Title Low WT1 transcript levels at diagnosis predicted poor outcomes of acute myeloid leukemia patients with t(8;21) who received chemotherapy or allogeneic hematopoietic stem cell transplantation
Authors Qin, Ya-Zhen
Wang, Yu
Zhu, Hong-Hu
Gale, Robert Peter
Zhang, Mei-Jie
Jiang, Qian
Jiang, Hao
Xu, Lan-Ping
Chen, Huan
Zhang, Xiao-Hui
Liu, Yan-Rong
Lai, Yue-Yun
Jiang, Bin
Liu, Kai-Yan
Huang, Xiao-Jun
Affiliation Peking Univ, Peoples Hosp, Inst Hematol, Beijing Key Lab Hematopoiet Stem Cell Transplanta, 11 Xizhimen South St, Beijing, Peoples R China.
Imperial Coll London, Dept Med, Div Expt Med, Haematol Res Ctr, London SW7 2AZ, England.
Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China.
Peking Univ, Peoples Hosp, Inst Hematol, Beijing Key Lab Hematopoiet Stem Cell Transplanta, 11 Xizhimen South St, Beijing, Peoples R China.
Huang, XJ (reprint author), Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China.
Keywords Acute myeloid leukemia
RUNX1-RUNX1T1 transcript level
WT1 transcript level
C-KIT mutation
Allogeneic hematopoietic stem cell transplantation
MINIMAL RESIDUAL DISEASE
TUMOR GENE WT1
POLYMERASE-CHAIN-REACTION
C-KIT MUTATIONS
PROGNOSTIC-SIGNIFICANCE
RISK STRATIFICATION
GROUP-B
MYELODYSPLASTIC SYNDROMES
CANCER PROGRAM
ADULT PATIENTS
Issue Date 2016
Publisher CHINESE JOURNAL OF CANCER
Citation CHINESE JOURNAL OF CANCER.2016,35.
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 oncogene v-KIT receptor tyrosine kinase (C-KIT) mutations at diagnosis, and RUNX1-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 (defined as <3-log reduction in RUNX1-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 and C-KIT mutations at diagnosis, and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested. Results: Patients who had a C-KIT mutation had significantly lower WT1 transcript levels than patients who did not have a C-KIT mutation (6.7%+/- 10.6% vs. 19.5%+/- 19.9%, P < 0.001). Low WT1 transcript levels (<= 5.0%) but not C-KIT mutation at diagnosis, a positive MRD test result after the second cycle of consolidation chemotherapy, and receiving 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% confidence 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 for WT1 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 prognosis in these patients.
URI http://hdl.handle.net/20.500.11897/433666
ISSN 1000-467X
DOI 10.1186/s40880-016-0110-6
Indexed SCI(E)
PubMed
中国科技核心期刊(ISTIC)
Appears in Collections: 人民医院

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