Qin Ya-Zhen, Wang Yu, Xu Lan-Ping, Zhang Xiao-Hui, Chen Huan, Han Wei, Chen Yu-Hong, Wang Feng-Rong, Wang Jing-Zhi, Chen Yao, Mo Xiao-Dong, Zhao Xiao-Su, Chang Ying-Jun, Liu Kai-Yan, Huang Xiao-Jun
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Peking-Tsinghua Center for Life Sciences, Beijing, 100871, China.
J Hematol Oncol. 2017 Feb 6;10(1):44. doi: 10.1186/s13045-017-0414-2.
The optimal monitoring schedules and cutoff minimal residual disease (MRD) levels for the accurate prediction of relapse at all time points after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear in patients with t(8;21) acute myeloid leukemia (AML).
RUNX1-RUNX1T1 transcript levels were measured in bone marrow samples collected from 208 patients at scheduled time points after transplantation (1530 samples in total).
A total of 92.3% of the requested samples were collected, and 74.0% of patients had complete sample collection. The 1-, 3-, and 6-month RUNX1-RUNX1T1 transcript levels could significantly discriminate between continuous complete remission and a hematologic relapse at 1.5-3, 4-6, and 7-12 months but not at >3, >6, and >12 months, respectively. Over 90% of the 175 patients who were in continuous complete remission had a ≥3-log reduction in RUNX1-RUNX1T1 transcript levels from the time of diagnosis at each time point after transplantation and a ≥4-log reduction at ≥12 months. A <3-log reduction within 12 months and/or a <4-log reduction at ≥12 months was significantly related to a higher 3-year cumulative incidence of relapse (CIR) rate in both the entire cohort and the patients with no intervention after HSCT (58.4 vs. 2.2%, 76.5 vs. 2.0%; all P < 0.0001). Patients who had received a preemptive donor lymphocyte infusion when the increase in RUNX1-RUNX1T1 transcripts was ≤1-log according to the above dual cutoff values had significantly lower 1-year CIR rate after intervention than the patients who had received an infusion when the increase was >1-log (0 vs. 55.0%, P = 0.015).
RUNX1-RUNX1T1 transcripts with a <3-log reduction from diagnosis within 12 months and/or a <4-log reduction at ≥12 months after allo-HSCT could accurately predict relapse and may prompt a timely intervention in patients with t(8;21) AML.
对于t(8;21)急性髓系白血病（AML）患者，异基因造血干细胞移植（allo-HSCT）后在所有时间点准确预测复发的最佳监测方案和最小残留病（MRD）临界水平仍不明确。
在移植后的预定时间点从208例患者采集的骨髓样本中测量RUNX1-RUNX1T1转录水平（共1530份样本）。
共采集了92.3%的所需样本，74.0%的患者完成了样本采集。1、3和6个月时的RUNX1-RUNX1T1转录水平可分别在1.5至3个月、4至6个月和7至12个月时显著区分持续完全缓解和血液学复发，但在大于3个月、大于6个月和大于12个月时则不能。175例持续完全缓解的患者中，超过90%在移植后各时间点RUNX1-RUNX1T1转录水平较诊断时降低≥3个对数，在≥12个月时降低≥4个对数。在整个队列以及HSCT后未进行干预的患者中，12个月内降低<3个对数和/或≥12个月时降低<4个对数与3年累积复发率（CIR）显著相关（58.4%对2.2%，76.5%对2.0%；所有P<0.0001）。根据上述双重临界值，当RUNX1-RUNX1T1转录本增加≤1个对数时接受抢先性供者淋巴细胞输注的患者，干预后的1年CIR率显著低于增加>1个对数时接受输注的患者（0对55.0%，P = 0.015）。
allo-HSCT后12个月内较诊断时降低<3个对数和/或≥12个月时降低<4个对数的RUNX1-RUNX1T1转录本可准确预测复发，并可能促使对t(8;21) AML患者及时进行干预。
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