Journal articles on the topic '828.996 67'

444 Background: Patients with pancreatic ductal adenocarcinoma (PDAC) have limited treatment options. Management of complex symptoms and psychosocial implications requires an interprofessional approach as prognosis is often measured in months. A multidisciplinary approach has been associated with improvement in clinical outcomes including survival. We aimed to evaluate the impact of an inter-professional approach for PDAC patients at the Wallace McCain Centre for Pancreatic Cancer (WMCPC) at PM on their management and clinical outcomes. Methods: We undertook retrospective review of all patients with PDAC seen at PM two years before (July ‘12 – June ‘14) and two years after (July ‘14 – June ‘16) establishment of the WMCPC. Standard therapies (surgical approach, chemotherapy, radiation therapy) were the same during both time periods. Comparison of overall survival (OS), stage at diagnosis, surgical outcomes, waiting times, and proportion seen by social worker, dietician and clinical nurse specialist (CNS) was explored with descriptive statistic and survival analysis. Results: A total of 993 patients were reviewed; 482 patients pre- and 511 patients post-WMCPC. Age (median 67 yrs), sex (54% men) and stage III/IV (52%) were similar in both groups. There was a trend to improved OS in the post-WMCPC group (9.6 vs. 10.9 m; p = 0.055); multivariable analysis found a significant improvement in OS after adjustment for performance status and stage (p = 0.023; HR 0.84, 95% CI 0.72-0.98). Rate of R0 versus R1/R2 resection for curative surgery (n = 264, 28%) was similar in both groups. Time from referral to first clinic visit significantly decreased from 13.4 to 8.8 days in the post-WMCPC group (p < 0.001) as did time from first clinic appointment to diagnostic biopsy (25.9 vs. 16.9 days, p = 0.022). Patients in the post-WMCPC were more frequently seen by a social worker, dietician or CNS (8% vs. 38%, 9% vs. 35% and 31% vs. 50% respectively, p < 0.001). Conclusions: Establishment of an interprofessional clinic for the treatment of PDAC patients at PM has streamlined diagnosis, aided symptom management and improved overall survival. This has implications for planning care delivery models and proves the value of this intervention.

In order to make chemical characterization of two Origanum vulgare L. subspecies in Montenegro, the essential oils of five wild growing populations were analyzed. Among 67 oil constituents, in O. vulgare subsp. hirtum dominant one was oxygenated monoterpene carvacrol (74.3%), while in O. vulgare subsp. vulgare prevailed sesquiterpene hydrocarbons: germacrene D (15.4–27.9%) and β-caryophyllene (7.7–14.6%), and among oxygenated monoterpenes: α- terpineol (4.8–17.8%), linalyl acetate (0.5–9.6%), linalool (3.0–8.8%), thymol (0.2–8.3), terpinene 4-ol (1.5–8.3%). Several of the main essential oil constituents appeared to be highly intercorrelated. Strong positive correlations (r > 0.70; P < 0.01) were observed between α-terpineol and linalyl acetate, α-terpineol and thymol, linalyl acetate and thymol, γ-terpenene and carvacrol, ( E)-β-ocimene and β-bisabolene, while strong negative correlations (r < −0.70; P < 0.01) were evidenced between γ-terpenene and β-caryophyllene, γ-terpenene and germacrene D, p-cymene and germacrene D. Multivariate analyses allowed the grouping of the populations into three distinct chemotypes. Population P5 (Origanum vulgare subsp. hirtum) was distinguished from O. vulgare subsp. vulgare populations by predominance of carvacrol, while within the typical subspecies the population P1 (Boljevići) separated from P2 (Radovče), P3 (Lipovo) and P4 (Grahovo) by high oil levels of α-terpineol, linalyl-acetate and thymol.

67 patients (mean age 48 ± 1 year) with diffuse liver diseases of various origins were examined. It has been established that an increase in the degree of fibrosis is associated with an increase in the resonance intensity of glucose-6-phosphates, adenosine monophosphate (AMP), inosine monophosphate (IMP), pyrophosphates, 2,3-DPH and a decrease in the resonances of inorganic phosphates and phosphocreatine, γ-, alpha- and beta- ATP, -UTP, Hb- and Mg-ATP, as well as beta- and alpha-ADP. The predictive value of a positive result of erythrocyte 31P NMR spectroscopy for liver fibrosis is 92.3% (sensitivity 85.71%, specificity 80%). In the IR spectra of the blood serum of patients with severe fibrosis, in contrast to moderate fibrosis, the resonance intensity is higher at 1280, 3190 and significantly lower at 776, 818, 889, 966, 1399.1450, 1570, 1635 cm-1, which indicates the presence of protein molecules with a secondary structure mainly in the form of a helix (alpha-helix) compared with the structure in the form of a folded sheet (beta-sheet) (p <0.001-0.05). The combined use of 31P NMR spectroscopy of erythrocyte suspensions and IR spectroscopy of blood serum made it possible to increase diagnostic accuracy (96%), sensitivity (97%) and specificity (91%) in distinguishing between degrees of liver fibrosis in contrast to the isolated use of these methods.

e19522 Background: BMF is known to occur in a minority of myeloma patients, but its incidence in American patients of African origin is not known. The impact of BMT on presenting clinical and laboratory findings, and its relationship to genetic variants has not been defined. Methods: Kings County Hospital is located in the East Flatbush section of Brooklyn, New York, where the population is mainly of African-Caribbean origin. Records and bone marrow specimens of myeloma patients who presented from 2000 through 2010 were reviewed. Degree of fibrosis was graded according to World Health Organization criteria: mild, moderate and severe. Results: Records of 113 patients were reviewed, 110 (97%) 97 of whom were African American or Caribbean; 62 (55%) were female and 51 (45%) male. Their ages ranged from 38 to 89 (median 65). Of the 27 patients with BMF (24%), 17 (63%) were female. Mild, moderate and severe BMF were present in 14 (52%), 7 (26%) and 6 (22%) patients respectively. Presentation calcium and creatinine levels were normal in all patients. Hemoglobin levels were similar (median 9.6 G/dl) in patients without BMF and in those with mild and moderate grades, the median level was 7.5 G/dl in those with severe BMF. Immunoglobulin G, A and D levels (67, 20 and 1) were similar in patients with and without BMF, but lambda light chain expression was greater in the BMF patients: 41 vs 24%. Cytogenetic data (CGD) was available in 46 patients; and abnormal in 10 (22%). All patients with abnormalities of chromosomal number were hyperdiploid. Of the 27 BMF patients CG data was available in 17, and was abnormal in 2 (12%). FISH results were normal in 23 of 25 patients, and in all of those with BMF. The fraction of the BMF and non BMF patients surviving after median follow up periods of 828 and 885 days were similar. Conclusions: BMF in this population was 24%, and severe in 5%. Female preponderance is a characteristic of MM patients of African origin, and was more marked in those with BMF. The BMF patients were characterized by more severe anemia and greater lambda light chain expression.

