An effective and chemotherapy-free strategy of all-trans retinoic acid and arsenic trioxide for acute promyelocytic leukemia in all risk groups (APL15 trial).

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has been demonstrated to have comparable effectiveness or better to ATRA and chemotherapy (CHT) in non-high-risk acute promyelocytic leukemia (APL). However, the efficacy of ATRA-ATO compared to ATRA-ATO plus CHT in high-risk APL remains unknown. Here we performed a randomized multi-center non-inferiority phase III study to compare the efficacy of ATRA-ATO and ATRA-ATO plus CHT in newly diagnosed all-risk APL to address this question. Patients were assigned to receive ATRA-ATO for induction, consolidation, and maintenance or ATRA-ATO plus CHT for induction followed by three cycles of consolidation therapy, and maintenance therapy with ATRA-ATO. In the non-CHT group, hydroxyurea was used to control leukocytosis. A total of 128 patients were treated. The complete remission rate was 97% in both groups. The 2-year disease-free, event-free survival rates in the non-CHT group and CHT group in all-risk patients were 98% vs 97%, and 95% vs 92%, respectively (P = 0.62 and P = 0.39, respectively). And they were 94% vs 87%, and 85% vs 78% in the high-risk patients (P = 0.52 and P = 0.44, respectively). This study demonstrated that ATRA-ATO had the same efficacy as the ATRA-ATO plus CHT in the treatment of patients with all-risk APL.

Typhaneoside prevents acute myeloid leukemia (AML) through suppressing proliferation and inducing ferroptosis associated with autophagy.

Leukemia remains a fatal disease for most patients and effective therapeutic strategies are urgently required. Typhaneoside (TYP) is a major flavonoid in the extract of Pollen Typhae, showing significant biological and pharmacological effects. In the present study, we explored the effects of TYP on acute myeloid leukemia (AML) progression. The results indicated that TYP markedly reduced the cell viability of AML cells and arrested the cell cycle at the G2/M phase by regulating the expression of associated proteins. In addition, TYP significantly induced apoptosis in AML cells by promoting the activation of Caspase-3. Intracellular and mitochondrial reactive oxygen species (ROS) accumulation were highly detected in AML cells after treatment with TYP. Moreover, TYP clearly induced ferroptosis in AML cells, and this process was iron-dependent and attendant with mitochondrial dysfunction. We also found that TYP significantly triggered autophagy in AML cells by promoting the activation of AMP-activated protein kinase (AMPK) signaling, contributing to ferritin degradation, ROS accumulation and ferroptotic cell death ultimately. In conclusion, the findings above provided solid evidences that TYP could be a promising therapeutic agent to prevent AML progression by inducing apoptosis, ROS production, autophagy and ferroptosis.

[Clinical analysis of retinoic acid syndrome developed in 11 patients with acute promyelocytic leukemia].

To explore the clinical features, risk factors an d treatment of retinoic acid syndrome (RAS) in patients with acute promyelocytic leukemia (APL) treated with retinoic acid, the clinical and laboratory data of 11 APL patients with RAS were retrospectively analysed. The results showed that earlier and more common symptoms of RAS were successively dyspnea (11/11), fever (10/11) and hydrothorax (6/11). Higher WBC count (> or = 15.0 x 10(9)/L) in the course of treatment of all-trans retinoic acid susceptible to develop RAS (9/11). The RAS patients were treated with dexamethasone without discontinuing the treatment of retinoic acid, complete remission was achieved in 10 cases and one patient died from disseminated intravascular coagulation. It is concluded that the identification and dexamethasone treatment of RAS in earlier period are extremely important for obtaining better clinical curative effect, and it does not influence therapeutic effect of continuing application of retinoic acid.