恶性血液病异基因造血干细胞移植后复发单中心临床分析

Analysis of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Hematological Malignancies:A Single-center Study

目的:分析恶性血液病患者异基因造血干细胞移植(allo-HSCT)后复发的生存情况、预后影响因素及复发的防治,探讨免疫重建、人类白细胞抗原丢失等与移植后复发的关系。方法:回顾性分析2012年7月至2020年6月行allo-HSCT后复发的47例恶性血液病患者临床资料,同胞HLA全合移植(MSD)20例,亲缘单倍体移植(HID)26例,非血缘HLA全合移植(MUD)1例,对可能影响复发后总生存率(PROS)的危险因素进行多因素分析。结果:47例患者均成功植入,移植后Ⅱ-Ⅳ和Ⅲ/Ⅳ度急性移植物抗宿主病(aGVHD)发生率分别为40.4%和10.6%,慢性移植物抗宿主病(cGVHD)的发生率为31.9%。HID组Ⅱ-Ⅳ度aGVHD、Ⅲ/Ⅳ度aGVHD发生率分别为42.3%、11.5%,全合(MD)组分别为38.1%、9.5%(P=0.579,P=1.000),两组cGVHD发生率分别为34.6%、28.6%(P=0.659)。移植后30 d NK细胞绝对值计数>190 cells/μl的患者比≤190 cells/μl的患者PROS高(P=0.021)。全部患者移植后1、3年PROS分别为68.1%、28.4%,HID组分别为78.9%、40.3%,MD组分别为54.4%、14%(P=0.048)。多因素分析结果显示,发生Ⅱ-Ⅳ度aGVHD、复发时间<3个月是影响PROS的危险因素(P<0.05)。结论:恶性血液病allo-HSCT后复发患者行单倍体移植疗效比全相合移植好,移植后30 d NK细胞绝对值计数高可提高PROS,移植后发生Ⅱ-Ⅳ度aGVHD、复发时间<3个月对移植后复发患者的长期生存具有预后意义。

Objective:To analyze the survival,prognostic factors,and prevention of relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with hematological malignancies,and explore the relationship between immune reconstruction,loss of human leukocyte antigen(HLA-loss)and relapse after transplantation.Methods:From July 2012 to June 2020,47 patients with hematological malignancies who relapsed after allo-HSCT were retrospectively analyzed,including 20 cases undergoing matched-sibling donor transplantation(MSD),26 cases undergoing haploidentical transplantation(HID),and 1 case undergoing matched-unrelated donor transplantation(MUD).Multivariate analysis was used to analyze the risk factors related to post-relapse overall survival(PROS).Results:All the 47 patients were implanted successfully.The cumulative incidence of gradeⅡ-Ⅳ,Ⅲ/Ⅳacute graft-versushost disease(aGVHD)and chronic GVHD(cGVHD)was 40.4%,10.6%,and 31.9%,respectively.The incidence of gradeⅡ-ⅣandⅢ/ⅣaGVHD in HID group was 42.3%and 11.5%,while in MD group was 38.1%and 9.5%(P=0.579,P=1.000),and the incidence of cGVHD in the two groups was 34.6%and 28.6%(P=0.659).The PROS of patients with NK cell absolute count>190 cells/μl 30 days after transplantation was higher than that of patients with NK cell absolute count≤190 cells/μl(P=0.021).The 1-year and 3-year PROS of all the patients was 68.1%and 28.4%,respectively,while in the HID group was 78.9%and 40.3%,in the MD group was 54.4%and 14%(P=0.048).Multivariate analysis showed that gradeⅡ-ⅣaGVHD and time of relapse<3 months were independent risk factors of PROS(P<0.05).Conclusion:The therapeutic effect of haploidentical transplantation in patients with relapsed hematological malignancies after allo-HSCT is better than that of matched donor transplantation.The high absolute count of NK cells 30 days after transplantation can increase PROS.GradeⅡ-ⅣaGVHD and time of relapse<3 months have prognostic significance for long-term survival of patients with relapsed hematological malignancies after transplantation.