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1.
van den Heuvel-Eibrink MM van der Holt B Burnett AK Knauf WU Fey MF Verhoef GE Vellenga E Ossenkoppele GJ Löwenberg B Sonneveld P 《Annals of hematology》2007,86(5):329-337
Clinical resistance to chemotherapy in acute myeloid leukemia (AML) is associated with the expression of the multidrug resistance
(MDR) proteins P-glycoprotein, encoded by the MDR1/ABCB1 gene, multidrug resistant-related protein (MRP/ABCC1), the lung resistance-related protein (LRP), or major vault protein
(MVP), and the breast cancer resistance protein (BCRP/ABCG2). The clinical value of MDR1, MRP1, LRP/MVP, and BCRP messenger RNA (mRNA) expression was prospectively studied in 154 newly diagnosed AML patients ≥60 years who were treated
in a multicenter, randomized phase 3 trial. Expression of MDR1 and BCRP showed a negative whereas MRP1 and LRP showed a positive correlation with high white blood cell count (respectively, p < 0.05, p < 0.001, p < 0.001 and p < 0.001). Higher BCRP mRNA was associated with secondary AML (p < 0.05). MDR1 and BCRP mRNA were highly significantly associated (p < 0.001), as were MRP1 and LRP mRNA (p < 0.001) expression. Univariate regression analyses revealed that CD34 expression, increasing MDR1 mRNA as well as MDR1/BCRP coexpression, were associated with a lower complete response (CR) rate and with worse event-free survival and overall survival.
When adjusted for other prognostic actors, only CD34-related MDR1/BCRP coexpression remained significantly associated with a lower CR rate (p = 0.03), thereby identifying a clinically resistant subgroup of elderly AML patients. 相似文献
2.
Ganser A Heil G Seipelt G Hofmann W Fischer JT Langer W Brockhaus W Kolbe K Ittel TH Brack N Fuhr HG Knuth P Höffken K Bergmann L Hoelzer D 《Annals of hematology》2000,79(1):30-35
Intensive chemotherapy followed by treatment with interleukin-2 (IL-2) was evaluated in a prospective, randomized, multicenter
trial including 18 patients with refractory anemia with excess of blasts in transformation (RAEB-T), 86 patients with acute
myeloid leukemia (AML) evolving from myelodysplastic syndromes, and six patients with secondary AML after previous chemotherapy.
Median age was 58 years (range: 18–76 years). Forty-nine patients (45%) achieved a complete remission (CR) after two induction
cycles with idarubicin, ara-C, and etoposide, 52% of them aged ≤60 years and 35% aged >60 years (p=0.06). After two consolidation courses, patients were randomized to four cycles of either high- or low-dose IL-2. Patients
aged up to 55 years with an HLA-identical sibling donor were eligible for allogeneic bone marrow transplantation. The median
relapse-free survival was 12.5 months, with a probability of ongoing CR at 6.5 years of 19%. Overall survival of all patients
was 8 months, and 21 months for the CR patients. Median survival was significantly longer among patients aged ≤60 years than
among the older patients (16 vs 6 months, p<0.001). Median duration of survival and relapse-free survival were not statistically different in the two IL-2 treatment
arms.
Received: March 23, 1999 / Accepted: June 23, 1999 相似文献
3.
Xuan Xiong Dongke Yu Qiaoyue Gao Yuan Zhang Qinan Yin Xiaotao Chen Hongtao Xiao Rongsheng Tong 《Medicine》2021,100(32)
Background:Acute leukemia (AL) is a kind of malignant tumor of hematopoietic system. A number of studies have suggested that Single Nucleotide Polymorphisms are significantly associated with risk of AL. Present study performs meta-analysis to evaluate the association between CYP2B6 c.516G>T variant and AL risk.Methods:Databases including PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang were searched for literatures to September 30, 2019, both in English and Chinese. Relative risk and its 95% confidence intervals were used to assess the associations. Statistical analyses of this meta-analysis were conducted by using STATA 13.0. software.Results:A total of 7 studies, including 1038 cases and 1648 controls, were analyzed. Our results indicated that CYP2B6 c.516G>T variant was significantly related to an increased the risk of AL under dominant model, recessive model, homozygote model, and allelic model. In addition, subgroup analyses were also performed by disease classification, country, and study design. No significant associations were obtained between CYP2B6 c.516G>T variant and the risk of AL under the recessive model in the design of hospital-based (relative risk = 0.98; 95% confidence interval: 0.95–1.01; P = 0.118).Conclusion:Our meta-analysis indicated that the CYP2B6 variant is significantly associated with AL risk, in which CYP2B6 c.516G>T is related to an increased risk of AL. 相似文献
4.
