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Noble metal-based catalytic material with maximum utilization is of prime attraction for conserving rare metal resources. Herein, highly dispersion Ni nanoparticles (NPs)-modified N-doped mesoporous carbon material (Ni-N@C) was fabricated by pyrolysis of Ni2+/Histidine cross-linked alginate hydrogels. In a step forward, the obtained Ni-N@C nanocatalyst was treated by the solution of Pd2+, and tiny amount of Pd NPs were deposited on the surface of Ni via the reducibility of Ni to achieve the high dispersion of precious metals material. In the degradation of highly-concentration p-nitrophenol, the catalyst presents excellent performance which could completely degrade pollutants within a very short period. It was demonstrated that pre-embedded Ni NPs could not only increase the efficiency of Pd NPs but also endow the facile separation characteristic to the catalyst. Besides, the catalyst maintained favorable catalytic capacity even after five reaction cycles. In brief, this work may provide novel guidance for the maximum utilization of noble metal-modified mesoporous N-doped carbon-supported catalysts in practical applications of industrial and the treatment highly-concentration p-nitrophenol. Unlabelled Image • Preparing highly dispersion Pd NPs catalyst by spontaneous reduction with Ni • Demonstrating excellent catalytic capacity toward p-NP under high-concentration conditions • Enhanced mechanism over catalytic performance was discussed in detail. • Pre-embedded Ni NPs toward enhanced stability and recyclability [ABSTRACT FROM AUTHOR]

Patients with t(16;21) acute myelogenous leukemia (AML) who receive chemotherapy have poor outcomes. The treatment efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) must be identified, and the usefulness of minimal residual disease (MRD) monitoring requires evaluation. Fourteen consecutive patients with t(16;21) AML undergoing allo-HSCT at our institution were included in this study. Translocation liposarcoma– ETS-related gene ( TLS-ERG ) transcript levels were serially monitored for a median of 15 months (range, 3-51 months) after allo-HSCT. Eight patients relapsed, 7 patients died from relapse-related causes, and 1 patient died from a non–relapse-related cause. The 2-year cumulative incidence rates of relapse, disease-free survival, and overall survival after HSCT were 66.2%, 30.8%, and 46.2%, respectively. Of the 3 patients who received an HLA-matched sibling transplant, 2 relapsed, and 1 (33.3%) was in hematologic complete remission (CR) but died of nonrelapse mortality, whereas 5 of 11 patients (45.5%) who received haploidentical transplantation were in CR and were alive. Two of 6 patients with undetectable TLS-ERG at the time of allo-HSCT relapsed, at 14 and 15 months, and 3 of 4 PCR-positive patients relapsed, at a median of 10 months after HSCT. Four patients with continually low post-HSCT TLS-ERG levels (mostly <.01%) remained alive and in CR. The TLS-ERG levels of all 8 patients who relapsed were significantly increased before the relapse, exceeding 1.0% in all 7 patients who experienced hematologic relapse. In total, 7 patients received modified donor lymphocyte infusion (DLI), and 1 patient received IFN-α. All 7 patients with a TLS-ERG level >5.0% at the time of intervention experienced an increase or a brief decrease in TLS-ERG level, followed by an increase, and 6 relapsed, whereas the TLS-ERG level of 1 patient with a TLS-ERG level <1.0% at intervention decreased to undetectable. Therefore, t(16;21) AML is an indication for allo-HSCT. Among the HSCT recipients, 30.8% responded to treatment with CR. TLS-ERG transcript levels reflect MRD and might predict relapse and guide effective intervention. [ABSTRACT FROM AUTHOR]

A series of 1-benzene acyl-2-(1-methylindol-3-yl)-benzimidazole derivatives were designed, synthesized and evaluated as potential tubulin polymerization inhibitors and for the cytotoxicity against anthropic cancer cell lines. Among the novel compounds, compound 11f was demonstrated the most potent tubulin polymerization inhibitory activity (IC 50 = 1.5 μM) and antiproliferative activity against A549, HepG2 and MCF-7 (GI 50 = 2.4, 3.8 and 5.1 μM, respectively), which was compared with the positive control colchicine and CA-4. We also evaluated that compound 11f could effectively induce apoptosis of A549 associated with G2/M phase cell cycle arrest. Docking simulation and 3D-QSAR model in these studies provided more information that could be applied to design new molecules with more potent tubulin inhibitory activity. [ABSTRACT FROM AUTHOR]

