[Effects of miR-144-3p on Proliferation, Cell Cycle and Apoptosis of K562 Cells].

OBJECTIVE: To investigate the effects of miR-144-3p on cell proliferation, cell cycle and apoptosis of blast phase chronic myelogenous leukemia (CML) K562 cells. METHODS: K562 cells were cultured in vitro and mimics negative control, hsa-miR-144-3p mimics, inhibitor negative control and miR-144-3p inhibitor were respectively transfected into K562 cells with transfection reagents. The cells were divided into five groups including blank control, mimics negative control, miR-144-3p mimics, inhibitor negative control and miR-144-3p inhibitor. After transfection, the cell proliferation activity was detected by CCK-8 assay. The cell cycle distribution and apoptosis were detected by flow cytometry. RESULTS: Compared with the blank control and mimics negative control groups, the proliferation rate of miR-144-3p mimics group was significantly decreased (P<0.05), the proportion of S phase cells was markedly increased (P<0.05), while the proportion of G1 phase cells was obviously decreased (P<0.05), and the apoptosis rate was significantly increased (P<0.05). Compared with the blank control and inhibitor negative control groups, the proliferation rate of miR-144-3p inhibitor group was obviously increased (P<0.05), the proportion of S phase cells was markedly decreased (P<0.05), while the proportion of G1 phase cells was obviously increased (P<0.05), and the apoptosis rate was significantly decreased (P<0.05). CONCLUSION: miR-144-3p can inhibit the proliferation and promote apoptosis of K562 cells, affect the cell cycle, and block K562 cells in S phase, which indicates that miR-144-3p is involved in the cell cycle activity of CML during blastic phase.

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.

Association of ST-T changes with all-cause mortality among patients with peripheral T-cell lymphomas.

Research has suggested a significant prognostic value of ST-T changes in various cardiovascular diseases and malignant tumors. However, their role in predicting prognosis in patients with peripheral T-cell lymphomas (PTCLs) remains unknown. Here, we investigated the prognostic potential of ST-T changes in all-cause mortality of PTCLs patients. In total, 131 patients with PTCLs between January 2015 and April 2020 were enrolled. Univariable and multivariable COX proportional hazards regression models were used to find the relationship between ST-T changes and all-cause mortality in these patients. A significant difference in all-cause mortality was found between patients with ST-T abnormalities and those without definite abnormalities in the ST-T segments (P = 0.027). Multivariable Cox risk regression analysis indicated that patients with ST-T changes had greater all-cause mortality than patients with normal ST-T segments in the intermediate-high/high-risk groups (P < 0.001). In addition, ST-T changes were markedly distinction in patients with hypoproteinemia than in those with no definite abnormalities in the ST-T segments (P = 0.021). ST-T changes may serve as potential, simple, and effective prognostic factors for all-cause mortality in PTCLs patients, especially in the intermediate-high/high-risk and hypoproteinemia groups. Therefore, regular ECG monitoring is recommended to guide the clinical treatment of patients with PTCLs.

Comprehensive analysis of clinicalf eatures, treatment options, overall survival, and prognostic factors in lymphoma cell leukemia patients: A retrospective study.

