继发急性髓系白血病异基因造血干细胞移植疗效及预后影响因素分析

Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia

目的探讨成人继发急性髓系白血病(AML)接受异基因造血干细胞移植(allo-HSCT)的疗效及预后影响因素。方法多中心回顾性临床研究。纳入2014年1月至2022年11月因继发AML在浙江省造血干细胞移植协作组4个中心接受allo-HSCT的18岁以上的成人患者,并进行疗效及预后影响因素分析。结果共纳入95例患者,其中66例(69.5%)为骨髓增生异常综合征(MDS)转化AML(MDS-AML),4例(4.2%)为MDS/骨髓增殖性肿瘤(MPN)转化AML(MDS/MPN-AML),25例(26.3%)为治疗相关AML(tAML)。所有患者的3年累积复发率(CIR)、无白血病生存(LFS)率和总生存(OS)率分别为18.6%(95%CI 10.2%~27.0%)、70.6%(95%CI 60.8%~80.4%)和73.3%(95%CI 63.9%~82.7%)。M-AML(包括MDS-AML、MDS/MPN-AML)组和tAML组的3年CIR分别为20.0%和16.4%(P=0.430);3年LFS率分别为68.3%和75.4%(P=0.176);3年OS率分别为69.7%和75.4%(P=0.233),两组间差异均无统计学意义。TP53突变组和无TP53突变组的3年CIR分别为60.0%和13.7%(P=0.003),3年LFS率分别为20.0%和76.5%(P=0.002),3年OS率分别为40.0%和77.6%(P=0.002)。根据2022欧洲白血病网(ELN2022)危险分层,低危、中危和高危3组患者的3年CIR分别为8.3%、17.8%和22.6%(P=0.639),3年LFS率分别为91.7%、69.5%和65.6%(P=0.268),3年OS率分别为91.7%、71.4%和70.1%(P=0.314)。多因素分析表明,移植时疾病未缓解和伴有TP53突变是影响患者CIR、LFS和OS的独立危险因素。结论M-AML组(MDS-AML、MDS/MPN-AML)与tAML组患者allo-HSCT预后相近。移植时疾病未缓解和伴有TP53突变是不良预后因素。ELN2022危险分层对继发AML患者allo-HSCT预后的预测价值有限。

Objective To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with secondary acute myeloid leukemia(sAML).Methods In this multicenter,retrospective clinical study,adult patients aged≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included,and the efficacy and prognostic factors of allo-HSCT were analyzed.Results A total of 95 patients were enrolled;66(69.5%)had myelodysplastic syndrome-acute myeloid leukemia(MDS-AML),4(4.2%)had MDS/MPN-AML,and 25(26.3%)had therapy-related AML(tAML).The 3-year CIR,LFS,and overall survival(OS)rates were 18.6%(95%CI 10.2%-27.0%),70.6%(95%CI 60.8%-80.4%),and 73.3%(95%CI 63.9%-82.7%),respectively.The 3-year CIRs of the M-AML group(including MDS-AML and MDS/MPN-AML)and the tAML group were 20.0%and 16.4%,respectively(P=0.430).The 3-year LFSs were 68.3%and 75.4%,respectively(P=0.176).The 3-year OS rates were 69.7%and 75.4%,respectively(P=0.233).The 3-year CIRs of the groups with and without TP53 mutations were 60.0%and 13.7%,respectively(P=0.003);the 3-year LFSs were 20.0%and 76.5%,respectively(P=0.002);and the 3-year OS rates were 40.0%and 77.6%,respectively(P=0.002).According to European LeukmiaNet 2022(ELN2022)risk stratification,the 3-year CIRs of patients in the low-,intermediate-,and high-risk groups were 8.3%,17.8%,and 22.6%,respectively(P=0.639).The three-year LFSs were 91.7%,69.5%,and 65.6%,respectively(P=0.268).The 3-year OS rates were 91.7%,71.4%,and 70.1%,respectively(P=0.314).Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR,LFS,and OS.Conclusion There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML,MDS/MPN-AML,and tAML groups.Advanced disease at transplantation and TP53 mutations were poor prognostic factors.ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.