Salvianolic acid A (SAA), one of the main derivatives of Salvia miltiorrhiza, has been shown to possess anti-inflammatory and anti-thrombotic activities. Its role in inhibiting tumor growth, however, remains elusive. The aim of this study was to investigate the effect of SAA on acute myeloid leukemia (AML). Here, SAA showed a dose-dependent cell viability inhibition and apoptosis induction in AML cells. At the molecular level, SAA increased the expression of Bak and decreased the expression of Bcl-xL, following by PARP cleavage and caspase-3 activation. SAA also markedly attenuated Akt phosphorylation in AML cells. In a xenograft mouse model, SAA significantly suppressed the growth of AML tumors in vivo. Furthermore, SAA exhibited a more profound pro-apoptotic effect on primary AML cells than on bone marrow mononuclear cells from patients with benign diseases. Therefore, the pro-apoptotic and anti-tumor properties of SAA suggested its promising therapeutic value for AML.

Graft-versus-host disease (GVHD) is a serious complication associated with allogeneic hematopoietic cell transplantation (allo-HCT). Antithymocyte globulin (ATG) is widely used prior to allo-HCT for GVHD prevention, though evidence of its efficacy remains unclear. We therefore identified nine randomized controlled trials (RCTs), enrolling 1089 patients (554 in the ATG group and 535 in the non-ATG group) to conduct a meta-analysis of the actions of ATG in allo-HCT. A relative risk or risk ratio (RR) and 95% confidence interval (CI) were calculated for each outcome. Rabbit ATG reduced overall acute (a) GVHD (RR 0.77, 95% CI 0.67-0.89, P = 0.0004), grade III-IV aGVHD (RR 0.53, 95% CI 0.32-0.88, P = 0.01), overall chronic (c) GVHD (RR 0.52, 95% CI 0.42-0.64, P < 0.00001) and extensive cGVHD (RR 0.28, 95% CI 0.18-0.43, P < 0.00001), without increased risk of relapse (RR 1.17, 95% CI 0.91-1.49, P = 0.23). By contrast, horse ATG did not reduce overall aGVHD (RR 1.25, 95% CI 0.88-1.79, P = 0.22) or cGVHD (RR 1.67, 95% CI 0.96-2.91, P = 0.07). ATG marginally reduced 100-day transplant related mortality (RR 0.75, 95% CI 0.56-1.00, P = 0.05) without compromising overall survival or increased risk of infections. Further studies are required to evaluate the optimal dosage and formulation of ATG in different conditioning regimens of transplantation with varied sources of graft and donor.

No abstract

Inhibin-β A (INHBA) is a ligand of the transforming growth factor β superfamily and associated with tumorigenesis and tumor progression in solid tumors. In this study, we investigated the expression levels and clinical significance of INHBA in acute myeloid leukemia (AML). The results showed that high expression of INHBA was significantly correlated with elderly age (>60 years) (p = .038), adverse cytogenetic risks (p = .034), negative NPM1 mutation (p = .016), positive FLT3 internal tandem duplications (p = .011), and low hemoglobin levels (<60 g/dL) (p = .04). Patients with high levels of INHBA had poor responses to therapies as indicated by lower complete remission rate (p = .004), higher early death rate (p = .018), and shorter relapse-free survival (p = .04) and overall survival (p = .003). Moreover, multivariate analysis showed that high expression of INHBA was an independent adverse prognostic factor for AML. Taken together, our study suggested that high expression of INHBA was an adverse prognostic factor for de novo AML.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or &lt;5 patients per year, p = 0.12) or age (≥60 or &lt;60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (&gt;10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.