OBJECTIVE: To investigate the characteristics of gene mutation in elderly patients with acute myeloid leukemia (AML) and its effect on prognosis. METHODS: The clinical and laboratorial characteristics of 54 AML patients (≥60 years old) in Department of Hematology, Tangdu Hospital were analyzed retrospectively during April 2016 to October 2019. Thirty-four AML/myelodysplastic syndrome/myeloproliferative neoplasm related mutant genes were detected by second-generation sequencing technology, and their clinical characteristics, treatment effect, and influence on prognosis were analyzed. RESULTS: All the patients received DAC+CAG induction treatment, after 1-2 couses of treatment, 36 cases (66.7%) achieved complete response, with a total effective rate of 75.9%, and the median survival time was 17 months. The most frequent mutant genes were TET2 (33.3%), CEBPA (31.5%), DNMT3A (18.5%), ASXL1 (16.7%), NRAS (14.8%), RUNX1 (14.8%), FLT3-ITD (12.9%), TP53 (12.9%), NPM1 (12.9%), and IDH2 (12.9%). Among 7 patients with TP53 mutation, 6 cases obtained complete response after 1-2 courses of induction treatment, but there was no statistically significant difference in the effect on prognosis. Patients with FLT3-ITD and NRAS mutations had shorter overall survival time compared with who had no mutation (P=0.47, P=0.48). Multivariate analysis showed that FLT3-ITD and NRAS mutations were poor prognostic factors. CONCLUSION The incidence of TET2 gene mutation is high in elderly AML patients. AML patients with TET2 and TP53 mutations may benefit from Decitabine-based chemotherapy. However, patients with FLT3-ITD and NRAS mutations have a short survival time, and may have a poor prognosis.
Aged ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Nucleophosmin ; Prognosis ; Retrospective Studies ; fms-Like Tyrosine Kinase 3

OBJECTIVE: To investigate the clinical characteristics and prognosis of acute myeloid leukemia(AML) patients with ASXL1 mutation. METHODS: The clinical data of 229 newly diagnosed AML patients treated in our hospital from April 2016 to October 2019 were analyzed retrospectively. The next-generation sequencing technology was used to detect gene mutations in all the patients, the clinical characteristics of the patients with ASXL1 mutation were analyzed. RESULTS: ASXL1 gene mutation was detected out in 45 patients(19.6%). Among these patients, the frameshift mutation (n=22,48.9%) was most common, followed by missense mutation (n=15, 33.3%) and nonsense mutation (n=8,17.8%), respectively, all of them were located at exon 12. The median mutation rate was 32.47%(range, 2.74%-53.50%). The median age of the patients with ASXL1 mutation was 54(range, 14-74) years old, and most of the patients were male, and most of them with the history of MDS or MPN, and low white blood cell count at the initial diagnosed (P<0.05). Patients with ASXL1 mutation showed a lower CR rate than that of without ASXL1 mutation. Patients with or without ASXL1 mutation showed a statistically significant difference in survival at 20 months (P=0.042), while there was no significant difference between the patients in the two groups over 20 months (P=0.505). All the 6 patients with ASXL1 mutation in low-risk group were survived, while the median OS time was 16 months in the high-risk group(P=0.034). Multivariate analysis showed that the history of MDS or MPN and CR rate from induction therapy were the independent risk factors affecting survival of the patients. CONCLUSION Frameshift mutation is commonly in AML patients with ASXL1 gene mutation, and ASXL1 mutation were more often in men, the history of MDS or MPN, and low white blood cell count. The CR rate of the patients with ASXL1 mutation was lower than that of the AML patients without ASXL1 mutations, AML patients with ASXL1 mutation showed poor short-term efficacy, but there was no significant difference between the two groups in long-term survival over 20 months.
Adolescent ; Adult ; Aged ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Male ; Middle Aged ; Mutation ; Prognosis ; Repressor Proteins/genetics* ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the factors affecting the early-death, overall survival (OS) and relapse-free survival (RFS) of acute promyelocytic leukemia (APL) patients.

METHODSThe clinical and laboratorial charachteristics of 176 APL patients in our center were analyzed retrospectively during January 2002 to Mar 2016. The risk factors of early death and factors affecting OS and RFS of patients were analyzed.