5.
Magdalena Szopa Malgorzata Malczewska-Malec Beata Wilk Jan Skupien Pawel Wolkow Maciej T. Malecki Jacek Sieradzki 《Acta diabetologica》2009,46(4):317-322
Several association studies of type 2 diabetes mellitus (T2DM) and adiponectin gene polymorphisms have been reported with
conflicting results. Our aim was to search for the association of three polymorphisms (−11.391G>A, +45T>G, and +276G>T) in
the adiponectin gene with T2DM and prediabetic quantitative traits in Polish Caucasians. The study groups comprised 495 unrelated
T2DM cases and 435 controls. We compared the distribution of genotypes between study groups. In addition, genotype-quantitative
trait analyses were also done in the controls. The study subjects were genotyped using the restriction fragment length polymorphism
technique. The frequencies of the minor alleles were as follows: 10.6 versus 8.2% for −11.391G>A (p = 0.0722), 7.0 versus 8.0% for +45T>G (p = 0.48), and 15.5% in T2DM versus 19.8% in controls (p = 0.0145) for +276G>T, respectively. The difference for genotype distribution between the groups was statistically significant
(p = 0.0247) for the +276G>T variant: 71.31 versus 62.99%, 26.46 versus 34.48% and 2.22 versus 2.53%, respectively, for GG,
GT and TT. In quantitative traits analysis, the T allele of +276G>T was associated (p < 0.05) with lower insulin resistance (HOMA-IR, fasting insulin) among controls. Additionally, the A allele at position −11.391
was associated (p < 0.05) with higher insulin resistance (HOMA-IR, fasting insulin). In multiple regression analysis, all identified association
remained significant after the inclusion in the model of gender, BMI and age. In addition, in this model, −11.391G>A and +276G>T
were independently associated with T2DM. Finally, we conclude that the adiponectin gene polymorphisms are associated with
T2DM and prediabetic quantitative traits in Polish Caucasians. 相似文献
6.
Asfour IA Fayek MH El-Kourashy SA Youssef SR El-Gohary GM Mohamed OF 《Annals of hematology》2008,87(3):213-221
Telomerase is activated in most tumors, but suppressed in normal human somatic cells. Current evidence indicates that telomerase
reactivation is a critical step in carcinogenesis, with a close relationship to apoptosis. The goal of this study was to investigate
the levels and relationship of telomerase activity to apoptosis and its impact on the survival of Egyptian adult acute lymphoblastic
leukemia patients. Telomerase activity was quantified by polymerase chain reaction (PCR) and detected by enzyme-linked immunosorbent
assay (ELISA), while apoptosis was measured at the single-cell level by fluorescence in situ detection using flow cytometry
in 15 control subjects and 40 acute lymphoblastic leukemia (ALL) patients at presentation. Telomerase activity in ALL patients
was negatively correlated to apoptosis [percent and mean fluorescence intensity (MFI)] (p < 0.001 for percent and p < 0.001 for MFI) and to the 4-year survival rate (p < 0.05), to which apoptosis (percent and MFI) was consequently positively correlated (p < 0.001 for percent and p < 0.05 for MFI). For telomerase, the highest positive predictive value (PPV) for mortality (93.3%) was at a cut-off value
of 13 amol/ml, while those for apoptosis (85% for percent of apoptotic cells and 90.9% for MFI) were at a cut-off of 8% and
0.19 MFI. This makes the measurement of telomerase activity in ALL patients a potential tool to predict disease with unfavorable
outcome and a candidate tumor marker. 相似文献
7.
Ernest R. Vina David C. Rhew Scott R. Weingarten Jason B. Weingarten John T. Chang 《Journal of general internal medicine》2009,24(7):833-840
BACKGROUND The Centers for Medicare & Medicaid Services (CMS)/Premier Hospital Quality Incentive Demonstration (HQID) project aims to
improve clinical performance through a pay-for-performance program. We conducted this study to identify the key organizational
factors associated with higher performance.