A new strategy for the manufacture of a turn-on fluorescent molecularly imprinted polymer (CdTe/SiO 2 /MIP) receptor for detecting tyrosine phosphopeptide (pTyr peptide) was proposed. The receptor was prepared by the surface imprinting procedure and the epitope approach with silica-capped CdTe quantum dots (QDs) as core substrate and fluorescent signal, phenylphosphonic acid (PPA) as the dummy template, 1-[3-(trimethoxysilyl) propyl] urea as the functional monomer, and octyltrimethoxysilane as the cross-linker. The synthetic CdTe/SiO 2 /MIP was able to selectively capture the template PPA and corresponding target pTyr peptide with fluorescence enhancement via the special interaction between them and the recognition cavities. The receptor exhibited the linear fluorescence enhancement to pTyr peptide in the range of 0.5–35 μM, and the detection limit was 0.37 μM. The precision for five replicate detections of pTyr peptide at 20 μM was 2.60% (relative standard deviation). Combining the fluorescence property of the CdTe QDs with the merits of the surface imprinting technique and the epitope approach, the receptor not only owned high recognition site accessibility and good binding affinities for target pTyr peptide, but also improved the fluorescence selectivity of the CdTe QDs, as well revealed the feasibility of fabrication of a turn-on fluorescence probe using the surface imprinting procedure and the epitope approach. [ABSTRACT FROM AUTHOR]

A series of novel pyrazoline-containing derivatives ( 15 – 47 ) has been designed, synthesized and evaluated for their biological activities. Among them, compound 18 displayed the most potent antiproliferative activity against A549, MCF-7 and HepG-2 cells line (IC 50 = 0.07 μM, 0.05 μM, 0.03 μM, respectively) and the tubulin polymerization inhibitory activity (IC 50 = 1.88 μM), being comparable to CA-4. Furthermore, we also tested that compound 18 was a potent inducer of apoptosis in HepG-2 cells and it had cellular effects typical for microtubule interacting agents, causing accumulation of cells in the G2/M phase of the cell cycle. These studies, along with molecular docking, provided a new molecular scaffold for the further development of antitumor agents that target tubulin. [ABSTRACT FROM AUTHOR]

Mature forests have been almost completely destroyed in China’s northern regions, but this has been followed by large-scale reforestation in the wake of environmental degradation. Although future forest plantations are expected to expand over millions of hectares, knowledge about the ecology and biodiversity of China’s replanted forests remains very limited. Addressing these knowledge gaps, we recorded ground beetle (Coleoptera: Carabidae) communities in five secondary forest types: plantations of Chinese Pine ( Pinus tabulaeformis ) and Prince Rupprecht’s Larch ( Larix principis-rupprechtii ), Oak ( Quercus wutaishanica ) and Asian White Birch ( Betula platyphylla ) woodlands, and naturally regenerated mixed forest. Species richness peaked in mixed forests, while pine and oak woodlands harboured discrete communities of intermediate species richness. Oak, pine and mixed forest habitats also showed high levels of species turnover between plots. Canopy closure was an important factor influencing ground beetle assemblages and diversity, and a number of forest specialist species only occurred in pine or oak forests. We believe that some forest specialists have survived earlier deforestation and appear to be supported by new plantation forests, but maintenance of secondary native oak and mixed forests is crucial to safeguard the overall species pool. [ABSTRACT FROM AUTHOR]

To clarify the prevalence and prognostic significance of c-KIT mutations in patients with core binding factor acute myeloid leukemia (CBF-AML), a total of 351 patients who were categorized as pediatric t (8;21), adult t (8;21), pediatric inv(16), or adult inv(16) were screened at diagnosis for c-KIT mutations in exons 17 and 8 using direct sequencing. A total of 250 patients underwent follow-up. Overall, 36.5% of the patients had a c-KIT mutation. Adult t (8;21) and inv(16) patients had mutations predominantly in exons 17 and 8, respectively. Higher White blood cell (WBC) count, WBC index, and AML1-ETO transcript levels in adult t (8;21) patients were significantly associated with c-KIT mutations and mutations in exon 17 ( P ≤ 0.030). c-KIT mutations in adult t (8;21) patients were significantly correlated with a high cumulative incidence of relapse (CIR, P = 0.0070) at 2 years and a low 2-year disease-free survival (DFS, P = 0.013) and overall survival (OS, P = 0.0055). However, no significant difference was revealed in the effect of c-KIT mutations on outcome of adult inv(16) and pediatric t (8;21) patients (all P > 0.05). Multivariate analysis revealed that c-KIT mutation is an independent prognostic factor for relapse, DFS, and OS ( P ≤ 0.016) in adult t (8;21) AML patients. Therefore, with regard to c-KIT mutation, CBF-AML is a heterogeneous disease. c-KIT mutations have a strong adverse effect on the relapse and survival of adult t (8;21) AML patients. [ABSTRACT FROM AUTHOR]