Objective: Lymphoma cell leukemia (LCL) is regarded as patients presenting a high extensive lymphoma cell ratio in bone marrow (BM), which is recognized as lymphoma of stage IV by invading into BM. This study aimed to investigate the clinical characteristics, treatment options, survival profiles, and prognostic factors in patients with LCL. Methods: Clinical data of 42 patients with LCL were retrospectively reviewed, and baseline characteristics and treatment records were extracted. In addition, overall survival (OS) was calculated, and the causes of death were analyzed. Results: Out of the 42 patients with LCL, 9 (21.4%) had primary BMLCL, 20 (47.6%) had Non-Hodgkin lymphoma (NHL) complicated with LCL, and 13 (31.0%) had NHL evolving into LCL. Common clinical characteristics included B syndromes (n = 21, 50.0%), abnormal white blood count (n = 28, 66.5%), decreased hemoglobin (n = 28, 66.7%), and platelet (n = 30, 71.4%). Additionally, elevated Eastern Cooperative Oncology Group (ECOG) with a score greater than one occurred in 26 patients (61.9%), and elevated lactate dehydrogenase (LDH) occurred in 25 patients (59.5%). For treatments, chemotherapy was the most common therapy (n = 35, 83.2%), followed by symptomatic treatment and radiotherapy plus chemotherapy. Additionally, the mean OS of the patients was 16.9 (95% CI: 12.8-20.9) months, among which primary patients with BMLCL showed shorter OS than those with NHL complicated with LCL and NHL evolving into patients with LCL. A total of 9 (21.4%) patients with LCL died during follow-up, among which the central nervous system (CNS) invasion was the most common cause of death. Furthermore, primary BMLCL, higher ECOG, and higher LDH were potential predictive factors for worse OS in patients with LCL. Conclusion: This study gives an overview of the treatment and prognosis of LCL, which provides additional information for the management of LCL.

Study on the Relationship Between the Expression of B Cell Mature Antigen and the Classification, Stage, and Prognostic Factors of Multiple Myeloma.

The expression level of BCMA in bone marrow of 54 MM patients was detected in this study to explore the relationship between the BCMA expression and the classification, stage, and prognostic factors of MM. The BCMA expression level of the stable group and remission group was lower than that of the newly diagnosed group and relapse group (P=0.001). There was no significant difference in BCMA expression of MM patients in different types and stages (P>0.05), but it was found that for the newly diagnosed MM patients, the BCMA expression level of IgG patients was higher than that of IgA or light-chain patients (rank average 11.20 vs 5.44, P=0.014). There was no significant correlation between the BCMA expression and the age and serum creatinine of MM patients (P>0.05). And there was no significant difference in BCMA expression between patients with different levels of age and serum creatinine (P>0.05). But it was found that the BCMA expression level of the newly diagnosed MM patients was moderately positively correlated with their age (P=0.025, r=0.595). There was no significant correlation between the BCMA expression and serum ß2-microglobulin, serum lactate dehydrogenase, free kap/lam ratio, and urine ß2-microglobulin (P>0.05). But we found that the BCMA expression of patients with high serum ß2-microglobulin was higher than that of patients with low serum ß2-microglobulin (rank average 28.89 vs 17.54, P=0.017). And the BCMA expression of patients with abnormal serum free kap/lam ratio was higher than that of patients with normal ratio (rank average 28.49 vs 13.55, P=0.004). The BCMA expression was strongly positively correlated with 24-h urine protein, was moderately positively correlated with serum M protein and the percentage of plasma cells in bone marrow, was moderately negatively correlated with albumin and hemoglobin count, and was weakly positively correlated with serum corrected calcium (P<0.05). And it was found that the BCMA expression of positive serum immunofixation electrophoresis patients was higher than that of negative patients (rank average 29.94 vs 16.75, P=0.017). And we try to clarify the relationship between the bone marrow BCMA expression and the peripheral blood sBCMA expression. However, we have not found a clear correlation between them so far (P>0.05).

Prognostic Potential of Heart Rate and Hypertension in Multiple Myeloma Patients.

Background: The prognosis of patients with multiple myeloma (MM) is variable and partly depends on their cardiovascular status. The presence of arrhythmias can lead to worse outcomes. Therefore, this study aimed to evaluate the potential of heart rate (HR) and hypertension in predicating the outcomes of MM patients. Methods: This study retrospectively enrolled patients with MM between January 1, 2010, and December 31, 2018, at the First Affiliated Hospital of Xi'an Jiaotong University. The endpoint was all-cause mortality. The Pearson's chi-square test was used to assess the association between hypertension and outcomes. Univariate and multivariate Cox proportional hazards models were developed to evaluate the relationship between HR and all-cause mortality. Results: A total of 386 patients were included. The mean HR was 83.8 ± 23.1 beats per minute (bpm). Patients with HR >100 bpm had a higher all-cause mortality (79.4%, 50/63) than those with 60 ≤ HR ≤ 100 bpm (39.9%, 110/276) and <60 bpm (19.1%, 9/47) (p < 0.001). Subgroup analysis based on the International Staging System and sex revealed similar relationships (p < 0.01). When stratified by age, patients with HR >100 bpm had higher all-cause mortality than those with a lower HR when age was <65 years or 65-75 years (p < 0.001) but not >75 years. The proportion of patients with hypertension was 54.7% (211/386). However, hypertension was not associated with all-cause mortality in MM patients (χ2=1.729, p > 0.05). MM patients with HR >100 bpm had the highest all-cause mortality. Conclusions: The prognostic potential of HR may be useful in aiding risk stratification and promoting the management of these patients.

