美国国家骨髓库20年回顾:儿童急性白血病无关供者骨髓移植

自1987年以来,NMDP有效推动了儿童无关供者造血干细胞移植(HCT)的发展.在庆祝NMDP成立20周年之际,本文就儿童急性白血病患者移植所取得的成果和经验加以总结,目的在于进一步提高移植疗效,把握未来研究方向.     

Rituximab and immune tolerance in severe hemophilia A: a consecutive national cohort

Summary.  Background and objectives:  he management of patients with severe hemophilia A and inhibitors to factor VIII (FVIII) resistant to standard immune tolerance is challenging. There have been recent case reports of the successful use of rituximab in up to 57% of patients as part of rescue immune tolerance regimens. Because case reports and small series are prone to the potential bias of reporting good outcomes and relatively short follow up, a consecutive cohort of all patients treated in the UK with prolonged follow up was analyzed. Methods:  A national survey of all Comprehensive Care Haemophilia Cente in the UK. Results:  A total of 15 patients were reported of whom six (40%) achieved a negative inhibitor titer by Bethedsa assay. Durable responses were unusual, observed in only 14% of cases. Clinically significant responses with either a negative inhibitor or an inhibitor titer < 5 BU mL⁻¹ and no spontaneous bleeding with FVIII replacement were observed in seven (47%) cases. Concomitant use of FVIII appeared to be important. Of the 12 patients treated with rituximab and FVIII, six (50%) achieved a negative inhibitor titer and seven (58%) had a clinically beneficial response. None of the three patients treated without FVIII responded. Conclusions:  hese data suggest that the use of rituximab combined with FVIII is a potentially useful treatment for patients with inhibitors resistant to standard immune tolerance, although sustained inhibitor eradication is uncommon.     

Can anaerobic threshold be used as an end-point for therapeutic trials in heart failure?: Lessons from a multicentre randomized placebo-controlled trial

‘Anaerobic threshold’ (AT), proposed as a non-invasiveindex of exercise tolerance, independent of patient motivation,is considered more reliable than exercise duration in assessingthe effect of drug therapy in chronic heart failure (CHF). However,inter-observer variation in patients may be more difficult thanin normal subjects. In a multicentre study, 85 patients from10 centres performed a total of 331 bicycle maximal tests (rampprotocols, 10 watts. min^–1) with respiratory gas analysisby different systems. A central committee reviewed all the tests.Percentages of AT determination ranged from 34% to 71% dependingon the method used. Apart from the respiratory exchange ratio(RER=1) method, which yielded the lowest rate of determination.and the crossing point (when RER=1), which yielded the highestrate, 71%, other methods of determination, such as carbon dioxide(42%), minute ventilation (52%) or ventilatory equivalents plottedvs time (57%), did not dtffer in the rate of AT determination. Thus, even among trained physicians, AT determination was notreliable. The crossing point may nevertheless be a valuableindex from a pragmatic standpoint, although it occurs afterthe actual AT Peak oxygen uptake should remain the main end-pointin assessment of exercise capacity.     

研究诊断准确性的论著的质量:STARD公布后无改变——STARD公布前后的比较研究

目的确定对诊断准确性进行研究的论著的规范(STARD)公布前、后该类论著的质量改善情况,并比较执行STARD和未执行STARD的杂志的该类论著质量有无差     

Survey of lupus anticoagulant diagnosis by central evaluation of positive plasma samples

OBJECTIVE: To determine whether the diagnosis of lupus anticoagulant (LAC) in a large cohort of positive patients was confirmed at a reference laboratory. METHODS: Over a 1-year period, each participating center collected samples from LAC-positive patients. Plasma was filtered and kept deep-frozen until it was sent on dry ice to the reference laboratory by express courier. Centers returned detailed laboratory information and clinical data from each patient. The reference laboratory screened plasma samples by diluted Russell viper venom time (dRVVT) and kaolin clotting time (KCT). When these were prolonged, 1:1 mixing studies were carried out, and confirmatory tests were performed as appropriate. Positive samples were further tested by thrombin time (TT). The presence of heparin was checked by measuring antifactor Xa activity when TT was prolonged. Negative samples were tested by activated partial thromboplastin time using hexagonal phospholipids. RESULTS: Plasma samples from 302 patients from 29 anticoagulation clinics were analyzed. LAC was excluded in 71 samples (24%), because dRVVT and KCT screening test results were normal (34) or reversed to normal by mixing studies (35). The remaining two samples were considered negative because they contained heparin. LAC-negative patients showed different characteristics from those in whom diagnosis was confirmed. They were significantly older (49.7 vs. 45.0 years, P < 0.03), were more often first diagnosed (66% vs. 41%, P < 0.001), and were more frequently judged as mild in LAC potency (60% vs. 25%, P < 0.0001). Moreover, anticardiolipin and anti-beta(2)-glycoprotein I antibody values were more often normal in LAC-negative (82%) than in LAC-positive (42%) samples (P < 0.0001). LAC-positive samples identified by both dRVVT and KCT (146/231, 63%) showed a LAC potency that was significantly stronger than that in samples in which LAC diagnosis was made by a single test. CONCLUSIONS: A false-positive LAC diagnosis is not uncommon across specialized centers. Patients' characteristics and a complete antiphospholipid antibody profile may help to identify these individuals.     

Meeting Report: Ninth and Tenth Workshops of the European Paediatric Network for Haemophilia Management (PedNet)

This meeting report presents an overview of the discussions at the ninth and tenth workshops of the European Paediatric Network for Haemophilia Management (PedNet) that occurred in 2005 and 2006. Among numerous topics, a major theme of these workshops was the formation of inhibitors to replacement factor.     

Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A

Recent reports have suggested that the incidence of inhibitors in haemophilia is the highest in those first exposed to factor VIII under 6 months of age. In this study, we investigated inhibitor development in children first exposed to FVIII as neonates and also examined the effect of other genetic and environmental variables. Three hundred and forty-eight children with severe haemophilia A were investigated. Inhibitors developed in 68 of 348 (20%), with 34 of 348 (10%) high titre inhibitors. The incidence in relation to initial FVIII exposure was: <1 month nine of 35 (26%), 1-6 months 13 of 51 (25%), 6-12 months 27 of 130 (21%), 12-18 months 13 of 66 (20%) and >18 months six of 66 (9%). While we observed a significant difference in inhibitor development and age at first exposure across all age groups (P = 0.018), no significant difference was observed in children treated at different time points during the first year of life (P = 0.44). Similar results were obtained for high titre inhibitors. There was also no difference in the incidence of inhibitors in relation to initial FVIII exposure in a subgroup of 144 children with the intron 22 mutation. Inhibitors developed more frequently in those initially treated with recombinant when compared with plasma-derived FVIII (P = 0.006) and in those with a major molecular defect (P = 0.009). In this study, exposure to FVIII during the neonatal period was not associated with a higher incidence of inhibitors than those treated later during the first year of life. Initial treatment with recombinant FVIII and the presence of a major molecular defect were the most important variables affecting inhibitor development.