METHODS An investigator-blinded, structured telephone survey of eligible hospitals’ (N = 92) quality improvement (QI) leaders was conducted among HQID hospitals in the top 2 or bottom 2 deciles submitting performance
measure data from October 2004 to September 2005. The survey covered topics such as QI interventions, data feedback, physician
leadership, support for QI efforts, and organizational culture.
RESULTS More top performing hospitals used clinical pathways for the treatment of AMI (49% vs. 15%, p < 0.01), HF (44% vs. 18%, p < 0.01), PN (38% vs. 13%, p < 0.01) and THR/TKR (56% vs. 23%, p < 0.01); organized into multidisciplinary teams to manage patients with AMI (93% vs. 77%, p < 0.05) and HF (93% vs. 69%, p < 0.01); used order sets for the treatment of THR/TKR (91% vs. 64%, p < 0.01); and implemented computerized physician order entry in the hospital (24.4% vs. 7.9%, p < 0.05). Finally, more top performers reported having adequate human resources for QI projects (p < 0.01); support of the nursing staff to increase adherence to quality indicators (p < 0.01); and an organizational culture that supported coordination of care (p < 0.01), pace of change (p < 0.01), willingness to try new projects (p < 0.01), and a focus on identifying system errors rather than blaming individuals (p < 0.05).
CONCLUSIONS Organizational structure, support, and culture are associated with high performance among hospitals participating in a pay-for-performance
demonstration project. Multiple organizational factors remain important in optimizing clinical care.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
8.
Colovic N Tosic N Aveic S Djuric M Milic N Bumbasirevic V Colovic M Pavlovic S 《Annals of hematology》2007,86(10):741-747
Mutations in the fms-like tyrosine kinase 3 (FLT3) gene, such as internal tandem duplication (FLT3/ITD) in the juxtamembrane domain and point
mutations in the tyrosine kinase domain, are the most common abnormalities in acute myeloid leukemia (AML). FLT3/ITD and FLT3/D835
mutations were analyzed in 113 Serbian adult AML patients using polymerase chain reaction. Twenty patients were found to be
FLT3/ITD positive (17.7%). The mutations occurred most frequently in M5 and M0 subtypes of AML. They were mainly associated
with the normal karyotype. All patients harboring FLT3/ITD had a higher number of white blood cells than patients without
it (p = 0.027). FLT3/ITD mutations were associated with lower complete remission (CR) rate (χ
2 = 5.706; p = 0.017) and shorter overall survival (OS; Log rank = 8.76; p = 0.0031). As for disease-free survival, the difference between FLT3/ITD-positive and FLT3/ITD-negative patients was not
statistically significant (Log rank = 0.78; p = 0.3764). In multivariate analysis, the presence of FLT3/ITD mutations was the most significant prognostic factor for both
OS and CR rate (p = 0.0287; relative risk = 1.73; 95% CI = 1.06–2.82). However, in the group of patients with the intermediate-risk karyotype,
the mere presence of FLT3/ITD was not associated with inferior clinical outcome. FLT3/D835 point mutation was found in four
patients (3.5%) only. Follow-up of the FLT3/ITD-positive patients revealed stability of this mutation during the course of
the disease. However, changes in the pattern of FLT3/D835 mutations in initial and relapsed AML were observed. Our results
indicate an association of FLT3/ITD with the adverse outcome in AML patients treated with standard induction chemotherapy.
Because FLT3/ITD mutation is a target for specific therapeutic inhibition, its early detection could be helpful in clinical
practice.
Ms. Colovic and Ms. Tosic contributed equally to this work. 相似文献
9.
Ralf Czymek Alexander Kempf Uwe Roblick Thomas Jungbluth Andreas Schmidt Stefan Limmer Peter Kujath Hans-Peter Bruch Frank Fischer 《International journal of colorectal disease》2009,24(8):983-988
Purpose To examine the treatment outcome for patients with acute bleeding from the lower gastrointestinal tract requiring transfusion
and acute surgical care as a function of various risk factors
Materials and methods Between 1999 and 2007, we collected data on 59 patients (39 male and 20 female patients) who received surgical intervention
for acute lower intestinal hemorrhage requiring transfusion at our university clinic. Treatment complications and mortality
were analyzed retrospectively.