Effective mobilization with etoposide and cyclophosphamide for collection of peripheral blood stem cell in patients with multiple myeloma.

PURPOSE: To evaluate the efficacy and toxicity of etoposide and cyclophosphamide for mobilization peripheral stem cells in multiple myeloma patients. METHODS: We retrospectively analyzed 46 patients with multiple myeloma who underwent peripheral blood stem cell collection for upfront autologous hematopoietic stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University between January 2010 and July 2019. The mobilization protocols included cyclophosphamide 2.0 g/m2 with G-CSF (CTX group) before January 2015, and two-days of 5 mg/kg.d etoposide and 1.0 g/m2.d cyclophosphamide with G-CSF (EC group) after January 2015. RESULTS: The success rate of harvest (≥2×106 cells/kg) during the first mobilization attempt was 82.1% in the EC group and 50.0% in the CTX group, and the rate of adequate harvest (≥4×106 cells/kg) was 57.1% in the EC group and 15.8% in the CTX group. After the second mobilization, a sufficient number of CD34+/kg cells for an auto-HSCT was obtained for all patients in the EC group and the majority (68.4%) of patients in CTX group. There was no significant difference of non-hematological adverse events between two groups. The mean neutrophil engraftment time was 11.22±1.56 days and 9.89±2.81days for the CTX and EC groups, respectively (P>0.05). Platelet engraftments were significantly faster in the EC group than the CTX group (P0.05). CONCLUSION: The etoposide and cyclophosphamide regimen could be an effective and safe method for mobilization in patients with multiple myeloma.

HIF-1α suppresses myeloma progression by targeting Mcl-1.

HIF-1α is involved in the carcinogenesis and progression of multiple types of cancer. However, the precise role of HIF-1α is unclear in multiple myeloma. Through the qRT-PCR and CCK-8 assays, we demonstrated that silencing the expression of HIF-1α and Mcl-1, MM proliferation can be decreased and apoptosis can be induced. Next, using the GEO database, we found that Mcl-1 was increased in MMs. Mcl-1 overexpression counterbalanced the tumor suppressing effect of siHIF-1α on MM apoptosis. Additionally, HIF-1α acting as a transcription factor, could directly target the promoter region of Mcl-1 to promote Mcl-1 expression. Based on the experimental result, our findings strongly suggest that HIF-1α regulated the progression of MMs by directly targeting the Mcl-1.

The Influence of Blood Collection Tubes in Biomarkers' Screening by Mass Spectrometry.

PURPOSE: Mass spectrometry is one of the rapidly developing bio-analytical techniques in recent years, and it shows that the results of biomarkers' screening can be influenced by pre-analytical process. The selection of the blood collection tubes is one of the most significant steps of pre-analytical process which is often neglected by researchers. So, it is urgent to define the influence of blood collection tubes clearly in biomarkers' screening. EXPERIMENTAL DESIGN: Two types of blood collection tubes, non-additive tubes and coagulant activator tubes, are used to collect serum samples from patients and healthy controls. All samples are analyzed using matrix-assisted laser desorption ionization-time of flight mass spectrum in this study. RESULTS: The serum protein profile changes while using coagulant tubes whether for patients or healthy controls. It is found that the effect of coagulant on serum protein of patients is smaller than that of control group. There are 27 significantly different peaks between the control group and the control coagulant group. However, between patient group and patient coagulant group, only one differential peak is obtained. Coagulant changes the expression differences between patients and healthy controls, making the differences expand, shrink or reverse, and most of the polypeptides are small molecule, which will change the results of biomarker's screening. CONCLUSIONS AND CLINICAL RELEVANCE: This research suggested that different types of blood collection tubes would influence the final laboratory results. So it's important for clinicians to choose the proper tubes to detect biomarkers and make correct diagnoses.

