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Tyrosine kinase inhibitors (TKI) have changed the natural course of chronic myeloid leukemia (CML). With the advent of second-generation TKI safety and efficacy issues have gained interest. The randomized CML - Study IV was used for a long-term evaluation of imatinib (IM). 1503 patients have received IM, 1379 IM monotherapy. After a median observation of 7.1 years, 965 patients (64%) still received IM. At 10 years, progression-free survival was 82%, overall survival 84%, 59% achieved MR 5 , 72% MR 4.5 , 81% MR 4 , 89% major molecular remission and 92% MR 2 (molecular equivalent to complete cytogenetic remission). All response levels were reached faster with IM800 mg except MR 5 . Eight-year probabilities of adverse drug reactions (ADR) were 76%, of grades 3–4 22%, of non-hematologic 73%, and of hematologic 28%. More ADR were observed with IM800 mg and IM400 mg plus interferon α (IFN). Most patients had their first ADR early with decreasing frequency later on. No new late toxicity was observed. ADR to IM are frequent, but mostly mild and manageable, also with IM 800 mg and IM 400 mg+IFN. The deep molecular response rates indicate that most patients are candidates for IM discontinuation. After 10 years, IM continues to be an excellent initial choice for most patients with CML.

It is unknown, why only a minority of chronic myeloid leukemia (CML) patients sustains treatment free remission (TFR) after discontinuation of tyrosine kinase inhibitor (TKI) therapy in deep molecular remission (MR). Here we studied, whether expression of the T-cell inhibitory receptor (CTLA-4)-ligand CD86 (B7.2) on plasmacytoid dendritic cells (pDC) affects relapse risk after TKI cessation. CML patients in MR displayed significantly higher CD86 + pDC frequencies than normal donors ( P <0.0024), whereas TFR patients had consistently low CD86 + pDC ( n =12). This suggested that low CD86 + pDC might be predictive of TFR. Indeed, in a prospective analysis of 122 patients discontinuing their TKI within the EURO-SKI trial, the one-year relapse-free survival (RFS) was 30.1% (95% CI 15.6–47.9) for patients with >95 CD86 + pDC per 10 5 lymphocytes, but 70.0% (95% CI 59.3–78.3) for patients with <95 CD86 + pDC (hazard ratio (HR) 3.4, 95% - CI: 1.9–6.0; P <0.0001). Moreover, only patients with <95 CD86 + pDC derived a significant benefit from longer (>8 years) TKI exposure before discontinuation (HR 0.3, 95% CI 0.1–0.8; P =0.0263). High CD86 + pDC counts significantly correlated with leukemia-specific CD8 + T - cell exhaustion (Spearman correlation: 0.74, 95%-CI: 0.21–0.92; P =0.0098). Our data demonstrate that CML patients with high CD86 + pDC counts have a higher risk of relapse after TKI discontinuation.

Minimal residual disease (MRD) after allogeneic stem cell transplantation (SCT) for Ph+ acute lymphoblastic leukemia (ALL) is predictive of relapse. Imatinib administration subsequent to SCT may prevent relapse, but the role of scheduling and its impact on outcome are not known. In a prospective, randomized multicenter trial, we compared the tolerability and efficacy of post-transplant imatinib administered either prophylactically (arm A; n =26) or following detection of MRD (arm B; n =29). Prophylactic imatinib significantly reduced the incidence of molecular recurrence after SCT compared with MRD-triggered imatinib (40% vs 69%; P =0.046). Median duration of PCR negativity was 26.5 and 6.8 months, respectively ( P =0.065). Five-year survival in both interventional groups was high (80 and 74.5%), despite premature discontinuation of imatinib in the majority of patients because of poor tolerability. Relapse probability was significantly higher in patients who became MRD positive ( P =0.017). In conclusion, post-transplant imatinib results in a low relapse rate, durable remissions and excellent long-term outcome in patients with BCR–ABL1 -positive ALL irrespective of whether it is given prophylactically or MRD-triggered. Reappearance of BCR–ABL1 transcripts early after SCT or at higher levels identifies a small subset of patients who do not benefit sufficiently from imatinib, and in whom alternative approaches should be explored.

In the face of competing first-line treatment options for CML, early prediction of prognosis on imatinib is desirable to assure favorable survival or otherwise consider the use of a second-generation tyrosine kinase inhibitor (TKI). A total of 1303 newly diagnosed imatinib-treated patients (pts) were investigated to correlate molecular and cytogenetic response at 3 and 6 months with progression-free and overall survival (PFS, OS). The persistence of BCR-ABL transcript levels >10% according to the international scale (BCR-ABL IS ) at 3 months separated a high-risk group (28% of pts; 5-year OS: 87%) from a group with >1–10% BCR-ABL IS (41% of pts; 5-year OS: 94%; P =0.012) and from a group with ⩽1% BCR-ABL IS (31% of pts; 5-year OS: 97%; P =0.004). Cytogenetics identified high-risk pts by >35% Philadelphia chromosome-positive metaphases (Ph+, 27% of pts; 5-year OS: 87%) compared with ⩽35% Ph+ (73% of pts; 5-year OS: 95%; P =0.036). At 6 months, >1% BCR-ABL IS (37% of pts; 5-year OS: 89%) was associated with inferior survival compared with ⩽1% (63% of pts; 5-year OS: 97%; P <0.001) and correspondingly >0% Ph+ (34% of pts; 5-year OS: 91%) compared with 0% Ph+ (66% of pts; 5-year OS: 97%; P =0.015). Treatment optimization is recommended for pts missing these landmarks.

