Key Points• Risk stratification treatment of t(8;21) acute myeloid leukemia may decrease relapse and improve longterm survival.• Allo-HSCT benefited high-risk patients, but impaired the survival of low-risk patients.We aimed to improve the outcome of t(8;21) acute myeloid leukemia (AML) in the first complete remission (CR1) by applying risk-directed therapy based on minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels. Risk-directed therapy included recommending allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk patients and chemotherapy/autologous-HSCT (auto-HSCT) for low-risk patients. Among 116 eligible patients, MRD status after the second consolidation rather than induction or first consolidation could discriminate high-risk relapse patients (P 5 .001).Allo-HSCT could reduce relapse and improve survival compared with chemotherapy for high-risk patients (cumulative incidence of relapse [CIR]: 22.1% vs 78.9%, P < .0001; disease-free survival [DFS]: 61.7% vs 19.6%, P 5 .001), whereas chemotherapy/auto-HSCT achieved a low relapse rate (5.3%) and high DFS (94.7%) for low-risk patients. Multivariate analysis revealed that MRD status and treatment choice were independent prognostic factors for relapse, DFS, and OS. We concluded that MRD status after the second consolidation may be the best timing for treatment choice. MRD-directed risk stratification treatment may improve the outcome of t(8;21) AML in CR1. This trial was registered at http://www.chictr.org as #ChiCTR- OCH-12002406. (Blood. 2013;121(20):4056-4062)
Oral RIF plus ATRA is not inferior to intravenous ATO plus ATRA as first-line treatment of APL and may be considered as a routine treatment option for appropriate patients.
Genistein, the major isoflavone in soybean, was recently reported to exert beneficial effects in metabolic disorders and inflammatory diseases. In the present study, we investigated the effects and mechanisms of a dietary concentration of genistein on the inflammatory response in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Our results demonstrated that genistein effectively inhibited the LPS-induced overproduction of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), as well as LPS-induced nuclear factor kappa B (NF-κB) activation. In addition, the data also showed that genistein prevented LPS-induced decrease in adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. These effects were obviously attenuated by an AMPK inhibitor. Taken together, our results suggest that the dietary concentration of genistein is able to attenuate inflammatory responses via inhibition of NF-κB activation following AMPK stimulation. The data provide direct evidence for the potential application of low concentrations of genistein in the prevention and treatment of inflammatory diseases.
A recombinant retrovirus vector containing the glial cell line-derived neurotrophic factor (GDNF) gene was constructed and transfected into Schwann cells (SCs) to investigate the possibility of GDNF transfection and functional expression of transfected SCs, including GDNF secretion and its mRNA expression. We found that transfection of the GDNF gene into SCs led to significantly enhanced expression of GDNF mRNA. The rate of GDNF secretion by GDNF-SCs was also increased. Functionally, more surviving motoneurons were seen when they were cocultured in GDNF-SC-conditioned medium than when they were in normal SC-conditioned medium. When bridging a rat sciatic nerve defect with a conduit filled with GDNF-transfected SCs, nerve regeneration was better than that of the control. In conclusion, transfection of SCs with the GDNF gene could enhance SC function. Application of genetically modified SCs could be a better way to promote nerve regeneration.
The relative merits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and imatinib for chronic myelogenous leukemia in the accelerated phase (AP-CML) have not previously been evaluated. This cohort study was designed to compare the outcomes of imatinib (n ؍ 87) versus allo-HSCT (n ؍ 45) for AP-CML. A multivariate analysis of the total population revealed that a CML duration > 12 months, hemoglobin < 100 g/L, and peripheral blood blasts > 5% were independent adverse prognostic factors for both overall survival (OS) and progression-free survival (PFS). Both treatments resulted in similar survival in low-risk (no factor) patients, with 6-year event-free survival (EFS), OS, and PFS rates of more than 80.0%. Intermediate-risk (any factor) patients showed no difference in EFS and OS, but 6-year PFS rates were 55.7% versus 92.9% (P ؍ .047) with imatinib versus allo-HSCT, respectively. Among highrisk (at least 2 factors) patients, imatinib was by far inferior to allo-HSCT, with 5-year EFS, OS, and PFS rates of 9.3% versus 66.7% (P ؍ .034), 17.7% versus 100% (P ؍ .008), and 18.8% versus 100% (P ؍ .006), respectively. We conclude that allo-HSCT confers significant survival advantages for high-and intermediate-risk patients with AP-CML compared with imatinib treatment; however, the outcomes of the 2 therapies are equally good in low-risk patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.