AbstractObjectiveNorwood palliation for patients with single ventricle heart disease is associated with a significant risk for acute kidney injury, which portends a worse prognosis. We sought to investigate the impact of hybrid stage I palliation (Hybrid) on acute kidney injury risk.DesignThis study is a single-centre prospective case–control study of seven consecutive neonates with single ventricle undergoing Hybrid palliation. Levels of serum creatinine and four novel urinary biomarkers, namely neutrophil gelatinase-associated lipocalin, interleukin-18, liver fatty acid-binding protein, and kidney injury molecule-1, were obtained before and after palliation. Acute kidney injury was defined as a ⩾50% increase in serum creatinine within 48 hours after the procedure. Data were compared with a contemporary cohort of 12 neonates with single ventricle who underwent Norwood palliation.ResultsPatients who underwent Hybrid were more likely to be high-risk candidates (86 versus 25%, p=0.01) compared with those who underwent Norwood. Despite similar preoperative serum creatinine levels, there was a trend towards higher levels of postoperative peak serum creatinine (0.7 [0.63, 0.94] versus 0.56 [0.47, 0.74], p=0.06) and rate of acute kidney injury (67 versus 29%, p=0.17) in the Norwood cohort. Preoperative neutrophil gelatinase-associated lipocalin (58.4 [11, 86.3] versus 6.3 [5, 16.2], p=0.07) and interleukin-18 (30.6 [9.6, 167.2] versus 6.3 [6.3, 16.4], p=0.03) levels were higher in the Hybrid cohort. Nevertheless, longitudinal mixed-effect models demonstrated Hybrid palliation to be a protective factor against increased postoperative levels of neutrophil gelatinase-associated lipocalin (estimate −1.8 [−3.0, −9.0], p<0.001) and liver fatty acid-binding protein (−49.3 [−89.7, −8.8], p=0.018).ConclusionsIn this single-centre case–control study, postoperative acute kidney injury risk did not differ significantly by single ventricle stage I treatment strategy; however, postoperative elevation in novel urinary biomarkers, consistent with subclinical kidney injury, was encountered in the Norwood cohort but not in the Hybrid cohort.

4075 Background: Bevacizumab (B) + FOLFOX is widely accepted as a standard first-line therapy for metastatic colorectal cancer (mCRC). Recent treatment strategies have included the use of targeted therapies combined with chemotherapy to improve efficacy and to reduce chemotherapy-related toxicities. This Phase II study assesses first-line mFOLFOX6 + B + cetuximab (C), a monoclonal antibody approved for use in irinotecan-refractory mCRC. Methods: All pts had ECOG PS = 1, normal bone marrow, hepatic and renal function. Pts received mFOLFOX6 + B (5mg/kg) biweekly and C weekly (initially at 400 mg/m2, then subsequent doses at 250 mg/m2). Tumor assessment by imaging was done every 8 weeks. Primary endpoints are response rate, progression free-survival (PFS), overall survival (OS), and safety. The regimen would be considered promising if there were = 32 responses, or if = 60% of pts were progression-free for at least 8 months. Results: 67 pts (37 males, 30 females) were enrolled from 12/04–11/06. Median age was 57. Toxicities included Grade 4: neutropenia (6%), thrombosis/embolism (5%). Grade 3: neutropenia (13%), rash (13%), fatigue (11%), diarrhea (11%), abdominal pain (6%), neuropathy (5%), infection with ≤ Grade 2 ANC (4.5%). There were 2 deaths, 1 due to neutropenia and diarrhea and 1 to pulmonary fibrosis. As of 12/06, 9 pts were too early to evaluate. Of the remaining 58 pts, there were 32 responses (55%; 95% CI: 42%, 68%), including 3 CRs and 29 PRs; Median PFS was 9.6 months (95% CI: 8.8, 13.9 months), 71% were progression-free for at least 8 months, and median OS was not reached after a median follow-up of 11.4 months (range 1.5–25.2 months). Conclusions: Treatment with mFOLFOX6+ B + C met the pre-specified criteria for objective response and PFS to be considered promising. This regimen is associated with an acceptable toxicity profile and merits further evaluation. Supported by N01-CA-62204. No significant financial relationships to disclose.

293 Background: We previously reported the introduction of S-1 improved overall survival (OS) in advanced pancreatic cancer (PC), but in a pooled analysis of 3 RCTs, a combination of gemcitabine and S-1 (GS) improved OS in locally advanced PC (LAPC), but not in metastatic PC (MPC), compared to gemcitabine (Gem) alone. More recently, FOLFIRINOX, a multiagent chemotherapy, is shown to improve OS in MPC. We conducted clinical trials of a combination of Gem, S-1 and leucovorin (GSL) to further enhance antitumor effects. Herein, we retrospectively studied whether these multiagent regimens, GSL & FOLFIRINOX, affected the prognosis of APC, especially MPC. Methods: A total of 408 pts with APC receiving chemotherapy were grouped by treatment era into 3 groups: Group 1 (Years 2001-5: 53 pts prior to S-1 introduction), Group 2(Years 2005-11: 240 pts post S-1 introduction) and Group 3 (2012-14: 115 pts post multiagent treatment introduction), and clinical outcomes were compared. Results: Patient characteristics and protocol are shown in Table 1. Treatment protocol was single in 233, dual 142, and multiagent in 33. Response rate & disease control rate in Groups 1/2/3 were 2/8/17% & 26/67/73%. In LAPC, PFS was 6.2/8.9/7.9 & OS was 13.4/17.2/19.7 months in Groups 1/2/3. Meanwhile, in MPC, PFS was 2.0/3.5/4.8 & OS was 6.7/8.6/9.6 months in Groups 1/2/3. When treatment protocols were compared, in LAPC, PFS & OS were 7.0/11.7/8.8 & 13.6/22.6/22.6 months in singe/dual/multiagent chemotherapy. In MPC, PFS & OS were 3.1/3.5/6.0 & 8.3/8.1/13.7 months in single/dual/multiagent chemotherapy. Conclusions: While the introduction of S-1 led to longer OS in LAPC, recent introduction of multiagent chemotherapy appeared to improve OS in MPC. Whether multiagent chemotherapy would lead to longer OS than dual chemotherapy in LAPC needs further investigation. Table 1. [Table: see text]

Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group comprising about 10-15% of non-Hodgkin lymphomas in Western populations. Only a minority (~30%) of patients with the most common PTCL subtypes achieve a durable remission and long-term survival. Data on the clinical features of PTCL in a Chinese population are limited. Methods: We retrospectively reviewed 342 patients with pathologically diagnosed T cell lymphoma at Guangdong Provincial People's Hospital from June 2007 through March 2019. We evaluated the incidence of PTCL subtypes, clinical characteristics and survival status. Results: Of the 342 patients, 17.3% (n=59) had PTCL-not otherwise specified(NOS), 9.4% (n=32) had angioimmunoblastic T-cell lymphoma(AITL), 19.6% (n=67) had anaplastic large cell lymphoma(ALCL) (anaplastic lymphoma kinase positive ALCL:12.0%, n=41; anaplastic lymphoma kinase negative ALCL: 9.6%, n=26), 36.2%(N=124) had NK/T cell lymphoma, 12.9% (n=44)had lymphoblastic lymphoma(LBL), and 4.6%(n=16) had other subtypes. For next data analysis, NK/T cell lymphoma and LBL were excluded. Finally, a total of 164 patients with integrally follow-up information were analyzed. The median age was 49.5 years (range 15-87) old and the median follow-up time was 15.8 months (range 0.5-124.3). Most patients were males (62.0%) with advanced stage disease (III/IV, 74.5%), and 51.0% of patients presented with B symptoms and 83.0% with no bulky disease. For the total population, the median progression-free survival(PFS) and overall survival(OS) was 6.5 months and 13.5 months, respectively. ALCL patients had better PFS and OS than PTCL-NOS and AITL (PFS: 51.2 vs. 5.8 vs.4.7 months, P = 0. 000; OS: not reached vs. 13.4 vs. 8.8 months, P = 0.000). There were no difference of PFS and OS between PTCL-NOS and AITL(P = 0. 550 and P = 0. 333, respectively). Conclusions: ALCL has better outcome than other PTCL subtypes. However, no efficacy therapy has emerged for patients with relapsed/refractory PTCL and outcomes in this setting are still poor. Novel potential targets for PTCL, with particular focus on identifying markers of response and resistance need further investigation. Disclosures Li: Guangdong Province Hospital: Employment.

239 Background: Although alopecia is common with systemic chemotherapy, its psychological impact is often overlooked in treatment (tx) decisions. We sought to better understand the impact of alopecia using data from SystHERs, an observational registry of pts with HER2+ MBC. Methods: SystHERs enrolled pts ≥ 18 years within 6 mos of an MBC diagnosis. Pt-reported outcomes are assessed quarterly. The Alopecia Patient Assessment (APA, Genentech) is a validated instrument measuring the incidence of hair loss in the prior 3 mos and the impact of hair loss in the prior 7 days. The APA includes 5 items scored on a 5-point scale (total range: 1–25). Higher scores indicate greater impact. Pts completed the APA within 30–90 days of initial MBC tx. Subgroups with no hair loss, hair loss without impact, or impactful hair loss were compared descriptively. Results: As of June 3, 2016, 591 of 976 pts were eligible for this analysis. Of these, 175 (30%) reported no hair loss, 123 (21%) reported hair loss without impact, and 293 (50%) reported impactful hair loss within 30–90 days of initial MBC tx. Respectively, 23% (41/175), 82% (101/123), and 79% (231/293) were on active chemotherapy, most commonly docetaxel (39% [16/41], 66% [67/101], and 62% [144/231]) and paclitaxel (5% [2/41], 27% [27/101], and 23% [54/231]). Median time from initial chemotherapy tx to APA was 55, 70, and 64 days. Of all pts with no hair loss, 39% had de novo MBC vs 56% of pts with hair loss but no impact and 55% with impactful hair loss. Relative to the no-hair-loss and hair-loss-but-no-impact subgroups, the subgroup with impactful hair loss was younger (median 57 and 59 vs 54 years, respectively) and had more pts with ≥ 2 metastatic sites (51% and 54% vs 63%) and visceral metastases (59% and 63% vs 69%). The median total APA score for pts with impactful hair loss was 8.8 (IQR 7.0–12.5). Conclusions: Of pts reporting hair loss, 79–82% were receiving systemic chemotherapy. Pts with impactful hair loss may have had greater disease burden. Alopecia impacted self-image and embarrassment more than work or social functioning. Clinical trial information: NCT01615068. [Table: see text]

e20020 Background: Exportin 1 (XPO1) mediates the nuclear export and functional inactivation of tumor suppressor proteins, is required for MM growth, is associated with poor prognosis in MM and mediates resistance to standard MM therapies. Selinexor (SEL) is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound approved in combination with dexamethasone (dex) ± bortezomib for patients (pts) with previously treated MM. Once MM becomes refractory to αCD38 mAb, pts have limited effective treatment options and poor prognosis. Overall response rate (ORR) to the first regimen after refractoriness to an αCD38 mAb is 31%, median progression-free survival (mPFS) is 3.4 months (m), and median overall survival (mOS) is 8.6 m. The doublet SEL-dex (Xd) has shown ORR ̃26% in triple-class (IMID, PI, αCD38 mAb) refractory MM; SEL-based triplets could be more effective in this population. Methods: STOMP (Selinexor and Backbone Treatments of Multiple Myeloma Patients) is a multi-arm, open-label, Phase 1b/2 study evaluating SEL in various triplet combinations. Here, we retrospectively analyzed the efficacy and safety of SEL-containing triplets in pts previously treated with αCD38 mAbs. Pts received SEL-dex (Xd) plus pomalidomide (XPd, n = 19), bortezomib (XVd, n = 4), lenalidomide (XRd, n = 4), daratumumab (XDd, n = 2) or carfilzomib (XKd, n = 18). ORR, mOS, mPFS and adverse events (AEs) were analyzed. Results: Among the 47 pts, median age 64 yrs, female 53%, median time from diagnosis 5.1 yrs, median number of prior regimens 5 (range, 2–11). Prior daratumumab (96%), isatuximab (4%); 96% had MM refractory to aCD38 mAb, 81% had triple-class refractory MM, 74% and 47% were quad- and penta-exposed, 43% and 15% had quad- and penta-refractory MM. αCD38 mAb was included in the immediate prior regimen of 57% of pts and median duration from end of most recent aCD38 mAb therapy to first dose of study treatment was 6.9 weeks (range, 2.6-114.9). ORR was 51% among the 45 evaluable pts, 59% in the XPd arm (n = 17; 2 pts were not efficacy evaluable) and 67% in the XKd arm. ORR was 47% (9/19) among pts with quad-refractory MM and evaluable efficacy. Among all evaluable pts mPFS was 8.8 m (95% CI: 4.9, NE) and mOS was 20.4 m (95% CI: 9.6, NE). Among the 25 pts with αCD38 mAb in their immediate prior regimen, efficacy was similar to that regimen: ORR 52% vs. 45%, mPFS 8.8 vs. 9.3 m. The most common treatment emergent AEs were nausea (72%), anemia (64%), thrombocytopenia (60%), fatigue (57%), which were managed with standard supportive care and dose modifications. Conclusions: SEL-containing triplets in pts with MM previously treated with αCD38 mAbs, most of whom had triple-class refractory MM, exhibit tolerability and comparable effectiveness to their most recent αCD38 mAb-containing regimens. Compared to historical control, mOS was much higher among these patients. Further investigation is warranted. Clinical trial information: NCT02343042.

