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Trimetazidine has been shown to prevent the risk of contrast-induced nephropathy (CIN) in patients with renal dysfunction undergoing percutaneous coronary intervention (PCI). However, the effect of trimetazidine on CIN in unselected patients is unknown. We aimed to evaluate the effect of trimetazidine on preventing CIN in unselected patients treated with PCI. 2154 consecutive patients were enrolled and divided into the trimetazidine (n = 529) and non-trimetazidine group (n = 1625). Patients in the trimetazidine group received trimetazidine 20 mg thrice daily starting at least 24 h before the procedure and continuing until discharge. The primary outcome was CIN. CIN was observed in 197 (9.2%) patients. The incidence of CIN was similar between two groups (9.1% vs. 9.2%, P = 0.947). After adjusting for other potential risk factors, trimetazidine did not significantly reduce the risk of CIN (OR = 0.70, 95% CI 0.46–1.08, P = 0.104). The results remained similar when using the alternate definitions of CIN and different subgroup analysis based on diabetes or chronic kidney disease. In additional, no significant difference between two groups was found with respect to in-hospital major adverse clinical events (1.89% vs. 1.66%, P > 0.05). Trimetazidine did not exert significant renal protective effect on preventing CIN and in hosptial major adverse clinical events in unselected patients undergoing PCI.

We report results of our prospective pilot trial evaluating safety/feasibility of peritransplantation ruxolitinib for myelofibrosis treatment. Primary objectives were to determine safety and maximum tolerated dose (MTD) of ruxolitinib. Ruxolitinib was administered at 2 dose levels (DLs) of 5 and 10 mg twice daily, with fludarabine/melphalan conditioning regimen and tacrolimus/sirolimus graft-versus-host disease (GVHD) prophylaxis. We enrolled 6 and 12 patients at DL1 and DL2, respectively. Median age at transplantation was 65 years (range, 25-73). Per Dynamic International Prognostic Scoring System, 4 patients were high and 14 intermediate risk. Peripheral blood stem cells were graft source from matched sibling (n = 5) or unrelated (n = 13) donor. At each DL, 1 patient developed dose-limiting toxicities (DLTs): grade 3 cardiac and gastrointestinal with grade 4 pulmonary DLTs in DL1, and grade 3 kidney injury in DL2. All patients achieved engraftment. Grade 2 to 4 and 3 to 4 acute GVHD cumulative incidence was 17% (95% confidence interval [CI], 6-47) and 11% (95% CI, 3-41), respectively. Cumulative incidence of 1-year chronic GVHD was 42% (95% CI, 24-74). With 22.6-month (range, 6.2-25.8) median follow-up in surviving patients, 1-year overall and progression-free survival were 77% (95% CI, 50-91) and 71% (95% CI, 44-87), respectively. Causes of death (n = 4) were cardiac arrest, GVHD, respiratory failure, and refractory GVHD of liver. Our results show peritransplantation ruxolitinib is safe and well tolerated at MTD of 10 mg twice daily and associated with dose-dependent pharmacokinetic and cytokine profile. Early efficacy data are highly promising in high-risk older patients with myelofibrosis. This trial was registered at www.clinicaltrials.gov as #NCT02917096.

INTRODUCTION: Despite advances in therapy for multiple myeloma, patients have continued to experience relapse. We sought to better understand this. OBJECTIVE: To identify factors that predict early relapse in patients with multiple myeloma who receive autologous hematopoietic peripheral stem cell transplant (HSCT). METHODS: Retrospective analysis of Kaiser Permanente Southern California patients who received HSCTs between 2008 and 2012. RESULTS: A total of 141 patients were included. Factors found to be associated with inferior progression-free survival were disease status less than complete response at the time of HSCT, no use of maintenance therapy after HSCT, International Staging System stage III, and high Freiburg Comorbidity Index. Disease status less than complete response, stage III, higher Freiburg Comorbidity Index, no use of maintenance therapy, and male sex were the most predictive factors for early relapse (< 18 months). DISCUSSION: Our results identified a subgroup of high-risk individuals with multiple myeloma who will continue to do poorly after HSCT with the best available treatment using a combination of proteasome inhibitors and immunomodulatory drugs. These results highlight the need for consideration of alternative therapy in such instances.

Background: Blinatumomab, a bispecific anti-CD19/CD3 antibody, demonstrated single-agent efficacy with 42% CR/CRh in R/R B-ALL. Upregulation of immune inhibitory molecules has been shown to confer resistance to blinatumomab. Here, we set out to test the combination of pembrolizumab and blinatumomab in a phase 1/2 trial (NCT03512405). Methods: Pts [≥18 years old (yo); ECOG Results: As of February 1, 2021, 7 pts were enrolled to phase 1, with one unevaluable. Six treated and evaluable pts received a median of 2 (1–5) cycles of treatment. At baseline, the median age was 51 yo (29–74) with median 2 (2–4) prior lines of regimens and median 29% (0–83) BM blasts. Two pts had extramedullary disease. In cycle 1, all 6 pts experienced grade (gr) 1–2 cytokine release syndrome. Neurologic toxicities were all reversible with only 1 ≥ gr3 AE. All-non-hematologic gr3 toxicities, were reversible. No dose-limiting toxicity, ≥ gr4 non-hematologic toxicity, or treatment-related deaths were seen. Five of 6 evaluable pts (83%) achieved MRD-negative CR after a median of 1 (1–2) cycle. Three pts in CR received alloHCT, all engrafted. With a median follow-up of 2.8 (1.1–9.6) months, 4 CRs are ongoing (1 post-transplant), and 5 of 6 pts are still alive at the data cut-off. Conclusions: The combination of pembrolizumab and blinatumomab in phase 1 of this study in pts with B-ALL was deemed safe with a manageable side effect profile and encouraging anti-leukemic activity. The study is now open for phase 2 with the primary objective of overall response rate.

Aim: To investigate the relationship between urinary pH (UpH) and clinical outcome in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention. Methods: Data of 2081 patients with ST-segment elevation myocardial infarction were analyzed, including UpH. Patients were divided into UpH

Background: Population-based cancer registry collects the data on cancer incidence and mortality deaths from covered population to describe and survey the epidemics in certain areas. The aim of this study was to estimate the cancer incidence and mortality in Wuwei, Gansu province, Northwestern China from 2003 to 2012. The goal is to better understand cancer distribution and long-term development of cancer prevention and treatment in Wuwei. Methods: Data were collected from the Wuwei Cancer Registry between 2003 and 2012. In this registry, data from 46 cancer report centers were included in this analysis. Incidence/mortality rates, age-specific incidence/mortality rates, age-standardized incidence/mortality rates, and cumulative incidence/mortality rates were calculated. Totally, 9,836,740 person-years (5,110,342 for males and 4,726,398 for females) had been monitored over this time period. The gender ratio of male/female was 1.08:1. The number of new cancer cases and related deaths was 24,705 and 17,287 from 2003 to 2012, respectively. Results: The proportion of morphological verification was 74.43%. The incidence of cases identified through death certification only was 1.21%, and the mortality to incidence ratio was 0.70. The average crude incidence was 251.15/100,000 persons (310.61 and 186.87 for males and females per 100,000 persons, respectively). The age-standardized rates by Chinese standard population (ASR-China) and by world standard population (ASR-world) were 207.76 and 245.42 per 100,000 persons, respectively. The crude cancer mortality was 175.74/100,000 persons (228.34 and 118.86 for males and females per 100,000 persons). ASR for China and the world was 149.57 and 175.13/100,000 persons, respectively. The most common cancers and leading causes of cancer-related deaths in Wuwei were as follows: cancers of stomach, esophagus, liver, lung, colorectum, breast, cervix, lymphoma, blood (leukemia), brain, and central nervous system. In Wuwei, during 2003 and 2012, cancer incidence and mortality rates increased by 1.32% and 1.31%/year, respectively. During this time, colorectum cancer incidence and mortality rates increased by 2.69% and 7.54%/year, respectively, in Wuwei. The incidence and mortality of other gastric, esophageal, liver, and lung cancers also all increased. Conclusions: The results of this study report a more accurate cancer burden among the population of Wuwei, China. Active research of cancers etiology and effective prevention should be established to reduce the incidence and mortality associated with cancers.