A series of metronidazole–thiazole derivatives has been designed, synthesized and evaluated as potential antibacterial inhibitors. All the synthesized compounds were determined by elemental analysis, 1 H NMR and MS. They were also tested for antibacterial activity against Escherichia coli , Bacillus thuringiensis , Bacillus subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The results showed that compound 5e exhibited the most potent inhibitory activity against E. coli FabH with IC 50 of 4.9 μM. Molecular modeling simulation studies were performed in order to predict the biological activity of proposed compounds. Toxicity assay of compounds 5a , 5b , 5d, 5e , 5g and 5i showed that they were noncytotoxic against human macrophage. The results revealed that these compounds offered remarkable viability. [ABSTRACT FROM AUTHOR]

Abstract: The molecular response of chronic myeloid leukemia (CML) patients to tyrosine kinase inhibitor treatment can be evaluated either by BCR-ABL mRNA levels on international scale (IS) or by log reduction from the baseline level of the laboratory. Both methods were compared in 248 newly diagnosed chronic phase CML patients treated with imatinib. The major molecular responses (MMR) obtained by both methods predict progression-free survival (PFS, all P <0.0001). Thirty-six patients, who were identified as MMR patients by the IS method but as non-MMR patients by the log reduction method, had the same PFS as MMR patients identified by both methods. The molecular responses of patients at 3 and 6 months, as evaluated by the two methods, have similar predictive values on their cytogenetic responses at 12 months and on their molecular responses at 18 months. Both ≤10%IS and ≥1 log reduction at 3 months and ≤1%IS at 6 months were significantly associated with PFS (P =0.0011, 0.0090, and 0.0064). The percentages of patients with BCR-ABLIS of ≤1%, >1–10%, and of >10% at 3 months and 6 months in the German CML Study IV were similar with those with corresponding BCR-ABLIS in our center, but was significantly different with those evaluated by the log reduction method. Therefore, the molecular response evaluated by BCR-ABLIS has similar trends in PFS and in response prediction, but can better differentiate patients than that by the log reduction method. Furthermore, the IS method allows comparison among molecular response results from different laboratories. [Copyright &y& Elsevier]

Abstract: A series of sulfonamides containing coumarin moieties had been prepared that showed a very interesting profile for the inhibition of two human carbonic anhydrase inhibitors. These compounds were evaluated for their ability to inhibit the enzymatic activity of the physiologically dominant isozymes hCA II and the tumor-associated isozyme hCA IX. The most potent inhibitor against hCA II and IX were compounds 5d (IC50 = 23 nM) and 5l (IC50 = 24 nM), respectively. These sulfonamides containing coumarin moieties may prove interesting lead candidates to target tumor-associated CA isozymes, wherein the CA domain is located extracellularly. Eighteen compounds were scrutinized by CoMFA and CoMSIA techniques of 3D quantitative structure–activity relationship. Nine of the compounds were evaluated for cytotoxicity against human macrophage. [Copyright &y& Elsevier]

Abstract: A new type of fuzzy filter of lattice implication algebras is introduced and it''s properties are investigated. Some equivalent characterizations of this new type fuzzy filter are obtained. Furthermore, the relations among this new type fuzzy filter, fuzzy filter and filter of lattice implication algebras are studied. [Copyright &y& Elsevier]

