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1.
Roberta Zanotti Franzesco Frattini Paolo Ghia Carlo Visco Alberto Zamò Omar Perbellini Stefania Stella Monica Facco Ilaria Giaretta Marco Chilosi Giovanni Pizzolo Achille Ambrosetti 《American journal of hematology》2010,85(7):494-498
Autoimmune cytopenias (AIC) are frequent in chronic lymphocytic leukemia (CLL) patients, but risk factors and prognostic relevance of these events are controversial. Data about the influence on AIC of biological prognostic markers, as ZAP‐70, are scanty. We retrospectively evaluated AIC in 290 CLL patients tested for ZAP‐70 expression by immunohistochemistry on bone marrow biopsy at presentation. They were 185 men, median age 63 years, 77.9% Binet stage A, 17.6% B and 4.5% C. AIC occurred in 46 patients (16%): 31 autoimmune hemolytic anemias, 10 autoimmune thrombocytopenias, four Evans syndromes, and one pure red cell aplasia. Of the 46 cases of AIC, 37 (80%) occurred in ZAP‐70 positive patients and nine (20%) in ZAP‐70 negatives. ZAP‐70 expression [Hazard Ratio (HR) = 7.42; 95% confidence interval (CI): 2.49–22.05] and age >65 years (HR = 5.41; 95% CI: 1.67–17.49) resulted independent risk factors for AIC. Among the 136 patients evaluated both for ZAP‐70 expression and IGHV status, the occurrence of AIC was higher in ZAP‐70 positive/IGHV unmutated cases (35%) than in patients ZAP‐70 negative/IGHV mutated (6%) or discordant for the two parameters (4%; P < 0.0001). In ZAP‐70 positive patients, occurrence of AIC negatively influenced survival (HR = 1.75; 95% CI: 1.06–2.86). The high risk of developing AIC in ZAP‐70 positive CLL, particularly when IGHV unmutated, should be considered in the clinical management. Am. J. Hematol. 2010. © 2010 Wiley‐Liss, Inc. 相似文献
2.
Tecchio C Nichele I Mosna F Zampieri F Leso A Al-Khaffaf A Veneri D Andreini A Pizzolo G Ambrosetti A 《European journal of haematology》2011,87(3):228-234
Purpose: A proliferation‐inducing ligand (APRIL), a tumor necrosis factor superfamily member involved in B‐lymphocytes differentiation and survival, plays a role in protecting B‐Cell Chronic lymphocytic leukemia (B‐CLL) cells from apoptosis. Having observed that APRIL serum (sAPRIL) levels were higher in B‐CLL patients with CLL at diagnosis as compared to healthy donors (14.61 ± 32.65 vs. 4.19 ± 3.42 ng/mL; P < 0.001), we tested the correlation existing in these patients between sAPRIL, clinical–biological parameters and disease progression. Experimental design: sAPRIL levels were measured by ELISA in 130 patients with B‐CLL at diagnosis and in 25 healthy donors. Results: sAPRIL levels did not correlate with gender, age, clinical stage, blood cell counts, β2‐microglobulin (β2M) levels, ZAP‐70 and CD38 expression. Using median sAPRIL natural logarithm (ln) as cutoff, we distinguished two groups of patients (APRILLOW and APRILHIGH) who were comparable with regard to clinical–biological parameters and overall survival, but different with regard to time to the first treatment (TTFT; P = 0.035). According to univariate analysis, high lymphocyte count, high β2M, Binet stage B–C, ZAP‐70 expression and ln(sAPRIL) above median were associated with earlier TTFT. Advanced clinical stage, high β2M, ZAP‐70 expression and ln(sAPRIL) above median remained independently predictive of shorter TTFT at multivariate analysis. Moreover, sAPRIL increased its prognostic significance when patients were stratified according to independent favorable clinical–biological characteristics (low β2M, stage A and lack of ZAP‐70 expression). Conclusions: sAPRIL is a novel indicator of shorter TTFT in B‐CLL and a predictor of progression especially in patients otherwise considered at low risk according to validated prognostic factors. 相似文献
3.