Norepinephrine-CREB1-miR-373 axis promotes progression of colon cancer.

The adrenergic system contributes to the stress-induced onset and progression of cancer. Adrenergic fibers are the primary source of norepinephrine (NE). The underlying mechanisms involved in NE-induced colon cancer remain to be understood. In this study, we describe the function and regulatory network of NE in the progression of colon cancer. We demonstrate that NE-induced phosphorylation of cAMP response element-binding protein 1 (CREB1) promotes proliferation, migration, and invasion of human colon cancer cells. The downstream effector of NE, CREB1, bound to the promoter of miR-373 and transcriptionally activated its expression. miR-373 expression was shown to be necessary for NE-induced cell proliferation, invasion, and tumor growth. We confirmed that proliferation and invasion of colon cancer cells are regulated in vitro and in vivo by miR-373 through targeting of the tumor suppressors TIMP2 and APC. Our data suggest that NE promotes colon cancer cell proliferation and metastasis by activating the CREB1-miR-373 axis. The study of this novel signaling axis may provide mechanistic insights into the neural regulation of colon cancer and help in the design of future clinical studies on stress biology in colorectal cancer.

Integrating transcriptome-wide association study and copy number variation study identifies candidate genes and pathways for diffuse non-Hodgkin's lymphoma.

BACKGROUND: The genetic basis of diffuse non-Hodgkin's lymphoma (DNHL) is largely unknown now. We conducted a large-scale transcriptome-wide association study (TWAS) of DNHL to identify novel candidates for DNHL. METHODS: The GWAS summary data of DNHL was obtained from the UKBiobank, involving 685 cases and 451,579 controls. TWAS of DNHL was performed using tissue-specific gene expression weights generated from the Genotype-Tissue Expression (GTEx) data. The DNHLTWAS results were further validated by a previous published copy number alterations (CNA) study of DNHL. Gene ontology (GO) and pathway enrichment analysis of identified candidate genes were conducted by the DAVID 6.8. RESULTS: We identified 214 genes with TWAS P value < 0.05 for DNHL, such as MRPL19 (PTWAS = 0.0010), CRCP (PTWAS = 0.0010) and SEMA3C (PTWAS = 0.0010). After further comparing the 214 genes with copy number variations of DNHL patients, we found 1 overlapped gene, BCL10 (PTWAS = 0.0100). We also detected 6 common GO terms shared between gene set enrichment analysis results of TWAS and CNAs, such as cytosol (PTWAS = 0.0003, PCNAs = 4.99 × 10-7) and membrane (PTWAS = 0.0048, PCNAs = 0.0046). The pathway enrichment analysis of TWAS and CNAs detected 3 common pathways, including HIF-1 signaling pathway (PTWAS = 0.0195, PCNAs = 1.96 × 10-5), mTOR signaling pathway (PTWAS = 0.0242, PCNAs = 6.75 × 10-5) and adipocytokine signaling pathway (PTWAS = 0.0392, PCNAs = 0.0103). CONCLUSIONS: Our study identified multiple DNHL associated genes and pathways, providing novel useful information for the pathogenetic studies of DNHL.

Treatment of non-high-risk acute promyelocytic leukemia with realgar-indigo naturalis formula (RIF) and all-trans retinoid acid (ATRA): study protocol for a randomized controlled trial.