Abstract: The purpose of this study is to investigate the effect of La doping on the photocatalytic property of CoO/SrTiO3. The experimental results show that a suitable concentration of La doping greatly improved the photocatalytic activity of CoO/SrTiO3. The activity first increased, reached a maximum, and then decreased drastically with increasing doping concentration. The physical properties of the catalyst were characterized using XRD, SEM and UV-visible diffuse reflectance spectra. The influence of loading amount of co-catalyst CoO on the photocatalytic activity of La-doped SrTiO3 was also studied and it was found that the optimum loading amount increased with increasing doping concentration. [Copyright &y& Elsevier]

Abstract: To clarify whether expression of the programmed cell death 5 (PDCD5) gene in leukemic cells is abnormal, real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) was used to examine its expression in marrow cells from leukemia patients. We found lower PDCD5 in both AML and CML marrow cells than in normal donor marrow cells. A negative correlation was found between relative levels of PDCD5 and BCR/ABL expression in all CML patients and in CML patients in the advanced phase. Treatment with the ABL tyrosine kinase inhibitor Imatinib mesylate increased PDCD5 expression in K562 and MEG-01 cells. These findings suggest that abnormal expression of PDCD5 in leukemia may be involved in the pathomechanism of AML and CML. [Copyright &y& Elsevier]

• Warming-induced decline in maize yields and WUE concentrated in high-yield areas. • Controlling the temperature rise within 1.5 °C could reduce maize yield loss. • China's main food-producing regions also is high-risk areas for maize yield reductions. • Help stakeholders optimize the management and adaptation strategies in production. Agricultural production is highly sensitive to climate change. Scientifically evaluating the impact of climate change on agriculture lays a foundation for stakeholders to make evidence-based decisions. However, the potential changes to China's maize production and water use efficiency (WUE) under the 1.5 °C and 2.0 °C global warming (GW1.5 and GW2.0) scenarios still remain unclear. In this study, the spatiotemporal changes in China's maize yield and WUE relative to the reference period (1986–2005) under GW1.5 and GW2.0 were simulated using the calibrated and validated CERES-Maize model. The climate of GW1.5 could be beneficial for maize yield and WUE, but these benefits declined when warming reached 2.0 °C above the pre-industrial level. Under GW2.0, China's main food-producing regions became high-risk areas for maize yield reductions. The decrease of maize yield in the north spring maize zone and Huanghuai Plain spring–summer maize zone were both higher than that in other planting zones. Increasing risk of yield reduction and a looming water use crisis are likely to bring unprecedented challenges to sustainable agricultural development. Controlling the temperature rise within 1.5 °C would reduce the yield reduction risk in each planting zone by 11.01–75.69%, which is conducive to ensuring China's food security. [ABSTRACT FROM AUTHOR]

Two new atranones T and U (1 and 2), and three known analogues atranone B (3), atranone Q (4), and stachatranone C (5) were isolated from the toxigenic fungus Stachybotrys chartarum. Their structures and absolute configurations were elucidated by spectroscopic data and calculated ECD analyses. The cytotoxicities of all the atranones (1 – 5) were evaluated against MG-63 human osteosarcoma cell lines. Compound 4 exhibited significant cytotoxic effect against MG-63 with IC 50 value of 8.6 μM, being more active than the positive control, 5-FU (IC 50 10.4 μM). Morphological features of apoptosis activities were evaluated in 4 -treated MG-63 cells. Compound 4 effectively induced apoptosis of MG-63, which was associated with G 0 /G 1 -phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 4 significantly induced MG-63 cell apoptosis in a dose-dependent manner. Unlabelled Image [ABSTRACT FROM AUTHOR]

