[Primary Prophylatic Effect of Voriconazole Against Invasive Infection of Pulmonary Aspergillosis during Remission-Induction Chemotherapy for Acute Myeloid Leukemia].

OBJECTIVE: To evaluate the efficacy of primary prophylaxis of voriconazole against invasive infection of pulmonary aspergillosis (IPA) during remission-induction chemotherapy (RIC) of patients with acute myeloid leukemia (AML). METHODS: Clinical data of 102 de novo AML patients who received primary anti-IPA prophylaxis during the first induction chemotherapy were analyzed retrospectively. All the cases were divided into voriconazole-treated group and posaconazole-treated group according to the prophylactic agent. The incidences of IPA and systemic antifungal treatment during induction chemotherapy were analyzed for both groups. RESULTS: Among 102 enrolled cases, 42 cases received voriconazole and other 60 received posaconazole as primary prophylaxis. IPA occurred in 3 cases of voriconazole group (1 probable, 2 possible); IPA occurred in 4 cases of posaconazose group, and all were possible cases. The incidence of IPA during remission-induction chemotherapy in variconazole group equaled to posaconazose group (7.1% vs. 6.7%) (P=0.925). Beside IPA cases, 2 cases in voriconazole group and 4 cases in posaconazole group received intravenous anti aspergillosis drugs preemptive treatment, and no significant difference of prophylactic success rate was observed between two groups (88.1% vs. 86.7%) (P=0.831). Visual disturbance was the most common adverse event occurred in voriconazole group, but no significant differences of incidences of other adverse effects were observed when compared with posaconazole group. CONCLUSION: According to similar prophylactic effect with posaconazole, voriconazole appears to be a good alternative for primary prophylaxis of IPA during remission-induction chemotherapy in AML patients.

[Values of Procalcitonin for Predicting Outcome of Infection in Acute Leukemia Patients with Bacterial Bloodstream Infection].

OBJECTIVE: To investigate the effects of serum procalcitonin(PCT) levels for predicting the outcome of bacteria bloodstream infection in acute leukemia patients. METHODS: Clinical data from 236 patients with acute leukemia accompanied by bacterial bloodstream infection during July 2014 to November 2017 were retrospectively analyzed, 236 patients were divided into 5 groups (<0.05 ng/ml, 0.05- <0.5 ng/ml, 0.5- <2.0 ng/ml, 2.0- <10.0 ng/ml and >10.0 ng/ml) according to PCT concentrations. RESULTS: The median age of patients was 40(13-73) years old. The male 123 cases(52.1%) and female 113 cases(47.9%) in 236 patients. The incidence of infection-related dealth in 5 groups was 0%, 1.4%, 13.8%, 25.0% and 33.3%, respectively; the incidence of septic shock and other serious complications in 5 groups was 0%, 2.1%, 13.8%, 25.0%, 33.3% and 6.4%, 7.0%, 24.1%, 41.7%, 50.0%, respectively, showing the concentration dependent manner and statistically significant difference (u=2127, P=0.000; u=2234, P=0.000; u=4102, P=0.000). Further analysis showed that with the increase of PCT concentration, the cumulative incidence of septic shock, infection-related death and other serious complications was gradually increased with statistically significance (HR=2.887, P=0.000, 95%CI:1.960-4.260; HR=3.158, P=0.000, 95%CI: 2.100-4.740; HR=2.158, P=0.000, 95%CI:1.550-3.000) respectively. Increased procalcitonin level is an independent risk factor for septic shock and infection-related death (HR=2.517, P=0.000, 95%CI: 1.520-4.168; HR=2.881, P=0.000, 95%CI: 1.692-4.904)respectively. CONCLUSION: Serum procalcitonin level positively correlates with the incidence of serious bacteria bloodstream infection complications in the patients with acute leukemia. Increased procalcitonin level is an independent risk factor for septic shock and infection-related death, indicating that procalcitonin may be an important prognostic factor for infection outcome in acute leukemia patients with bacteremia.

[FLT3-ITD Mutation in Newly Diagnosed Patients with Acute Promyelocytic Leukemia].

OBJECTIVE: To evaluate the influence of FLT3-ITD mutation on long term survival of newly diagnosed patients with acute promyelocytic leukemia (APL). METHODS: Long term survival of 170 newly diagnosed APL patients was retrospective analyzed. Mutation rate of FLT3-ITD was assayed, and its influence on disease-free survival(DFS) or overall survival (OS) was analyzed. RESULTS: The mutation rate of FLT3-ITD in newly diagnosed patients with APL was 14.1%. WBC count at diagnosis was higer in FLT3-ITD positive group than that in negative group, and the mutation rate of FLT3-ITD was highest in high risk group. Induction death rate in FLT3-ITD positive and negative group were 12.5% and 2.9%, respectively (P=0.031). Complete remission(CR) rate in 2 groups were 83.3% and 97.1%(P=0.004). The 5-year OS rates in 2 groups were 87.5±6.8% and 90.6±2.6% (P=0.740). The 5-year DFS in 2 groups were 82.8±9.1% and 83.6±3.4%(P=0.928). CONCLUSION: FLT3-ITD mutation is related with high peripheral white blood cell count in APL, the APL with FLT3-ITD mutation has higher induction death rate and lower CR rate than those in that without FLT3-ITD mutation, but FLT3-ITD mutation did not affect on long term DFS and OS.

[Characteristics of karyotypes and gene mutations for elder acute myeloid leukemia].