Abstract Chelation therapy is the conventional treatment for transfusional iron overload, which leads to complications in the heart, liver and endocrine glands. A 1-year, open-label, multicenter, Phase III study compared the investigational, once-daily, oral iron chelator deferasirox (DSX) with deferoxamine (DFO) in adult and pediatric β-thalassemia patients aged ≥ 2 years. Patients with liver iron concentration (LIC) of 2–3, &gt;3–7, &gt;7–14 and &gt;14 mg Fe/g dw were randomized to receive daily DSX 5, 10, 20 and 30 mg/kg or DFO 20–30, 25–35, 35–50 and ≥ 50 mg/kg, respectively. In total, 586 patients received treatment; 299 (51%) were aged &lt;16 years, of whom 154 were treated with DSX. Baseline demographics and changes in LIC and serum ferritin after 1 year of treatment are shown in the table; data are presented as mean ± SD (standard deviation). DSX produced a fall in LIC in all age groups. A more moderate reduction in LIC occurred in patients aged &lt;6 years despite the administration of an average dose of 21.9 mg/kg in this subgroup; these patients had the highest mean transfusional iron intake. The results strongly suggest that transfusional iron intake is the major factor in determining response and should be considered carefully when dosing iron chelators in children. In those with high transfusion requirements, a dose of 30 mg/kg may be considered. DSX DFO EOS = end of study; SF = serum ferritin; aAll patients with a baseline and EOS LIC assessment Age at baseline, years &lt;6 (n=30) 6–11 (n=67) 12–15 (n=57) &lt;6 (n=28) 6–11 (n=68) 12–15 (n=49) Female: male, n 12:18 35:32 35:22 9:19 33:35 30:19 Average daily dose, mg/kg 21.9 ± 7.61 21.1 ± 8.49 18.0 ± 9.00 43.6 ± 9.17 42.5 ± 9.11 43.5 ± 9.62 Baseline LICa, mg Fe/g dw 13.2 ± 7.4 15.2 ± 10.6 12.4 ± 10.5 12.6 ± 6.0 13.2 ± 9.4 13.3 ± 10.4 EOS LICa, mg Fe/g dw 12.1 ± 4.4 11.1 ± 7.7 9.6 ± 7.0 8.8 ± 3.8 10.6 ± 7.4 9.8 ± 6.6 Baseline SF, ng/mL 2479 ± 843 3058 ± 1834 2813 ± 1567 2260 ± 874 2745 ± 1633 2847 ± 1507 EOS SF, ng/mL 2791 ± 1066 2710 ± 1526 2787 ± 1494 1774 ± 769 2439 ± 1356 2495 ± 1529 Transfusional iron intakea, mg/kg/day 0.48 ± 0.11 0.43 ± 0.09 0.37 ± 0.10 0.47 ± 0.12 0.44 ± 0.12 0.40 ± 0.10 DSX was well tolerated in children as young as 2 years of age at all dose levels, with a safety profile similar to that observed in adults. The most common adverse events (AEs) with a suspected relationship to DSX were abdominal pain, nausea, vomiting, diarrhea and skin rash. Of 154 pediatric patients who received DSX, 5 (3.2%) discontinued due to suspected drug-related AEs. There was no treatment-related neutropenia, agranulocytosis or arthralgia. Sexual development proceeded normally with no differences between the treatment groups. DSX has a safety profile that is compatible with long-term use in children as young as 2 years and is generally well tolerated at doses as high as 30 mg/kg in these heavily transfused patients.

Introduction: Hodgkin lymphoma (HL) is one of the most treatable cancers affecting adolescent and young adult (AYA) patients (15 - 39 years), however optimal therapy for de novo disease in this population remains a subject of debate. Population-based studies in HL consistently report a survival disadvantage for AYAs when compared with younger patients. Though the etiology of these disparities is unclear, analyses of clinical trials data suggest that observed survival differences may relate to treatment, rather than to age. Because registry analyses are often limited by lack of information about clinical characteristics and therapeutic exposures, the independent effect of age on HL-outcome outside of the cooperative group setting is unknown. To address this gap in the literature, we: (1) examined initial treatment regimen and patterns of care in a population-based cohort of AYAs compared to children with de novo HL, and (2) examined the impact of sociodemographic and clinical variables on overall survival (OS) and disease-specific survival (DSS) by age, after adjusting for therapy. Methods: Data for 4,426 patients aged 0 - 39 years diagnosed with classical HL between 2007 and 2016 were obtained from the California Cancer Registry (CCR). Detailed treatment information for each patient was extracted from unstructured free-text fields in the CCR database. Chemotherapy regimens were classified based on standard treatment approaches for adult and pediatric HL (Table). Multivariable cox proportional hazards regression models were used to examine the influence of sociodemographic and clinical variables on OS and DSS, overall and by age group, and are presented as adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Models were adjusted for race/ethnicity, sex, insurance, neighborhood socioeconomic status, histology, stage, B symptoms, treatment location at a NCI (National Cancer Institute)-designated cancer center, and radiation therapy (RT). Results: Of the 4,426 patients in this cohort, 33% were <21 years (y) (N= 1,479) and 67% were 22 - 39y (N= 2,947). At median follow-up of 4.4 years, 3-year OS in the full cohort was 95%. Front-line therapy for patients with HL differed significantly across age groups (Table). Approximately 42% of patients <21y received ABVD vs. 69% of older patients. Compared with older patients, a higher proportion of younger patients received ABVE-PC (younger: 8.8% vs. <1%) and modified treatment regimens (younger: 24% vs. 9.6%). Regimens were considered modified if they omitted one drug from a standard protocol but were otherwise administered according to expected dosing schedules; the most common were ABV (18%) and AVD (15%). A higher proportion of patients with private (vs. public/no) insurance received STANFORD V chemotherapy. In total, 40% of patients aged <21y received RT as part of initial therapy vs. 27% of patients 22 - 39y. In survival models, increasing age was associated with a higher risk of death. Compared with patients <14y, the hazard of death from HL was over three-fold higher in patients 22 - 29y (aHR=3.1, CI: 1.1, 9.1) and 30 - 39y (aHR=3.8, CI: 1.3, 11.2). In multivariable models stratified by age, race/ethnicity, insurance, B-symptoms and stage were each significantly associated with survival. In patients <21y, NHBs (aHR: 7.1, CI: 2.4, 20.6) and Hispanics (aHR: 2.5, CI: 1.0, 6.4) experienced worse DSS than NHWs. Having public or no insurance also conferred worse OS (aHR: 1.9, CI: 1.1, 3.5), but initial therapy did not significantly impact OS or DSS. Among those aged 22 - 39y, NHB patients had worse OS (aHR: 1.7, CI: 1.0, 2.8) as did patients with public or no insurance (aHR: 1.7, CI: 1.2, 2.3). Stage IV disease was associated with inferior OS (aHR: 2.9, CI: 1.3, 6.8) and DSS (aHR: 3.3, CI: 1.1, 9.6). Finally, modified treatment regimens (vs. ABVD) were associated with worse OS (aHR: 1.6, CI: 1.0, 2.5), but did not significantly impact DSS in AYAs. Conclusion: In this large, population-based cohort of children and AYAs with HL, we observed that initial therapy varies, but that the majority of AYAs receive ABVD. Variation in therapy was largely insufficient to explain observed survival disparities, as older age, NHB and Hispanic race/ethnicity, and public or no insurance each conferred increased risk of death, even after adjustment for chemotherapy regimen. Further analyses examining comorbidities, treatment-related toxicities, and cause of death are ongoing. Disclosures No relevant conflicts of interest to declare.