BACKGROUND: Acute promyelocytic leukemia (APL) is a highly curable disease when treated with all-trans retinoid acid (ATRA) and arsenic trioxide (ATO). The combination of ATO and ATRA has become the standard therapeutic protocol for induction therapy in non-high-risk APL. An oral arsenic realgar-indigo naturalis formula (RIF) has also showed high efficacy and it has a more convenient route of administration than the standard intravenous regimen. Unlike in previous trials, the arsenical agent was used simultaneously with ATRA during post-remission therapy in this trial. METHODS: This study was designed as a multicenter, randomized controlled trial. The trial has a non-inferiority design with superiority being explored if non-inferiority is identified. All patients receive ATRA-ATO during the induction therapy. After achieving hematologic complete remission (HCR), patients were randomly assigned (1:1) to receive treatment with ATRA-RIF (experimental group) or ATRA-ATO (control group) as the consolidation therapy. During the consolidation therapy, the two groups receive ATRA plus RIF or intravenous ATO 2 weeks on and 2 to ~ 4 weeks off until molecular complete remission (MCR), then ATRA and oral RIF 2 weeks on and 2 to ~ 4 weeks off giving a total of six courses. DISCUSSION: This trial aims to compare the efficacy of ATRA-ATO versus ATRA-RIF in non-high-risk patients with APL, to demonstrate that oral RIF application reduces the total hospitalization days and medical costs. The simple schedule was studied in this trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02899169. Registered on 14 September 2016.

Causal effects of serum metabolites on amyotrophic lateral sclerosis: A Mendelian randomization study.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that is affected by both genetic and environmental factors. Nowadays, OMIC technologies, such as genomics and metabolomics, are providing a systematic readout of genetic structures and physiological states for understanding human diseases. However, the comprehensive analysis of cross-omics is often lacking. Here, we conducted a Mendelian randomization analysis to provide a comprehensive analysis of metabolomics and genomics to estimate the causal relationships between non-targeted human serum metabolites and the development of ALS. Using genetic variants as predictors, our study detected 18 metabolites that might have causal effects on the development of ALS, including a group of gamma-glutamyl amino acids. Our findings suggested that glutathione metabolism dysfunction might be involved in the pathogenesis of ALS. Furthermore, our study provides a novel method to understand the pathogenesis of human diseases and develop therapeutic strategies for diseases by combining metabolomics with genomics.

As4S4 Exhibits Good Killing Effect on Multiple Myeloma Cells Via Repressing SOCS1 Methylation-Mediated JAK2/STAT3 Signaling Pathway.

OBJECTIVE: This study aimed to investigate the effect of tetra-arsenic tetra-sulfide on treating multiple myeloma and its potential regulation on suppressor of cytokine signaling 1 methylation-mediated Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway. METHODS: Tetra-arsenic tetra-sulfide with different concentrations were used to treat U266 cells, and cell viability was measured at 12, 24, and 48 hours with 0 µM tetra-arsenic tetra-sulfide treatment as control by Cell Counting Kit-8 assay. Suppressor of cytokine signaling 1 methylation and expression were determined by methylation-specific polymerase chain reaction, quantitative polymerase chain reaction, and Western blot, respectively, in U266 cells and normal plasma cells and in U266 cells treated by tetra-arsenic tetra-sulfide. Then, rescue experiments were performed by transfecting suppressor of cytokine signaling 1 small interfering RNA into tetra-arsenic tetra-sulfide-treated U266 cells. Besides, phosphor-Janus kinase 2, Janus kinase 2, phospho-signal transducer and activator of transcription 3, and signal transducer and activator of transcription 3 expressions were determined by Western blot. RESULTS: Tetra-arsenic tetra-sulfide inhibited U266 cell viability efficiently in a dose- and time-dependent manner. Suppressor of cytokine signaling 1 methylation was higher while suppressor of cytokine signaling 1 expression was lower in U266 cells compared to normal plasma cells; when treated by tetra-arsenic tetra-sulfide, suppressor of cytokine signaling 1 methylation was decreased while suppressor of cytokine signaling 1 expression was increased in U266 cells, along with the reduced phospho-Janus kinase 2 and phospho-signal transducer and activator of transcription 3 expressions. Then, suppressor of cytokine signaling 1 small interfering RNA enhanced the cell viability and phospho-Janus kinase 2 as well as phospho-signal transducer and activator of transcription 3 expressions in both tetra-arsenic tetra-sulfide treatment-free and tetra-arsenic tetra-sulfide-treated U266 cells. CONCLUSION: Tetra-arsenic tetra-sulfide exhibits good killing effect on multiple myeloma cells via repressing suppressor of cytokine signaling 1 methylation and downstream Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, which might serve as a potential treatment option for multiple myeloma.

