Different treatment strategies versus a common standard arm (CSA) in patients with newly diagnosed AML over the age of 60 years: a randomized German inter-group study.

A randomized inter-group trial comparing more intensive treatment strategies to a common standard arm 3 + 7 (CSA) was conducted in patients with non-M3 AML. Untreated patients ≥ 60 years were allocated to the CSA (n = 132) or to the study group arms (n = 1154) of the AMLCG (TAD/HAM versus HAM/HAM ± G-CSF followed by TAD and maintenance) and the OSHO (intermediate-dose ara-C/mitoxantrone followed by ara-C/mitoxantrone). Median age of the 1147 eligible patients was 69 (range 60-87) years. CR/CRi status at 90 days was not significantly different between the CSA (54% (95%CI: 45-64)) and the study group arms (53% (95%CI: 47-60) and 59% (95%CI: 58-63)). The five-year event-free survival (EFS) probability (primary endpoint) was 6.2% (95%CI: 2.7-14.0) in the CSA, 7.6% (95%CI: 4.5-12.8) in study group A and 11.1% (95%CI: 9.0-13.7) in B. The 5-year OS was 17.2% (95%CI: 11.0-26.9), 17.0% (95%CI: 2.0-23.9), and 19.5% (95%CI: 16.7-22.8) in CSA, study group A and B, respectively. Neither study group differed significantly from the CSA regarding EFS, OS, or relapse-free survival. In multivariate analyses, allocation to the treatment strategy was not significantly associated with the time-to-event endpoints. The evaluation of more intensive treatment strategies did not show clinically relevant outcome differences when compared to CSA.

Allogeneic hematopoietic stem cell transplantation improves long-term outcome for relapsed AML patients across all ages: results from two East German Study Group Hematology and Oncology (OSHO) trials.

Relapse of acute leukemia is a frequent complication with uncertain outcome and poorly defined risk factors. From 1621 patients entered into two prospective clinical trials (AML02; n = 740 and AML04; n = 881), 74.2% reached complete remission (CR) 1 after induction(s) and 59 patients after additional induction ± hematopoietic cell transplantation (HCT). Of the non-refractory patients, 48.4% with a median age of 63 (range 17-85) years relapsed. Relapses occurred within 6 months after CR in 46.5%, between 7 and 18 months in 38.7%, and after 18 months in 14.8% of patients. Relapse treatment resulted in CR2 in 39% of patients depending upon age (54.5% of ≤ 60 and 28.6% of > 60 years), duration of CR1, and treatment of relapse. Overall survival (OS) was 10.9 (7.4-16.2) %, but OS after HCT ± intensive chemotherapy (ICT) was 39.3% (31.8-48.6) at 5 years and not different in younger and older patients. Donor lymphocyte infusion ± chemotherapy and ICT alone resulted only in OS of 15.4% and of 5%, respectively. Independent favorable factors for OS were long CR1 duration, and HCT, while non-monosomal disease was beneficial for OS in elderly patients. Leukemia-free survival [LFS; 24.9 (19.5-31.7) % at 10 years] was affected by similar risk factors. In a competing risk model, the relapse incidence at 5 years was 53.5 ± 3.5% and the non-relapse mortality rate 21.7 ± 2.9%. Lower relapse incidence was observed in patents with HCT, long CR1 duration, and female gender. Risk factors for non-relapse mortality were HCT in younger and type of AML in elderly patients. In conclusion, allogeneic HCT ± IC improved the results in relapsed AML in younger and elderly patients. Increasing CR2 rates and HCT frequency will be the challenge for the next years. Relapse of the disease remains the major problem.

An ultrafast and flexible liquid chromatography/tandem mass spectrometry system paves the way for machine learning driven in vivo sample processing in early drug discovery.

RATIONALE: The low speed and low flexibility of most liquid chromatography/tandem mass spectrometry (LC/MS/MS) approaches in early drug discovery delay sample analysis from routine in vivo studies within the same day. A high-throughput platform for the rapid quantification of drug compounds in various in vivo assays was developed and established in routine bioanalysis. METHODS: Automated selection of an efficient and adequate LC method was realized by autonomous sample qualification for ultrafast batch gradients (9 s/sample) or for fast linear gradients (45 s/sample) if samples required chromatography. The hardware and software components of our Rapid and Integrated Analysis System (RIAS) were streamlined for increased analytical throughput via state-of-the-art automation while maintaining high analytical quality. RESULTS: Online decision-making was based on a quick assay suitability test (AST), based on a small and dedicated sample set evaluated by two different strategies. 84% of the acquired data points were within ±30% accuracy and 93% of the deviations between the lower limit of quantitation (LLOQ) values were ≤2-fold compared with standard LC/MS/MS systems. Speed, flexibility and overall automation significantly improved. CONCLUSIONS: The developed platform provided an analysis time of only 10 min (batch-mode) and 47 min (gradient-mode) per standard pharmacokinetic (PK) study (62 injections). Automation, data evaluation and results handling were optimized to pave the way for machine learning based on decision-making regarding the evaluation strategy of the AST.

