Low WT1 transcript levels atdiagnosis predicted poor outcomes ofacute myeloid leukemia patients witht(8;21) who received chemotherapy or allogeneic hematopoietic stem cell transplantation
10.1186/s40880-016-0110-6
- Author:
YaZhenQin
1
;
YuWang
;
HongHuZhu
;
RobertPeterGale
;
MeiJieZhang
;
QianJiang
;
HaoJiang
;
LanPingXu
;
HuanChen
;
XiaoHuiZhang
;
YanRongLiu
;
YueYunLai
;
BinJiang
;
KaiYanLiu
;
Huang XIAOJUN
Author Information
1. Peking University People’s Hospital
- Keywords:
Acute myeloid leukemia;
RUNX1-RUNX1T1 transcript level;
WT1 transcript level;
C-KIT mutation;
Allogeneic hematopoietic stem cell transplantation
- From:Chinese Journal of Cancer
2016;35(7):350-358
- CountryChina
- Language:Chinese
-
Abstract:
Background:Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease. Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy. This study aimed to evaluate the impact of Wilm tumor gene?1 (WT1) transcript levels and cellular homolog of the viral oncogenev?KIT receptor tyrosine kinase (C?KIT) mutations at diagnosis, andRUNX1?RUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes.
Methods:Eighty?eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation (allo?HSCT) were included. Patients who achieved remission, received two or more cycles of consolidation chemotherapy, and had a positive measureable residual disease (MRD) test result (deifned as<3?log reduction inRUNX1?RUNX1T1 transcript levels compared to baseline) after 2–8 cycles of consolidation chemotherapy were recommended to receive allo?HSCT. Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles.WT1 transcript levels andC?KIT mutations at diagnosis, andRUNX1?RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested.
Results:Patients who had aC?KIT mutation had signiifcantly lowerWT1 transcript levels than patients who did not have aC?KIT mutation (6.7%±10.6% vs. 19.5%±19.9%,P<0.001). LowWT1 transcript levels (≤5.0%) but notC?KIT mutation at diagnosis, a positive MRD test result after the second cycle of consolidation chemotherapy, and receiv?ing only chemotherapy were independently associated with high cumulative incidence of relapse in all patients (hazard ratio [HR]=3.53, 2.30, and 11.49; 95% conifdence interval [CI] 1.64–7.62, 1.82–7.56, and 4.43–29.82;P=0.002, 0.034, and<0.001, respectively); these conditions were also independently associated with low leukemia?free survival (HR=3.71, 2.33, and 5.85; 95% CI 1.82–7.56, 1.17–4.64, and 2.75–12.44;P<0.001, 0.016, and<0.001, respectively) and overall survival (HR=3.50, 2.32, and 4.34; 95% CI 1.56–7.82, 1.09–4.97, and 1.98–9.53;P=0.002, 0.030, and<0.001, respectively) in all patients.
Conclusions: Testing forWT1 transcript levels at diagnosis in patients with AML and t(8;21) may predict outcomes in those who achieve remission. A randomized study is warranted to determine whether allo?HSCT can improve prog?nosis in these patients.