Summary Background Patients seropositive for cytomegalovirus (CMV) and undergoing allogeneic haemopoietic stem-cell transplantation (HCT) are at risk for CMV reactivation. Stimulating viral immunity by vaccination might achieve CMV viraemia control without the need for antiviral agents. CMVPepVax is a chimeric peptide composed of a cytotoxic CD8 T-cell epitope from CMV pp65 and a tetanus T-helper epitope. It is formulated with the adjuvant PF03512676, a Toll-like receptor 9 agonist, which augments cellular immunity. We aimed to assess safety, immunogenicity, and possible clinical benefit of the CMVPepVax vaccine in patients undergoing HCT. Methods We did a randomised, open-label, phase 1b trial at one transplant centre in the USA. Eligible patients were CMV-seropositive, positive for HLA-A*0201 , aged 18–75 years, and undergoing HCT from a matched-related or matched-unrelated donor. Patients were reassessed for eligibility on day 28 after HCT. We randomly allocated patients to either the CMVPepVax vaccine or observation, in blocks stratified by CMV donor serostatus. CMVPepVax was administered subcutaneously on days 28 and 56. The primary outcome was safety, which consisted of secondary graft failure, grade III–IV acute GVHD, non-relapse mortality by day 100, serious adverse events related to the vaccine (judged by the data and safety monitoring committee [DSMC]) grade 3–4 adverse events related to the vaccine (judged by the DSMC) within 2 weeks of vaccination, and development of double-strand (ds) DNA autoantibodies. Statistical analyses included all randomised patients and were done per-protocol. This study is registered with ClinicalTrials.gov, number NCT01588015. This trial is closed to accrual and the final analysis is presented in this report. Findings Between Oct 31, 2012, and Nov 5, 2014, 36 eligible patients were allocated to either CMVPepVax (n=18) or observation (n=18), with no adverse effect on HCT (no secondary graft failures in either group) or cases of acute GVHD (seven patients assigned vaccine and six under observation had acute GVHD of grade 2 or less), and no unexpected adverse events. Compared with observation, better relapse-free survival was recorded in patients allocated the vaccine (seven vs one; hazard ratio [HR] 0·12, 95% CI 0·01–0·94; p=0·015). No patients had non-relapse mortality by day 100. One serious adverse event (grade 1 fever) was attributed to CMVPepVax but resolved within 48 h. Four patients assigned the vaccine had a serious adverse event, which was unrelated to the vaccine (grade 3 thrombocytopenia, grade 3 device-related infection, grade 2 nausea, and grade 1 fever), compared with nine patients under observation (grade 4 maculopapular rash, grade 3 nausea, grade 3 infection, grade 3 thrombotic thrombocytopenic purpurea, grade 2 nausea, grade 2 generalised muscle weakness, grade 2 infection, grade 1 fever, and grade 1 fatigue; p=0·16). 54 grade 3–4 adverse events were reported in patients assigned the vaccine compared with 91 in patients who were under observation (p=0·2). No patients had grade III–IV acute GVHD or developed dsDNA autoantibodies. Interpretation The results show safety and immunogenicity of the CMVPepVax vaccine. The prospect of substantial clinical benefits warrant testing in a phase 2 trial. Funding National Cancer Institute.

Ruxolitinib (Rux), a potent JAK1/2 inhibitor, is the only FDA-approved drug for treatment of primary and secondary myelofibrosis (MF). Rux has been recently approved for treatment of steroid refractory acute graft-versus-host disease (GVHD), a major cause of non-relapse mortality (NRM) after allogeneic hematopoietic cell transplant (HCT). In MF patients proceeding with transplant, Rux is typically discontinued pre-HCT. Given the therapeutic, immunologic, and anti-inflammatory properties of Rux, we hypothesized that continuous peri-HCT administration of the drug is safe and can result in better transplant outcomes in MF patients. Here, we are reporting outcomes of our single arm, single center pilot study (NCT02917096) investigating the safety and efficacy of Rux administration in patients with primary or secondary MF undergoing HCT with fludarabine (125 mg/m2) and melphalan (140 mg/m2) as reduced intensity conditioning and sirolimus/tacrolimus (target levels: 5-10ng/ml for both) as GVHD prophylaxis. This pilot study is being conducted in MF patients with the goal of extending the therapy to other hematologic malignancies. The primary objective was to identify the maximum tolerated dose and recommended phase II dose. Rux was given at 2 dose levels (DL) of 5 and 10 mg BID, starting from day -3 pre-HCT until day +30 post-HCT, then tapered off by day +33. DLs were chosen based on previous retrospective studies identifying the drug dose for treatment of GVHD. Primary endpoint was safety. Dose limiting toxicity (DLT) was defined as grade 4 neutropenia associated with fever, infection, or engraftment failure or any grade ≥3 non-hematologic toxicities over 45 days. Key secondary endpoints were grade 2-4 acute GVHD, engraftment, infection, overall survival (OS), progression-free survival (PFS), NRM, relapse and chronic GVHD. So far, we have enrolled 12 patients: 6 for DL1 arm and 6 for DL2. Median age at the time of HCT was 53 years (range: 25-66) for DL1 and 68 years (range: 56-72) for the DL2 arm. Detailed patient/transplant characteristics are listed in table 1. One-year OS, PFS and NRM for all patients were 80% (95%CI: 39-95), 68% (95%CI: 30-89) and 21% (95%CI: 3-50), respectively. All patients engrafted (n=12), with the median time to neutrophils engraftment of 19 days (range: 13-23) for DL1 and 16 days (range: 12-22) for the DL2 arm. Hematologic DLTs were not observed in patients at either dose level. At DL1, by day +60, grade ≥3 toxicities were cardiac (n=1), pulmonary (n=1) and gastrointestinal (n=1). Only one case of grade ≥3 pulmonary toxicity was observed in patients at DL2. After median follow-up time of 373 days (range: 365-744) in DL1 and 98 days (range: 30-379) for DL2, there were two deaths; one due to respiratory failure in DL1, and another due to acute GVHD at DL2. Median time of acute GVHD onset was 20 days (range: 19-35) in DL1 and 51 days (range: 26-76) in DL2. Grade III-IV acute GVHD was seen in only 1 out of 12 patients and grade 1 acute GVHD was seen in 4 patients. One patient in DL1 relapsed at 9 months and re-entered remission with post-HCT treatment. CMV infection was seen in only 1 patient at DL2. Pharmacokinetics (PK) studies were done for five patients at DL1 and all patients at DL2. PK was dose-proportional, in which doubling of the dose corresponded to the twice greater Cmax and AUC. The half-lives and oral clearances were not different between the two DLs. The Cmax and AUC were lower in our patients compared to a previously published report in healthy volunteers. Furthermore, the elimination half-life was similar to the published data, indicating that the lower drug exposures measured on the current trial is most likely due to decreased oral absorption. Lastly, GVHD biomarkers and inflammatory cytokines levels were not different between patients receiving Rux at DL1 and DL2. In conclusion, early results of this pilot study indicate that Rux administration at 10 mg BID in MF patients undergoing HCT is safe and feasible, with 100% engraftment and low rate of acute GVHD. We are currently accruing an expansion cohort of 6 patients at DL2. Results of our PK studies indicated a direct correlation between Cmax and AUC and that higher oral clearance compared to previous study is most likely due to poor GI absorption of the drug in HCT patients. More follow up is needed to see the impact of this combination on incidence of chronic GVHD. This regimen may also be useful for patients undergoing HCT for other hematologic malignancies. Disclosures Palmer: Gilead Sciences: Consultancy. Salhotra:Celgene: Other: Research Support; Kadmon Corporation: Other: Non paid consultant. Mei:Seattle Genetics, Inc.: Research Funding. Nakamura:Celgene: Other: support for an academic seminar in a university in Japan; Alexion: Other: support to a lecture at a Japan Society of Transfusion/Cellular Therapy meeting ; Merck: Membership on an entity's Board of Directors or advisory committees; Kirin Kyowa: Other: support for an academic seminar in a university in Japan.

Mantle cell lymphoma (MCL) is an aggressive and incurable lymphoma. Standard of care for younger patients with MCL is induction chemotherapy followed by autologous stem cell transplantation (auto-HCT). Rituximab maintenance after auto-HCT has been shown to improve progression-free survival (PFS) and overall survival (OS) in MCL. Bortezomib maintenance therapy has also been shown to be tolerable and feasible in this setting. However, the combination of bortezomib and rituximab as maintenance therapy post-auto-HCT has not been studied. We conducted a multicenter, phase II trial of bortezomib given in combination with rituximab as maintenance in MCL patients after consolidative auto-HCT. Enrolled patients (n = 23) received bortezomib 1.3 mg/m2 subcutaneously weekly for 4 weeks every 3 months (up to 24 months) and rituximab 375 mg/m2 intravenously weekly for 4 weeks every 6 months (up to 24 months) for a total duration of 2 years. The primary study endpoint was disease-free survival (DFS). With a median follow-up of 35.9 months, the 2-year DFS probability was 90.2% (95% CI 66–97), and 2-year OS was 94.7% (95% CI 68–99). The most frequent grade 3/4 toxic events were neutropenia (in 74% of patients) and lymphopenia (in 35%). The incidence of peripheral neuropathy was 48% for grade 1, 9% for grade 2, and 0% for grade 3/4. We also examined the role of quantitative cyclin D1 (CCND1) mRNA in monitoring minimal residual disease. Combined bortezomib and rituximab as maintenance therapy in MCL patients following auto-HCT is an active and well-tolerated regimen. ClinicalTrials.gov NCT01267812 , registered Dec 29, 2010.

