieved full donor chimerism from decrease of T cell chimerism rate after reduction of immunosuppressant dose.Of the 24 patients relapsed,6 patients had 10 times of reduction in blood cell chimerism rate,and achieved full donor chimerism temporarily after reduction of immunosuppressant dose,but all were finally relapsed.Donor lymphocyte infusion were also given 23 times to 12 patients when the disease was relapsed or progressed,8 of them also received chemotherapy pre-or post-donor lymphocyte infusion.Five of these patients achieved complete remission again,and the others died of relapse.The incidences of grade Ⅱ-Ⅳ acute GVHD was 28.3%,chronic GVHD was 55.7%.Sixty-five patients survived free of diseases and 41 patients died after a median follow up of 17 months.Expected 3-year survival rate of standard risk patients was 59.0%,high risk patients was 44.7%.Conclusions T,B and NK lymphocyte chimerism could be used as a relapse predictor of hematological malignancy.Individualized immunotherapy based on changes of blood cell chimerism could delay or avoid clinical relapse,and did not increase the incidence of acute GVHD.

关 键 词：同种异基因造血干细胞移植 嵌合 免疫抑制剂 供者淋巴细胞输注 

分 类 号：R552[医药卫生—血液循环系统疾病]