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. Issue 1 (19th May 2016)

• Record Type: Journal Article
• 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
• Is Part Of: Cancer communications. Volume 35:Issue 1(2016)
• Page Start: 1
• Page End: 9
• Publication Date: 2016-05-19
• Subjects: Acute myeloid leukemia -- RUNX1‐RUNX1T1 transcript level -- WT1 transcript level -- C‐KIT mutation -- Allogeneic hematopoietic stem cell transplantation; Cancer -- Periodicals; Neoplasms; Electronic journals; Periodical; Fulltext; Internet Resources; Periodicals; Periodicals; 616.994005
• DOI: 10.1186/s40880-016-0110-6
• Languages: English
• ISSNs: 2523-3548

Abstract

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.