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A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11 , NPM1 , RUNX1 , ASXL1 , TET2 , DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3 /ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.

Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1 , CEBPA , IDH2 , RUNX1 , WT1 , ASXL1 , DNMT3A and FLT3 , that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis ( P <0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.

Although the clinical features of the Isocitrate dehydrogenase 2 ( IDH2 ) mutation in acute myeloid leukemia (AML) have been characterized, its prognostic significance remains controversial and its stability has not been investigated. We analyzed 446 adults with primary non-M3 AML and found IDH2 R172, R140 and IDH1 R132 mutations occurred at a frequency of 2.9, 9.2 and 6.1%, respectively. Compared with wild-type IDH2 , mutation of IDH2 was associated with higher platelet counts, intermediate-risk or normal karyotype and isolated +8, but was inversely correlated with expression of HLA-DR, CD34, CD15, CD7 and CD56, and was mutually exclusive with WT1 mutation and chromosomal translocations involving core-binding factors. All these correlations became stronger when IDH1 and IDH2 mutations were considered together. Multivariate analysis revealed IDH2 mutation as an independent favorable prognostic factor. IDH2 − / FLT3 -ITD + genotype conferred especially negative impact on survival. Compared with IDH2 R140 mutation, IDH2 R172 mutation was associated with younger age, lower white blood cell count and lactate dehydrogenase level, and was mutually exclusive with NPM1 mutation. Serial analyses of IDH2 mutations at both diagnosis and relapse in 121 patients confirmed high stability of IDH2 mutations. In conclusion, IDH2 mutation is a stable marker during disease evolution and confers favorable prognosis.

Background Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the world. In 2010, a goal released by the American Heart Association (AHA) Committee focused on the primary reduction in cardiovascular risk. Methods Data collected from 7683 men and 7667 women aged 18–69 years were analyzed. The distribution of ideal cardiovascular health metrics based on 7 cardiovascular disease risk factors or health behaviors in according to the definition of AHA was evaluated among the subjects. The association of the socioeconomic factors on the prevalence of meeting 5 or more ideal cardiovascular health metrics was estimated by logistic regression analysis, and a chi-square test for categorical variables and the general linear model (GLM) procedure for continuous variables were used to compare differences in prevalence and in means among genders. Results Seven of 15350 participants (0.05 %) met all 7 cardiovascular health metrics. The women had a higher proportion of meeting 5 or more ideal health metrics compared with men (32.67 VS.14.27 %). The subjects with a higher education and income level had a higher proportion of meeting 5 or more ideal health metrics than the subjects with a lower education and income level. A comparison between subjects with meeting 5 or more ideal cardiovascular health metrics with subjects meeting 4 or fewer ideal cardiovascular health metrics reveals that adjusted odds ratio [OR, 95 % confidence intervals (95 % CI)] was 1.42 (0.95, 2.21) in men and 2.59 (1.74, 3.87) in women for higher education and income, respectively. Conclusions The prevalence of meeting all 7 cardiovascular health metrics was low in the adult population. Women, young subjects, and those with higher levels of education or income tend to have a greater number of the ideal cardiovascular health metrics. Higher socioeconomic status was associated with an increasing prevalence of meeting 5 or more cardiovascular health metrics in women but not in men. It’s urgent to develop comprehensive population-based interventions to improve the cardiovascular risk factors in Shandong Province in China.

Dasatinib is an inhibitor of BCR-ABL and SRC-family kinases for patients with imatinib-resistant or -intolerant chronic myelogenous leukemia (CML). In this international phase II trial, dasatinib was administered orally (70 mg twice daily) to patients with myeloid blast phase (MBP, n =109) or lymphoid blast phase (LBP, n =48) CML. After a minimum follow-up of 12 months (range 0.03–20.7 months), major hematologic responses were induced in 34% (MBP-CML) and 35% (LBP-CML) of patients. Major cytogenetic responses were attained in 33% (MBP-CML) and 52% (LBP-CML) of patients and complete cytogenetic responses were attained in 26 and 46%, respectively. Median progression-free survival was 6.7 (MBP-CML) and 3.0 (LBP-CML) months. Median overall survival was 11.8 (MBP-CML) and 5.3 (LBP-CML) months. Overall, dasatinib had acceptable tolerability. Fluid retention events were more frequent in the MBP-CML than the LBP-CML cohort: pleural effusion occurred in 36 and 13% (all grades) and 15 and 6% (grades 3/4), respectively. Other non-hematologic side effects were primarily grade 1/2; grade 3/4 events were recorded in ⩽6% of patients, except febrile neutropenia (15%). Cytopenias were noted in the majority of patients, and were manageable with dose interruptions/reductions. Dasatinib is associated with a promising rate of response in this high-risk population.