Soluble CD23 (sCD23) was proposed as a marker of disease activity and as an important prognostic parameter in B-cell chronic lymphocytic leukemia (B-CLL). In this study, prognostic significance of sCD23 in B-CLL was examined according to its temporal relationship with the known clinical parameters of the disease, CD38 and ZAP-70. Serum sCD23 levels of 36 B-CLL patients, followed up in our clinic between 1999 and 2005, and 15 healthy subjects were measured with enzyme-linked immunosorbent assay. The mean serum sCD23 level of the B-CLL patients (210.72 +/- 193.67 and 6-600 U/ml) was significantly higher than the control group (18.20 +/- 14.30 and 6-50 U/ml). Seventy-eight percent of the B-CLL patients with lymphocyte doubling time (LDT) <12 months and 24% of patients with LDT >12 months had high sCD23 levels (P = 0.008). Meanwhile, 81% of the patients with diffuse bone marrow infiltration and 33% of patients with nondiffuse infiltration had high levels of serum sCD23 (P = 0.029). A significant difference was found between B-CLL patients with Binet stages A and C (P = 0.009). Peripheral blood flow cytometry of the patients revealed a significant CD38 expression in patients with high serum sCD23 levels (P = 0.002). Similarly, an increased bone marrow zeta-chain associated protein kinase-70 (ZAP-70) expression was seen in patients with high serum sCD23 levels (P = 0.009, correlation co-efficient was 0.714). Cumulative and the progression free survivals of the patients with low serum sCD23 levels were 60.1 +/- 5.7 months [95% confidence interval (CI); 49.0-71.2] and 51.1 +/- 6.6 months (95% CI; 38.0-64.1), respectively. However, they were 43.8 +/- 6.5 months (95% CI; 31.0-56.6) and 26.5 +/- 6.4 months (95% CI; 14.0-39.1) in patients with high levels. Serum sCD23 is increased in B-CLL patients and can be used in the clinical follow-up of the disease in prediction of the tumor mass and prognosis. 相似文献
4.
《British journal of haematology》2018,181(2):259-261
Richter Syndrome, an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia (CLL), has a generally poor prognosis and anthracycline‐based chemoimmunotherapy regimens designed to treat de novo diffuse large B‐cell lymphoma achieve modest clinical benefit. R‐EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) has demonstrated greater activity against aggressive B‐cell histologies but has not been studied in Richter Syndrome. We conducted a retrospective cohort study of 46 Richter Syndrome patients treated with first‐line R‐EPOCH at our institution between 1 January 2006 and 31 May 2014. The median progression‐free survival (PFS) was 3·5 months [95% confidence interval (CI): 2·0–7·6] and median overall survival (OS) was 5·9 months (95% CI: 3·2–10·3). Toxicity was high and 30% of patients died without progression or response. Patients with a complex CLL karyotype had significantly shorter PFS and OS (P = 0·005 and P = 0·002, respectively). Multivariable analysis identified complex CLL karyotype as the most significant predictor of decreased survival [Hazard ratio (HR) 2·72, 95% CI: 1·14–6·52, P = 0·025], adjusting for number of prior CLL treatments (P = 0·036). Richter Syndrome patients with complex CLL karyotype experience poor survival with R‐EPOCH treatment and novel approaches are needed for these patients. In contrast, survival of patients without a complex CLL karyotype was similar to patients with de novo diffuse large B‐cell lymphoma. 相似文献
5.
Objectives: Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. This retrospective study is planned to assess the prognostic value of serum free light chain (sFLC) levels and FLC ratio (FLCR) in CLL. Methods: Quantitative levels of sFLC were measured nephelometrically in sera collected at diagnosis. The expressions of ZAP70 and CD38 were quantified by flow cytometry. Chromosomal abnormalities were determined by interphase fluorescence in situ hybridization (FISH). Results: In a cohort of 101 patients with a median follow‐up of 29 (1–234) months, sFLC levels were found to be high in 55 patients (54.5%). An abnormal FLCR was found in 30 patients (29.7%). FISH‐based genetic risk groups did not differ significantly with respect to sFLC and FLCR (P > 0.05). Median time to first treatment was shorter in patients with high sFLC levels (P = 0.02). Median overall survival (OS) was shorter in patients with high sFLC levels (P = 0.01) and abnormal FLCR (P = 0.05). In patients with early stage disease, median OS was shorter in high sFLC (P = 0.03) and abnormal FLCR groups (P = 0.048). A relationship was observed between abnormal sFLC levels and CD38 positivity on logistic regression analysis (P = 0.003; OR: 4.44; 95% CI: 1.66–11.8). Conclusions: This study highlighted the adverse prognostic impact of high sFLC levels and abnormal FLCR with regard to survival in CLL, even in early stage patients. Prospective studies are warranted to validate the adverse impact of sFLC and FLCR on clinical outcome. 相似文献
6.