We report the findings of three randomized, double-blind, placebo-controlled Phase I studies undertaken to support licensure of the liquid formulation of the human G1P[8] rotavirus (RV) vaccine (RIX4414; GlaxoSmithKline Biologicals SA) in China. Healthy adults aged 18-45 y (n=48) and children aged 2-6 y (n=50) received a single dose of the human RV vaccine or placebo. Healthy infants (n=50) aged 6-16 weeks at the time of first vaccination received two oral doses of the human RV vaccine or placebo according to a 0, 1 mo schedule. In infants, blood samples were collected prior to vaccination and one month post-dose 2 to assess anti-RV IgA antibody concentrations using ELISA. Stool samples were collected from all infants on the day of each vaccination, at 7 and 15 d after each vaccination and one month post-dose 2. Stool samples were analyzed by ELISA for detection of RV antigen to assess RV antigen excretion. The reactogenicity profile of the human RV vaccine was found to be comparable to that of placebo in all age groups studied. The anti-RV IgA antibody seroconversion rate in infants after two vaccine doses was 86.7% (95% CI: 59.5-98.3). Vaccine take in infants who received the liquid human RV vaccine was 86.7% (95% CI: 59.5-98.3). A Phase III efficacy study of the human RV vaccine in the infant population in China has now been completed (ROTA-075/NCT01171963).

We report a consecutive series of 59 patients with MDS who underwent reduced-intensity hematopoietic stem cell transplantation (RI-HSCT) with fludarabine/melphalan conditioning and tacrolimus/sirolimus-based GVHD prophylaxis. Two-year OS, EFS, and relapse incidences were 75.1%, 65.2%, and 20.9%, respectively. The cumulative incidence of non-relapse mortality at 100 days, 1 year, and 2 years was 3.4%, 8.5%, and 10.5%, respectively. The incidence of grade II-IV acute GVHD was 35.4%; grade III-IV was 18.6%. Forty of 55 evaluable patients developed chronic GVHD; of these 35 were extensive grade. This RI-HSCT protocol produces encouraging outcomes in MDS patients, and tacrolimus/sirolimus-based GVHD prophylaxis may contribute to that promising result.

InGaAs cells have the advantages of low absorption bandgap, high efficiency and great stability, which are widely used in thermophotovoltaic(TPV) devices. In this paper, the material growth, device fabrication and system integration of 0.73 eV In0.53Ga0.47As (lattice matched to InP substrate) and 0.6 eV In0.68Ga0.32As (lattice mismatched to InP substrate) thermophotovoltaic cells are studied, respectively. Based on the calculation of buffer layer thickness, the strain relaxation mechanism of the compositionally undulating step-graded InAsP buffer is analyzed. The buffer layer can release 84% of the mismatch strain at a single-layer thickness of 150 nm. The room temperature photoluminescence wavelengths of In0.53Ga0.47As and In0.68Ga0.32As are 1.69 μm and 2.05 μm, respectively. The conversion efficiencies of the 0.73 eV and 0.6 eV InGaAs TPV cells are 12.38% and 8.41%, respectively, at the AM1.5G standard spectrum. However, at 1323 K radiation temperature, the conversion efficiencies of the 0.6 eV InGaAs TPV cells outperform that of the 0.73 eV InGaAs TPV cells, which are 26.9% and 25.4% respectively after being calibrated with the blackbody radiation formula. A prototype system of thermophotovoltaic is set up by series-parallel connection of InGaAs TPV cells. It achieves output power about 5 W at a radiation temperature of 1470 K and completes a stable conversion of thermal radiation energy to electrical energy.

In this study, the authors employ a multi-point die-support structure to hold the punch plate of a stamping die in order to intercept useless force from the slide of a press machine. The developed multi-point support structure has 12 support cells (support units) between the punch plate and the slide of the press machine; the cells are metal cylinders working as springs. The support unit has a ball contact at the interface of the punch plate, and the interface freely for rotates and slides horizontally. The support unit has strain gauges on the side surface, and we can determine the bearing load at each unit, as well as elastic deformation. We can observe the bearing load distribution and then relocate the support units to better distribute the supporting points. The authors discuss the relocation of support units and demonstrate the efficiency of the proposed structure for reducing the jolt of a stamping die set. The range of jolt between the punch plate and the die plate of the experimental die is 0.711mm with normal support for piercing a 30mm-diameter hole on a 1.2mm-thick JSC980Y sheet. However, it is 0.355mm with the proposed die-support structure after several relocations of the support units.

The law relating to the registration and priorities of charges has generated much confusion over the years. One of the purported objectives of a registration system is to provide certainty to lenders, yet it is by no means clear that this objective is entirely satisfied at present. While this article considers the law in relation to the registration and priorities of charges in Hong Kong, the discussion may be of interest to those examining the English rules in the area, as the two regimes are similar to a large extent. This article will consider some problematic areas that have arisen in relation to constructive notice of the contents of company charges and then argue that the recent law reform proposals in Hong Kong may not go far enough to address these problems. Finally, suggestions will be made on how the system for the registration of company charges may be reformed to adequately address these problems.

This paper seeks to provide a critical analysis of the regulation of data protection in Hong Kong, and then to suggest several recommendations in that regard. In particular, three aspects of regulation will be considered, namely, enforced compliance, public consultation and public education. The article concludes that while there have been commendable efforts in the area of public consultation and education, the time has come for a greater degree of regulatory compulsion in the form of various suggested reforms, in order for Hong Kong to develop a robust data protection regime. This is particularly important in our digital age, where data protection is crucial for the maintenance of trust in e-commerce and online transactions.

A robotic system for complete denture manufacturing, which can realize automatic implanting of artificial teeth, is described. The tooth arrangement algorithm is presented, including the equations of jaw-arch curve and teeth-arch curve, setup of a single tooth coordinate system and calculation of tooth position in teeth-arch curve. An expert system software is developed that integrates high-level dentist experiences and dexterous technician skills. Three-dimensional (3-D) display of tooth arrangement, human-computer interactive adjustment of tooth position and orientation in teeth-arch curve are achieved. Robot path planning and control data creation are realized by this software also. Finally, an experiment of complete denture manufacturing is made for a patient, a pair of complete dentures is obtained, and the results are analyzed. This robotic system is expected to change the manner of complete denture manufacturing wholly, and significantly improve product quality and manufacturing efficiency.

The successful application of robots in surgery and other medical fields prompts us that robots can also play an important role in oral restoration. The traditional way of complete denture manufacturing is manual and only high‐level dentists and skilled technicians can do this work well. But we believe that a robot can do this work better and more easily. Artificial teeth are very complicated in shape, and not easy to be grasped and manipulated accurately by a robot gripper. Aiming at improving our previous robot manufacturing system of complete dentures, we present a new method to perform teeth implanting. We improve the previous manufacturing procedure by adding several components in the operating process. By this method, the robot gripper only needs to grasp and implant intermediate blocks, which have very simple shapes and are easy to handle precisely. The 3D human‐machine tooth arrangement software performs the calculation of intermediate blocks’ positions and orientations. We perform the experiment of tooth arrangement for a patient, and obtain a pair of ideal tooth arches. A complete denture can be manufactured according to this result.

Room-temperature operation of cw GaN based multi-quantum-well laser diodes (LDs) is demonstrated. The LD structure is grown on a sapphire (0001) substrate by metalorganic chemical vapour deposition. A 2.5 mu m x 800 mu m ridge waveguide structure is fabricated. The electrical and optical characteristics of the laser diode under direct current injection at room temperature are investigated. The threshold current and voltage of the LD under cw operation are 110mA and 10.5V, respectively. Thermal induced series resistance decrease and emission wavelength red-shift are observed as the injection current is increased. The full width at half maximum for the parallel and perpendicular far field pattern (FFP) are 12 degrees and 32 degrees, respectively.

