Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance

Background: In this single-arm phase II study (NCT03557099), we evaluated the efficacy and safety of hetrombopag, a small molecule thrombopoietin (TPO) receptor agonist, in patients with severe aplastic anemia (SAA) who were refractory to standard first-line immunosuppressive therapy (IST). Methods: SAA patients who were refractory to standard first-line IST were given hetrombopag orally at an initial dose of 7.5 mg once daily to a maximum of 15 mg once daily, for a total of 52 weeks. The primary endpoint was proportion of patients achieving hematologic responses in ⩾1 lineage at week 18. Results: A total of 55 eligible patients were enrolled and received hetrombopag treatment. This study met its primary endpoint, with 23 [41.8%, 95% confidence interval (CI) = 28.7–55.9] patients achieving hematologic response in ⩾1 lineage at week 18 after initiation of hetrombopag treatment. Twenty-four (43.6%, 95% CI = 30.3–57.7) and 27 (49.1%, 95% CI = 35.4–62.9) of the 55 patients responded in ⩾1 lineage at weeks 24 and 52, respectively. Median time to initial hematologic response was 7.9 weeks (range = 2.0–32.1). The responses were durable, with a 12-month relapse-free survival rate of 82.2% (95% CI = 62.2–92.2). Adverse events occurred in 54 (98.2%) patients, and 28 (50.9%) patients had treatment-related adverse events. Seventeen (30.9%) patients had adverse events of grade ⩾3. Serious adverse events occurred in 15 (27.3%) patients and three deaths (5.5%) were reported. Conclusion: Hetrombopag showed encouraging efficacy with durable hematologic responses in patients with SAA who were refractory to IST. Hetrombopag was well tolerant and safe for long-term use. ClinicalTrials.gov identifier: NCT03557099

Cytogenetic and Genetic Mutation Features of de novo Acute Myeloid Leukemia in Elderly Chinese Patients Acute myeloid leukemia;cytogenetics;genetic mutations;Chinese elderly cases; Objectives: The present study aimed to examine the cytogenetic and genetic mutation features of acute myeloid leukemia (AML) in elderly Chinese patients. Methods: A retrospective analysis of cytogenetics and genetic mutations was performed in 113 cases (age range 50-82 years) with de novo AML. Results: The most frequent cytogenetic abnormality was t (15;17) (q22;q21), detected in 10.0% (n = 9) of successfully analyzed cases, followed by t (8;21) (q22;q22) in 8.89% (n = 8), and complex karyotypes in 5.56% (n = 5). Those with complex karyotypes included 4 cases (4.44%) of monosomal karyotypes. The frequencies of NPM1, FLT3-ITD, c-kit, and CEBPA mutations were 27.4% (31/113), 14.5% (16/110), 5.88% (6/102), and 23.3% (7/30), respectively. The complete remission rates of patients in low, intermediate, and high risk groups were 37.5%, 48.6%, and 33.3%, respectively (${\chi}^2$ = 0.704, P = 0.703) based on risk stratification. Conclusion: Cytogenetics and genetic mutations alone may not be sufficient to evaluate the prognoses of elderly AML patients. The search for a novel model that would enable a more comprehensive evaluation of this population is therefore imperative.

Background: Rapid clearance of peripheral blood blasts (PBBs) predicts complete remission (CR) and survival in patients with acute myeloid leukemia (AML). We aimed to explore the correlation between induction therapy response, outcome, and the PBB percentage. Methods: Forty-six consecutive patients with de novo AML (excluding acute promyelocytic leukemia) were enrolled in this study. Flow cytometry was performed to identify cells with a leukemia-associated aberrant immunophenotype in the initial bone marrow aspirate and in peripheral blood on day 7 of induction therapy. Results: The PBB percentage on day 7 (D7PBBP) was significantly lower in patients who achieved CR (0.03% (0.0%, 0.45%)) than in those who did not (10.85% (1.13%, 19.38%); u =-3.92, P <0.001). The CR rate was significantly higher among patients with a D7PBBP of <0.945% (84.62%, 22/26) than among those with a D7PBBP of ≥0.945% (25.0%, 5/20; χ ² = 16.571, P <0.001). D7PBBP was significantly correlated with overall survival (OS; r=-0.437, P=0.003) and relapse-free survival (RFS; r=-0.388, P=0.007). OS and RFS were significantly higher in patients with a D7PBBP of <0.43% than in those with a D7PBBP of ≥0.43% (P <0.001 and P=0.039, respectively). D7PBBP was also found to be an independent prognostic indicator in multivariate analysis for both OS (P=0.036) and RFS (P=0.035). Conclusion: D7PBBP may be an important risk factor for the achievement of complete remission, for overall survival, and for relapse-free survival.