Results The average age of the patients in this study is 70.0 ± 12.2 years (range, 39 to 97 years) with an overall mortality of 15.3%.
Blood transfusions >10 U (p = 0.031), postoperative need for ventilation (p = 0.004), necessary reoperations (p = 0.016), and an initial hemoglobin level <80 g/L (p = 0.043) proved to be significant risk factors for death. Blood transfusions >10 U (p = 0.028), necessary reoperations (p = 0.001), and an initial hemoglobin level <80 g/L (p = 0.033) were found to be significant risk factors for postoperative complications. All other parameters have no significant
impact.
Conclusions The decisive factors for the outcome of lower gastrointestinal hemorrhage requiring surgery are the severity of bleeding,
beginning of treatment (initial hemoglobin level, need for packed red blood cells), and treatment efficiency (necessary reoperation). 相似文献
10.
Topcuoglu P Arat M Ozcan M Arslan O Ilhan O Beksac M Gurman G 《Annals of hematology》2012,91(4):577-586
This retrospective case-matched study evaluated the efficacy of reduced intensity conditioning (RIC) regimen on early and
late allogeneic transplant outcome in chronic myeloid leukemia (CML) patients. Twenty-eight patients conditioned with RIC
regimen were matched to 56 patients who received a myeloablative conditioning (MAC) regimen. The main criteria for case matching
among our CML allotransplant cohort were the Gratwohl scoring system. The median score was 2 (1–4) in each group. The pretransplant
disease status was first chronic phase (CP1, n = 20), CP2 (n = 2), and advanced phase (n = 6) in RIC, and CP1 (n = 46), CP2 (n = 3), and advanced phase (n = 7) in MAC. The duration of neutropenia and thrombocytopenia was shorter in RIC than MAC. The grade and duration of mucositis
were less in RIC. The need for total parenteral nutrition (21% vs. 77%, p < 0.0001) and febrile neutropenic episodes (50% vs. 95%, p < 0.0001) were observed less frequently in RIC compared with MAC-given patients. Acute or chronic graft versus host diseases
(GvHD) were not affected by the intensity of conditioning regimen. The incidence of transplant-related mortality was higher
in MAC (7% vs. 14%, p = 0.01). Although more relapse/progression was observed in the RIC group, the probability of 5- and 10-year leukemia-free-
and overall survival were similar regardless of conditioning regimen intensity (p > 0.05). In early first CP, the pair of female donor–male recipient and the development of chronic GvHD prolonged both leukemia-free
survival and overall survival in multivariate analysis. According to our single-center matched-pair analysis, the use of RIC
regimens in patients with low-risk CML results with toxicities less, responses later, and relapses more frequent than the
MAC regimens. 相似文献
11.
S. C. Lim J. J. Liu H. Q. Low N. G. Morgenthaler Y. Li L. Y. Yeoh Y. S. Wu S. K. Goh C. Y. Chionh S. H. Tan Y. C. Kon P. C. Soon Y. M. Bee T. Subramaniam C. F. Sum K. S. Chia 《Diabetologia》2009,52(7):1343-1351
Aims/hypothesis Evolving research suggests that common and rare alleles jointly constitute the genetic landscape of complex disease. We studied
the association between 43 pathway-related candidate genes with ‘intermediate phenotype’ (i.e. corresponding plasma protein)
and diabetic nephropathy in a customised microarray of 1,536 SNPs.
Methods In this case–control study of type 2 diabetic Chinese individuals with and without diabetic nephropathy, cases (n = 545) were defined on the basis of a spot urinary albumin/creatinine ratio (ACR) > 113 mg/mmol; the value for controls (n = 503) was ACR < 3.3 mg/mmol. Genotyping was performed using Illumina GoldenGate assay.
Results No single nucleotide polymorphism (SNP) remained significant in single locus analysis after correction for multiple testing.