Abstract MDS is a heterogeneous group of hematopoietic stem cell disorders. Various prognostic models have been established to categorize patients with MDS including the International Prognostic Scoring System (IPSS), the Revised-IPSS (r-IPSS) and MDACC Scoring System. In this analysis, we compared those three classification schemas for their outcome predictability after HSCT. We analyzed 291 MDS patients with a median age of 55 (interquartile range (IQR) 47-60.7 years) who underwent HSCT between January 2001 and December 2011. Histology by WHO classification included RA/RARS 48 (16.5%), RCMD 28 (9.6%), RAEB-1 59 (20.2%), RAEB-2 63 (21.7%), MDS unclassified 67 (23%), and CMML 26 (9%). Of 291, 117 patients (40.2%) had therapy related MDS (t-MDS). Conditioning regimen was myeloablative in 201 patients (69.1%) and reduced intensity in 90 patients (30.9%). Donors were matched related (MRD), matched unrelated (MUD), mismatched (MMD) in 131 (45%), 114 (39.2%) and 46 (15.8%) patients respectively. Risk categorization was performed by IPSS, r-IPSS and MDACC scoring systems at the time of diagnosis. IPSS, r-IPSS and MDACC scoring systems could be assessed in 239 (82.1%), 241 (82.8%) and 231 (79.4%) patients respectively. The median follow up time of 109 survivors was 45 months. The median time from diagnosis to HSCT was 7.3 months (IQR 4.6-12.4 months). Three-year overall survival (OS) was 38.1% (95%CI 32.3-43.9) with 3-year event free survival (EFS) of 34.2% (95%CI 28.4-40). Cumulative relapse incidence (RI) at 3-year was 28.8% (95%CI 23.3-34.5). Cumulative incidence of treatment related mortality (TRM) at 3 year post-transplant was 27.9% (95%CI 22.6-33.6). In univariate analysis, IPSS and r-IPSS were able to differentiate 2 risk groups for OS and EFS. High risk group per IPSS and very high risk group per r-IPSS had lower OS with hazard ratio (HR) of 2.4 to 3.1, lower EFS with HR of 2.2 to 2.7. While IPSS could not predict RI, very high risk group by r-IPSS had higher RI with HR of 3.6 compared with lower risk groups. Both IPSS and r-IPSS did not identify different risk groups for TRM. On the other hand, MDACC scoring system was able to identify 4 different risk groups for EFS and OS in univariate analysis. Three-year OS was 68%, 46.1%, 30.3% and 11.4% for patients with MDACC risk score of 0-4, 5-6, 7-8 and ≥9 respectively (p<0.001) (figure1). Three-year EFS with MDACC risk score of 0-4, 5-6, 7-8 and ≥9 was 61.7%, 40.8%, 28.1% and 7.4% respectively (p<0.001). For RI and TRM, only MDACC risk scores of ≥9 was associated with poor outcomes with 3-year RI of 38.9% and 3-year TRM of 41.7% compared with 13.3% and 15.5% in risk scores of 0-4 (p=0.01 and p=0.01 respectively). In multivariate analysis, MDACC score, matched unrelated and mismatched donors were associated with inferior OS (table1). As a summary, MDACC risk scoring system for MDS better differentiates prognostic groups than IPSS or r-IPSS. Considering the high frequency of t-MDS among transplanted MDS patients, we propose that MDACC scoring system should be used for prognostic classification for hematopoietic transplantation. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Aurora kinases play essential roles in regulating cell division, and increased expression has been noted in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We previously conducted a phase I study of alisertib combined with "7+3" induction chemotherapy in untreated patients with AML, and found the combination to have an adverse event profile similar to 7+3 alone, with promising efficacy, particularly for patients with high-risk disease, such as those who were older, with high-risk molecular features, or with secondary AML. These patients collectively have a historically grim prognosis, with an approximate rate of remission, in trials, of 45%. CPX-351, a liposomal daunorubicin-cytarabine product, was recently approved for use in secondary AML after it was demonstrated to be superior to 7+3 induction, with a median survival of 9.6 months versus 5.9 months among older patients, in a phase 3 trial. We recently completed accrual to a phase II study of alisertib plus induction chemotherapy in patients with untreated, high-risk AML. Methods: Patients were eligible if they had AML defined by WHO 2016 and either an adverse-risk karyotype (European Leukemia Net Guidelines), secondary (post-MDS/MPN) AML, therapy-related AML, or age ≥ 65 vears. We used a Simon two-stage design, assuming a null composite remission rate (complete remission [CR] and CR with incomplete count recovery [CRi]) of 45%. Patients could be enrolled prior to cytogenetic classification, but those without adverse-risk karyotype who lacked other eligibility criteria were removed before day 8 and replaced. All patients received continuous infusion cytarabine 100mg/m2 on days 1-7 [D1-7] and idarubicin 12mg/m2 [or daunorubicin 60mg/m2] D1-3 (7+3). On D8 through D15, alisertib at 30mg BID orally (PO) was administered. All underwent a mid-induction marrow biopsy to assess for residual disease, which if present, was treated with 5+2 re-induction without alisertib. Following remission, patients could receive up to 4 consolidation cycles with cytarabine (3g/m2 BID D1,3,5 for age <60 and 2g/m2 daily D1-5 for age ≥60) with alisertib PO at 30mg BID, D6-12, and alisertib maintenance at 30mg BID PO (D1-7 of 3 week cycles) thereafter for 12 months. Patients who pursued stem cell transplant (SCT) were followed for EFS and OS. Results: 39 eligible patients were enrolled. The median age was 67 (range 33-83); 25 (64%) were male, and 33 (85%) were Caucasian. 22 patients (56%) had secondary AML (16 with antecedent MDS, 2 with antecedent CMML, 1 with antecedent MPN, and 3 with therapy-related AML). 13 (33%) exhibited adverse risk karyotype. FLT3 mutations were seen in 7 (18%), NPM1 in 7 (18%), IDH1 in 5 (13%), IDH2 in 5 (13%), CEBPA in 3 (8%), and TP53 mutations in 4 (10%) patients. 33 patients (85%) demonstrated an ablated marrow at mid-treatment, and six (15%) received re-induction at mid-treatment. 8 patients (21%) were refractory to induction, and five (13%) died prior to response assessment due to infection or bleeding. The 30-day and 60-day mortality rates were 8% and 13%, respectively. Patients experienced expected grade 4 toxicities of leukopenia, anemia, thrombocytopenia, and febrile neutropenia; no new attributable safety signals were detected. The CR+CRi rate was 64% (2-stage 95% CI 48-79%) with 20 patients (51%) achieving CR and 5 (13%) achieving Cri. The CR+CRi rate was 59% (13 of 22) in those with secondary AML, 67% (18 of 27) in those aged ≥ 65, 77% (10 of 13) in those with adverse risk karyotype, and 75% (3 of 4 patients) in patients with TP53 mutations. One (3%) patient achieved a partial remission. Based on the composite remission rate of 64%, the combination was deemed effective per study design. 5 patients have relapsed to date. 10 have received at least 1 cycle of consolidation, 16 patients (41%) have gone on to SCT. With a median follow-up of 14 months (Figure), the 12-month overall survival (OS) is 51% (37-65%). Although the data continues to mature, median OS is 12.2 months (90% CI 8.8-NA). In the subset of patients achieving a CR+CRi, the 12-month relapse-free survival was 52% (90% CI 34-67%). Conclusions: Alisertib, a novel aurora A kinase inhibitor, combined with conventional induction, is efficacious and demonstrates a promising rate of remission and survival among patients with previously untreated high-risk AML. Larger randomized studies are under consideration to better assess the promise of this novel combination. Figure. Figure. Disclosures Brunner: Takeda: Research Funding; Novartis: Research Funding; Celgene: Consultancy, Research Funding. DeAngelo:Glycomimetics: Research Funding; ARIAD: Consultancy, Research Funding; BMS: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria; Shire: Honoraria; BMS: Consultancy; Amgen: Consultancy; Pfizer Inc: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Glycomimetics: Research Funding; ARIAD: Consultancy, Research Funding; Amgen: Consultancy; Takeda: Honoraria; Blueprint Medicines: Honoraria, Research Funding. Amrein:Takeda: Research Funding. Steensma:Acceleron: Consultancy; Amphivena: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; H3 Biosciences: Research Funding; Janssen: Consultancy, Research Funding; Kura: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Onconova: Consultancy; Otsuka: Membership on an entity's Board of Directors or advisory committees; Syros: Research Funding; Takeda: Consultancy. Garcia:Celgene: Consultancy. Rosenblatt:Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees. Chen:Magenta Therapeutics: Consultancy; REGiMMUNE: Consultancy; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Consultancy. Fathi:Astellas: Honoraria; Seattle Genetics: Consultancy, Honoraria; Boston Biomedical: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Agios: Honoraria, Research Funding; Jazz: Honoraria.