Injections for traditional Chinese medicine have over 60 years of history of development and application. In recent years, however, their adverse reactions have been reported one after another. Consequently, studies on screening sensitinogens (sensibiligens) from injections for traditional Chinese medicine have drawn people's attention and become a tough problem all over the world. This essay analyzes the current state of studies on screening techniques of sensitinogens in injections for traditional Chinese medicine according their mechanism of immunotoxicity, and then proposes to adopt the synthetic immunoassay combining immunity bottle chip, immunity cover chip and immunity chromatographic fingerprint to screen sensitinogens from injections for traditional Chinese medicine, in order to build a safety evaluation barrier for development and clinical application of injections for traditional Chinese medicine.

We report on a prospective phase II trial of 32 patients who underwent unrelated donor hematopoietic cell transplantation, with a tacrolimus, sirolimus and rabbit anti-thymoctye globulin GVHD prophylactic regimen. The primary study endpoint was incidence of grades II-IV acute GVHD, with 80% power to detect a 30% decrease compared to institutional historical controls. Median age at transplant was 60 (19-71). Twenty-three patients (72%) received reduced-intensity conditioning, while the remainder received full-intensity regimens. Median follow up for surviving patients was 35 months (range: 21 - 49). The cumulative incidence of acute GVHD was 37.3% and the 2-year cumulative incidence of cGVHD was 63%. We observed TMA in seven patients (21.8%), one of whom also developed sinusoidal obstructive syndrome (SOS). Four patients of 32 (12.5%) failed to engraft, and three of these four died. As a result, enrollment to this trial was closed before the targeted accrual of 60 patients. Two-year overall survival was 65.5% and event-free survival was 61.3%. Two-year cumulative incidence of relapse was 12.5% and non-relapse mortality (NRM) was 15.6%. NRM and aGVHD rates were lower than historical rates; however, the unexpectedly high incidence of graft failure requires caution in the design of future studies with this regimen.

Background: Hodgkin lymphoma (HL) patients who are relapsed/refractory to induction chemotherapy are salvaged with multiagent chemotherapy such as ICE followed by autologous hematopoietic cell transplantation (AHCT). This strategy yields a 2 year EFS of ~65%. Brentuximab vedotin (BV), an antibody drug conjugate, selectively induces apoptosis of CD30+ HL. We previously reported the response rates and toxicities of a multicenter phase II trial evaluating BV as first line salvage therapy in relapsed/refractory HL prior to AHCT. We now report the transplant outcome results of BV as first line salvage therapy in relapsed/refractory HL followed by AHCT. Patients and Methods: This is a prospective, multicenter (City of Hope, Cornell Weill Medical College), phase II trial in patients with relapsed/refractory HL prior to AHCT. All patients had biopsy proven relapsed/refractory HL post induction therapy with ABVD, BEACOPP or a combination +/- consolidative XRT. Patients were treated with 1.8 mg/kg of BV intravenously every 3 weeks for a maximum of 4 cycles. Patients who do not achieve CR after BV are allowed to receive multiagent salvage chemotherapy prior to AHCT. The primary endpoint was the best response rate according to revised Cheson criteria. Secondary endpoints were toxicities, stem cell mobilizations, engraftment analysis, and 2 year PFS/OS post AHCT Results: 37 patients were accrued (Table 1). The overall best response (CR+PR) rate was 69% and CR rate was 35%. 33/37 (89%) patients successfully proceeded to AHCT (1went to alloHCT, 3 could not be salvaged). Among the 13 CR patients, all proceeded to AHCT without additional chemotherapy. Among the 12 PR patients, 4 proceeded to AHCT without additional chemotherapy while 8 received additional chemotherapy (ICE/DICE/IGEV/GND). All patients with SD/PD received additional chemotherapy with exception of 1 patient who received XRT. 24/33 patients were in CR at with 8/33 in PR and 1/33 in SD at time of AHCT. All patients were primed with cyclophosphamide/G-CSF and 9 patients received plerixafor per institutional guidelines. The median time to collect was 2 days and median cells collected was 5.9 x 10^6 CD34 cells. As AHCT conditioning regimens, 22 patients received BEAM, 9 patients received CBV, and 2 patients received BEAM plus yttrium-90 labeled anti-CD25. The median time to reach ANC engraftment was 11 days and platelet engraftment was 14 days. The response rate post AHCT was 100% in all evaluable patients. Peritransplant toxicities are not evaluated on all patients but will be updated by ASH to include all 33 patients. With a median follow up of 17.6 months, the 18 month PFS is 73%, OS is 97%, and NRM is 3%. When stratified by disease status at time of AHCT, the 18 month PFS is 78% for CR and 50% for non CR patients. The 18 month OS is 89% for CR and 88% for non CR patients. When stratified by patients who received BV only vs. BV followed by combination chemotherapy, the 18 month PFS is 80% for BV only vs. 65% for BV followed by combination chemotherapy (Fig 1). The 2 year PFS and OS will be updated by ASH presentation. Conclusion: BV as first line salvage therapy results in 89% of patient successfully going to AHCT. The overall 18 month PFS of patients who underwent AHCT is 73%, which compares favorably with historical control. Patients who received BV as the only salvage therapy prior to AHCT without combination chemotherapy had an 18 month PFS of 80%, which also compares favorably with historical control. BV prior to AHCT did not negative impact stem cell collection, engraftment, 18 month NRM, PFS or OS. Given the excellent post transplant outcome, BV as first line salvage is a viable option for relapsed/refractory HL patients undergoing AHCT. Table 1. Characteristics N (%) or Median (Range) Age 34 (11-67) Institution City of Hope Weill Cornell 31 (84%) 6 (16%) Stage at Diagnosis I-II III-IV 19 (51%) 18 (49%) B symptoms 23 (62%) Bulky Disease (> 5 cm) 32 (86%) Induction Chemotherapy ABVD ABVD/BEACOPP ABVE-PC 34 (92%) 2 (5%) 1 (3%) Prior XRT 9 (24%) Best Response to Induction Primary Refractory Relapsed (within 7 months) 24 (65%) 13 (35%) Figure 1. Figure 1. Disclosures Chen: Seattle Genetics, Inc.: Consultancy, Other: Travel expenses, Research Funding, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Millennium: Consultancy, Research Funding, Speakers Bureau. Off Label Use: 90-Y ibritumomab tiuxetan is a radiotherapeutic antibody targeting CD20. It is part of a regimen indicated for treating patients with relapsed/refractory, low-grade or follicular B cell non-Hodgkin lymphoma (NHL), or patients with previously untreated follicular NHL who achieved a complete or partial response to first-line chemotherapy. Martin:Genentech, Inc.: Consultancy, Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES, Speakers Bureau; Janssen: Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES; Celgene: Consultancy, Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES; Gilead: Consultancy. Siddiqi:Seattle Genetics: Speakers Bureau; Kite pharma: Other: attended advisory board meeting; Pharmacyclics/Jannsen: Speakers Bureau. Nademanee:Spectrum: Research Funding; Gilead: Consultancy; Celgene: Consultancy; Seattle Genetics Inc.: Research Funding. Forman:Mustang: Research Funding; Amgen: Consultancy.

With a view to improving treatment response and the quality of life of cancer patients, this study investigated the clinical efficacy of combining lentinan, a flavonoid compound with antitumor abilities, with traditional chemotherapy in individuals with esophageal carcinoma (EC), with a particular focus on its effect on immune function. A total of 50 patients undergoing treatment for EC were evenly divided into two groups: control and experimental. Patients in the control group were treated with the chemotherapeutic agent tegafur (1,000 mg/day for 5 days); patients in the experimental group were treated with the same dosage of tegafur combined with 1 mg lentinan diluted in 250 ml normal saline. Patients were monitored for their general condition, symptoms and signs, quality of life and clinical efficacy (remission vs. progression). Additionally, the effects of lentinan on immune function were assessed through analysis of serum levels of pro-inflammatory and anti-inflammatory cytokines using enzyme-linked immunosorbent assay (ELISA) prior to and following the first and second course of treatment. The results of the scores showed that the general condition (Karnofsky performance scale; KPS), the symptoms and signs (Zubrod-ECOG-WHO score; ZPS) and the quality of life (QOL scale) of the patients following the first and second course of treatment were better in both groups compared to the scores prior to treatment; however, patients in the experimental group exhibited significantly greater improvement than those in the control group (P

We report feasibility and response results of a phase II study investigating prolonged weekly bortezomib and dexamethasone followed by thalidomide and dexamethasone as maintenance therapy after single autologous stem cell transplantation (ASCT) in patients with multiple myeloma. Within 4 to 8 weeks of ASCT, patients received weekly bortezomib and dexamethasone for six cycles, followed by thalidomide and dexamethasone for six more cycles. Thalidomide alone was continued until disease progression. Forty-five patients underwent ASCT. Forty patients started maintenance therapy; of these, 36 patients received four cycles, and 32 completed six cycles of maintenance bortezomib. Of these 40 patients, nine (22%) were in complete response (CR) before ASCT, 13 (32%) achieved CR after ASCT but before bortezomib maintenance therapy, and 21 (53%) achieved CR after bortezomib maintenance therapy. Nine patients not previously in CR (33%) upgraded their response to CR with bortezomib maintenance. At 1 year post-ASCT, 20 patients achieved CR, and two achieved very good partial response. Twenty-seven patients experienced peripheral neuropathy during bortezomib therapy, all grade 1 or 2. Our findings indicate that prolonged sequential weekly bortezomib, dexamethasone, and thalidomide maintenance therapy after single ASCT is feasible and well tolerated. Bortezomib maintenance treatment upgraded post-ASCT CR responses with no severe grade 3/4 peripheral neuropathy.

