Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor.     

DESIGN OF EXPERIMENTS TO INVESTIGATE RESIDUAL STRESSES AND FATIGUE LIFE IMPROVEMENT BY A SURFACE TREATMENT

Abstract— The careful design of experiment (DOE) technique has been utilized to analyze the residual stress state and to investigate the fatigue life improvement of a material (nitriding steel) subjected to thermal and mechanical treatment.
Nitriding treatments have been performed on several specimens which have been subsequently shot- peened, varying the main parameters controlling the process. The design of experiment method has been accomplished in order to evaluate the influence of the main shot-peening parameters on the distribution and values of the residual stresses close to the surface, and also in order to estimate the influence of these parameters on fatigue resistance.     

Solid Acid‐Catalysed Michael‐Type Conjugate Addition of Indoles to Electron‐Poor CC Bonds: Towards High Atom Economical Semicontinuous Processes

In this paper a novel application of solid acid catalysts in the chemoselective Friedel–Crafts (FC) alkylation of indoles is reported. The optimal protocol allows highly functionalised indolyl compounds to be synthesised in excellent yields through conjugate addition of indoles with α,β‐unsaturated ketones and nitro compounds. Finally, the use of commercial Amberlyst‐15 as the heterogeneous catalyst for highly atom efficient continuous and semicontinuous Friedel–Crafts processes is described.     

MicroRNA-16 Restores Sensitivity to Tyrosine Kinase Inhibitors and Outperforms MEK Inhibitors in KRAS-Mutated Non-Small Cell Lung Cancer

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Chemotherapy, the treatment of choice in non-operable cases, achieves a dismal success rate, raising the need for new therapeutic options. In about 25% of NSCLC, the activating mutations of the KRAS oncogene define a subclass that cannot benefit from tyrosine kinase inhibitors (TKIs). The tumor suppressor miR-16 is downregulated in many human cancers, including NSCLC. The main objectives of this study were to evaluate miR-16 treatment to restore the TKI sensitivity and compare its efficacy to MEK inhibitors in KRAS-mutated NSCLC. Methods: We performed in vitro and in vivo studies to investigate whether miR-16 could be exploited to overcome TKI resistance in KRAS-mutated NSCLC. We had three goals: first, to identify the KRAS downstream effectors targeted by mir-16, second, to study the effects of miR-16 restoration on TKI resistance in KRAS-mutated NSCLC both in vitro and in vivo, and finally, to compare miR-16 and the MEK inhibitor selumetinib in reducing KRAS-mutated NSCLC growth in vitro and in vivo. Results: We demonstrated that miR-16 directly targets the three KRAS downstream effectors MAPK3, MAP2K1, and CRAF in NSCLC, restoring the sensitivity to erlotinib in KRAS-mutated NSCLC both in vitro and in vivo. We also provided evidence that the miR-16–erlotinib regimen is more effective than the selumetinib–erlotinib combination in KRAS-mutated NSCLC. Conclusions: Our findings support the biological preclinical rationale for using miR-16 in combination with erlotinib in the treatment of NSCLC with KRAS-activating mutations.     

Thermal-hydraulics analyses of ELSY lead fast reactor with open square core option

Among the next generation of nuclear reactors, well-known as Gen-IV, the LFR (Lead Fast Reactor) is one of the most promising advanced reactor able to comply the principles of sustainability, economics, safety and proliferation resistance. The ELSY project (European Lead-cooled SYstem), funded by the 6th European Framework Programme, aims at investigating the technical/economical feasibility of a high power lead fast reactor with waste transmutation capability.Several innovative design solutions have been proposed at system level and some of them regard the core region with open-assemblies that represents the reference option. To support the design phase and the safety assessment of ELSY, the thermal-hydraulic code RELAP5, modified to treat heavy liquid metals, has been taken into account.The paper deals with the development of the ELSY thermal-hydraulic and point kinetic model for RELAP5 focusing the attention at core assembly level to verify that the temperatures at nominal power conditions stay within the safety limits both in Beginning-of-Cycle (BOC) and in End-of-Cycle (EOC) conditions. Moreover, in order to have a first evaluation of the system behavior in accidental conditions, an Unprotected Loss-of-Flow Accident (ULOF) simulation at BOC has been analysed and discussed.

List of acronyms

ADS

Accelerator Driven System

BOC

Beginning-of-Cycle

DEC

Design Extension Condition

EFIT

European Facility for Industrial Transmutation

ELSY

European Lead-cooled SYstem

EOC

End-of-Cycle

FA

Fuel Assembly

FP6

6th Framework Programme

Gen-IV

Generation IV (four)

GESA

Gepulste ElektronenStrahlanlage (Pulsed Electron Beam Facility)

HX

Heat eXchanger

IC

Isolation Condenser

LFR

Lead Fast Reactor

LMFR

Liquid Metal Fast Reactor

PDS-XADS

Preliminary Design Studies on eXperimental ADS

RVACS

Reactor Vessel Air Cooling System

ULOF

Unprotected Loss-of-Flow

W-DHR

Water Decay Heat Removal