U. AXDORPH B. I. NILSSON B. R. NILSSON M. BJ
RKHOLM 《Journal of internal medicine》1995,237(2):205-209
Abstract. Objective . To assess leucocyte doubling time (LDT) in relation to progression-free survival in patients with chronic lymphocytic leukaemia (CLL). In addition, to define the impact of a second LDT in both untreated and treated patients. Design . Retrospective study of LDT in previously untreated patients with CLL. Subjects and setting . Sixty patients diagnosed over a 13-year period at a county hospital. In forty-five of the 60 patients, an LDT could be defined. These patients were included in the final analysis. Main outcome measures . LDT below and above 12 months, progression-free and overall survival. Results . Patients in Binet stages B and C had a median LDT of 4 months as compared to 26 months in stage A patients (P < 0.01). The projected progression-free survival at 3 years was 24% in patients with an LDT of < 12 months. The corresponding figure for the remaining patients was 68% (P < 0.01). The overall 5-year survival did not differ significantly between patients with an LDT below and above 12 months, respectively. In seven untreated patients, a second LDT could be calculated which was shorter than the first recorded LDT. A second LDT was also identified in five patients post treatment that was consistently shorter than their first LDT. Conclusions . Measurement of LDT is a simple complement in predicting progression-free survival in patients with CLL. Thus, monitoring of LDT may add to the clinical evaluation and therapeutic decision making for the many elderly patients with this often indolent disease. 相似文献
7.
Cytomegalovirus infection does not impact on survival or time to first treatment in patients with chronic lymphocytic leukemia
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Helen Marie Parry Sarah Damery Christopher Hudson Matthew J. Maurer James R. Cerhan Annette Pachnio Jusnara Begum Susan L. Slager Christopher Fegan Stephen Man Christopher Pepper Tait D. Shanafelt Guy Pratt Paul A. H. Moss 《American journal of hematology》2016,91(8):776-781
Human cytomegalovirus (HCMV) is a widely prevalent herpes virus which establishes a state of chronic infection. The establishment of CMV‐specific immunity controls viral reactivation and leads to the accumulation of very large numbers of virus‐specific T cells which come to dominate the immune repertoire. There is concern that this may reduce the immune response to heterologous infections and HCMV infection has been associated with reduced survival in elderly people. Patients with chronic lymphocytic leukemia (B‐CLL) suffer from a state of immune suppression but have a paradoxical increase in the magnitude of the CMV‐specific T cell and humoral immune response. As such, there is now considerable interest in how CMV infection impacts on the clinical outcome of patients with B‐CLL. Utilizing a large prospective cohort of patients with B‐CLL (n = 347) we evaluated the relationship between HCMV seropositivity and patient outcome. HCMV seropositive patients had significantly worse overall survival than HCMV negative patients in univariate analysis (HR = 2.28, 95% CI: 1.34–3.88; P = 0.002). However, CMV seropositive patients were 4 years older than seronegative donors and this survival difference was lost in multivariate modeling adjusted for age and other validated prognostic markers (P = 0.34). No significant difference was found in multivariate modeling between HCMV positive and negative patients in relation to the time to first treatment (HR = 1.12, 95% CI: 0.68–1.84; P = 0.65). These findings in a second independent cohort of 236 B‐CLL patients were validated. In conclusion no evidence that HCMV impacts on the clinical outcome of patients with B‐CLL was found. Am. J. Hematol. 91:776–781, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
8.
Pascal Richette Ghazi Ayoub Sophie Lahalle Eric Vicaut Abdul‐Monem Badran Francisca Joly Bernard Messing Thomas Bardin 《Arthritis care & research》2007,57(8):1496-1501
Objective
To determine an association between magnesium (Mg) depletion and chondrocalcinosis, which has been reported but not investigated in a cross‐sectional study.Methods
Prevalence of chondrocalcinosis was investigated in 144 individuals: 72 patients receiving home parenteral nutrition (HPN) compared with 72 age‐ and sex‐matched controls. Presence of chondrocalcinosis was assessed by knee radiographs. Blood serum and globular Mg levels and 24‐hour urinary Mg content were compared.Results
Mean ± SD age for both patients and controls was 51 ± 17 years, and 51% in both groups were women. Mean duration of HPN was 6.4 years. Prevalence of chondrocalcinosis was markedly higher in patients receiving HPN than controls (16.6% versus 2.7%; P = 0.006, odds ratio [OR] 7.0, 95% confidence interval [95% CI] 1.45–66.1). Mean ± SD serum and globular Mg levels were significantly lower in patients than controls (serum: 0.75 ± 0.09 mmoles/liter versus 0.81 ± 0.08 mmoles/liter, P = 0.0006; globular Mg: 1.8 ± 0.31 mmoles/liter versus 2.0 ± 0.35 mmoles/liter, P = 0.0003). Twenty‐four‐hour urinary Mg level was lower in patients than controls (mean ± SD 3.85 ± 1.50 mmoles versus 5.37 ± 3.71 mmoles; P = 0.001). Prevalence of chondrocalcinosis was significantly higher in patients with a low serum Mg level (OR 13.5, 95% CI 2.76–127.3, P < 0.0001), with a similarly high but not significant occurrence of chondrocalcinosis in patients with a low globular Mg level (OR 4.09, 95% CI 0.603–20.26, P = 0.08) and in patients with a low 24‐hour urinary Mg level (OR 3.9, 95% CI 0.77–16.34, P = 0.05).Conclusion
Long‐lasting Mg depletion is strongly associated with chondrocalcinosis. 相似文献9.
Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TP 《Clinical endocrinology》2011,75(3):388-394
Objective Amiodarone is frequently associated with thyroid dysfunction. Identifying predictors for amiodarone‐associated thyroid dysfunction and assessing treatment outcome may aid clinicians in daily practice. Methods We included 303 consecutive patients with amiodarone therapy for cardiac arrhythmias (260 with atrial fibrillation and 43 with ventricular arrhythmias). Thyroid function tests were performed every 6 months. Results Mean age was 63 ± 12 years and 66% was male. After median follow‐up of 3·3 (0·1–24) years, 23 (8%) patients developed amiodarone‐associated thyrotoxicosis (incidence rate 1·9 per 100 person years) and 18 (6%) hypothyroidism (incidence rate 1·1 per 100 person years). The only predictor for amiodarone‐associated thyrotoxicosis was age <62 years [HR = 2·4 (95% CI 1·0–5·7), P = 0·05]. Predictors for amiodarone‐associated hypothyroidism were thyroid stimulating hormone >1·4 mU/l at baseline [HR = 5·1 (95% CI 1·1–22·4), P = 0·03], left ventricular ejection fraction <45% [HR = 3·8 (95% CI 1·1–13·3), P = 0·04] and diabetes mellitus at baseline [HR = 3·3 (95% CI 1·1–10·3), P = 0·04]. Gender was not a predictor for amiodarone‐associated thyroid dysfunction. Five out of 12 (42%) patients with thyrotoxicosis exhibited spontaneous normalization of thyroid function on continuation of amiodarone therapy. Mean time to normalization in the total group was 6·2 ± 3·3 months, with no difference between continuing or discontinuing amiodarone (6·6 ± 3·8 vs 5·8 ± 2·8 months, P = 0·5). Conclusions During median follow‐up of 3·3 years, the incidence of amiodarone‐associated thyrotoxicosis was higher compared to hypothyroidism. Only general predictors for amiodarone‐associated thyroid dysfunction were observed. Discontinuation of amiodarone did not influence treatment outcome. 相似文献
10.
Stefano Molica Giovanna Digiesi Caterina Battaglia Giovanna Cutrona Anna Antenucci Matteo Molica Diana Giannarelli Isabella Sperduti Massimo Gentile Fortunato Morabito Manlio Ferrarini 《European journal of haematology》2010,85(4):314-320
We analyzed the correlation between well‐established biological parameters of prognostic relevance in B‐cell chronic lymphocytic leukemia (CLL) [i.e. mutational status of the immunoglobulin heavy chain variable region (IgVH), ZAP‐70 and CD38 expression] and serum levels of B cell–activating factor (BAFF of the TNF family) by evaluating the impact of these variables on the time to first treatment (TFT) in a series of 169 previously untreated CLL patients in Binet stage A. Higher levels of BAFF were more frequently associated with female gender (P = 0.02), younger age (P = 0.01), Rai stage 0 (P = 0.002), higher platelet count (P = 0.005), mutated IgVH disease (P = 0.002), higher occurrence of normal cytogenetic profile or presence of 13q deletion (P = 0.02), low ZAP‐70‐ (P = 0.003), and CD38‐expression (P = 0.02). Maximally selected log‐rank statistic plot identified a serum BAFF concentration of 0.313 ng/mL as the best cut‐off (P < 0.0001). This threshold recognized two subsets of patients with different TFT (P < 0.0001). Because in multivariate analysis soluble BAFF [Hazard ratio (HR), 8.23; confidence Interval (CI) 95%,3.0–22.6, P < 0.0001] and mutational status of IgVH (HR = 2.60; CI 95% 1.10–6.14, P = 0.03) maintained the discriminating power their combined effect on clinical outcome was assessed. When three groups were considered: ( 1 ) low‐risk (n = 93), patients with concordant IgVHmut and higher soluble BAFF; ( 2 ) intermediate‐risk (n = 50), patients with IgVHmut and low BAFF levels or IgVHunmut and soluble higher BAFF;( 3 ) high‐risk (n = 26), patients with concordant IgVH unmut and low soluble BAFF, the 2‐yr TFTs were, respectively, 95%, 85%, and 41% (P < 0.0001). In conclusion, our results indicate that in early B‐cell CLL, the biological profile including among other parameters soluble BAFF may provide a useful insight into the complex interrelationship of prognostic variables. 相似文献
11.