Background: Cytomegalovirus (CMV) infection causes significant complications in recipients of hematopoietic cell transplant (HCT). Preemptive anti-viral therapy limits CMV viremia and disease, though its use is associated with toxicity, delayed immune reconstitution, and risk of late-onset CMV disease. We developed a novel CMV vaccine (CMVPepVax) based on the HLA-A*0201 pp65495-503 CD8+T-cell epitope (NLVPMVATV) fused with the Tetanus toxin P2 epitope (tt830-843:QYIKANSKFIGITE). The vaccine was formulated with PF03512676 (1.0 mg), a synthetic single-stranded phosphorothioate DNA containing CpG motifs provided by Pfizer Inc. In a Phase 1b healthy volunteer trial, CMVPepVax was found to be safe and immunogenic [LaRosa et al. 2012]. We report on clinical results demonstrating reliable safety, reduced CMV reactivation and chronic (c)GVHD in HCT recipients injected with CMVPepVax compared to randomized observational HCT recipients. Objectives: The primary study objective was safety, with secondary objectives including immunologic responses of HCT recipients to CMVPepVax measured by pentamer assay, prevention of CMV reactivation, and clinical outcome. Patients and methods: Eligible recipients (R+) wereCMV seropositive, HLA-A*0201, between 18-75 years (y) receiving allogeneic T-replete HCT for hematologic malignancy from matched-related (MRD) or 8/8 and 7/8 matched unrelated donors (MUD), excluding those with acute leukemia not in remission. Patients were reassessed on day (d)28 for eligibility and randomized unless they failed to engraft, experienced pre-d28 CMV reactivation or grade 3-4 acute (a)GVHD, received prednisone >1mg/kg/day within 7d of immunization, or had ongoing non-hematologic toxicity (CTCAE >=grade 3). Randomization was stratified by donor (D) CMV serostatus D- vs D+. Patients randomized to the vaccine arm (VA) received CMVPepVax on d28 and d56. Patients randomized to the observation arm (OA) were followed as per standard of care. All patients were monitored for safety/toxicity, CMV-related events, and immune recovery. Results: As of July 2014, of 36 planned patients, 30 patients were enrolled and followed for at least 100d. The median age was 50y (range: 20-76y), with balanced gender accrual. All patients received peripheral blood stem cell grafts, while hematologic diagnosis, pre-HCT conditioning regimens, and GVHD prophylaxis were similar in the VA vs OA. Vaccinations were well tolerated in all 14 patients, and no patient met the safety stopping rule per-protocol. Of three VA patients who developed serious adverse events (SAE), 2 were unrelated and only one was probable (Grade 1 fever), while 8 patients experienced SAE in the OA. The frequency and severity of unrelated AE was similar between arms across all organ systems. None of 6 monitored vaccine recipients developed anti-dsDNA antibodies. In 9 VA patients who reached d180 without reactivation, increases in CMVpp65 pentamer levels after 1st and 2ndinjections were compared to 10 OA patients, using generalized estimating equations. The model indicates an average 6.5fold positive vaccine effect (p=0.02). While this pilot trial was not powered to detect reduced CMV reactivation, we observed a ~5-fold lower rate of CMV reactivation in the VA (1/14 =7%) compared to the OA (6/16=37%, p=0.09) by d100. aGVHD occurred post-randomization in 6/16 (grade II; 5, III: 1) subjects on the OA, and in 2/14 subjects (grade II: 2) on the VA (p = 0.2). An unexpected and striking finding was differing rates of cGVHD in patients who reached d180 in the VA (1/11) vs. OA (7/12, p=0.03). Noteworthy is that the vaccine formulation is more likely to stimulate TH1 responses, yet TH2 immunity is mechanistically associated with cGVHD. An interesting, but unexplained difference in relapse was observed in the OA (3/16) vs VA (0/14) patients, though the observation period is short. Recent observations relating CMV reactivation and reduced relapse have driven strong interest in a mechanistic understanding of the phenomena observed in this trial related to CMV vaccine or the adjuvant, PF03512676. Conclusions: Trial results indicate safety of injecting CMVPepVax in HCT recipients on d28 and d56, no increase in aGVHD, and reduced CMV reactivation associated with vaccine-stimulated immunity. Compelling observations of reduced cGVHD and relapse will be further tested in a recently NIH-funded multi-institution expanded accrual phase 2 trial. Disclosures Merson: Pfizer Inc.: Employment.

It is very important to identify probability distributions fast and efficiently in data analysis. The paper analyzes data distributions automatic identification using a combined structure mode via self-organizing map and support vector machines. First, the paper sets up data distributions identification training sets, which are based on summary statistics including kurtosis, skewness, quantile and cumulative probability. Then, different data distributions are clustered using a self-organizing map. Furthermore, the clusters are learned and classified respectively using support vector machines. Finally, identification of random data distribution time series is tested in combined structure mode. The results indicate that the approach of the paper is feasible and efficient for automatically identifying data distributions in comparison with other methods.

Background The prognosis of patients with Hodgkin lymphoma (HL) who relapse following autologous hematopoietic cell transplantation is poor. Although reduced intensity allogeneic hematopoietic cell transplantation (RIC allo-HCT) can induce durable remissions in some patients with relapsed/refractory HL, its use is limited by patient co-morbidities, lack of disease control prior to HCT, and transplant related morbidities/mortalities. Brentuximab vedotin (BV), a novel antibody-drug conjugate, has a 75% objective response rate in patients with relapsed/refractory HL (Younes 2012). We performed a retrospective analysis comparing patient characteristics prior to HCT and outcomes after HCT in relapsed/refractory HL patients who received BV and underwent RIC allo-HCT versus those who did not receive BV but underwent RIC allo-HCT. Methods Between Jan 2003 and July 2009 (Pre-BV era), we identified a consecutive case-series of 23 HL patients who underwent RIC allo-HCT with no prior BV exposure (no-BV group). From July 2009 to Dec 2012, we identified a consecutive case-series of 21 additional HL patients who received BV prior to RIC allo-HCT (BV group). Co-morbidities at the time of HCT were measured by the HCT-CI. The Bearman scale was used to capture toxicities associated with RIC allo-HCT. PFS and OS were calculated using Kaplan-Meier method. Results Baseline characteristics are listed in Table 1. All patients received fludarabine and melphalan conditioning regimens. Groups were similar in terms of age, stage, response to induction, number of prior therapies, donor type, cell source, and prior auto-HCT. Groups differed in terms of GVHD prophylaxis (institutional shift to tacro/siro from 2005), remission status, and co-morbidity index (HCT-CI) at the time of HCT. Patients in the BV group were more likely to be in complete remission (CR) at the time of transplant (p=0.04). The median HCT-CI was better in the BV group (0 vs. 2, p=0.003). Also the Bearman toxicity score during transplant showed fewer grade III-IV events in the BV patients (0 vs. 7, p=0.015). The median follow-up for living patients in the no-BV group was 70.2 month and 23.3 months for the BV group (5 year lag for BV group). The 2-yr PFS for the no-BV group was 26.1% (95% CI: 21.5, 30.9) compared to 51.8% (95% CI: 38.5, 63.6) for the BV group, p=0.099. The 2-yr cumulative incidence of relapse/progression for no-BV was 56.5% (95% CI: 33.2, 74.4) compared to 28.9% (95% CI: 9.9, 51.4) for BV, p= 0.066. The 2-yr OS was 56.5% (95% CI: 44.3, 67) for no-BV compared to 66.6% (95% CI: 47.8, 80.0) for BV. Non-relapse mortality (NRM) at day 100 was 4.3% and 17.4% at 1 yr for the no-BV group. For the BV group NRM at day 100 was 0% and 11.8% at 1 yr. The rate of aGVHD and cGVHD were 56.5% and 78.3% for no-BV, and 33.3% and 76.2% for BV groups, respectively. Conclusion BV prior to RIC allo-HCT in relapsed HL leads to improvements in 1) HCT-CI 2) CR status at time of transplant, and 3) reduced peri-transplant toxicity. Disclosures: Chen: Seattle Genetics, Inc.: Consultancy, Research Funding, Speakers Bureau, Trave expenses Other. Siddiqi:Seattle Genetics: Speakers Bureau.