Dynamic changes in the level of WT1 as an MRD marker to predict the therapeutic outcome of patients with AML with and without allogeneic stem cell transplantation.

Monitoring minimal residue disease (MRD) is an effective approach to evaluate the response to chemotherapy, and it is used to select the ideal therapeutic strategy and to predict the recurrence during therapy for hematological disorders. The Wilm's tumor 1 (WT1) gene, which is highly expressed in >80% of patients with acute myeloid leukemia (AML) and its increased expression level may cause poor clinical outcomes, is a potential MRD marker of hematological neoplasms. In the present study, the expression levels of WT1 and other molecular markers were retrospectively analyzed by reverse transcription­quantitative PCR in 195 patients with AML. The expression level of WT1 was significantly lower in patients with remission compared with patients with early­stage and recurrent AML. Moreover, WT1 expression was significantly decreased in patients with RUNX family transcription factor 1­RUNX1 translocation partner 1 fusion, but higher in patients with promyelocytic leukemia­retinoic acid receptor α fusion. WT1 expression was significantly reduced during remission. In patients with AML who underwent allogeneic hematopoietic stem cell transplantation (allo­HSCT), the mortality rate 2 years after allo­HSCT was significantly lower in patients with low expression level of WT1 compared with subjects presenting high expression level of WT1. Collectively, the upregulation of the expression level of WT1 in combination with the identification of other genetic abnormalities may be used as MRD markers of hematological neoplasms.

Platycodin D inhibits proliferation, migration and induces chemosensitization through inactivation of the NF-κB and JAK2/STAT3 pathways in multiple myeloma cells.

Multiple myeloma (MM) is a malignancy characterized by the proliferation of malignant plasma cells. Platycodin D (PLD) is a triterpenoid saponin that exerts anti-tumour activity through multiple mechanisms. However, the role of PLD in MM remains unknown. Here, we investigated the effect of PLD on MM cell lines NCI-H929 and U266B1, and elucidated the underlying molecular mechanism. Cell Counting Kit-8 assay showed that the proliferation of NCI-H929 and U266B1 cells was significantly decreased after PLD treatment. Transwell assay confirmed that PLD treatment suppressed migration of NCI-H929 and U266B1 cells. Flow cytometry results indicated that the apoptotic rates of bortezomib (BTZ)-treated NCI-H929 and U266B1 cells were markedly increased after PLD treatment. Western blot analysis revealed that bcl-2 expression was decreased, while bax expression was increased in PLD-treated NCI-H929 and U266B1 cells compared with that in BTZ-treated cells. Furthermore, PLD treatment blocked the activation of nuclear factor-kappa B (NF-κB) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signalling pathways in NCI-H929 cells. Taken together, these data showed that PLD inhibited proliferation and migration, and enhanced chemosensitization to BTZ through inactivation of the NF-κB and JAK2/STAT3 pathways in MM cell lines. These findings indicated that PLD might serve as a novel therapeutic agent for the treatment of MM.

Arsenic trioxide and all-trans retinoic acid (ATRA) treatment for acute promyelocytic leukemia in all risk groups: study protocol for a randomized controlled trial.

BACKGROUND: The 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. METHODS: This 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. DISCUSSION: In 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 REGISTRATION: Chinese Clinical Trials Registry, ID: ChiCTR-IPR- 15006821 . Registered on 27 July 2015.

[Relationship between the Therapeutic Dose of Arsenic Trioxide and Relapse in Acute Promyelocytic Leukemia].