Therefore, we explored the best ∼1% SNPs. Of these 13 SNPs, four clustered to a 5′ end NADPH oxidase homologue 4 (NOX4) haplotype (GGCC frequency = 0.776) with estimated OR for diabetic nephropathy of 2.05 (95% CI 1.04–4.06) (heterozygous)
and 2.48 (1.27–4.83) (homozygous) (p = 0.0055). The haplotype was correlated with plasma Cu/Zn superoxide dismutase (SOD) concentration, suggesting increased
oxidative burden. Endothelin-1 SNP (rs1476046G>A, frequency = 0.252) was correlated with plasma C-terminal pro-endothelin-1
concentrations with an estimated OR for diabetic nephropathy of (heterozygous) 1.26 (0.96–1.66) and (homozygous) 1.87 (1.13–3.12)
(p = 0.0072). Nitric oxide synthase 1 (NOS1) 5′ haplotype (TGTC frequency = 0.38) also revealed a suggestive association with diabetic nephropathy: heterozygous 1.26
(0.95–1.67), homozygous 1.57 (1.04–2.35) (p = 0.0073). A rare NADPH oxidase homologue 1 (NOX1)-coding non-synonymous SNP (Arg315His, frequency = 0.006) was found exclusively among cases.
Conclusions/interpretation Our preliminary observations suggest that common haplotypes from NOX4 and endothelin-1 SNP correlated with plasma Cu/Zn SOD and C-terminal pro-endothelin-1 concentrations, respectively, and might
have conferred diabetic nephropathy susceptibility. Common NOS1 and rare NOX1 variants also revealed a suggestive association with diabetic nephropathy. Future studies to validate our observation are
needed.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users. 相似文献
12.
Mariusz Panczyk Ewa Balcerczak Sylwester Piaskowski Krzysztof Jamroziak Grażyna Pasz-Walczak Marek Mirowski 《International journal of colorectal disease》2009,24(8):895-905
Purpose The aim of this study was to determine the significance of three most common single-nucleotide polymorphisms (SNPs) of ABCB1 gene in the development of colorectal cancer and to estimate the influence of these SNPs to surviving patients' treatment
combination adjuvant therapy 5-fluorouracil/leucovorin. Haplotype structure of ABCB1 was analysed, and degree of linkage disequilibrium (LD) between SNPs of ABCB1 was estimated.
Materials and methods Tumour specimens of 95 patients with colorectal cancer and blood samples of 95 healthy cases were studied. Genotyping of ABCB1 gene was performed by automated sequencing or polymerase chain reaction-restriction fragment length polymorphism method.
Comparison of frequencies of alleles/genotypes/haplotypes between the studied group (colorectal cancer samples) and the control
group (blood samples) were analysed. These results were correlated with the surviving patients after treatment of adjuvant
chemotherapy.
Results Significant differences in ABCB1
1236C>T (p = 0.00043) and ABCB1
2677G>T/A (p = 0.04) genotype distribution and T1236 allele distribution (CT1236 or TT1236 vs CC1236; p = 0.0499, OR = 0.55, Fi–Yule coefficient = 0.14) were found. A strong LD between ABCB1
1236C>T and ABCB1
2677G>T/A SNPs (D′ = 0.621, r
2 = 0.318) was detected. All SNPs were located in one haplotype block. There were significant differences in haplotype distributions
between colorectal cancer patients and healthy population (p = 0.03). Significant differences in survival probability of colorectal cancer patients' treatment chemotherapy according
to allele of ABCB1
3435C>T was observed. Survival probability of patients with wild-type C3435 allele were higher than among patients without this allele (p = 0.04572).
Conclusions These results suggested that three studied SNPs of ABCB1 were located in one haplotype block. Differences in ABCB1
1236C>T and ABCB1
2677G>T/A genotypes and T1236 allele distribution between investigated populations indicate significant impact of these SNPs on risk of development of
colorectal cancer. Polymorphism ABCB1
3435C>T may be a prediction marker of cancer chemotherapy effectiveness. Differences in haplotype distributions between colorectal
cancer patients and healthy population suggested that other potential SNPs, especially in regulatory region of ABCB1 gene, may influence P-glycoprotein expression and function. 相似文献
13.
Basu R Basu A Chandramouli V Norby B Dicke B Shah P Cohen O Landau BR Rizza RA 《Diabetologia》2008,51(11):2031-2040
Aims/hypothesis We sought to determine whether pioglitazone and metformin alter NEFA-induced insulin resistance in type 2 diabetes and, if
so, the mechanism whereby this is effected.
Methods Euglycaemic–hyperinsulinaemic clamps (glucose ∼5.3 mmol/l, insulin ∼200 pmol/l) were performed in the presence of Intralipid–heparin
(IL/H) or glycerol before and after 4 months of treatment with pioglitazone (n = 11) or metformin (n = 9) in diabetic participants. Hormone secretion was inhibited with somatostatin in all participants.