Low chromatic Fresnel lens for broadband attosecond XUV pulse applications.

Fresnel zone plates show a great potential in achieving high spatial resolution imaging or focusing for XUV and soft/hard X-ray radiation, however they are usually strictly monochromatic due to strong chromatic dispersion and thus do not support broad radiation spectra, preventing their application to attosecond XUV pulses. Here we report on the design and theoretical simulations based on the design of an achromatic hybrid optics combining both, a refractive and diffractive lens in one optical element. We are able to show by calculation that the chromatic dispersion along the optical axis can be greatly reduced compared to a standard Fresnel zone plate while preserving the temporal structure of the attosecond XUV pulses at focus.

Patients receiving allogeneic haematopoietic stem-cell transplantation and clinical outcomes after early access to palliative care.

Allogeneic haematopoietic stem-cell transplantation is a potential curative therapy for otherwise fatal haematological diseases. This treatment modality is complex, burdensome, and can involve considerable or life-threatening adverse events requiring high-quality symptom control. In contrast to patients with solid tumours, the transition to end-of-life care can be abrupt if the underlying disease relapses or other severe transplantation-related complications occur. This Viewpoint elucidates the relationships between transplantation and palliative care teams and discusses why patients who have undergone transplantation might benefit considerably from early admittance to palliative care, even when the treatment goal is clearly curative. Close and early collaboration between transplantation teams and palliative care teams is clearly endorsed.

Monitoring the surface quality of silver plasmon waveguides with nonlinear photoemission electron microscopy and in-situ ion sputtering.

We use photoemission electron microscopy (PEEM) with single- and two-photon excitation to study the properties of surface plasmon polaritons (SPPs) in tapered silver stripe waveguides. Arrays of waveguides with different widths, grating coupler geometries, and taper angles are fabricated using electron beam lithography (EBL) on Si and indium-tin-oxide (ITO)-covered glass substrates. The presence of propagating SPP modes is indicated by modulations of the non-linear photoemission intensity which run along the length of the waveguide - the result of interfering SPPs reflected from the edges. Surface roughness also results in the presence of random emission hot spots and strong edge diffraction, which hinders an analysis of the effect of waveguide geometry on SPP propagation length and nanofocusing. Accordingly, we develop a relatively simple, in-situ method of reducing the surface roughness by argon ion sputtering using low-energy (∼ 300eV) ions. Surface roughness is qualitatively assessed by the ratio of the photoemission from the central interference fringes to that from the edges, and from the hot spot intensity. The improvement of the surface quality is a critical step for reducing radiative losses and therefore increasing the propagation length of plasmonic waveguides.

Allogeneic stem cell transplantation in patients above 55: suggestion for a further stratification of the HCT-CI.

INTRODUCTION: Allogeneic stem cell transplantation (alloSCT) has become available for elderly patients or for patients with comorbidities by introduction of reduced-intense conditioning. Comorbidity-related prognosis after alloSCT can be estimated by the hematopoietic cell transplantation comorbidity index (HCT-CI). MATERIAL AND METHODS: The charts from 85 patients who have undergone 90 alloSCTs between 1999 and 2011 were analysed. Most patients received a dose-reduced conditioning and a graft from an unrelated donor. Patients were stratified for age, HCT-CI, cGvHD versus no cGvHD, and a modified HCT-CI with a further split high-risk score. RESULTS: Age over 60 years did not affect the outcome. Manifestation of cGvHD improved the prognosis significantly. An additional stratification of the high-risk group of the HCT-CI revealed that even a fraction of these patients can have considerable benefit from an alloSCT. Furthermore, this high-risk collective could be clearly discriminated into two groups with different outcomes. CONCLUSIONS: The investigation confirms that age is no absolute risk factor for alloSCT and demonstrates the heterogeneity of the high-risk group of the HCT-CI. A comprehensive investigation of an additional stratification is suggested. Furthermore, the authors encourage early withdrawal of immunosuppression, even in elderly patients and patients with comorbidities to permit graft-versus-leukaemia/lymphoma, since cGvHD is associated with a significantly better prognosis.