RESULTSAmong total of 176 patients, early death occured in 10 patients. Multivariate analysis showed both age ≥60 years and fibrinogen<1.5 g/L (HR=6.4, 95%CI 1.4-28.2) (P=0.015), (HR=12.2, 95%CI 1.5-102.8) (P=0.021), respectively were the independent risk factors for the early death during the induction therapy. Among 154 patients with full follow-up data (median follow-up time was 101(2-262) months), the estimated 5-year OS and RFS rate were (98± 1)% and (77± 4)%, respectively. Cox regression analysis showed relapse during treatment as well as initial WBC count≥30× 10/L were independent prognostic indicators for OS. Accompanied psoriasis indicated higher relapse rate of APL(HR=4.8, 95%CI 1.8-12.5)(P=0.002), while the low-risk APL indicated lower relapse rate (HR=0.4, 95%CI 0.2-0.99)(P=0.048).

CONCLUSIONImportance should be attached to the early-death events in elder and low-fibrinogen APL patients. As for patients with psoriasis or non low-risk group, emphasizing the intensified dynamic supervision during the treatment helps to detect the early-relapse events. For relapsed patients and patients with ≥30× 10/L WBC count, seeking more optimized therapy strategy seems allow this cohorts to get better prognosis.

OBJECTIVETo investigate the safety and efficacy of decitabine combined with CAG regimen in the treat-ment of newly diagnosed elderly patients with acute myeloid leukemia(AML).

METHODSFourty-nine patients with newly diagnosed acute myeloid leukemia (except M3) who were admitted to our hospital were selected. All the patients were older than 50 years old, and allogeneic hematopoietic stem cell transplantation could not be performed for various reasons. Decitabine-based chemotherapy regimens were used during induction therapy including single decitabine therapy(DAC), decitabine combined with CAG regimen(DAC-CAG) and decitabine combined with HAAG regimen(DAC-HAAG). Most of patients continued to use the original treatment after complete remission, while others were given the standard "3+7" regimen chemotherapy. A total of 2-4 courses of treatment was conducted in the majority of patients.

RESULTSAll of the 49 patients completed the induction therapy, in which 26 cases achieved complete remission(CR), 7 cases achieved partial remission(PR) and no response(NR) existed in 16 cases. The complete remission and the overall response rate(ORR) were 53% and 67% respectively. The overall response rate of DAC group, DAC-CAG group and DAC-HAAG group were 17%, 77% and 63% respectively. 14 patients were infected and 1 patients died of pulmonary infection during the induction therapy. The median number of suspended red blood cells and platelet infused were 9 units and 69 units respectively. Neutrophil recovery time was 15.1 days while the platelet recovery time was 20.1 days during the induction therapy. The mean follow-up time was 21 months. Overall survival(OS) was 75% at 6 months, 30% at 1 year, and 26% at 2 year, while disease-free survival(DFS) was 83% at 3 months, 54% at 1 year, and 47% at 2 year. The induction therapy could reach CR that was an independent prognostic factor, however, the initial white blood cell count, platelet count, age, chemotherapy regimen, prognostic stratification and whether complical by pnenmonia during chemotherapy were not independent prognostic factors.

CONCLUSIONThe induction efficacy of decitabine combined with chemotherapy is superior to that of decitabine alone. The outcome of induction chemotherapy is an independent prognostic factor, however, the high white blood cell count, poor karyotype, complications and AML with myelodysplasia-related changes do not affect long-term survival. DAC-CAG regimen is effective and have relatively few adverse reactions in AML. It is suitable for the patients who are ineligible for conventional chemotherapy.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; Azacitidine ; analogs & derivatives ; Cytarabine ; Decitabine ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; Middle Aged ; Remission Induction ; Treatment Outcome

OBJECTIVETo explore the ratio of lymphocyte subsets in peripheral blood of patients with aplastic anemia (AA) and patients with hypoplastic myelodysplastic syndrome (hypo-MDS) patients and to evaluate their significance.

METHODSThe clinical data of 181 cases of AA and 111 cases of hypo-MDS from January 2008 to December 2014 were collected from Blood Diseases Hospital of Chinese academy of medical sciences, and then the differences of lymphocyte subsets and its effect in 2 groups were analyzed.

