Acute myeloid leukemia with positive TLS-ERG fusion gene: report of 9 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.

BCOR mutation and TLS-ERG expression in acute myeloid leukemia with monoclonal immunoglobulinemia.

Acute myeloid leukemia (AML) originates from the abnormal clonal proliferation of myeloblasts. Immunoglobulin is secreted by B cells. AML with monoclonal antibody often indicates a poor prognosis. Here we report a case of BCOR mutation and TLS-ERG expression in AML with monoclonal immunoglobulinemia. After chemotherapy, the patient achieved bone marrow complete remission. BCOR mutation and TLS-ERG fusion gene in patient's bone marrow were not detected, at the same time, peripheral blood monoclonal immunoglobulin also disappeared. BCOR mutation or TLS-ERG fusion gene expression is associated with poor prognosis, AML with monoclonal immunoglobulin may have the same prognostic significance.

Adult acute myeloid leukemia with TLS-ERG fusion gene positive: report of two cases and review of literature / 白血病·淋巴瘤

Objective@#To investigate the clinical characteristics and prognosis of adult acute myeloid leukemia (AML) with TLS-ERG fusion gene positive.@*Methods@#Adult two AML patients with TLS-ERG fusion gene positive in the First Affiliated Hospital of Zhengzhou University in January 2017 and March 2018, respectively were enrolled, and their clinical characteristics and prognosis were analyzed.@*Results@#Both patients with TLS-ERG fusion gene positive were males. According to morphology classification, the first case was classified to AML-M5, and the other one was AML-M4. Both patients' immunophenotypic features showed CD56 expression, and CD25 was expressed in the first patient simultaneously. Both patients were treated with induction and consolidated intensive therapy based on Chinese guidelines for diagnosis and treatment of adult AML (not acute promyelocytic leukemia) and the guidelines for diagnosis and treatment of AML (relapse/refractory) in China. The first patient died 11 months after diagnosis, and the second patient remained in remission until the end of follow-up in February 2019 (12 months after diagnosis).@*Conclusion@#TLS-ERG fusion gene has low incidence rate, high recurrence rate, poor reinduction effect, poor prognosis and short survival time in adult AML.

Outcome and Minimal Residual Disease Monitoring in Patients with t(16;21) Acute Myelogenous Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Patients with t(16;21) acute myelogenous leukemia (AML) who receive chemotherapy have poor outcomes. The treatment efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) must be identified, and the usefulness of minimal residual disease (MRD) monitoring requires evaluation. Fourteen consecutive patients with t(16;21) AML undergoing allo-HSCT at our institution were included in this study. Translocation liposarcoma- ETS-related gene (TLS-ERG) transcript levels were serially monitored for a median of 15 months (range, 3-51 months) after allo-HSCT. Eight patients relapsed, 7 patients died from relapse-related causes, and 1 patient died from a non-relapse-related cause. The 2-year cumulative incidence rates of relapse, disease-free survival, and overall survival after HSCT were 66.2%, 30.8%, and 46.2%, respectively. Of the 3 patients who received an HLA-matched sibling transplant, 2 relapsed, and 1 (33.3%) was in hematologic complete remission (CR) but died of nonrelapse mortality, whereas 5 of 11 patients (45.5%) who received haploidentical transplantation were in CR and were alive. Two of 6 patients with undetectable TLS-ERG at the time of allo-HSCT relapsed, at 14 and 15 months, and 3 of 4 PCR-positive patients relapsed, at a median of 10 months after HSCT. Four patients with continually low post-HSCT TLS-ERG levels (mostly <.01%) remained alive and in CR. The TLS-ERG levels of all 8 patients who relapsed were significantly increased before the relapse, exceeding 1.0% in all 7 patients who experienced hematologic relapse. In total, 7 patients received modified donor lymphocyte infusion (DLI), and 1 patient received IFN-α. All 7 patients with a TLS-ERG level >5.0% at the time of intervention experienced an increase or a brief decrease in TLS-ERG level, followed by an increase, and 6 relapsed, whereas the TLS-ERG level of 1 patient with a TLS-ERG level <1.0% at intervention decreased to undetectable. Therefore, t(16;21) AML is an indication for allo-HSCT. Among the HSCT recipients, 30.8% responded to treatment with CR. TLS-ERG transcript levels reflect MRD and might predict relapse and guide effective intervention.

Impact of clinical factors on outcome of leukemia patients with TLS-ERG fusion gene.

We report the clinical features and outcome of 22 TLS-ERG+ leukemia patients (20 AML and 2 B-ALL). TLS-ERG was tightly associated with extramedullary disease (EMD), complex chromosome abnormalities, and high risk gene mutations including IKZF1, WT1, TET2, NOTCH2, and PHF6. The 6-month leukemia free survival (LFS) with and without EMD was 75% and 83.3% (p = .017). 11/20 AML patients received allogeneic hematopoietic stem cell transplantation (HCT). The 1-year overall survival (OS) in non-HCT and HCT group was 62.5% and 90% (p = .026), but the 6-month LFS in non-HCT and HCT group was 55.6% and 100% (p = .192). The 6-month LFS of patients with complete remission (CR) before HCT versus those with no response (NR) was 67.5% and 0, respectively (p = .034). In conclusion, the leukemia burden before HCT and EMD had negative impact on the outcome of TLS-ERG patients; HCT could prolong OS, but could not overcome the poor prognostic impact of TLS-ERG.