单核苷酸多态性-PCR检测供者细胞嵌合率对年轻中危急性髓系白血病患者异基因造血干细胞移植后的预后价值

Prognostic value of donor chimerism at+90 days after allogeneic hematopoietic stem cell transplantation in young patients with intermediate-risk acute myeloid leukemia

目的探讨单核苷酸多态性(SNP)-PCR法检测异基因造血干细胞移植(allo-HSCT)后供者细胞嵌合率与复发的关系。方法回顾性分析2010年1月至2019年1月接受allo-HSCT且无复发生存(RFS)期>90 d 105例中危组急性髓系白血病(AML)患者的临床资料。采集移植后15、30、60、90、180、270、360 d患者骨髓标本,应用SNP-PCR法检测供者细胞嵌合率。结果全部105例患者中,男43例,女62例,中位年龄为38(16~60)岁。中位随访843(94~3261)d,移植90 d后复发18例,死亡33例,存活72例。3年总生存率为(66.8±5.1)%,RFS率为(65.1±5.0)%。移植前疾病状态、移植前MRD情况、移植后90 d嵌合率均为影响RFS的独立危险因素。移植后90 d供者细胞嵌合率≤97.24%的患者复发风险显著升高[HR=6.921(95%CI 2.669~17.950),P<0.001],对复发有预警作用。结论SNP-PCR法对移植后患者的供者细胞嵌合率有较好的覆盖性,移植后90 d嵌合率≤97.24%的患者具有较高的复发风险。

Objective To investigate the relationship between donor chimerism and relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods The clinical data of 105 patients with acute myeloid leukemia(AML)who underwent allo-HSCT and recurrence-free survival>90 days from January 2010 to January 2019 were retrospectively analyzed.The bone marrow samples were collected at 15,30,60,90,180,270,360 days after transplantation.Donor chimerism was detected by single nucleotide polymorphism(SNP)-PCR.Results Of the 105 patients,43 cases were male and 62 cases were female,with a median age of 38(16-60)years.Till April 2019,the median follow-up was 843(94-3261)days.Ninety days after transplantation,18 cases relapsed,33 cases died,and 72 cases survived.The 3-year overall survival(OS)rate was(66.8±5.1)%,and the recurrence-free survival(RFS)rate was(65.1±5.0)%.Pre-transplant disease status,pre-transplant minimal residual disease(MRD),and 90 day post-transplantation chimerism were independent risk factors related to RFS.The risk of recurrence was significantly increased in patients with a donor chimerism rate≤97.24%at 90 days after transplantation[HR=6.921(95%CI 2.669-17.950),P<0.001],which was considered as a sign of early relapse.Conclusion SNP-PCR is an applicable method for detecting donor chimerism in patients after allo-HSCT.Chimerism rate equal or less than 97.24%at 90 days after transplantation predicts a higher risk of relapse.