Background Treatment options in patients with amyloidotic transthyretin (ATTR) cardiomyopathy are limited. Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea (GT), inhibits fibril formation from several amyloidogenic proteins in vitro. Thus, it might also halt progression of TTR amyloidosis. This is a single-center observational report on the effects of GT consumption in patients with ATTR cardiomopathy. Methods 19 patients with ATTR cardiomyopathy were evaluated by standard blood tests, echocardiography, and cardiac MRI ( n  = 9) before and after consumption of GT and/or green tea extracts (GTE) for 12 months. Results Five patients were not followed up for reasons of death ( n  = 2), discontinuation of GT/GTE consumption ( n  = 2), and heart transplantation ( n  = 1). After 12 months no increase of left ventricular (LV) wall thickness and LV myocardial mass was observed by echocardiography. In the subgroup of patients evaluated by cardiac MRI a mean decrease of LV myocardial mass (−12.5 %) was detected in all patients. This was accompanied by an increase of mean mitral annular systolic velocity of 9 % in all 14 patients. Total cholesterol (191.9 ± 8.9 vs. 172.7 ± 9.4 mg/dL; p  < 0.01) and LDL cholesterol (105.8 ± 7.6 vs. 89.5 ± 8.0 mg/dL; p  < 0.01) decreased significantly during the observational period. No serious adverse effects were reported by any of the participants. Conclusions Our observation suggests an inhibitory effect of GT and/or GTE on the progression of cardiac amyloidosis. We propose a randomized placebo-controlled investigation to confirm our observation.

Background: After acute myocardial infarction, the structural protein T is released considerably longer than cytosolic creatine kinase (CK), CK MB isoenzyme (CK-MB), or lactate dehydrogenase (LDH) and late troponin T release (> 48 hours after onset of chest pain) appears to be less affected by early coronary reperfusion. Objective: To investigate the precision of a single measurement of circulating troponin T concentrations 72 hours after onset of chest pain compared with standard scintigraphic and enzymatic estimates of myocardial infarct size. Methods: Quantitative single photon emission computed tomography thallium-201 scintigraphy at rest was performed in 37 patients 2–3 weeks after myocardial infarction (group 1: 14 patients without early coronary reperfusion; group 2: 23 patients with early reperfusion achieved by thrombolytic therapy, by percutaneous transluminal coronary angioplasty, or by both). Results: In both groups, the number of myocardial segments with abnormal thallium-201 uptake indicating the individual extent of irreversible myocardial damage correlated significantly with the troponin T concentrations 72 hours after infarction as well as with peak concentrations of CK, CK-MB, and LDH. Conclusion: The data show that a single measurement of circulating troponin T 72 hours after onset of chest pain—independent of reperfusion—is superior for the estimation of myocardial infarct size to measurement of peak CK, CK-MB, or LDH, which require serial determinations and depend on coronary reperfusion.

This corrects the article DOI: 10.1038/leu.2017.9

High-resolution, long-range detection of person-borne concealed weapons has recently been demonstrated using a terahertz imaging radar. However, the radar’s image acquisition time must be greatly shortened, from minutes to less than one second, before the system can be effectively deployed in a real-life threat environment. Here we analyze the major system modifications necessary for increasing the speed of a terahertz imaging radar by up to two orders of magnitude.

A chronic (auto)immune response is the critical mechanism in atherosclerosis. Interleukin-17A is a pivotal effector cytokine, which modulates immune cell trafficking and initiates inflammation in (auto)immune and infectious diseases. However, expression of IL-17A in the context of human atherosclerosis has hardly been explored. Carotid artery plaques were collected from 79 patients undergoing endarterectomy. Patients were grouped according to their symptomatic status (TIA, stroke), plaque morphology and medication. Quantitative RT-PCR was used to analyze tissue inflammation and immunohistochemistry to assess cellular source of IL-17A expression and lesion morphology. Carotid plaques from patients with ischemic symptoms were characterized by a highly activated inflammatory milieu including accumulation of T cells ( p  = 0.04) and expression of IL-6 and VCAM1 ( p  = 0.02, 0.01). Expression of IL-17A and its positive regulators IL-21 and IL-23 was present in atherosclerotic lesions, significantly upregulated in atheromas of symptomatic patients ( p  = 0.005, 0.004, 0.03), and expression of IL-17A and IL-21 showed a strong correlation ( p  = 0.002, r  = 0.52). The cellular sources of lesional IL-17A expression are T cells, macrophages, B cells and plasma cells. Vulnerable/ruptured (complicated) plaques were significantly associated with IL-17A expression levels ( p  = 0.003). In addition, IL-17A showed a marked negative correlation with the potent anti-inflammatory/atheroprotective cytokine IL-10 ( p  = 0.0006, r  = −0.46). Furthermore, treatment with a HMG-CoA reductase inhibitor or acetylsalicylic acid showed reduced levels of IL-21 , IL-23 and VCAM1 (all p  < 0.05), but did not influence IL-17A . The association of IL-17A with ischemic symptoms and vulnerable plaque characteristics suggests that the pro-inflammatory cytokine IL-17A may contribute to atherosclerosis und plaque instability.