Investigations of the prognostic value of RUNX1 mutation in acute myeloid leukemia patients: Data from a real-world study.

RUNX1 is one of the recurrent mutated genes in newly diagnosed acute myeloid leukemia (AML). Although historically recognized as a provisional distinct entity, the AML subtype with RUNX1 mutations (AML-RUNX1mut) was eliminated from the 2022 WHO classification system. To gain more insight into the characteristics of AML-RUNX1mut, we retrospectively analyzed 1065 newly diagnosed adult AML patients from the First Affiliated Hospital of Soochow University between January 2017 and December 2021. RUNX1 mutations were identified in 112 patients (10.5%). The presence of RUNX1 mutation (RUNX1mut) conferred a lower composite complete remission (CRc) rate (40.2% vs. 58.4%, P＜0.001), but no significant difference was observed in the 5-year overall survival (OS) rate (50.2% vs. 53.9%; HR=1.293; P=0.115) and event-free survival (EFS) rate (51.5% vs. 49.4%; HR=1.487, P=0.089), even within the same risk stratification. Multivariate analysis showed that RUNX1mut was not an independent prognostic factor for OS (HR=1.352, P=0.068) or EFS (HR=1.129, P=0.513). When patients were stratified according to induction regimen, RUNX1mut was an unfavorable factor for CRc both on univariate and multivariate analysis in patients receiving conventional chemotherapy, and higher risk stratification predicted worse OS. In those who received venetoclax plus hypomethylating agents, RUNX1mut was not predictive of CRc and comparable OS and EFS were seen between intermediate-risk and adverse-risk groups. The results of this study revealed that the impact of RUNX1mut is limited. Its prognostic value depended more on treatment and co-occurrent abnormalities. VEN-HMA may abrogate the prognostic impact of RUNX1, which merits a larger prospective cohort to illustrate.

Rapid molecular response to dasatinib in Ph-like acute lymphoblastic leukemia patients with ABL1 rearrangements: case series and literature review.

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype with a poor prognosis under conventional chemotherapy. Ph-like ALL has a similar gene expression profile to Philadelphia chromosome-positive (Ph+) ALL, but is highly heterogeneous in terms of genomic alterations. Approximately 10-20% of patients with Ph-like ALL harbor ABL class (e.g. ABL1, ABL2, PDGFRB, and CSF1R) rearrangements. Additional genes that form fusion genes with ABL class genes are still being researched. These aberrations result from rearrangements including chromosome translocations or deletions and may be targets of tyrosine kinase inhibitors (TKIs). However, due to the heterogeneity and rarity of each fusion gene in clinical practice, there is limited data on the efficacy of tyrosine kinase inhibitors. Here, we report three cases of Ph-like B-ALL with ABL1 rearrangements treated with the dasatinib backbone for the CNTRL::ABL1, LSM14A::ABL1, and FOXP1::ABL1 fusion genes. All three patients achieved rapid and profound remission with no significant adverse events. Our findings suggest that dasatinib is a potent TKI for the treatment of ABL1-rearranged Ph-like ALL and can be used as a first-line treatment option for such patients.

The synergistic efficacy and safety of combined low-concentration atropine and orthokeratology for slowing the progression of myopia: A meta-analysis.

PURPOSE: To explore the efficacy and safety of combined low-concentration atropine and orthokeratology (OK) for slowing the progression of myopia. METHODS: We performed a systematic search of English and Chinese databases to collect potentially eligible randomised controlled trials (RCTs), nonrandomised controlled trials (non-RCTs) and retrospective cohort studies (REs) published between the establishment of the database and 1 January 2022. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated for each outcome. RESULTS: Fifteen studies were ultimately included in the meta-analysis, which indicated that compared with OK lenses alone, the combination of low-concentration atropine with OK lenses significantly slowed axial growth (WMD = -0.12 mm; 95% CI: -0.13 to -0.11, p < 0.001) and reduced the rate of change of the spherical equivalent refraction (WMD = 0.15 D; 95% CI: 0.06 to 0.24, p < 0.001). Additionally, the combined treatment may cause a slight increase in pupil diameter (WMD = 0.62 mm; 95% CI: 0.42 to 0.81, p < 0.001). No significant difference in the amplitude of accommodation, intraocular pressure, tear film break-up time or corneal endothelial cell density was found between the OK and combination therapy groups. CONCLUSIONS: The combination therapy of low-concentration atropine and OK lenses had a greater effect in slowing myopia progression during a 6-to-12-month treatment interval and was still effective over a 24-month period. Increased pupil diameter was the major side effect of the combination therapy, with no negative impact on the amplitude of accommodation, intraocular pressure, tear film break-up time or corneal endothelial cell density.