We report the recent result of GaAs/GaInP dual-junction solar cells grown by all solid-state molecular-beam-epitaxy (MBE). The device structure consists of a GaIn0.48P homojunction grown epitaxially upon a GaAs homojunction, with an interconnected GaAs tunnel junction. A photovoltaic conversion efficiency of 27% under the AM1.5 globe light intensity is realized for a GaAs/GaInP dual-junction solar cell, while the efficiencies of 26% and 16.6% are reached for a GaAs bottom cell and a GaInP top cell, respectively. The energy loss mechanism of our GaAs/GaInP tandem dual-junction solar cells is discussed. It is demonstrated that the MBE-grown phosphide-containing III—V compound semiconductor solar cell is very promising for achieving high energy conversion efficiency.

Single-junction, lattice-mismatched In0.69Ga0.31As thermophotovoltaic (TPV) devices each with abandgap of 0.6 eV are grown on InP substrate by metal—organic chemical vapour deposition (MOCVD). Compositionally undulating step-graded InAsyP1−y buffer layers with a lattice mismatch of ~1.2% are used to mitigate the effect of lattice mismatch between the device layers and the InP substrate. With an optimized buffer thickness, the In0.69Ga0.31As active layers grown on the buffer display a high crystal quality with no measurable tetragonal distortion. High-performance single-junction devices are demonstrated, with an open-circuit voltage of 0.215 V and a photovoltaic conversion efficiency of 6.9% at a short-circuit current density of 47.6 mA/cm2, which are measured underthe standard solar simulator of air mass 1.5-global (AM 1.5 G).

Abstract 3699 Background: A defining feature of HL is CD30 expression by Reed-Sternberg cells. Brentuximab vedotin, an antibody drug conjugate (ADC), selectively induces apoptotic death of CD30+ cells by binding, internalizing, and releasing monomethyl auristatin E, a microtubule agent. A pivotal phase II trial of brentuximab vedotin in heavily pretreated patients with HL demonstrated an overall objective response rate of 75% (CR, PR) and CR of 34% with manageable toxicities. This novel ADC compares favorably with historical first-line salvage regimens such as ICE and DHAP (CR 17–21%) To examine the outcomes (e.g., toxicity, response) of brentuximab vedotin when given as first-line salvage therapy for HL, we retrospectively analyzed data from a consecutive case-series of patients who received brentuximab vedotin as first -line salvage therapy at COH. Patients and Methods: Three patients received brentuximab vedotin as salvage therapy on IRB 10089 (expanded access protocol) and 8 patients received brentuximab vedotin as salvage therapy on IRB 11051 (prospective phase II trial). All patients had relapsed/refractory HL post induction therapy with ABVD, BEACOPP or a combination +/− consolidative XRT. Patients were treated with 1.8 mg/kg of brentuximab vedotin intravenously every 3 weeks as outpatients for a maximum of 4 cycles. Descriptive statistics were generated for response, toxicity, stem cell mobilization/collection and engraftment (for those patients who went on to autologous HCT). Response rate post brentuximab vedotin treatment was determined with either CT or PET at cycle 2 and CT/PET at cycle 4 as per Cheson 2007 criteria. Results: A total of 11 patients were treated at COH from 8/2011 to 7/2012 (Table 1). The median age was 34 years (22, 64); 7/11 were female. All patients received ABVD or ABVD/BEACOPP combination induction therapy. Three patients had also received consolidative radiation therapy. Six were considered primary refractory and 5 had relapsed HL. Thus far, 8 were evaluable for response and 10 were evaluable for toxicity. The overall response rate was 87.5% (7/8); CR was 50% (4/8) and PR was 37.5% (3/8); one patient achieved SD after 4 cycles. Three out of 4 patients who achieved CR did so after 2 cycles. No one developed progressive disease while on treatment. Overall the regimen is considered well tolerated. No grade 2 neuropathy was reported. The incidence of grade 1 neuropathy was 20% (2/10). There were no grade 3 or 4 adverse events or hospitalizations during brentuximab vedotin treatment. Additionally, the use of growth factors or red blood cell or platelet transfusions was not required. A total of 6/11 patients have undergone stem cell mobilization with cyclophosphamide/G-CSF priming after the 4th dose of brentuximab vedotin. The median cells dose collected was 5.87 × 10⋀6 CD34+ cells (2.78–11.13, minimum acceptable is 2 × 10⋀6 CD 34+ cells). The median time to reach the minimum collection was 1.5 days (1–5). All six patients have undergone ASCT using either BEAM or CBV for conditioning. The median time for neutrophil engraftment (ANC>500) was 10 days (10–11) and platelet engraftment (>20K) was 11 days (10–13). All 6/6 patients achieved CR after stem cell transplantation. The other five patients are undergoing stem cell mobilization or are have not completed brentuximab vedotin treatment. Conclusion: These data show brentuximab vedotin as first-line salvage therapy can produce an adequate ORR of 87.5% and CR of 50%. Brentuximab vedotin also has acceptable toxicity and does not adversely impact stem cell collection or post autologous HCT engraftment. Disclosures: Chen: Seattle Genetics, Inc.: Consultancy, Research Funding, Speakers Bureau, Travel Expenses Other. Off Label Use: This clinical trial involves the use of brentuximab vedotin as first line salvage therapy in Hodgkin lymphoma, which is an off-label use. Siddiqi:Seattle Genetics, Inc.: Consultancy, Research Funding.

Abstract 2399 The quality and depth of response particularly achievement of complete remission (CR) have been associated with significant improvement in progression free survival (PFS) and overall survival in multiple myeloma patients undergoing autologous stem cell transplant. Achievement of CR is considered a valid surrogate endpoint for survival in clinical trials for patients with multiple myeloma. We performed a phase II study investigating the role of sequential bortezomib/dexamethasone followed by thalidomide/dexamethasone as maintenance therapy post single autologous PSCT. The objectives were to examine the feasibility, toxicities, CR, PFS and overall survival rates. Within 4–8 weeks of autologous PSCT using melphalan 200mg/m2, pts received weekly bortezomib (bor) at 1.3mg/m2 /wk × 3 weeks with 1 week rest and dexamethasone (dex) at 40mg/d × 4 d for 6 months, followed by thalidomide (thal) at 50 –200mg/d and dexamethasone (dex) at 40mg/dx4 d for 6 more months. Single agent thalidomide was then continued until disease progression. Between March 2008 and June 2010, forty-five pts were enrolled. Median age was 54 years (29-71). Median time from diagnosis was 6.1 mo. (3.5 – 145.9). Disease stage at diagnosis; by Salmon-Durie (I/II/III 2/8/34/1 not available) and by ISS (I/II/III 18/14/8/ 5 not available). Pts received prior induction treatment with thal/dex (15), bortezomib based (27) and lenalidomide based regimens (10). Median B2M at enrollment was 1.8 mg/L (1.05 -5.3). Disease status at enrollment included complete remission (CR) (11), very good partial response (VGPR) (11), partial response (PR) (23). Six pts had chromosome 13 abnormalities (1 pt by karyotype and 5 pts by FISH), 2 pts had t 4;14 (one with concurrent ch 17 p del) and 3 pts had complex cytogenetic abnormalities. Results: Forty-five pts have been enrolled and undergone transplant. Five pts were unable to start planned maintenance therapy due to development of grade II or more neuro toxicities (4), and persistent thrombocytopenia (1) after PSCT. Thirty nine pts started maintenance bor/dex within 4–8 weeks of PSCT. One pt is too early for maintenance therapy. Twenty-five pts have completed the planned 6 months of bor/dex. Ten pts stopped bor/dex because of low WBC (2), PN (4), diagnosis of adrenal cancer (1), myocardial infarction (MI) (1), and relapse (2). Six pts are still receiving maintenance bortezomib. With a median F/U of 8.5 mo. (0.2 -24.0) twelve of 44 evaluable pts (27%) have achieved CR post PSCT and 17 of 33 evaluable pts (51%) have achieved CR after bor/dex on an intention to treat (ITT) analysis. Fifteen of 25 pts (60%) who have completed 6 months of bor/dex have achieved CR. Nine of 25 pts (36%) have upgraded their response with bor/dex. Eight pts (24%) could not complete bortezomib due to toxicities. At one year post PSCT fourteen of 28 evaluable pts (50%) remain in CR. Six pts have relapsed of whom 2 died of relapsed myeloma (leptomeningeal disease 1 pt). One pt experienced MI while receiving bortezomib (grade IV). Grade III toxicities have occurred in 17 pts; low platelet (1), asthenia (2), mood alteration (1), GI (severe constipation due to partial bowel obstruction on thalidomide) (1), skin rash (1), hyperglycemia (1), lymphopenia (10), sinus bradycardia (1), elevated triglyceride (1), DVT (1), low phosphate (3), leukopenia (1), edema (1). Sixteen pts had peripheral neuropathy (PN) grade I prior to start of bortezomib. Only 8 pts have developed new PN on the study and all are grade I-II. No patient has experienced grade III-IV PN. Median bortezomib dose is 1.3 mg /m2 per week. Conclusion: Prolonged weekly bortezomib maintenance therapy is well tolerated and can upgrade response post single autologous PSCT with no severe peripheral neuropathy. Fifty one percent of pts have achieved CR and 36% have upgraded their response after six months of bortezomib/dexamethasone therapy suggesting this is an active maintenance strategy post PSCT. Disclosures: No relevant conflicts of interest to declare.

