Objective: To investigate the risk factors of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with t (8;21) acute myeloid leukemia (AML) . Methods: The clinical features of patients with t (8;21) AML who received allo-HSCT between January 2008 and October 2020 in the Hospital of Blood Disease and the Chinese Academy of Medical Sciences were retrospectively analyzed. Univariate and multivariate analyses were performed on the factors that might influence relapse. Results: A total of 73 patients were enrolled. The analysis revealed that, out of the 73 cases, 10 had relapses, with a 3-year cumulative incidence of relapse (CIR) of 15.7% (95% CI 7.3%-26.8%) . The median time of relapse was 9.2 (2.0-47.6) months. Furthermore, 19 cases died, with a 3-year overall survival (OS) of 68.9% (95% CI 56.4%-81.4%) . Compared with the RUNX1-RUNX1T1 at first diagnosis, a ≥ 3-log reduction within 3 months and/or 4-log reduction within 3-12 months can significantly decrease 3-year CIR after HSCT (13.3% vs 57.1%; 5.1% vs 25.0%, both P<0.001) . Cox multivariate analysis showed that high levels of RUNX1-RUNX1T1 (≥1.58%) on the day of transplantation (day 0) [P=0.006; HR=28.849 (95% CI 2.68-310.524) ] and the flow cytometric analysis of blasts ratio in bone marrow ≥60% at first diagnosis [P=0.015; HR=6.64 (95% CI 1.448-30.457) ] were independent risk factors for relapse. Furthermore, no significant difference in the effect of c-Kit and Flt3 gene mutations on relapse after transplantation was observed (P=0.877 and P=0.773, resp) . The flow cytometric analysis of blasts ratio in bone marrow ≥60% at first diagnosis [P<0.001; HR=8.925 (95% CI 2.702-29.476) ] and the number of courses to achieve complete remission ≥ 2[P=0.013; HR=4.495 (95% CI 1.379-14.649) ] were independent risk factors for OS. Conclusion: Both high levels of RUNX1-RUNX1T1 (≥1.58%) on the day of transplantation (day 0) and the ratio of flow cytometric analysis of blasts in bone marrow at first diagnosis increase the chance of t (8;21) AML relapse after allo-HSCT. Detection of the transcription levels of RUNX1-RUNX1T1 after allo-HSCT at different times could help predict the hazard of relapse.
目的： 探讨t（8;21）急性髓系白血病（AML）异基因造血干细胞移植（allo-HSCT）后复发的影响因素。 方法： 对2008年1月至2020年10月期间在中国医学科学院血液病医院接受allo-HSCT的t（8;21）AML患者进行回顾性分析。 结果： 73例t（8;21）AML患者纳入研究，男39例，女34例，中位年龄36（13~54）岁。73例患者中10例出现血液学复发，3年累积复发率（CIR）为15.7%（95%CI 7.3%~26.8%），中位复发时间为9.2（2.0~47.6）个月。73例患者中19例死亡，移植后3年总生存（OS）率为68.9%（95%CI 56.4%~81.4%）。移植后3个月内融合基因下降≥3个对数级组移植后3年CIR明显低于下降<3个对数级组[13.3%（95%CI 4.5%~26.8%）对57.1%（95%CI 13.2%~85.6%），P<0.001]；移植后12个月内融合基因水平下降≥4个对数级组移植后3年CIR明显低于下降<4个对数级组[5.1%（95%CI 0.9%~15.4%）对25.0%（95%CI 0.3%~71.3%），P<0.001]。Cox多因素分析显示移植当天造血干细胞回输前（0 d）RUNX1-RUNX1T1融合基因高定量（≥1.58%）[P=0.006，HR=28.849（95%CI 2.680~310.524）]及初诊时骨髓流式细胞术原始细胞比例≥60%[P=0.015，HR=6.640（95%CI 1.448~30.457）]是血液学复发的独立危险因素；c-Kit及Flt3基因突变对移植后血液学复发无明显影响（P=0.877，P=0.773）。初诊时骨髓流式细胞术原始细胞比例≥60%[P<0.001，HR=8.925（95%CI 2.702~29.476）]、达到完全缓解所需的疗程数≥2个[P=0.013，HR=4.495（95%CI 1.379~14.649）]是影响OS的独立危险因素。 结论： 0 d RUNX1-RUNX1T1融合基因定量水平≥1.58%及初诊时骨髓流式细胞术原始细胞比例≥60%是影响t（8;21）AML患者allo-HSCT后血液学复发的独立危险因素。移植后RUNX1-RUNX1T1融合基因监测有助于评估复发的危险性。.
Keywords: Hematopoietic stem cell transplantation; Leukemia, myeloid, acute, t (8;21); Minimal residual diseases; Relapse.