• The CCl4-triggered liver inflammation recruited lots of T and B lymphocytes and induce AIH of Balb/c mice in the presence of CYP2D6. • The Ad-triggered liver inflammation could not fully induce AIH of Balb/c mice in the presence of CYP2D6 because of few T cells infiltration. • The genetic predisposition could determine the liver tolerance in Balb/c mice. • The other factors related with the breakdown of liver tolerance might also promote the initiation and development of AIH. Autoimmune hepatitis (AIH) is a chronic liver disease mediated by immunity, and could lead to liver fibrosis and hepatocellular carcinoma. However, the mechanisms for breaking hepatic tolerance and driving AIH still remain elusive. We herein reported that the non-specific liver inflammation triggered by carbon tetrachloride (CCl 4) recruited high numbers of CD4+T, CD8+T and B cells, and elevated the expression of proinflammaitory cytokines in Balb/c mice, further breaking liver tolerance and inducing autoimmune response, AIH inflammation and liver fibrosis in the presence of CYP2D6 antigen mimicry. In contrast, adenovirus infection could not break liver tolerance and induce AIH in Balb/c mice even in the presence of CYP2D6 antigen mimicry. These results suggested that genetic predisposition could determine liver tolerance in Balb/c mice. The chemical induced inflammation in the liver breaks tolerance and might be considered important for the initiation and development of AIH in Balb/c mice. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel 1-(2-hydroxypropyl)-2-styryl-5-nitroimidazole derivatives had been designed, synthesized, isolated and evaluated as potentiators of antibacterial agents. All these synthesized compounds were determined by elemental analysis, 1H NMR, and MS. Their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa and two Gram-positive bacterial strains: Bacillus thuringiensis and Bacillus subtilis by MTT method as potential FabH inhibitory. The results showed that compound 30 exhibited the most potent E. coli FabH inhibitory activity with IC50 of 4.6 μM. Molecular modeling simulation studies were performed in order to predict the biological activities of the proposed compounds. All compounds have been tested for toxicity by MTT assay on human macrophage. [Copyright &y& Elsevier]

Abstract: Heavy metal and organic pollutants in sediments along the coastal zone of southeastern China have been investigated. Sediment samples are retrieved from three depositional environments: coast, estuary, and tide-affected river mouth. The relative abundance of heavy metal and organic pollutants is related to their geochemical properties as well as depositional environments and anthropogenic discharge. Based on a sequential extraction method, it is revealed that anthropogenic Pb, Cr, Cu, and Cd are mainly bound to Fe–Mn oxides, suggesting that adsorption and co-precipitation of Fe–Mn oxides are in the control of their transfer processes from water column to sediment. Heavy metal bound to carbonates is also an important pool especially for Cd, Mn, and Pb. The main organic pollutants found in the study area include petroleum-related alkanes, phthalic acid ester, organic silicon, chlorophenol, phenyl ether, and amine. The accumulation of heavy metals and organics in surficial sediments has a decrease tendency from estuarine environment to coastal environment and to tide-affected river mouth. [Copyright &y& Elsevier]

This work aimed to develop a novel colorimetric indicator film for monitoring of food freshness based on gelatin/polyvinyl alcohol matrix incorporated with anthocyanin extracts from mulberry. The color of anthocyanin extracts solutions obviously changed from bright red to dark green in the pH range of 2.0–11.0. FTIR spectra and isothermal titration calorimetry showed that the anthocyanin extracts were successfully combined with gelatin/polyvinyl alcohol matrix by hydrogen binding and electrostatic interaction, which enhanced the stability of anthocyanin. The scanning electric microscopy showed that the compatibility between polyvinyl alcohol and gelatin were improved owing to the addition of anthocyanin extracts. With the anthocyanin extracts addition from 0 to 45 mg/100 mL mixed solution, the tensile strength decreased from 30.80 to 21.01 MPa and the elongation at break increased from 589.22% to 905.86%. The color response of film in buffer solution of different pH were in accordance with anthocyanin extracts solutions, and its color changes were clearly visible with naked eye. Finally, the film was evaluated by a test on monitoring fish spoilage, which presented visible color changes due to volatile nitrogenous compounds formed over time. These results showed that this developed film could be used as an effective method for the monitoring of food freshness. Unlabelled Image • A colorimetric film was developed by using gelatin, PVA and mulberry anthocyanin. • The anthocyanin stability was enhanced by combining with film matrix. • The mechanical properties of films were improved due to the addition of anthocyanin. • Color changes of film in buffer solution of different pH were visible with naked eye. • The film could be used as an effective method for the monitoring of fish spoilage. [ABSTRACT FROM AUTHOR]