Pepper C Majid A Lin TT Hewamana S Pratt G Walewska R Gesk S Siebert R Wagner S Kennedy B Miall F Davis ZA Tracy I Gardiner AC Brennan P Hills RK Dyer MJ Oscier D Fegan C 《British journal of haematology》2012,156(4):499-507
Approximately 70% of chronic lymphocytic leukaemia (CLL) patients present with early stage disease, therefore defining which patients will progress and require treatment is a major clinical challenge. Here, we present the largest study of prognostic markers ever carried out in Binet stage A patients (n = 1154) with a median follow‐up of 8 years. We assessed the prognostic impact of lymphocyte doubling time (LDT), immunoglobulin gene (IGHV) mutation status, CD38 expression, ZAP‐70 expression and fluorescence in situ hybridization (FISH) cytogenetics with regards to time to first treatment (TTFT) and overall survival (OS). Univariate analysis revealed LDT as the most prognostic parameter for TTFT, with IGHV mutation status most prognostic for OS. CD38 expression, ZAP‐70 expression and FISH were also prognostic variables; combinations of these markers increased prognostic power in concordant cases. Multivariate analysis revealed that only LDT, IGHV mutation status, CD38 and age at diagnosis were independent prognostic variables for TTFT and OS. Therefore, IGHV mutation status and CD38 expression have independent prognostic value in early stage CLL and should be performed as part of the routine diagnostic workup. ZAP‐70 expression and FISH were not independent prognostic markers in early stage disease and can be omitted at diagnosis but FISH analysis should be undertaken at disease progression to direct treatment strategy. 相似文献
12.
Yi Jiang Jie Zhao Ting Jiang Liuqing Ge Feng Zhou Zhitao Chen Yuan Lei Sha Huang Bing Xia 《Journal of gastroenterology and hepatology》2010,25(6):1157-1161
Background and Aims: Methylenetetrahydrofolate reductase (MTHFR) encoding genes were associated with ulcerative colitis in Chinese in our previous study. We further studied association of a new polymorphism of MTHFR G1793A with ulcerative colitis and assessed relationship of this polymorphism with hyperhomocysteinemia (HHcy, ≥ 15 mmol/L) and deficiency of folate (≤ 7 nmol/L) and vitamin B12 (≤ 150 pmol/L) in a cohort of patients with ulcerative colitis in central China. Methods: A total of 252 patients and 654 healthy controls were recruited. Polymorphism of MTHFR G1793A was examined using a polymerase chain reaction‐restriction fragment length polymorphism method. Plasma levels of homocysteine (Hcy), folate and vitamin B12 were determined by enzymatic cycling assay and corpuscle immune chemiluminescence assay, respectively. Results: Frequencies of alleles and genotypes in MTHFR G1793A gene differed significantly between ulcerative colitis patients and the healthy controls (20.83% vs 10.47%, 95% confidence interval [CI]: 1.703–2.972, P = 0.0006; 40.48% vs 19.88%, 95% CI: 1.997–3.761, P = 0.0002, respectively). Plasma Hcy levels were higher and folate and vitamin B12 concentrations were lower in the patients than in the healthy controls (21.72 ± 6.59 vs 12.47 ± 5.02, 95% CI: ?10.93–?7.58, P < 0.0001; 11.25 ± 6.19 vs 15.28 ± 7.72, 95% CI: 2.03–6.04; P < 0.001; 322.81 ± 128.47 vs 442.59 ± 129.36, 95% CI: 62.61–136.95, P < 0.0001, respectively). HHcy and folate deficiency were more prevalent in patients with ulcerative colitis (45.32% vs 26.17%, 95% CI: 1.285–4.378, P = 0.005; 30.68% vs 13.0%, 95% CI: 1.416–6.197, P = 0.003, respectively). Conclusions: MTHFR G1793A gene polymorphism, HHcy, folate deficiency and low vitamin B12 concentration were associated with ulcerative colitis in central China. Our findings demonstrate that the Hcy‐related gene and metabolites are involved in pathogenesis of ulcerative colitis. 相似文献
13.