Results Pioglitazone increased insulin-stimulated glucose disappearance (p < 0.01) and increased insulin-induced suppression of glucose production (p < 0.01), gluconeogenesis (p < 0.05) and glycogenolysis (p < 0.05) during IL/H. However, glucose disappearance remained lower (p < 0.05) whereas glucose production (p < 0.01), gluconeogenesis (p < 0.05) and glycogenolysis (p < 0.05) were higher on the IL/H study day than on the glycerol study day, indicating persistence of NEFA-induced insulin
resistance. Metformin increased (p < 0.001) glucose disappearance during IL/H to rates present during glycerol treatment, indicating protection against NEFA-induced
insulin resistance in extrahepatic tissues. However, glucose production and gluconeogenesis (but not glycogenolysis) were
higher (p < 0.01) during IL/H than during glycerol treatment with metformin, indicating persistence of NEFA-induced hepatic insulin
resistance.
Conclusions/interpretation We conclude that pioglitazone improves both the hepatic and the extrahepatic action of insulin but does not prevent NEFA-induced
insulin resistance. In contrast, whereas metformin prevents NEFA-induced extrahepatic insulin resistance, it does not protect
against NEFA-induced hepatic insulin resistance.
B. R. Landau died after the completion of this study. 相似文献
14.
Lymphoma-associated hemophagocytic syndrome: clinical features and treatment outcome 总被引:1,自引:0,他引:1
Han AR Lee HR Park BB Hwang IG Park S Lee SC Kim K Lim HY Ko YH Kim SH Kim WS 《Annals of hematology》2007,86(7):493-498
The clinical features and prognostic factor of lymphoma-associated hemophagocytic syndrome (LAHS), diagnosed according to
World Health Organization classification, were investigated by reviewing the clinical records of 29 patients between September
1994 and September 2006. Compared with patients with T or natural killer (NK)/T cell LAHS, patients with B cell LAHS were
older (p = 0.022), were less likely to exhibit disseminated intravascular coagulation (DIC; p = 0.011), and had less direct involvement of bone marrow (p = 0.03). Clinical response was achieved in 15 (65.2%) and complete remission (CR) was achieved in 4 (17%) of 23 patients
who received chemotherapy. Four patients received high-dose chemotherapy and autologous stem cell transplantation (A-SCT),
and three of these four patients showed CR. The median survival was 36 days (95%CI, 20.2–51.8). Univariate analysis showed
that poor performance status (p = 0.028), T or NK/T cell lymphoma (p = 0.016), presence of jaundice (p = 0.063), the presence of DIC (p = 0.002), and poor clinical response to treatment (p < 0.001) predicted poor overall survival. These data suggest that the clinical features differ significantly between B cell
LAHS and T or NK/T cell LAHS. Intensive treatment including high-dose chemotherapy and A-SCT should be investigated.
A-Reum Han and Hye Ran Lee contributed equally to this study. 相似文献
15.
This study evaluated the prognostic value of minimal residual disease (MRD) monitoring by four-color flow cytometry (FCM)
in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).
MRD was examined with four-color FCM at different time points in 139 patients (including pediatric and adult patients) with
ALL after allo-HSCT. Real-time quantitative polymerase chain reaction (RQ-PCR) was applied to evaluate the MRD of Philadelphia
chromosome-positive ALL (Ph+ ALL) patients. Patients who were FCM-positive (FCM+) after transplantation had a lower event-free
survival (EFS) of 0.54 and a higher cumulative incidence of relapse (CIR) of 0.54 compared to an EFS of 0.80 and a CIR of
0.08 in FCM-negative (FCM−) patients (EFS, p < 0.001; CIR, p < 0.001). Similar results were obtained in high-risk patients and Ph+ ALL patients. Moreover, a FCM+ status after the second
month post-HSCT (defined as MRD positive) proved to be a predictor of leukemia relapse. Multivariate analysis for EFS, OS
and CIR showed that MRD status after transplantation was an independent prognostic factor (p < 0.001, p = 0.013, and p < 0.001, respectively). A good correlation was found between the MRD results of FCM and RQ-PCR (n = 126 pairs, Spearman r = 0.8139, p < 0.001). MRD monitoring by four-color FCM post-transplantation is an important tool for relapse prediction in ALL patients.