We report our recent progress of investigations on InGaN-based blue-violet laser diodes (LDs). The room-temperature (RT) cw operation lifetime of LDs has extended to longer than 15.6 h. The LD structure was grown on a c-plane free-standing (FS) GaN substrate by metal organic chemical vapor deposition (MOCVD). The typical threshold current and voltage of LD under RT cw operation are 78 mA and 6.8 V, respectively. The experimental analysis of degradation of LD performances suggests that after aging treatment, the increase of series resistance and threshold current can be mainly attributed to the deterioration of p-type ohmic contact and the decrease of internal quantum efficiency of multiple quantum well (MQW), respectively.

InGaN/GaN multi-quantum-well-structure laser diodes with an array structure are successfully fabricated on sapphire substrates. The laser diode consists of four emitter stripes which share common electrodes on one laser chip. An 800-mu m-long cavity is formed by cleaving the substrate along the . orientation using laser scriber. The threshold current and voltage of the laser array diode are 2A and 10.5 V, respectively. A light output peak power of 12W under pulsed current injection at room temperature is achieved. We simulate the electric properties of GaN based laser diode in a co-planar structure and the results show that minimizing the difference of distances between the different ridges and the n-electrode and increasing the electrical conductivity of the n-type GaN are two effective ways to improve the uniformity of carrier distribution in emitter stripes. Two pairs of emitters on a chip are arranged to be located near the two n-electrode pads on the left and right sides, and the four stripe emitters can laser together. The laser diode shows two sharp peaks of light output at 408 and 409 nm above the threshold current. The full widths at half maximum for the parallel and perpendicular far field patterns are 8 degrees and 32 degrees, respectively.

Abstract 3403 Poster Board III-291 Autologous PSCT remains standard treatment in younger patients (pts) with multiple myeloma. However, relapse is the major cause of treatment failure. Several studies have reported improved progression-free survival (PFS) and possibly overall survival with thalidomide alone or in combination with steroid and chemotherapy as maintenance/consolidation therapy post autologous PSCT. We performed a phase II study investigating the role of sequential velcade/thalidomide/dexamethasone (VTD) as maintenance therapy post single PSCT. The objectives were to examine the toxicities of prolonged course of sequential VTD, CR rate, PFS and overall survival following single autologous PSCT. Within 4-8 weeks of autologous PSCT using melphalan 200mg/m2, pts received weekly velcade (vel) at 1.3mg/m2 /wk x 3 weeks with 1 week rest and dexamethasone (dex) at 40mg/d x 4 d for 6 months, followed by thalidomide (thal) at 50 -200mg/d and dexamethasone (dex) at 40mg/dx4 d for 6 more months. Single agent thalidomide was then continued until disease progression. Twenty-eight pts have been enrolled. Median age is 54 years (29-66). Median time from diagnosis is 7.9 mo. (4.2 – 145). Disease stage at diagnosis; by Salmon-Durie (II/III 6/22) and by ISS (I/II/III 11/9/7/missing data in 1 pt). Pts received induction treatment with thal/dex (14), velcade based (15) and revlimid based regimens (7). Median B2M at enrollment is 1.75 mg/L (1.14 -5.3). Disease status at enrollment; CR (7) VGPR (9), PR (11), SD (1). Three pts have chromosome 13 abnormalities (1 pt by karyotype and 2 pts by FISH). Results: All pts have undergone transplant. Four pts were unable to start planned maintenance therapy due to development of grade II or more neuro toxicities (3), and persistent thrombocytopenia (1) after PSCT. Twenty-four pts started maintenance vel/dex within 4-8 weeks of PSCT. Nine pts have completed 6 months of vel/dex. Two pts stopped vel/dex because of low WBC (1) or PN (1). With a median F/U of 5.2 mo. (1.2 -17.3) nine of 28 pts (33%) have achieved CR post PSCT and six out of 11 evaluable pts (55%) have achieved CR after vel/dex. Six out of 9 pts (66%) who have completed 6 mo. of vel/dex achieved CR. Two out of 9 pts (22%) have upgraded their response with vel/dex. Four pts have completed 6 month of thal/dex and are beyond 1 year post PSCT. Two out of 4 pts remain in CR at one year post PSCT. One pt is in PR and 1 pt has progressed. Two pts could not complete thal/dex phase of therapy because of relapse (1) and grade III GI toxicity (1). Three pts have relapsed of whom 1 pt died of relapsed myeloma (leptomeningeal disease). No grade IV toxicity has been noted. Grade III toxicities have occurred in 4 pts; low platelet (1), fatigue (1), mood alteration (1), GI (severe constipation) (1). Thirteen pts have peripheral neuropathy (PN). Ten pts had PN grade I at enrollment. Only 3 pts have developed PN on the study and all are grade I - II. Median velcade dose is 1.3 mg /m2/wk and thalidomide dose is 100mg /d. Conclusion: Prolonged sequential velcade/thalidomide/dexamethasone maintenance therapy post single autologous PSCT is well tolerated with no severe peripheral neuropathy. Fifty-five percent of pts have achieved CR and 22% have upgraded their response after six months of velcade/dexamethasone therapy suggesting this is an active and well tolerated maintenance strategy post PSCT. Disclosures: Sahebi: Celgene: Honoraria; Millennium Pharmaceutical: Research Funding. Off Label Use: The use of bortezomib(Velcade)in combination with thalidomide and dexamethasone is investigated as maintenance therapy post autologuous stem cell transplant in patients with multiple myeloma.

Abstract 2771 Poster Board II-747 We previously reported an encouraging result with RI-HCT for MDS (Bone Marrow Transplant 2007; 40:843-50) using flugarabine/melphalan conditioning and cyclosporine (CSA)/mycophenolate (MMF) as GVHD prophylaxis. In order to further improve upon the outcome in the RI-HCT setting, we initiated a series of clinical trials at City of Hope National Medical Center designed to evaluate the impact of tacrolimus (FK)/sirolimus (SIRO)-based GVHD prophylaxis. Here we report the combined, updated results from a consecutive case-series of 89 patients with MDS (including AML progressed from MDS) who underwent RI-HCT from 2000 to 2008 and received either CSA/MMF (n =44) or FK/SIRO (n=45)-based GVHD prophylaxis. All patients received fludarabine 125 mg/m2 plus melphalan 140 mg/m2 followed by an allogeneic HCT (peripheral blood: n=83, bone marrow: n=6) from an HLA-identical sibling (SIB: n=35) or unrelated donor (MUD: n=54). Additional ATG was given to 12 patients. For MUD transplants a short course of methotrexate was added to CSA/MMF or FK/SIRO. The median age was 59 years (range: 20-71) and 31 (35%) patients were female, 58 (65%) were male. Diagnoses at transplant were RA (n=21), RARS (n=1), RAEB/RAEBT (n=36), and AML from prior MDS (n=31). Cytogenetic risk was low in 15 (17%), intermediate in 37 (41.5%), high in 37 (41.5%) patients. By IPSS criteria (for MDS only), 2 patients had low, 24 had int-1, 20 had int-2, and 12 had high-risk MDS. Twenty-seven patients had therapy-related MDS including 14 with prior autologous HCT. The median follow-up time for surviving patients was 39 months (range: 24-68) for the CSA/MMF group and 17 months (range: 4-39) for the FK/SIRO group. All but two patients (1 in CSA/MMF, 1 in FK/SIRO) engrafted with the median neutrophil recovery at 15 days (range: 11-55). The baseline patient, disease and transplant characteristics were similar between CSA/MMF and FK/SIRO, except for an increased percentage of therap-related MDS in the CSA/MMF group (43% vs. 18%, p10% (n=22)baseline 2.13 (0.92–4.96)0.08HLA match (sibling donor or 10/10 MUD, n=72)HLA < mismatch MUD ( Disclosures: Off Label Use: cyclosporine, cellcept, tacrolimus, sirolimus, and methotrexate for GVHD prophylaxis.