Abstract The combustion behaviors of three oil sludge samples and their corresponding semicoke prepared from a laboratory-scale pyrolysis/gasification reactor were investigated using a thermogravimetric-differential scanning calorimeter-mass spectrum (TG-DSC-MS) system over the temperature range of 313-1173 K under atmospheric pressure. The obtained results revealed that the combustion process can be divided into five stages, and the interval temperature and mass loss of each stage were given. To explain the combustion characteristics of the oil sludges and semicokes during ignition and subsequent burning in detail, a series of combustion characteristic parameters and the derived comprehensive indexes were determined based on the DTG and DSC results. Both the Starink method and Friedman method were employed to conduct combustion kinetics analysis, and the distribution and mean value of the activation energy were obtained. The emissions of the main combustion products, incomplete combustion products, gaseous pollutants, and oxidizing agent during the combustion process were detected by mass spectrometry. Finally, the product yield from the previous pyrolysis/gasification experiments and the data extracted from the former sections were used to conduct a PCA. The synthetical evaluation results indicated that the comprehensive thermochemical treatment scheme might be a more effective choice for the treatment and recovery of oil sludge. Graphical abstract Image Highlights • The combustion process of oil sludge was divided into five stages. • The comprehensive treatment scheme is a better choice for oil sludge treatment. • Pyrolysis/gasification process is helpful to reduce the combustion reaction barrier. • A sudden release of volatiles occurred in the combustion process of the LOS sample. [ABSTRACT FROM AUTHOR]

Highlights • A seven-color panel including CD34 and TdT was built to detect MRD in T-ALL. • The panel could be applied to >97% T-ALL patients independent of initial phenotype. • Only one MRD false-negative result occurred because of antigen shifts. • MRD positive detected by the panel at post-HSCT could effectively predict relapse. Abstract A seven-color panel was used to detect minimal residual disease (MRD) in T cell acute lymphoblastic leukemia (T-ALL) via flow cytometry (FCM). Its availability and clinical significance were studied in T-ALL patients with newly diagnosed (n = 64), relapsed (n = 48) and morphologically complete remission (n = 103). The following four features were used to identify immature cCD3+ T cells: CD34+, TdT+, but mCD3-/dim+, and CD45dim+. Among these features, either TdT or CD34 expression was the most useful and were found in 93.8% of patients at diagnosis and 86.7% of patients who relapsed. Although some of the immature markers had disappeared in 23 of 59 cases after therapy, only one case presented with a false negative MRD. Of the 74 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), MRD-positive patients showed a higher relapse rate, a higher cumulative incidence of relapse at 4 years and a shorter median relapse-free survival than MRD-negative patients at post-HSCT(72.7% vs 17.3%, P = 0.000; 100% vs 19.9%, P < 0.0001; and 16 months vs undefined, P < 0.0001). We demonstrated that this panel could be applied to>97% of T-ALL patients to detect MRD and predict relapse after allo-HSCT even in the absence of the initial immunophenotype. [ABSTRACT FROM AUTHOR]

In the present work, twenty-five nicotinoyl pyrazoline derivates bearing N-methyl indole moiety have been designed and synthesized. The biological evaluation of these compounds as tubulin assembly inhibitors revealed that most of them were potential antitumor agents. Among them, compound 28 exhibited most potency against cancer cell line panels (GI 50  = 29–90 nM for HeLa, HepG2 and MCF-7 cells) without toxicity to non-tumor cells (CC 50  > 300 μM for 293 T cell), bound to the colchicine site of tubulin and displayed excellent inhibitory activity in tubulin assembly assay (IC 50  = 1.6 μM, better than CA-4). Molecular dynamics simulation was carried out to validate the docking pose of compound 28 with tubulin crystalline. Further investigation on HepG2 and HeLa cells demonstrated that compound 28 could cause mitosis arrest to G2/M phase, and subsequently induced cell apoptosis. The efficiency in vivo of compound 28 was also evaluated on HeLa-Xenograft nude mice, and the relative tumor inhibition ration was up to 61.52% without noticeable weight loss and tissue damage (examined by H&E staining), which was comparable to CA-4 (inhibited 59.92%). In brief, compound 28 is a promising candidate for tumor therapy as tubulin assembly inhibitor. [ABSTRACT FROM AUTHOR]

