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

摘要

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 RUNXTRUNX1T1 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 WTl 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 WTl 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 WTl 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.