RESULTSCD4/CD8ratio, proportion of CD3cells and its subsets CD3CD4/CD3CD8cells in hypo-MDS group were not significant different from AA group (P>0.05). the proportion of CD3CD16/CD56NK cells and CD3CD57T-LGL cells in hypo-MDS group was significantly higher than that in AA group (P<0.05, P<0.01), but CD19B lymphocyte percentage in hypo-MDS patients was lower than that in AA patients (P<0.05). After dividing group according to CD4/CD8ratio, the ratios of CD3CD16/CD56NK cells and CD3/CD57T-LGL cells were higher only in normal CD4/CD8ratio group of hypo-MDS patients than those in AA patients, while the ratio of B lymphocytes was significant different in inverted CD4/CD8ratio group between hypo-MDS and AA patients. The CD19B lymphocyte ratio in hypo-MDS patients was significantly lower than that in AA patients (P<0.05). As well, the levels of erythrocytes and platelets in peripheral blood between hypo-MDS and AA patients only in normal CD4/CD8ratio group were significantly different, while the significant difference of WBC count and reticulocyte ratio were observed in high CD4/CD8ratio and non-inverted CD4/CD8ratio groups, respectively; the significant difference of bone marrow blast ratio and muture monocyte ratio was found in high CD4/CD8ratio group.

CONCLUSIONThe changes of lymphocyte subsets can be used as an reference indicator for differential diagnosis of hypo-MDS and AA. The comparative analysis of patients with these 2 kinds of diseases after dividing into subgroups according to ratio of CD4/CD8cells is beneficial to differentiat diagnosis.

OBJECTIVETo investigate the effects of sorafenib on human acute promyelocytic leukemia cell NB4 and its mechanism.

METHODSThe human acute promyelocytic leukemia cell NB4 was treated with different concentrations (0, 1.5, 3, 6 and 12 µmol/L) of sorafenib, the proliferation inhibitory rate of NB4 cells was assayed by MTT, the apoptosis of NB4 was determined with flow-cytomatry after treatment; after extraction of total protein, the Western blot was performed to determine the expressions of apoptosis-relatived molecules Caspase-3, Caspase-8 and MCL-1. The mRNA expressions of Caspase-3, Caspase-8 and MCL-1 were determined by RT-PCR.

RESULTSAs compared with the control group, the proliferation of NB4 significantly decreased after treatment with different concentrations of sorafenib. The sorafenib significantly induced the apopotosis of NB4 cells in time- and dose-dependent manners. Furthermore, sorafenib treatment resulted in the obvious increase of the Caspase-3 and Caspase-8 protein and mRNA expressions, and down-regulated the MCL-1 protein and mRNA expressions in NB4 cells.

CONCLUSIONSorafenib can inhibit proliferation and induce apopotosis of human acute promyelocytic leukemia cell NB4 through the expression of Caspase-3 and Caspase-8, and down-regulation of the expression of MCL-1.

Antineoplastic Agents ; Apoptosis ; Caspase 3 ; Caspase 8 ; Cell Line, Tumor ; Down-Regulation ; Humans ; Leukemia, Promyelocytic, Acute ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; T-Lymphocytes, Helper-Inducer

OBJECTIVETo establish the mouse model for the expression of PD-L1 by hydrodynamic injection and to study the effects of myeloablative conditioning on hydrodynamic injection-mediated PD-L1 expression.

METHODSPlasmid amplification, hydrodynamic injection, collagenase perfusion, real time PCR, ELISA and flow cytometry were applied to test the expression and function of PD-L1. Also, animal models were set up to test the effects of chemical or radiactive myeloablative conditioning on hydrodynamic injection-mediated PD-L1 expression.

RESULTSThe expression of PD-L1 mRNA and protein could be detected as early as 8 h after hyrodynamic injection and reached peak expression by 24 h, and returned to baseline level by 7 d after injection. Serum PD-L1 level reached to 100 µg/ml as early as 24 h after injection and plateaued at 7 d after injection. Serum PD-L1 persisted for 3 weeks and declined to baseline after 1 month of hydrodynamic injection. The PD-L1 function induced by hydrodynamic injection was consistent with literature reports. At each time point, the PD-L1 expression was not different significantly between the myeloablative conditioning group and control group; the mice transfected with PD-L1 showed a higher survival rate than that in control group.

CONCLUSIONMyeloablative conditioning does not affect hydrodynamic injection-mediated PD-L1 expression, indicating that the PD-L1 can be used in HSCT mouse model.