OBJECTIVE: To analyze the correlation of ATO therapeutic dose with the relapse of patients with acute promyelocytic leukemia (APL) and to investigate the optimal dose and courses of ATO. METHODS: The clinical data of 102 patients with APL from January 2008 to June 2015 were analyzed retrospectively. The clinical characteristics of APL patients in relapsed group and maintained remission group were compared. According to ATO dose in 2 years recommended in chinese guideline as criteria of grouping, the patients were divided into ATO high and low dose groups, then the relapse rate in groups was compared. The cut-off value of ATO dose was analyzed by ROC curve. RESULTS: Univariate analysis showed that the relapse rate in high ATO and low ATO groups on 2 year treatment was 2.5% and 17.7% respectively (P<0.05); multiple variate analysis demonstrated that the ATO dose>22.4 mg/kg on 2 year treatment was independent preventive factor for the relapse of APL (OR=0.119, P<0.05). The ROC curve showed that the cut-off value of ATO dose on 2 year treatment was 8.765 mg/kg. The relapse rate of APL in group of ATO dose >8.765 mg/kg group was significantly lower than that in group of ATO dose <8.765 mg/kg. CONCLUSION: The relapse of APL relates with used ATO dose, sufficient use of ATO dose can decrease the relapse rate of APL.

[Relationship between Peripheral Blood White Blood Cell Count and Early Death Rate in Patients with Acute Promyelocytic Leukemia].

OBJECTIVE: To investigate the relationship between peripheral white blood cell count and early death rate of the patients with acute promyelocytic leukemia (APL). METHODS: Through retrospective study, the relationship of early death rate in 116 cases newly diagnosed APL patients with maximum of peripheral blood white blood cell count should be analyzed before and after induction therapy as well as in the whole course of disease during the past 8 years. RESULTS: There was a close relationship between the peripheral white blood cell count and the early death rate in APL patients. Peripheral blood white blood cell count in the early died patients was significantly higher than that of the survival patients (P<0.05). ROC analysis showed that the highest risk threshold of peripheral white cell count was 70×109/L (P<0.05) before treatment, while the highest risk threshold after treatment and in the whole course of disease were 96.4×109/L(P<0.05) and 91.5×109/L(P<0.01) respectively. The dealth rate of patients with highest risk threshold was significantly increased (P<0.05). CONCLUSION: The highest peripheral blood white blood cell count closely relates with the early death rate of patients at different time points in the whole course of disease. Control of peripheral white blood cell count may effectively reduce the early death rate of APL patients.

[Risk Factors and Therapeutic Outcome of Intestinal Acute Graft Versus Host Disease in Acute Leukemia Patients after Haploidentical Peripheral Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the risk factors and therapeutic outcome of acute graft versus host disease (aGVHD) in patients with acute leukemia after haploidentical peripheral hematopoietic stem cell transplantation. METHODS: The clinical data of 19 cases of acute leukemia underwent haploidentical hematopoietic stem cell transplanttion during January 2010 and December 2010 were retrospectively analyzed. The effects of patients sex, donor-recipient sex difference, donor age, conditioning regimen, dosage of anti-thymocyte globulin(ATG), mononuclear cell and CD34+ cell counts on the intestinal aGVHD were analyzed by Logistic regression. RESULTS: Intestinal aGVHD occurred in 5 cases with 1 case at stage II 3 cases at stage III and 1 case at stage IV on the 7th, 22th, 27th, 70th and 154th day after transplantation, respectively. Single factor analysis showed that the patient's sex, donor-recipient sex difference, donor age, dosage of ATG, mononuclear cell and CD34+ cell counts were not related with the occurrence of the intestinal aGVHD, and the conditoning regimen was the risk factor for the intestinal aGVHD. 2 cases among 5 cases with intestinal aGVHD were treated with methylprednisolone at dosage of 1 mg/kg per day, 1 case was treated with methylprednisolone therapy combined with tacrolimus. 2 cases of methylprednisolone-resistance were treated with CD25 monoclonal antibody. Intestinal aGVHD of all patients was improved after the above-mentioned treatment. CONCLUSION: Conditioning regimen of haploidentical peipheral hematopoieitc stem cell transplantaion has effects on the intestinal aGVHD, which needs to be confirmed by further research.