Abstract Therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute myeloid leukaemia (ICD-O code 9920/3) (t-AML) represent a serious long term complication in patients successfully treated for primary malignancies (PM) using chemotherapy, radiation therapy or a combination of these therapies. Factors that contribute to the incidence of t-MDS/t-AML include, the type and duration of the therapeutic regime used to treat the PM and host predisposition. Conventional techniques to identify genomic aberrations in t-MDS/t-AML, suffer from low throughput and poor resolution. Recent developments in single-nucleotide polymorphisms (SNP) microarray technology have enabled the exploitation of SNP arrays for high-resolution genome-wide genotyping. We investigated the frequency of chromosomal aberrations and polymorphisms in the GSTM1, GSTT1, GSTP1 and NAT2 enzymes in patients developing t-MDS/t-AML following adjuvant therapy for breast cancer. Using 250K SNP arrays we have analysed two cohorts of similarly treated patients (median age 56 years, range 26–75 years), one group developing t-MDS/t-AML (+t-MDS) and the other remaining disease free (control) within the same follow up time. In all cases constitutive DNA was also simultaneously analysed. We detected multiple chromosomal aberrations including copy number aberrations (CNA) and UPD summarised in Table 1. Table 1 Amplifications Deletions UPD No.of pts (%) Median (range) Mb No. of pts (%) Median (range) Mb No. of pts (%) Median (range) Mb + t-MDS (n=17) 10 (48) 1.4(0.2–105) 13 (62) 8.8(0.04–125) 9 (43) 4.4(2.1–35.4) Control (n=30) 6 (20) 0.4(0.2–2.5) 9 (30) 0.3(0.2–0.7) 15 (50) 3(2–14) There is a distinct difference in CNA between both groups of patients. Interestingly, we identified CNA in the peripheral blood of patients (67%) not developing t-MDS/t- AML which was not observed in any of our normal control samples with no history of chemotherapy. The frequency of both deletions and amplifications was almost twice in + tMDS group in comparison to control samples. Furthermore, the frequency (43% vs. 50%) and median size of UPD (4.4Mb vs. 3Mb) was similar between both groups respectively. SNP array data was also used to test for an association with t-MDS/t-AML. Relative risk (RR) was estimated to determine the effect of each SNP on the risk of t-MDS/t-AML development, with patients not developing t-MDS/t-AML. SNP’s were included in the analysis if they physically mapped onto a gene, tagging SNP’s and met a significance criteria (p&lt;0.001 and 3&lt;RR&lt;0.33). Our results show tagging SNP’s on XRCC4 (p=0.000027, RR=0.020, RUNX1 (p=0.000074, RR=7.8), L3MBTL3 (p=0.0000093, RR=9.6), SUFU (p=0.000087, RR=5.42), ANXA11 (p=0.0002, RR=13.99) and ETFDH (p=0.000865, RR=8.01) to be significantly associated in breast cancer patients developing t-MDS/t- AML. There was no significant difference in the frequency of the GSTM1 homozygous deletion, however, the GSTT1 homozygous deletion was significantly present (p&lt;0.05) in the + t-MDS group. In addition, the double polymorphic deletion (GSTM1 & GSTT1) was significantly present (p&lt;0.01) in patients developing t-MDS/t-AML in comparison to de-novo AML and MDS patients, agreeing with previously published data. There was no significant difference in the incidence of GSTP1 exon 5/6 mutations or NAT2 mutations in both the groups. Our data clearly identifies the utility of using high resolution SNP arrays to identify significant SNP’s in genes which may contribute to the pathogenesis of t-MDS/t-AML as well as suggesting that the double deficiency of GSTT1/GSTM1 or single GSTT1 deletion marks a risk for developing haematological malignancies after adjuvant therapy for breast cancer.