V. Di Marco V. Calvaruso S. Grimaudo D. Ferraro R. M. Pipitone R. Di Stefano A. Craxì 《Journal of viral hepatitis》2013,20(2):113-121
Summary. Genetic factors can influence the outcome of antiviral therapy in chronic hepatitis C (HCV). We evaluated the role of interleukin‐28B single nucleotide polymorphisms (SNPs) and inosine triphosphatase (ITPA) gene variants in HCV cirrhosis treated with Peg‐Interferon and ribavirin. A prospective cohort of 233 patients with compensated cirrhosis received 1–1.5 μg/kg/week of Peg‐Interferon alpha‐2b plus 1000–1200 mg/day of RBV for 48 weeks. A sustained virologic response (SVR) was achieved in 27% of patients. On multivariate logistic analysis, the absence of oesophageal varices (OR 3.64 CI 95% 1.27–10.44 P = 0.016), infection with genotype 2 or 3 (OR 4.06, CI 95% 1.08–15.26, P = 0.038), C/C alleles of rs12979860 SNP (OR 7.04, CI 95% 2.40–20.72, P < 0.001) and rapid virologic response (RVR) (OR 78.29, CI 95% 16.07–381.29, P < 0.001) were independently associated with SVR. Patients who experienced post‐treatment relapse received lower total doses of Peg‐Interferon (52.0 ± 15.8 μg/kg vs 65.7 ± 13.3 μg/kg, P < 0.001) and lower total dose of RBV (3829 ± 1210 mg vs 4709 ± 954 mg, P < 0.001) than patients who achieved an SVR. ITPA variants predictive of high ITPase activity were associated with reduction of haemoglobin ≥3 g/dL in the first 4 weeks (P < 0.001), and with reduction of haemoglobin <10 g/dL (P = 0.03) on treatment. In conclusion, combination therapy with Peg‐Interferon and RBV in patients with HCV cirrhosis must be guided by virus genotype, severity of portal hypertension, favourable IL‐28B polymorphisms and ITPA variants, and RVR on treatment. 相似文献
14.
Zhao J Jiang Y Lei Y Zou K Wang C Huang S Yi F Xia B 《Journal of gastroenterology and hepatology》2011,26(3):593-598
Background and Aim: The aim of the present study was to evaluate the contribution of the dimorphism (MICA‐129 val and met) to the genetic susceptibility and functions of ulcerative colitis (UC) in patients in central China. Methods: Genotyping of MICA‐129 was performed in 272 consecutive UC patients and 560 age‐ and sex‐matched healthy individuals by using a polymerase chain reaction‐sequencing based typing (PCR‐SBT) method. A total of 93 patients and 98 healthy individuals serum soluble MICA (sMICA) concentrations were detected by enzyme‐linked immunosorbent assay. Results: Both the frequencies of the variant allele (val) and genotype (val/val) in the MICA‐129 gene were significantly higher in UC patients than in the controls (77.4% vs 71.7%, P = 0.015, 95% confidence interval [CI]: 1.064–1.716; 56.9% vs 46.4%, P = 0.005, 95% CI: 1.142–2.047). Serum sMICA levels were significantly higher in UC patients than in the controls (560 ± 140 pg/mL vs 157 ± 67 pg/mL, P < 0.0001). The genotype also affected the extent and the activity of UC. Furthermore, patients with the MICA‐129 val/val genotype had higher serum sMICA levels than those with the val/met + met/met genotype (661 ± 352 SD pg/mL vs 523 ± 245 SD pg/mL, 95% CI: 13.47–265.35, P = 0.03). In addition, patients with severe colitis were more susceptible to higher levels of sMICA than those with mild colitis. Conclusions: Our findings showed that the MICA‐129 gene polymorphism as a functionally relevant gene was associated with UC and seems to play a potential role in the development of UC in patients in central China. 相似文献
15.
Amanda M. Termuhlen Lynette M. Smith Sherrie L. Perkins Mark Lones Jonathan L. Finlay Howard Weinstein Thomas G. Gross Minnie Abromowitch 《British journal of haematology》2013,162(6):792-801
The Children's Oncology Group's A5971 trial examined central nervous system (CNS) prophylaxis and early intensification in paediatric patients diagnosed with CNS‐negative Stage III and IV lymphoblastic lymphoma. Using a 2 × 2 factorial design, the study randomized patients to Children's Cancer Group (CCG) modified Berlin‐Frankfurt‐Muenster (BFM) acute lymphoblastic leukaemia (ALL) regimen with intensified intrathecal (IT) methotrexate (MTX) (Arm A1) or an adapted non‐Hodgkin lymphoma/BFM‐95 therapy with high dose MTX in interim maintenance but no IT‐MTX in maintenance (Arm B1) . Each cohort was randomized ± intensification (cyclophosphamide/anthracycline) (Arms A2/B2). For the 254 randomized patients, there was no difference in 5‐year event‐free survival (EFS) for the four arms: Arm A1 , 80% [95% confidence interval (CI) 67–89%] and Arm A2 , 81% (95% CI 69–89%); Arm B1 , 80% (95% CI 68–88%) and Arm B2 , 84% (95% CI 72–91%). The cumulative incidence of CNS relapse was 1·2%. Age <10 years and institutional imaging response at 2 weeks was associated with improved outcomes (P < 0·001 and P = 0·014 for overall survival). CNS positive patients (n = 12) did poorly [5‐year EFS of 63% (95% CI 29–85%)]. For CNS‐negative patients, there was no difference in outcome based on CNS prophylaxis (IT‐MTX versus HD‐MTX) or with intensification. 相似文献
16.