Prompt and appropriate pre-emptive anti-leukemia treatment could be considered based on the status of MRD after HSCT. 相似文献
16.
Tzankov A Strasser U Dirnhofer S Menter T Arber C Jotterand M Rovo A Tichelli A Stauder R Günthert U 《Annals of hematology》2011,90(8):901-909
Treatment options for patients with high-risk acute myeloid leukemia (AML) include high-dose chemotherapy regimens in combination
with allogeneic hematopoietic stem cell transplantation, which takes advantage of the donor T-cell-mediated graft-versus-leukemia
effect. Together with beneficial responses observed in assays targeted at leukemia-associated antigens (LAA), this encouraged
research on cancer vaccines and adoptive cellular therapies in AML. The receptor for hyaluronic acid-mediated motility (RHAMM,
CD168) was identified as one of the most promising LAA in AML. Thus far, little is known about in situ expression in leukemic
bone marrow blasts or the prognostic role of RHAMM and its interaction partners in AML. We immunohistochemically analyzed
the expression and prognostic significance of RHAMM on trephine bone marrow biopsies from 71 AML cases that had been evaluated
for cytogenetics and presence of FLT3-internal tandem duplications and NPM1 mutations. Fifty-five patients (77%) were treated with curative intent, while 16 (23%) received the most appropriate supportive
care. Twenty of 71 (28%) AML cases were considered RHAMM+. Receiver operating characteristic curves showed significant discriminatory
power considering overall survival (OS) in AML patients treated curatively for RHAMM (p = 0.015). Multivariable analysis revealed that expression of RHAMM in >5% of leukemic blasts identifies a subgroup of curatively
treated cases with adverse OS independent of failures to achieve complete remission. RHAMM not only represents a promising
LAA with specific T-cell responses in AML but, if assessed in situ on blasts, also a probable prognostic factor. 相似文献
17.
Haemoglobin levels are associated with bone mineral density in the elderly: a population-based study
Hypoxemia has been associated with low bone mineral density (BMD) in animal and human models. We assessed the association
of haemoglobin levels with ultrasound-derived (UD) T score, Z score and the stiffness index in all 358 subjects aged 75+ living
in Tuscania (Italy). Also, we searched for the haemoglobin cutoff levels that might best identify participants with osteoporosis.
In the multivariable linear regression analysis, haemoglobin levels were associated among participants with the UD T score
[β = 0.13; 95% confidence interval (CI) = 0.01–0.25; p = 0.030], Z score (β = 0.11; 95% CI = 0.01–0.22; p = 0.045) and stiffness index (β = 1.87; 95% CI = 0.51–3.21; p = 0.007) after adjusting for potential confounders. Haemoglobin levels <140 g/L in men and <130 g/L in women best predicted
osteoporosis in linear discriminant analysis. Haemoglobin is independently associated with all UD-BMD parameters. Haemoglobin
levels <140 g/L in men and 130 g/L in women might be adopted in clinical practice to identify older subjects in whom screening
for osteoporosis might yield higher effectiveness. 相似文献
18.
Kalifa J Bernard M Gout B Bril A Cozma D Laurent P Chalvidan T Deharo JC Djiane P Cozzone P Maixent JM 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2007,21(1):47-53
Introduction Atrial dilatation is commonly associated with atrial fibrillation (AF), but the electrophysiological mechanisms and the implications
for anti-arrhythmic therapy are poorly understood. In a model of acute stretch-related AF in isolated rabbit hearts, we evaluated
the electrophysiological effects of three different anti-arrhythmic drugs: dofetilide, flecainide and BRL-32872 (associating
I
Kr and I
CaL blocking properties).
Methods After 30 min of sustained stretch-related AF, we perfused BRL 10–7 M, BRL 3.10–7 M, BRL 10–6 M, flecainide 2.4 10–6 M and
dofetilide 10–7 M and iteratively measured atrial effective refractory periods (ERPs), AF inducibility and AF cycle length
(AFCL) 15, 30 and 60 min after drug perfusion, respectively.