All bacterial isolates from 7058 patients admitted to haemato-oncology wards at National Taiwan University Hospital between 2002 and 2006 were characterized. In total 1307 non-duplicate bloodstream isolates were made from all patients with haematological malignancy; 853 (65%) of these were from neutropenic patients. Gram-negative bacteria predominated (60%) in neutropenic isolates with Escherichia coli (12%), Klebsiella pneumoniae (10%), Acinetobacter calcoaceticus-baumannii complex (6%), and Stenotrophomonas maltophilia (6%) the most frequent. Coagulase-negative staphylococci (19%) and Staphylococcus aureus (4%) were the most common Gram-positive pathogens. Resistance to ciprofloxacin was found in 50% of E. coli and 20% of K. pneumoniae isolates from neutropenic patients. Extensively drug-resistant A. calcoaceticus-baumannii complex and vancomycin-resistant enterococci were also found during the study period. Emerging antimicrobial resistant pathogens are an increasing threat to neutropenic cancer patients.

To estimate the prevalence and incidence of diabetes mellitus and impaired glucose regulation (IGR) in a Chinese population aged 20-94 years. A group of 5,628 randomly selected adults, aged 20-94 years, living in the Huayang and Caoyang communities in Shanghai, China, were investigated between 1998 and 2001. During 2002-04, 2,666 subjects were followed up. All the participants underwent anthropometric measurements, blood biochemical analyses and a 75-g OGTT. Based on the 2000 census data of China, the age-standardised prevalences were 6.87% for diabetes and 8.53% for IGR at baseline. More than two in five cases with diabetes were undiagnosed. The age-adjusted prevalence of diabetes and IGR increased with age. The age-adjusted prevalences of hypertension, dyslipidaemia and overweight in males were significantly higher (p < 0.001) than in females. The 3-year cumulative incidence rates of diabetes and IGR were 4.96 and 11.10%, respectively. The relative risk of developing diabetes was significantly higher in subjects with IGR than in subjects with NGT (p < 0.001). The prevalence and incidence rates for diabetes or IGR have increased dramatically over the last decades, especially in younger age groups. A large proportion of cases are undiagnosed. We strongly recommend that population-based diabetes screening programmes should be implemented and generalised for younger people.

The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

To explore the validity and prognostic significance of minimal residual disease detection by quantitative polymerase chain reaction (qPCR) in patients of acute myeloid leukemia (AML) bearing Nucleophosmin (NPM1) mutations, we quantified mutants in 194 bone marrow samples from 38 patients with a median follow-up time of 20.6 months. Following induction chemotherapy, a median of 2.78 log decline in mutant copy number was observed. Relapse was always accompanied by significant increase of mutant numbers (P<0.001). After achieving complete remission (CR), the mutant copy number was significantly higher in patients with subsequent relapse than in those remaining in continuous CR (P<0.001). Presence of detectable mutants after treatment predicted relapse if no further chemotherapy was administered. Furthermore, the patients with any rise of mutant signals during serial follow-up had 3.2-fold increase of relapse risk compared to those with persistently low or undetectable signals (P<0.001). Patients who could achieve mutant reduction to <0.1% of internal control had significantly longer overall survival (OS) (P=0.004) and relapse-free survival (RFS) (P<0.001). Failure to achieve 2 logs of reduction after consolidation predicted shorter OS (P=0.01) and RFS (P=0.001). In conclusion, qPCR monitoring may have prognostic impact in AML patients with NPM1 mutations.

Acute myeloid leukemia (AML) with t(7;11)(p15;p15), which results in a NUP98 – HOXA9 fusion, is a distinct entity, but this subtype has not been characterized in detail. In a comprehensive study comparing 11 such patients with another 482 adult patients, we found that those with t(7;11) were younger ( P =0.0076) and female ( P =0.0111), with almost all having the M2-subtype of AML ( P <0.0001). Even when those with low-risk karyotypes were excluded, patients with t(7;11) had poorer overall survival than the other AML group (median 13.5 and 20 months, respectively, P =0.045) and poorer relapse-free survival (median 6 and 12 months, respectively, P =0.003). The NUP98–HOXA9 fusion was strongly associated with KRAS and WT1 mutations ( P =0.015 and P =0.0018, respectively). We characterized four varieties of this fusion, among which NUP98 exon 12/ HOXA9 exon 1b was present in all 11 patients. We developed a highly sensitive and specific assay to quantify the abundance of leukemic cells, and found that the fusion remained detectable in morphological complete remission, even after allogeneic stem cell transplantation, suggesting that this disease was highly refractory to very intensive treatment. AML with NUP98 – HOXA9 fusion therefore appears to have a distinct clinical and biological profile, and should be regarded as a poor prognostic group.