Bieri S Roosnek E Ozsahin H Huguet S Ansari M Trombetti A Helg C Chapuis B Miralbell R Passweg J Chalandon Y 《European journal of haematology》2011,87(2):138-147
Objectives: The aim of this retrospective study was to assess the incidence of late complications occurring ≥2 years after allogeneic hematopoietic stem cell transplantation (HSCT) for malignant diseases using a T‐cell depletion strategy. Methods: Between 1984 and 2004, 142 patients were eligible for the study. Total body irradiation (TBI) was carried out in 85% of the patients and T‐cell depletion in 84%. Results: Non‐relapse mortality (NRM) was 3% (95% CI 0–11) at 10 years, and serious late events affected a substantial number of patients. The cumulative incidence (CI) of chronic graft‐versus‐host disease (cGvHD) was 30% (95% CI 23–40), and that of infectious complications was 17% (95% CI 11–23). Multivariate analysis showed a higher risk for late complications in patients with cGvHD (HR 1.9, 95% CI 1.2–3.2, P = 0.011) and patients receiving methylprednisolone during conditioning (HR 1.9, 95% CI 1.1–3.3, P = 0.019 1), patients with cGvHD also having a higher risk for NRM (HR 13.2, 95% CI 1.2–143, P = 0.03), as well as those receiving steroids for >3 months (HR 40.3, 95% CI 2.3–718, P = 0.02) and those receiving antithymocyte globulin (HR 9.6, 95% CI 0.8–68, P = 0.024). Conclusions: A significant proportion of long‐term survivors of HSCT had late complications. cGvHD remained an important risk factor for late complications despite T‐cell depletion resulting in immunosuppression and infectious complications. 相似文献
17.
Sarah Harding Sarit Khimdas Ashley Bonner Canadian Scleroderma Research Group Murray Baron Janet Pope 《Arthritis care & research》2012,64(9):1405-1414
Objective
This study was performed to determine the prevalence of elevated C‐reactive protein (CRP) levels and the significance of CRP in clinical parameters in systemic sclerosis (SSc; scleroderma) patients.Methods
Canadian Scleroderma Research Group data were used. Statistical comparisons were made for CRP levels ≤8 mg/liter versus >8 mg/liter, early (≤3 years from first non–Raynaud's phenomenon symptom) versus late SSc, and diffuse cutaneous SSc (dcSSc) versus limited cutaneous SSc (lcSSc). A survival analysis was analyzed between patients with normal versus elevated CRP levels.Results
A total of 1,043 patients (mean ± SD age 55.4 ± 12.1 years, mean ± SD disease duration of 11.0 ± 9.5 years) were analyzed; elevation of CRP level and erythrocyte sedimentation rate (ESR; >20 mm/hour) occurred in 25.7% and 38.2%, respectively. Mean ± SD baseline CRP level in dcSSc (11.98 ± 25.41 mg/liter) was higher than in lcSSc (8.15 ± 16.09 mg/liter; P = 0.016). SSc patients with an early disease duration had a higher mean ± SD CRP level (12.89 ± 28.13 mg/liter) than those with a late disease duration (8.60 ± 17.06 mg/liter; P = 0.041). Although not consistent in all subsets, CRP was significantly associated (P < 0.01) with ESR, modified Rodnan skin score (MRSS), worse pulmonary function parameters, disease activity, damage, and Health Assessment Questionnaire. CRP level seemed to normalize in many SSc patients over time. Total lung capacity <80% predicted, MRSS, and serum creatinine were predictors of elevated CRP levels in SSc (odds ratio [OR] 2.76 [95% confidence interval (95% CI) 1.73–4.40], P = 0.0001; OR 1.03 [95% CI 1.01–1.05], P = 0.005; and OR 1.005 [95% CI 1.001–1.010], P = 0.02, respectively). Survival for patients with elevated CRP levels was less than for patients with normal CRP levels (P = 0.001).Conclusion
CRP level is elevated in one‐quarter of SSc patients, especially early disease. It is correlated with disease activity, severity, poor pulmonary function, and shorter survival. 相似文献18.