This article explores the concepts of privacy and identity in Hong Kong in relation to the law relating to data protection. It first considers the notions of privacy and identity in the light of Hong Kong's socioeconomic situation and recent postcolonial heritage. It then highlights the importance of identity management and considers the distinctions and overlaps between identity management and privacy protection. With this conceptual framework in mind, the article then considers the various laws in Hong Kong pertaining to data protection, with a focus on the aspects relating to identity management. It observes that while there is some legal protection in respect of the data relating to an individual's identity, there are other priorities which may take precedence in determining the extent of identity management under the legal system in Hong Kong. Finally, recommendations are made as to how to improve identity management within the context of data protection in Hong Kong.

Current CGVHD prognostic and staging systems are still undergoing development and have identified plt count; CGVHD types progressive(P), quiescent(Q), de novo(DN); KPS, and GI involvement as significant risk factors affecting outcome. A simple reproducible staging system such as used for AGVHD to apply in clinical trials is still lacking. We evaluated whether the PSE dose required to control CGVHD at 3 months from diagnosis would have a prognostic effect on survival and in and of itself serve as a criteria for secondary intervention or investigational therapy. We hypothesized that by 3 months from start of treatment patients would be on the lowest dose dictated by medical necessity rather than by physician driven dose preference. A retrospective analysis of charts from 109 patients diagnosed with CGVHD between 6/2000 and 6/2003 was done. Data collected included age, donor type(mud/sib), plt count, CGVHD type(P/Q/DN), KPS, GI involvement. Outcome analysis included survival and cause of death. PSE dose was calculated in mg/kg at 3 months from first diagnosis of CGVHD. With a median follow up of 47.2 months(range 6.6–67.2) relapse censored survival of patients on a 3 month PSE dose of more than .3 mg/kg was 53% compared to all lower doses 86%(P.03). In a univariate analysis only PSE dose (P .05) and KPS (P Table Univariate Multivariate Variable Value N # of deaths Hazard Rate Ratio (95% CI) p value Hazard Rate Ratio (95% CI) p value Prednisone at 3 month 0 20 1 Baseline 0.05 Baseline 0.1–0.14 18 2 3.0 (0.3–32.7) 3.7 (0.3–43.4) 0.33 0.15–0.29 22 3 2.9 (0.3–28.2) 3.4 (0.3–34.5) 0.32 0.3–0.59 16 7 9.8 (1.2–79.4) 9.3 (1.1–76.0) 0.04 0.6–0.99 0 0 n/a n/a n/a ≥1.0 0 0 n/a n/a n/a cGVHD class Denovo 29 5 Baseline 0.54 Progressive 23 7 1.9 (0.6–6.0) Quiescent 57 13 1.3 (0.5–3.8) Donor type Sibling 48 9 Baseline 0.40 Unrelated 61 16 1.4 (0.6–3.2) Platelet count at 3 month The analysis of this data to date suggests the PSE dose at 3 months may be an important independent clinical marker for subsequent CGVHD prognosis which could be used to decide which patients to include in 2nd line and experimental therapy trials.

Although autologous transplant remains standard of care for patients with multiple myeloma, it is rarely curative. Allogeneic peripheral stem cell transplant (PSCT) using reduced intensity conditioning (RIC) or non-myeloablative conditioning following autologous PSCT (auto-allo) have been used in an attempt to improve survival. Although the graft vs. myeloma effect is an important therapeutic aspect of these approaches higher relapse rates have been reported using reduced intensity regimens suggesting that cytoreduction with auto PSCT (auto-allo) is required for optimal disease control. To examine the differences between RIC and auto-allo PSCT we performed a retrospective analysis of 49 patients who underwent auto-allo and RIC transplants. Thirty-seven patients received an auto-allo PSCT using melphalan (200mg/m2) prior to auto PSCT and TBI (200 cGy) prior to allograft PSCT and twelve patients underwent RIC allograft PSCT following fludarabine (125mg/m2) and melphalan (140mg/m2), between Feb 2000 to April 2005. Donors included HLA matched siblings (47) or matched unrelated donors (2 in the RIC group). Median follow up for the alive patients is 4.5 and 5.4 years for the auto-allo and the RIC groups, respectively. Median age was 51 years in the auto-allo group (range 38–66) and 48 years in the RIC group (range 42–62). Patients in the auto-allo group received their allograft within 60–120 days following autologous PSCT. In the RIC group, 7 patients failed a previous single (1) or tandem (6) auto PSCT. Cytogenetic data were available in 47 patients prior to transplant, with chromosome 13 deletion present in 2 patients in the auto-allo group and in 4 patients in the RIC group. Median B2-microglobulin was 1.8 in the auto-allo group and 2.1 in the RIC group. There were more patients in complete remission (CR)/partial remission (PR) in the auto-allo group (76%) than in the RIC group (17%, P= 0.0005), and there were more patients who received early transplant (< one yr) in the auto-allo group (68%) than the RIC group (8%, P= 0.0005). There was no difference in 1 year non-relapse mortality between the two groups (5% auto-allo vs. 8% RIC, P=1.00. Three year overall survival (OS) was statistically superior in the auto-allo group (81%) versus the RIC group (35%, P=0.02). Three year PFS was 54% in the auto-allo group and 21% in the RIC groups (P=0.11). However, when Cox regression analysis was performed adjusting for the disease status and time from diagnosis, there was no statistically difference in the OS between the 2 groups (P=0.27). Conclusion: Our data suggest that RIC allograft and auto-allo PSCT-associated treatment related mortality is similar, and RIC allograft when administered earlier during the disease course may result in similar outcome. However whether using early reduced intensity allogeneic transplant could eliminate the need for cytoreductive auto-PSCT needs to be addressed in prospective clinical trial.

Natural and efficient 3D interaction techniques play one of the key roles in the development of virtual reality systems. Most of these techniques, which are used currently, mainly aim at supporting the implementation of interaction tasks in geometric level. As a result, they usually lack of the sufficient ability for executing those interaction tasks that orient to high-level application. Based on the cognitive principles in the real world, interaction objects in virtual environments not only include some geometric attributes in the visual view, but also own some specific semantic attributes such as interaction rules, constraints and affordances, which are related with interaction process tightly. In this paper these objects are called semantic objects, in the sense that they know how the user can interact with them, giving clues to aid the interaction. Through parsing and interpreting interaction semantics, these semantic objects can help to realize high-level interaction metaphors above "direct manipulation". Because they hide low-level details about the implementation of interaction techniques, this kind of metaphors evidently improve the efficiency and usability of interaction techniques, and enable user to concentrate more on the high-level interaction control directly related with the special applications.

Patients with peripheral T cell lymphoma (PTCL) have a poor prognosis with current treatment approaches. We examined the outcomes of high-dose therapy (HDT) and autologous hematopoietic cell transplant (AHCT) on the treatment of PTCL and the impact of patient/disease features on long-term outcome. Sixty-seven patients with PTCL–not otherwise specified (n = 30), anaplastic large cell lymphoma (n = 30), and angioimmunoblastic T cell lymphoma (n = 7) underwent HDT/AHCT at the City of Hope. The median age was 48 years (range: 5-78). Twelve were transplanted in first complete remission (1CR)/partial remission (PR) and 55 with relapsed or induction failure disease (RL/IF). With a median follow-up for surviving patients of 65.8 months (range: 24.5-216.0) the 5-year overall survival (OS) and progression-free survival (PFS) were 54% and 40%, respectively. The 5-year PFS was 75% for 1CR/PR compared to 32% for RL/IF patients (P = .01). When the Prognostic Index for PTCL unspecified (PIT) was applied at the time of transplant, patients in the PIT 3-4 group had 5-year PFS of only 8%. These results show that HDT/AHCT can improve long-term disease control in relapsed/refractory PTCL and that HDT/AHCT should ideally be applied either during 1CR/PR, or as part of upfront treatment. More effective and novel therapies are needed for patients with high-risk disease (PIT 3-4 factors) and allogeneic HCT should be explored in these patients.