OBJECTIVE: To investigate the incidence of karyotypes and gene mutations for elder acute myeloid leukemia and to explore the relationship between each other. METHODS: Clinical data and bone marrow samples of elder AML patients were collected. Karyotype and gene mutation (FLT3, NPM1, C-Kit, CEBPα, DNMT3A) test were performed, characteristics of karyotypes and gene mutations were analysed. RESULTS: The incidence of better risk karyotype was 16.6%, in which the incidences of t(15;17), t(8;21) and inv (16)/t(16;16) were 3.90%, 10.73%, and 1.95% respectively; the incidence of intermediate risk karyotype was 72.2%, in which the incidence of normal karyotype was 57.86%; the incidence of poor risk karyotype was 11.20%, in which the incidence of of MLL/11q23, complex karyotype and monosomal karyotype were 1.95%, 6.34%, 5.85% respectively; the incidences of FLT3, NPM1, C-Kit, CEBPα, DNMT3A mutation were 12.57%, 22.06%, 2.16%, 14.71%, 15.71% respectively. Compared with patients older than 60 years, patients with age of 55-60 years were with less complex karyotype (1.09% vs 10.62%)(P=0.003) and monosomal karyotype (2.17% vs 8.85%)(P=0.032), and more t(8;21)(17.39% vs 5.31%)(P=0.008) and inv (16)/t(16;16)(4.35% vs 0.00%)(P=0.045). CONCLUSION: For older AML patients, great difference in the distribution of karyotyes was found between the patients older than 60 years and patients with age of 55-60 years, while no such characteristics was found for gene mutations. Good elucidation of karyotypes and gene mutations are key for the treatment of older acute myeloid leukemia patients.

[Efficacy Analysis of MAC Regimen as Salvage Treatment Protocol for Acute Myeloid Leukemia Patients Older Than 55 Years].

OBJECTIVE: To evaluate the efficacy and safety of MAC regimen in the treatment of acute myeloid leukemia(AML) patients older than 55 years. METHODS: A total of 33 relapsed or non-remission AML patients older than 55 years were enrolled in this research. MAC regimen was given as the salvage treatment. Complete remission rate(CR), partial remission rate(PR), overall survival(OS), relapse-free survival(RFS) and adverse effect were analysed. RESULTS: CR rate after the salvage therapy with MAC was 51.1%, partial remission (PR) rate was 6.1%, the overall response rate (ORR) was 57.6%, the median OS was 8 months (1.0-66.0 months), the median relapse-free survival (RFS) was 10.1 months (2.3-40.4 months). Mortality related with salvage treatment in 30 days was 9.1%. Low incidence of severe organ damage were found. CONCLUSION: MAC can be used as a relative effective and safe regimen for the salvage treatment of the older AML patients.

Cyclin-dependent kinase 5 regulates the proliferation, motility and invasiveness of lung cancer cells through its effects on cytoskeletal remodeling.

Determining the molecular phenotype is a key to understanding and predicting the metastatic potential and the prognosis for patients with lung cancer. Our previous study demonstrated that increased expression of cyclin­dependent kinase 5 (CDK5) in patients with non­small cell lung cancer (NSCLC) is associated with a poorer prognosis. The present study aimed to further investigate the underlying mechanism of CDK5 in vitro and in vivo using the A549 human NSCLC cell line. A 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide assay was used to quantify the proliferation of the A549 cells; migration assay and invasiveness assays were performed using Transwell chambers and wound healing assays were used to assess cell motility, which was assessed by measuring the movement of cells. Inhibition of CDK5 by roscovitine and small interfering (si)RNA was used to investigate the mechanism of CDK5 in the process of A549 lung cancer cell proliferation, migration and invasion. The results demonstrated that functional inhibition of CDK5 using roscovitine and siRNA markedly suppressed the proliferation of A549 cells and resulted in a reduced tumor mass in vivo. In addition, the hinhibition of CDK5 reduced the migration and invasiveness of the A549 cells in vitro and in vivo. Notably, CDK5 inhibition also impaired tumor cell cytoskeletal remodeling and led to loss of cell polarity, which may partially explain the reduction of A549 cell mobility and invasiveness. The results of the present study revealed that CDK5 may be important in the regulation of migration and invasiveness in NSCLC through its effects on cytoskeletal remodeling.

High dose zinc supplementation induces hippocampal zinc deficiency and memory impairment with inhibition of BDNF signaling.

Zinc ions highly concentrate in hippocampus and play a key role in modulating spatial learning and memory. At a time when dietary fortification and supplementation of zinc have increased the zinc consuming level especially in the youth, the toxicity of zinc overdose on brain function was underestimated. In the present study, weaning ICR mice were given water supplemented with 15 ppm Zn (low dose), 60 ppm Zn (high dose) or normal lab water for 3 months, the behavior and brain zinc homeostasis were tested. Mice fed high dose of zinc showed hippocampus-dependent memory impairment. Unexpectedly, zinc deficiency, but not zinc overload was observed in hippocampus, especially in the mossy fiber-CA3 pyramid synapse. The expression levels of learning and memory related receptors and synaptic proteins such as NMDA-NR2A, NR2B, AMPA-GluR1, PSD-93 and PSD-95 were significantly decreased in hippocampus, with significant loss of dendritic spines. In keeping with these findings, high dose intake of zinc resulted in decreased hippocampal BDNF level and TrkB neurotrophic signaling. At last, increasing the brain zinc level directly by brain zinc injection induced BDNF expression, which was reversed by zinc chelating in vivo. These results indicate that zinc plays an important role in hippocampus-dependent learning and memory and BDNF expression, high dose supplementation of zinc induces specific zinc deficiency in hippocampus, which further impair learning and memory due to decreased availability of synaptic zinc and BDNF deficit.