The dynamics of RUNX1-RUNX1T1 transcript levels after allogeneic hematopoietic stem cell transplantation predict relapse in patients with t(8;21) acute myeloid leukemia.
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.
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Ya-Zhen
YZ
Qin
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Yu
Y
Wang
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Lan-Ping
LP
Xu
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Xiao-Hui
XH
Zhang
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Huan
H
Chen
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Wei
W
Han
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Yu-Hong
YH
Chen
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Feng-Rong
FR
Wang
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Jing-Zhi
JZ
Wang
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Yao
Y
Chen
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Xiao-Dong
XD
Mo
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Xiao-Su
XS
Zhao
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Ying-Jun
YJ
Chang
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
Kai-Yan
KY
Liu
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China. xjhrm@medmail.com.cn.|Peking-Tsinghua Center for Life Sciences, Beijing, 100871, China. xjhrm@medmail.com.cn.
Xiao-Jun
XJ
Huang
D000293:Adolescent; D000328:Adult; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics / Q000648:ultrastructure*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics / Q000648:ultrastructure*; D050676:Core Binding Factor Alpha 2 Subunit / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015973:Gene Expression Regulation, Leukemic; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D000075142:RUNX1 Translocation Partner 1 Protein / Q000096:biosynthesis* / Q000235:genetics; D012008:Recurrence; D014178:Translocation, Genetic; D055815:Young Adult
C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000075142:RUNX1 Translocation Partner 1 Protein
Acute myeloid leukemia; Allogeneic hematopoietic stem cell transplantation; Donor lymphocyte infusion; RUNX1-RUNX1T1 transcript levels; Relapse