BackgroundThe treatment of acute promyelocytic leukemia (APL) has been revolutionized in the past two decades by the advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). It suggests that non-high-risk APL patients can be cured without chemotherapy. However, ATRA plus chemotherapy is still the standard therapy for the high-risk patients. Central nervous system (CNS) relapse remains a significant cause of treatment failure in high-risk patients. However, increasing the ATO concentration in cerebrospinal fluid (CSF) may reduce CNS relapse in high-risk patients. Mannitol can allow ATO to penetrate the blood-brain barrier (BBB) and reach therapeutically effective levels in the CSF. It is used for the treatment of CNS relapse in patients APL. We compare ATRA-ATO with ATRA-ATO plus chemotherapy in both high-risk and non-high-risk patients with APL.MethodsThis study was designed as a multicenter randomized controlled trial. Patients with APL were randomly assigned into two groups: the ATRA-ATO group (experimental group) and the ATRA-ATO plus chemotherapy group (control group). The experimental group receives therapy with ATRA-ATO for induction, consolidation and maintenance therapy. In the high-risk patients, mannitol will be used with ATO in the consolidation and maintenance therapy. Hydroxyurea will be used in patients who developed leukocytosis in the induction therapy. The control group receives therapy with ATRA-ATO plus chemotherapy for induction and consolidation therapy.DiscussionIn this study, a randomized clinical trial design is described. It aims to compare the efficacy of ATRA-ATO versus ATRA-ATO plus chemotherapy in all-risk patients with APL.Trial registrationChinese Clinical Trials Registry, ID: ChiCTR-IPR-15006821. Registered on 27 July 2015.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2812-3) contains supplementary material, which is available to authorized users.

No abstract

PurposeTripartite-motif-containing protein 56 (TRIM56) has been found to exhibit a broad antiviral activity, depending upon E3 ligase activity. Here, we attempted to evaluate the function of TRIM56 in multiple myeloma (MM) and its underlying molecular basis.Materials and MethodsTRIM56 expression at the mRNA and protein level was measured by qRT PCR and western blot analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry analysis was performed to investigate the effect of TRIM56 on MM cell proliferation and apoptosis. The concentrations of interferon (IFN)-β, interleukin (IL)-6, and tumor necrosis factor-α in MM cell culture supernatants were detected with respective commercial ELISA kits. Western blot was employed to determine the effect of TRIM56 on toll-like receptor 3 (TLR3)/toll-IL-1 receptor (TIR) domain-containing adaptor inducing IFN-β (TRIF) signaling pathway.ResultsTRIM56 expression was prominently decreased in MM cells. Poly (dA:dT)-induced TRIM56 overexpression in U266 cells suppressed proliferation, induced apoptosis, and enhanced inflammatory cytokine production, while TRIM56 knockdown improved growth, diminished apoptosis, and inhibited inflammatory cytokine secretion in RPMI8226 cells. Moreover, TRIM56 knockdown blocked TLR3 signaling pathway. Furthermore, poly (I:C), a TLR3 agonist, markedly abolished TRIM56 depletion-induced increase of proliferation, decrease of apoptosis, and reduction of inflammatory factor in MM cells.ConclusionTRIM56 may act as a tumor suppressor in MM through activation of TLR3/TRIF signaling pathway, contributing to a better understanding of the molecular mechanism of TRIM56 involvement in MM pathogenesis and providing a promising therapy strategy for patients with MM.

All-trans retinoic acid (ATRA)/arsenic trioxide (ATO) combination based therapy has become recommended first line treatment for de novo diagnosed low- to intermediate-risk acute promyelocytic leukemia (APL) patients. Though highly curable, relapses of APL could happen due to various reasons. In this research, we retrospectively analyzed data from patients who were diagnosed and treated APL between 2007 and 2015 in a tertiary hospital in northwest China. 123 APL patients were included, among which, 13 patients experienced relapse despite intensive treatment of ATRA plus ATO or ATRA plus chemotherapy or ATRA plus ATO plus chemotherapy. Although they all achieved complete remission after first induction therapy, 2 patients relapsed during maintenance therapy, 3 patients discontinued treatment then relapsed, 6 patients relapsed during consolidation therapy. Relevant data were subsequently compared with guidelines and multi-centre clinical researches to find out possible reasons of relapse. The results showed, all 13 relapsed patients received less than recommended dose of ATRA and ATO. 6 patients had longer than 4 months' treatment intervals, 4 patients received more than 5 courses of chemotherapy as consolidation or maintenance therapy, among which 2 patients relapsed during maintenance therapy till received chemotherapy 12 and 16 courses respectively. Risk assessment: 5 patients with low-risk, 4 patients with intermediate-risk, 4 patients with high-risk. Conclusion: It is highly possible that the relapse of APL is related to insufficient prescription of ATRA and ATO, and too many courses of chemotherapy may exert negative effects on outcome. Disclosures Wang: National Natural Science Foundation of China: Research Funding. Zhang:National Natural Science Foundation of China: Research Funding. Li:National Natural Science Foundation of China: Research Funding. Zhang:National Natural Science Foundation of China: Research Funding. Chen:National Natural Science Foundation of China: Research Funding.