Abstract Introduction Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable, potentially life-threatening complication of conditioning for hematopoietic stem cell transplant (HSCT). Severe VOD/SOS (ie, with multi-organ dysfunction [MOD]) may be associated with >80% mortality. Defibrotide is approved for treatment of severe VOD/SOS in the EU. In the US, defibrotide is available through an ongoing, expanded-access study. The optimal time to initiate VOD/SOS treatment with defibrotide is of interest. Methods In the expanded-access study, patients were eligible in the original protocol if they had VOD/SOS and renal/pulmonary MOD by Baltimore criteria post-HSCT or by biopsy. The protocol was amended to include (1) post-chemotherapy patients, (2) patients without MOD, and (3) VOD/SOS per modified Seattle criteria. Defibrotide 25 mg/kg/day was given in 4 divided doses for a recommended ≥21 days. Here, Day +100 survival in patients with HSCT was examined post hoc based on time from VOD/SOS diagnosis (with or without MOD as relevant to study entry criterion) to initiation of defibrotide. Two analyses were conducted: (1) survival rate analyzed by treatment initiation for the entire population before or after each of the following days: 1, 2, 3, 4, 7, and 14, using Fisher's exact test; (2) survival rate for only those patients with treatment initiated on a particular day: 0, 1, 2, 3, 4, 5, 6, 7, 8-14, and ≥15, with a Cochran-Armitage test for trend across days. Results Among HSCT patients enrolled through 2013 who received ≥1 dose of defibrotide, treatment date was available for 573 patients. Of these, 351 also had MOD. Defibrotide was started on the day of diagnosis in >30% of patients; >90% of patients started defibrotide before day 7 post-diagnosis. In the population-wide analysis of treatment initiation before or after days 1, 2, 3, 4, 7, and 14, earlier initiation of defibrotide was associated with higher survival rates (Table), and was statistically significant for all cut-points considered except 14 days, with only 2.8% of patients beginning treatment post-day 14. Survival differences between earlier vs. later initiation ranged from 8.8% to 22.1% overall (MOD: 12.8% to 25.6%; Table) for the cut-points considered. In the analysis of relationship between Day +100 survival and treatment initiation day, survival rates were generally higher if treatment was initiated earlier. This was demonstrated by a statistically significant trend over time for better outcomes with earlier initiation (Figure). Similar results for both analyses were obtained for all patients with VOD/SOS and for the subgroup of patients with MOD. Conclusions Data indicate decreased Day +100 survival associated with longer treatment delays, confirmed by the Cochran Armitage trend test (P<0.001). Thus, defibrotide treatment should be initiated as soon as possible after VOD/SOS diagnosis. Table. Day +100 Survival by Defibrotide Initiation Day n (%) HSCT VOD/SOS (N=573) HSCT VOD/SOS with MOD (n=351) Initiation Period Alive Dead Unknown Alive Dead Unknown ≤1 Day 183 (53.5) 142 (41.5) 17 (5.0) 103 (50.2) 93 (45.4) 9 (4.4) >1 Day 105 (45.5) 116 (50.2) 10 (4.3) 56 (38.4) 85 (58.2) 5 (3.4) Difference (95% CI)a 8.8% (0.2%, 17.3%) 12.8% (2.0%, 23.4%) P valueb 0.045 0.021 ≤2 Days 235 (55.7) 166 (39.3) 21 (5.0) 132 (52.2) 111 (43.9) 10 (4.0) >2 Days 53 (35.1) 92 (60.9) 6 (4.0) 27 (27.6) 67 (68.4) 4 (4.1) Difference (95% CI)a 22.1% (12.6%, 31.2%) 25.6% (13.8%, 36.9%) P valueb <.001 <.001 ≤3 Days 251 (53.5) 193 (41.2) 25 (5.3) 138 (49.5) 129 (46.2) 12 (4.3) >3 Days 37 (35.6) 65 (62.5) 2 (1.9) 21 (29.2) 49 (68.1) 2 (2.8) Difference (95% CI)a 20.3% (9.6%, 30.8%) 21.7% (8.6%, 34.5%) P valueb <.001 0.001 ≤4 Day 263 (52.6) 212 (42.4) 25 (5.0) 146 (48.7) 142 (47.3) 12 (4.0) >4 Day 25 (34.2) 46 (63.0) 2 (2.7) 13 (25.5) 36 (70.6) 2 (3.9) Difference (95% CI)a 20.2% (7.7%, 32.4%) 24.2% (9.1%, 38.9%) P valueb 0.002 0.002 ≤7 Days 275 (51.6) 232 (43.5) 26 (4.9) 152 (47.4) 156 (48.6) 13 (4.0) >7 Days 13 (32.5) 26 (65.0) 1 (2.5) 7 (23.3) 22 (73.3) 1 (3.3) Difference (95% CI)a 20.9% (4.5%, 37.1%) 25.2% (6.1%, 43.8%) P valueb 0.013 0.011 ≤14 Days 282 (50.6) 249 (44.7) 26 (4.7) 156 (45.9) 171 (50.3) 13 (3.8) >14 Days 6 (37.5) 9 (56.3) 1 (6.3) 3 (27.3) 7 (63.6) 1 (9.1) Difference (95% CI)a 13.1% (-12.9%, 39.5%) 17.7% (-14.6%, 51.5%) P valueb 0.433 0.344 aAlive and Dead. 95% CI calculated using exact method. bFisher's exact test, Alive and Dead. Support: Jazz Pharmaceuticals. Disclosures Richardson: Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Defibrotide is an investigational treatment for hepatic veno-occlusive disease/sinusoidal obstruction syndrome in the United States.. Kernan:Gentium S.p.A.: Research Funding. Grupp:Novartis: Consultancy, Research Funding. Antin:Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Miloslavsky:Jazz Pharmaceuticals: Employment, Equity Ownership. Hume:Jazz Pharmaceuticals: Employment, Equity Ownership. Hannah:Jazz Pharmaceuticals: Consultancy. Nejadnik:Jazz Pharmaceuticals: Employment, Equity Ownership. Soiffer:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees.