Results After a significant shortening of the ERPs by acute atrial stretch in the five groups individually (p < 0.001, stretch vs baseline for each group individually), drug perfusion led to a strong lengthening of AFCL, a very significant
prolongation of ERPs (p < 0.001 vs stretch) and a reduction of AF inducibility (p < 0.01 vs control group) for each of the five experimental groups. The relative ERP increase was comparable in all groups,
whereas a significantly lower AF inducibility was observed in the BRL 10–6 M group (p < 0.05 vs other BRL concentrations).
Conclusion In a model of acute stretch-related AF, dofetilide, flecainide and BRL-32872 terminated AF and prevented its immediate reinduction
after having comparatively prolonged AFCL and ERPs. These comparative results suggest that those drugs are equally efficacious,
albeit with different mechanisms, in the setting of acute atrial stretch. 相似文献
19.
Aims/hypothesis Our aims were to compare osteoclastic activity between patients with acute Charcot’s osteoarthropathy and diabetic and healthy
controls, and to determine the effect of the receptor activator of nuclear factor-kappaB ligand (RANKL) and its decoy receptor
osteoprotegerin (OPG).
Methods Peripheral blood monocytes isolated from nine diabetic Charcot patients, eight diabetic control and eight healthy control
participants were cultured in the presence of macrophage-colony stimulating factor (M-CSF) alone, M-CSF and RANKL, and also
M-CSF and RANKL with excess concentrations of OPG. Osteoclast formation was assessed by expression of tartrate-resistant acid
phosphatase on glass coverslips and resorption on dentine slices.
Results In cultures with M-CSF, there was a significant increase in osteoclast formation in Charcot patients compared with healthy
and diabetic control participants (p = 0.008). A significant increase in bone resorption was also seen in the former, compared with healthy and diabetic control
participants (p < 0.0001). The addition of RANKL to the cultures with M-CSF led to marked increase in osteoclastic resorption in Charcot
(from 0.264 ± 0.06% to 41.6 ± 8.1%, p < 0.0001) and diabetic control (0.000 ± 0.00% to 14.2 ± 16.5%, p < 0.0001) patients, and also in healthy control participants (0.004 ± 0.01% to 10.5 ± 1.9%, p < 0.0001). Although the addition of OPG to cultures with M-CSF and RANKL led to a marked reduction of resorption in Charcot
patients (41.6 ± 8.1% to 5.9 ± 2.4%, p = 0.001), this suppression was not as complete as in diabetic control patients (14.2 ± 16.5% to 0.45 ± 0.31%, p = 0.001) and in healthy control participants (from 10.5 ± 1.9% to 0.00 ± 0.00%, p < 0.0001).
Conclusions/interpretation These results indicate that RANKL-mediated osteoclastic resorption occurs in acute Charcot’s osteoarthropathy. However, the
incomplete inhibition of RANKL after addition of OPG also suggests the existence of a RANKL-independent pathway. 相似文献
20.
Li JM Wang L Shen Y Xia ZG Chen Y Chen QS Chen Y Zeng XY You JH Qian Y Shen ZX 《Annals of hematology》2007,86(9):639-645
The objective of this study is to evaluate the long-term efficacy and safety of rituximab combined with cyclophosphamide,
doxorubicin, vincristine, and prednisone (CHOP) in Chinese patients with newly diagnosed diffuse large B cell lymphoma (DLBCL).
The study comprised a retrospective analysis of patients treated at a single center. Patients received four to six infusions
of rituximab (375 mg/m2 per dose) on day 1 of each cycle of CHOP chemotherapy. CHOP was initiated on day 3 of each cycle; cycles were repeated at
21-day intervals. A total of 82 patients with a median age of 45 years (range 18–76 years) was included. The overall response
(OR) and complete response (CR) rates were 90.2 and 70.7%, respectively. The estimated 5-year progression-free survival (PFS)
and overall survival (OS) rates were 56.4 ± 8.3% and 74.1 ± 7.4%, respectively. Patients with International Prognostic Index
(IPI) scores ≤2 had significantly higher OR, CR, PFS, and OS rates (p = 0.01, p = 0.02, p = 0.01, p < 0.001, respectively) compared with patients with IPI scores >2. The hematologic toxicity was mild. Five patients with a
history of chronic hepatitis B experienced a reactivation of viral hepatitis. The rituximab–CHOP combination was effective
and well tolerated in Chinese patients with newly diagnosed DLBCL.
This study was conducted in accordance with the Chinese Good Clinical Practice (GCP), including ethical approval. 相似文献