S. Petta A. Handberg G. Marchesini C. Cammà V. Di Marco D. Cabibi F. S. Macaluso A. Craxì 《Journal of viral hepatitis》2013,20(3):174-182
Summary. Soluble CD36 (sCD36) plasma levels, a known marker of cardiometabolic disorders, are associated with surrogate markers of steatosis, while experimental and human studies show a link between CD36 expression in the liver and steatosis. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of sCD36 plasma levels with host and viral factors and sustained virological response (SVR). One hundred and seventy‐five consecutive biopsy‐proven patients were studied. sCD36 plasma levels were assessed by an in‐house ELISA. All biopsies were scored by one pathologist for staging and grading (Scheuer) and graded for steatosis, which was considered moderate–severe if ≥20%. Patients underwent standard of care therapy with pegylated interferon and ribavirin. The severity of steatosis progressively increased according to sCD36 quartiles (P = 0.02); total and low‐density lipoprotein (LDL) cholesterol levels were significantly higher in patients in the lower quartile compared to all the others. Gamma‐glutamyl transferase (P = 0.02), homoeostasis model assessment (HOMA) score (P = 0.002) and sCD36 (P = 0.04) were independently associated with the severity of steatosis as continuous variable. Multivariate logistic regression analysis showed that HOMA (OR 1.243, 95% CI 1.04–1.484, P = 0.01) and sCD36 (OR 1.445, 95%CI 1.135–1.839, P = 0.003) were independently linked to steatosis ≥20%. No association was found between sCD36 and SVR. CD36 is linked to steatosis and insulin resistance in patients with G1 CHC, but does not predict response to treatment. The potential of sCD36 as a surrogate marker of steatosis should be further investigated. 相似文献
19.
Soluble CD23 (sCD23) and beta-2 microglobulin (beta2-m) are reliable prognostic parameters in B-cell chronic lymphocytic leukemia (CLL); however, their merit over well-established clinical variables such as clinical stages, bone marrow (BM) histology and lymphocyte doubling time (LDT) remains to be defined. Furthermore, information dealing with the impact on overall survival of the simultaneous increase of either beta2-m or sCD23 are lacking. In this prospective study based on 106 B-cell CLL patients, we propose a combination of beta2-m and sCD23 as a strong prognostic system whose statistical significance was mainly due to an excess of deaths in the subgroup displaying increased serum levels of either beta2-m or sCD23. Multivariate survival analysis confirmed the important dominant role of such a finding, thus excluding features with a high degree of codependence (i.e. clinical stages, LDT) and including variables with low association (i.e. BM histology) in the final regression model. The presence of increased serum levels of beta2-m/sCD23 and diffuse BM histology signified high-risk disease, whereas the absence of any adverse variable was associated with prolonged survival; in between there was a subgroup with only 1 characteristic which displayed an intermediate pattern of survival. Finally, on the basis combined increased serum levels of beta2-m and sCD23, a better stratification of low- and intermediate-risk patients could be obtained, thus allowing the formulation of a clinico-biological staging for CLL. 相似文献
20.
Tatsuji ENOMOTO Arata AZUMA Ayumi KOHNO Kazuyo KANEKO Hitoshi SAITO Minako KAMETAKA Jiro USUKI Akihiko GEMMA Shoji KUDOH Seiichi NAKAMURA 《Respirology (Carlton, Vic.)》2010,15(1):126-131
Background and objective: The incidence of Pneumocystis jirovecii pneumonia (PCP) in patients with predisposing immunodeficiencies other than AIDS is growing. Knowing the different characteristics and outcomes of PCP according to HIV status would help physicians manage and treat patients with PCP. Methods: The medical charts of all patients with a proven first episode of PCP, diagnosed between 1997 and 2007 were retrospectively reviewed, and clinical and laboratory data abstracted. Results: Of the 35 patients with PCP, 18 were HIV‐positive and 17 were HIV‐negative with other immunosuppressive conditions. HIV‐negative patients were significantly older than HIV‐positive patients. The WCC (10 952 ± 5669 vs 9750 ± 3133/µL; P = 0.015), neutrophil counts (9631 ± 5421 vs 5680 ± 2628/µL; P = 0.01) and CD4+ lymphocyte counts (329 ± 502 vs 47 ± 50/µL; P < 0.001) were significantly higher in HIV‐negative patients. Six of the 17 HIV‐negative patients had a CD4+ lymphocyte count >300/µL. Serum IgG levels were lower in HIV‐negative patients (943 ± 379 vs 1635 ± 657 mg/dL; P = 0.017). Mortality was higher in HIV‐negative (52.9%) than in HIV‐positive patients (0%). On univariate analysis, risk factors for mortality from PCP were the presence of underlying pulmonary disease (odds ratio 4.000, 95% CI: 1.501–10.658) and HIV‐negative status (odds ratio 2.125, 95% CI: 1.283–3.518). Conclusions: The characteristics and outcomes of PCP differ significantly depending on HIV status. The existence of underlying pulmonary diseases may be associated with the prognosis of HIV‐negative patients with PCP. 相似文献