The identification of materials suitable for non-volatile phase-change memory applications is driven by the need to find materials with tailored properties for different technological applications and the desire to understand the scientific basis for their unique properties. Here, we report the observation of a distinctive and characteristic feature of phase-change materials. Measurements of the dielectric function in the energy range from 0.025 to 3 eV reveal that the optical dielectric constant is 70-200% larger for the crystalline than the amorphous phases. This difference is attributed to a significant change in bonding between the two phases. The optical dielectric constant of the amorphous phases is that expected of a covalent semiconductor, whereas that of the crystalline phases is strongly enhanced by resonant bonding effects. The quantification of these is enabled by measurements of the electronic polarizability. As this bonding in the crystalline state is a unique fingerprint for phase-change materials, a simple scheme to identify and characterize potential phase-change materials emerges.

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Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients’ and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.

Allogeneic HSCT in younger adults with high-risk AML has a significant beneficial impact on outcome, and allogeneic HSCT from MRD and MUD yields similar results.

Key Points• DNMT3A mutations are frequent in younger adults with AML and have no significant impact on survival end points.• Only moderate effects on outcome, depending on molecular subgroup and DNMT3A mutation type, could be observed.In this study, we evaluated the frequency and prognostic impact of DNMT3A mutations (DNMT3A mut ) in 1770 younger adult patients with acute myeloid leukemia (AML) in the context of other genetic alterations and the European LeukemiaNet (ELN) classification. DNMT3A mut were found in 20.9% of AMLs and were associated with older age (P < .0001), higher white blood cell counts (P < .0001), cytogenetically normal AML (CN-AML; P < .0001), NPM1 mutations (P < .0001), FLT3 internal tandem duplications (P < .0001), and IDH1/2 mutations (P < .0001). In univariable and multivariable analyses, DNMT3A mut did not impact event-free, relapse-free (RFS), or overall survival (OS) in either the entire cohort or in CN-AML; a negative prognostic effect was found only in the ELN unfavorable CN-AML subset (OS, P 5 .011).

The purpose of our study was (i) to evaluate the impact of alltrans retinoic acid (ATRA) given as adjunct to chemotherapy and (ii) to compare second consolidation vs maintenance therapy in elderly patients with acute myeloid leukemia (AML). A total of 242 patients aged X61 years (median, 66.6 years) with AML were randomly assigned to ATRA beginning on day þ 3 after the initiation of chemotherapy (ATRA-arm, n ¼ 122) or no ATRA (standard-arm, n ¼ 120) in combination with induction and first consolidation therapy. A total of 61 patients in complete remission (CR) were randomly assigned to second intense consolidation (n ¼ 31) or 1-year oral maintenance therapy (n ¼ 30). After induction therapy the intention-to-treat analysis revealed a significant difference in CR rates between the ATRA-and the standard-arm (52 vs 39%; P ¼ 0.05). Eventfree (EFS) and overall survival (OS) were significantly better in the ATRA-compared to the standard-arm (P ¼ 0.03 and 0.01, respectively). OS after second randomization was significantly better for patients assigned to intensive consolidation therapy (Po0.001). The multivariate model for survival revealed lactate dehydrogenase, cytogenetic risk group, age, and first and second randomization as prognostic variables. In conclusion, the addition of ATRA to induction and consolidation therapy may improve CR rate, EFS and OS in elderly patients with AML.

Early allogeneic hematopoietic stem cell transplantation (HSCT) has been proposed as primary treatment modality for patients with chronic myeloid leukemia (CML). This concept has been challenged by transplantation mortality and improved drug therapy. In a randomized study, primary HSCT and best available drug treatment (IFN based) were compared in newly diagnosed chronic phase CML patients. Assignment to treatment strategy was by genetic randomization according to availability of a matched related donor. Evaluation followed the intention-to-treat principle. Six hundred and twenty one patients with chronic phase CML were stratified for eligibility for HSCT. Three hundred and fifty four patients (62% male; median age, 40 years; range, 11-59 years) were eligible and randomized. One hundred and thirty five patients (38%) had a matched related donor, of whom 123 (91%) received a transplant within a median of 10 months (range, 2-106 months) from diagnosis. Two hundred and nineteen patients (62%) had no related donor and received best available drug treatment.