Here we compare outcomes between the tyrosine kinase inhibitors (TKIs) plus chemotherapy regimen and allogeneic hematopoietic stem cell transplantation (transplantation cohort) in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) and explore factors associated with prognosis. Data from 145 Ph+ ALL patients were analyzed retrospectively. Patients were treated with imatinib plus chemotherapy and then transplantation or continuous TKIs with chemotherapy based on patient preference. A total of 145 Ph+ ALL patients were recruited for this study (median age, 37 years; range, 14 to 65). Among these patients, 81 were men (55.9%) and 86 underwent IKZF1 detection, which identified 59 patients (68.6%) with IKZF1 deletions. After treatment 136 patients (95.8%) achieved complete remission (CR) eventually. With a median follow-up of 33 months (range, 4 to 114) for CR patients, 77 patients (57.9%) underwent transplantation and 56 (42.1%) received continuous TKIs with chemotherapy. At the 4-year follow-up the cumulative incidence of relapse (CIR), disease-free survival (DFS), and overall survival (OS) were 29.4% (95% confidence interval [CI], 24.9% to 34.4%), 60.9% (95% CI, 56.5% to 65.3%), and 69.2% (95% CI, 65.1% to 73.3%), respectively. Multivariate analysis showed that WBC counts < 30 × 10 9 /L at diagnosis (hazard ratio [HR], 4.2; 95% CI, 1.9 to 9.2; P   < .001; HR, 2.6; 95% CI, 1.4 to 4.9; P  = .003; HR, 2.7; 95% CI, 1.4 to 5.4; P  = .003), 3-log reduction of BCR-ABL levels from baseline after 2 consolidation cycles (HR, 4.4; 95% CI, 1.9 to 9.9; P  < .001; HR, 3.1; 95% CI, 1.7 to 5.9; P   < .001; HR, 3.5; 95% CI, 1.9 to 8.7; P  = .001; defined as “minimal residual disease low level”), and transplantation (HR, 5.0; 95% CI, 2.2 to 11.2; P   < .001; HR, 3.3; 95% CI, 1.7 to 6.4; P    < .001; HR, 4.1; 95% CI, 1.9 to 8.7; P    < .001) were the favorable factors of CIR, DFS, and OS. According to the first 2 risk factors, CR patients were divided into 3 groups: low risk (no factor, n = 42, 31.6%), intermediate risk (1 factor, n = 73, 54.9%), and high risk (2 factors, n = 18, 13.5%). In the low-risk group at the 4-year follow up no significant difference existed between the transplant and nontransplant arms for the probabilities of CIR (8.5% versus 7.7%, P  = .671), DFS (88.2% versus 83.9%, P  = .426), and OS (96.6% versus 83.3%, P  = .128). In the intermediate- and high-risk groups at the 4-year follow-up, CIR (23.6% versus 36.9%, P  = .017; 37.5% versus 100.0%, P    <   .001), DFS (62.4% versus 43.8%, P  = .048; 56.2% versus 0%, P    <   .001), and OS (76.1% versus 47.7%, P  = .037; 51.4% versus 6.3%, P  = .001) rates were significantly better in the transplant arm than in the nontransplant arm. In surviving patients of the low-risk group, no difference in complete molecular response (CMR) rates (85.7% versus 72.7%, P  = .379) between the transplant and nontransplant arms was found. However, in the intermediate-risk group the proportion of CMR was significantly higher in the transplant arm than in the nontransplant arm (82.8% versus 42.9%, P  = .006). In the high-risk group 4 of 7 transplant patients (57.1%) were in CMR, and no patients survived in the nontransplant arm. Allogeneic hematopoietic stem cell transplantation confers significant survival advantages for Ph+ ALL patients compared with TKIs plus chemotherapy, especially in intermediate- and high-risk patients. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains an important curative option for children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who have a poor response to chemotherapy plus imatinib. For such children, if there are no matched related or unrelated donors, alternative donor transplantation may be a choice. The role of haploidentical donor (HID) HSCT in pediatric patients with Ph+ ALL has not been reported. The study population included pediatric patients with Ph+ ALL who underwent HID-HSCT. BCR-ABL transcript levels were analyzed using real-time quantitative reverse transcription polymerase chain reaction. At a median follow-up of 34 months, the 5-year probabilities of event-free survival (EFS) and overall survival (OS) were 61.0% and 70.0%, respectively in HID HSCT. The 3-year incidence of relapse and non-relapse mortality was 22.7% and 16.4%. Multivariate analysis showed that the post-HSCT BCR-ABL transcript level on +30 day was a significant factor affecting relapse rate. HID HSCT for the treatment of pediatric patients with Ph+ ALL yielded promising long-term survival. Post-HSCT BCR-ABL transcript positivity was a significant factor for clinical relapse after allo-HSCT in the imatinib era. [ABSTRACT FROM AUTHOR]