Animals ; B7-H1 Antigen ; pharmacology ; Disease Models, Animal ; Flow Cytometry ; Hydrodynamics ; Injections ; Mice ; Myeloablative Agonists ; pharmacology ; RNA, Messenger ; Transfection ; Transplantation Conditioning

The purpose of study was to analysis the clinical manifestation and treatment protocol of acute promyelocytic leukemia (APL) accompanied by craniopharyngioma so as to promote the understanding of this disease. The APL was diagnosed by morphologic examination of bone marrow cells, the leukemia bone marrow cells were analyzed by immunophenotyping technique, the qualitative and quantitative changes of PML-PARα fusion gene before and after treatment were monitored by using molecular biological test; the cytogenetic features were analyzed by using conventional karyotype and FISH analysis. The results indicated that the clinical manifestation of this disease was diverse and disease status was complex. The good therapeutic efficacy could be achieved, the misdiagnosis and delayed treatment could be avoided through early detection, timely treatment and multidisciplinary cooperation. It is concluded that when other clinical symptoms reappear after APL achieves remission, the possibility of second tumor must be considered, the clinical presentation should be carefully monitored, the early detection and timely treatment should be performed to improve the survival of patients.
Craniopharyngioma ; complications ; Humans ; Leukemia, Promyelocytic, Acute ; complications ; Male ; Middle Aged ; Pituitary Neoplasms ; complications

This study was aimed to investigate the changes of CD34(+) and CD71(+)CD45(-) cell levels in MDS and AA patients. A total of 25 cases MDS and 43 cases of AA (18 cases SAA and 25 cases of NSAA) from January 2010 to October 2013 in the Department of Hematology, affiliated hospital of Hebei United University were enrolled in this study. The complete blood count, bone marrow smears, bone marrow biopsy, karyotype analysis and bone marrow blood cell immune genotyping (mainly the proportion of CD34(+) cells, CD71(+)CD45(-) cells in nucleated cells) were carried out for all patients; the changes of CD34(+) and CD71(+)CD45(-) cell levels in patients with MDS and AA (SAA NSAA) were compared; the differences of white blood cell count, platelet count and hemoglobin concentration in patients with count of CD71(+)CD45(-) ≥ 15% or <15% were analyzed. The results showed that the count of CD34(+) in MDS group was higher than that in AA (NSAA and SAA) group (P < 0.05). The count of CD71(+)CD45(-) cells in MDS group was higher than that in SAA (P < 0.05), there was no significant difference between NSAA group and MDS group. In MDS group with CD71(+)CD45(-) ≥ 15%, the platelet count was significantly higher than that in NSAA group (P < 0.05); and there was no statistical difference for leukocyte, platelet count and hemoglobin level between MDS and NSAA group with CD71(+)CD45(-) <15% (P > 0.05). It is concluded that the count of CD34(+) cells in MDS patients is significantly higher than that in AA and SAA patients. The count of CD71(+)CD45(-) cells in MDS group is significantly higher than that of SAA group. The platelet count in MDS patients with CD71(+)CD45(-) cells ≥ 15% is significantly higher than that of the NSAA group.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia, Aplastic ; pathology ; Antigens, CD ; immunology ; Antigens, CD34 ; immunology ; Blood Cell Count ; Bone Marrow ; Bone Marrow Cells ; cytology ; immunology ; Female ; Flow Cytometry ; Humans ; Leukocyte Common Antigens ; immunology ; Male ; Middle Aged ; Myelodysplastic Syndromes ; pathology ; Receptors, Transferrin ; immunology ; Young Adult

OBJECTIVETo explore the risk factors and their differences of metabolic syndrome (MS) on male criminal police, thereby provide the scientific basis to make prevention and control strategies about the metabolic syndrome for the criminal police career.

METHODSBased on physical examination data of criminal police in 2010, 439 patients with MS (CDS) were randomly selected as cases. And as the 1:2 matched nested case-control study, 878 health controls were employed, which were matched with on the basis of sex and age (±1 year). An face-to-face epidemiological investigations on the past exposure status of several possible risk factors was conducted, such as the family history of hypertension and other social economic status, as well as body height and weight, waist circumference, blood pressure, serum lipid and plasma sugar. and the data were analyzed with logistic regression.

RESULTS1317 cases were surveyed, through single factor logistic regression analysis found that 12 factors are related to exposure. Multivariate logistic regression analysis suggested that six factors, such as stress events (OR = 1.989, 95%CI: 1.467∼2.696), snoring (OR = 1.672, 95%CI: 1.218∼2.294), sweets (OR = 0.562, 95%CI: 0.412∼0.766), meat and products (OR = 1.494, 95%CI: 1.065∼2.094), siting after dinner for more than 3 h (OR = 1.399, 95%CI: 1.023∼1.915).

CONCLUSIONSMS has become a important public health problems among criminal police. For their professional special, a series of bad habits , unhealthy life style and psychological problems became important risk factors of MS on criminal police. Targeted prevention and control measures should be taken to reduce the incidence of MS.

Adult ; Case-Control Studies ; Humans ; Male ; Metabolic Syndrome ; epidemiology ; Middle Aged ; Occupations ; Police ; Risk Factors