Методом цитратной золь-гель технологии получен новый двойной борат рубидия–гольмия состава Rb3HoB6O12. Соединение кристаллизуется в тригональной сингонии (пр. гр. R32, a = 13.4038(7), с = 30.315(2) Å, V = 4716.76 Å3) и плавится инконгруэнтно при 818 °С. Попытки получить в однофазном состоянии Rb3HoB6O12 методом твердофазных реакций не привели к положительному результату REFERENCES Wu C., Yang G., Humphrey M.G., Zhang C. Recent advances in ultraviolet and deep-ultraviolet secondorder nonlinear optical crystals // Chem. Rev., 2018, v. 375, pp. 1–30. https://doi.org/10.1016/j.ccr.2018.02.017 Bubnova R., Volkov S., Albert B., Filatov S. Borates – crystal structures of prospective nonlinear optical materials: high anisotropy of the thermal expansion caused by anharmonic atomic vibrations // Crystals, 2017, v. 7, pp.1–32. DOI: 10.3390/cryst7030093 Becker P. Borate materials in nonlinear optics // Mater., 1998, v. 10, pp. 979–992. https://doi.org/10.1002/(SICI)1521-4095(199809)10:13<979::AIDADMA979>3.0.CO;2-N Chen C., Li R. The anionic group theory of the nonlinear optical effect and its applications in the development of new high-quality NLO crystals in the borate series // Rev. Phys. Chem., 1988, v. 8, pp. 65–91. https://doi.org/10.1080/01442358909353223 Chen C., Wu Y., Jiang A., Wu B., You G., Li R., Lin S. New nonlinear-optical crystal: LiB3O5 // Opt. Soc. Am. B: Opt. Phys., 1989, v. 6, pp. 616–621. https://doi.org/10.1364/JOSAB.6.000616 French R. H., Ling J. W., Ohuchi F. S., Chen C. T. Electronic structure of b-BaB2O4 and LiB3O5 nonlinear optical crystals // Rev. B: Condens. Matter, 1991, v. 44, pp. 8496–8502. https://doi.org/10.1103/Phys-RevB.44.8496 Yusuke Mori, Ikio Kuroda, Satoshi Nakajima, Takamoto Sasaki, Sadao Nakai. New nonlinear optical crystal: Cesium lithium borate // Phys. Lett., 1995, v. 67, pp. 1818–1820. https://doi.org/10.1063/1.115413 Haohai Yu, Zhongben Pan, Huaijin Zhang, Jiyang Wang. Recent advances in self-frequency-doubling crystals // Materiomics, 2016, v. 2, pp. 55–65. https://doi.org/10.1016/j.jmat.2015.12.001 Bajor A.L., Kisielewski J., Klos A., Kopzyński K., Lukasiewicz T., Mierczyk J., Mlyńczak J. Assessment of gadolinium calcium oxoborate (GdCOB) for laser applications // Opto-electronics Review, 2011, v. 19, pp. 439–448. https://doi.org/10.2478/s11772-011-0042-2 Dan Zhao, Cong-Kui Nie, Ye Tian, Bao-Zhong Liu, Yun-Chang Fan, Ji Zhao. A new luminescent host material K3GdB6O12: synthesis, crystal structure and luminescent properties activated by Sm3+ // Kristallogr., 2018, v. 233, pp. 411–419. https://doi.org/10.1515/zkri-2017-2101 Dan Zhao, Fa-Xue Ma, Rui-Juan Zhang, Wei Wei, Juan Yang, Ying-Jie Li. A new rare-earth borate K3LuB6O12: crystal and electronic structure, and luminescent properties activated by Eu3+ // Mater Sci: Mater Electron., 2017, pp. 1–9. https://doi.org/10.1007/s10854-016-5501-6 Atuchin V. V., Subanakov A. K., Aleksandrovsky A. S., Bazarov B. G., Bazarova J. G., Dorzhieva S. G., Gavrilova T. A., Krylov A. S., Molokeev M. S., Oreshonkov A. S., Pugachev A. M., Tushinova Yu. L., Yelisseyev A. P. Exploration of structural, thermal, vibrational and spectroscopic properties of new noncentrosymmetric double borate Rb3NdB6O12 // Powder Technol., 2017, v. 28, pp. 1309–1315. https://doi.org/10.1016/j.apt.2017.02.019 Atuchin V. V., Subanakov A. K., Aleksandrovsky A. S., Bazarov B. G., Bazarova J. G., Gavrilova T. A., Krylov A. S., Molokeev M. S., Oreshonkov A. S., Stefanovich S. Yu. Structural and spectroscopic properties of new noncentrosymmetric selfactivated borate Rb3EuB6O12 with B5O10 units // Des., 2018, v. 140, pp. 488–494. https://doi.org/10.1016/j.matdes.2017.12.004 Sangen Zhao, Guochun Zhang, Jiyong Yao, Yicheng Wu. K3YB6O12: A new nonlinear optical crystal with a short UV cutoff edge // Res. Bull., 2012, v. 47, pp. 3810–3813. https://doi.org/10.1016/j.materresbull.2012.05.062 Miriding Mutailipu, Zhiqing Xie, Xin Su, Min Zhang, Ying Wang, Zhihua Yang, Muhammad Ramzan Saeed Ashraf Janjua, Shilie Pan. Chemical cosubstitution- oriented design of rare-earth borates as potential ultraviolet nonlinear optical materials // Am. Chem. Soc., 2017, v. 139, pp. 18397–18405. https://doi.org/10.1021/jacs.7b11263 Li Yang, Yingpeng Wan, Honggen Weng, Yanlin Huang, Cuili Chen, Hyo Jin Seo. Luminescence and color center distributions in K3YB6O12 : Ce3+ phosphor // Phys. D: Appl. Phys., 2016, v. 49 (325303), pp. 1–12. https://doi.org/10.1088/0022-3727/49/32/325303

Abstract Background: In the AZA-001 trial, azacitidine (AZA) altered the natural history of patients with higher-risk MDS (Fenaux et al., Lancet 2009) by significantly improving overall survival compared to conventional care regimens (24.5 months versus 15.0 months). Once approved for drug reimbursement by the provincial health ministry, Cancer Care Ontario (CCO) mandated that all eligible patients be enrolled in a prospective registry to ensure compliance with eligibility criteria and schedules of drug administration. Baseline characteristics were recorded and treatment response were to be submitted every 6 cycles of treatment. Our objectives were to audit this clinical program for results after 6 years and identify the prognostic markers for survival in a homogenous higher-risk MDS/low blast count AML patient population. Methods: Only higher-risk MDS patients (intermediate-2, high) as defined by the International Prognostic Scoring System (IPSS) and low blast count AML (20-30% blasts) treated with AZA in Ontario, Canada from June 1, 2010 to March 2, 2016 were eligible and included. Our primary outcome was overall survival (OS) from date of first AZA treatment. Our secondary outcomes were overall response rates and the predictors of OS including administration schedules, centre size or type (regional cancer versus community). Univariate and multivariable Cox proportional hazard model were used to determine the predictors of OS. Hazard ratios and generalized R2 (higher the R2, stronger association with OS) were also calculated. Results: 825 higher-risk MDS and 276 low blast count AML were included (n = 1101 total). Median age was 74 years (range 19 to 99), 65.2% were male and the IPSS scores were intermediate-2 (64.3%) and high-risk (35.7%). Sixty-six percent of patients were transfusion dependent (TD) at time of AZA initiation and 15.5% had received previous chemotherapy. By dosing schedule, 24.7% received AZA for 7 consecutive days (7d), 12.4% for 6 consecutive days (6d) and 62.9% by the 5-2-2 schedule. Overall, the median number of cycles received was 6 (range 1 to 67) and 8 (range 6 to 14) when restricted to the 692 (63%) patients who received at least 4 cycles of treatment. Dose reductions were seen in 33.3% of patients (mean 11.1 mg/m2 in those with reductions) and were more common over time (negative slope 0.178; p < .0001). Of those with repeat bone marrow (n = 293) best response was complete response (CR) in 16.7% and partial response (PR) in 10.6%. Of those without CR/PR/progressive disease on bone marrow (n = 814), 20.4% experienced hematologic improvement including those with marrow CR and marrow stable disease. The actuarial median survival was 11.6 months (95% CI 10.7- 12.4) with a significantly longer OS for MDS compared with low blast count AML (12.4 months vs. 9.6 months; p = .0002) and 16.7 months (95% CI 15.2-18.1) for those receiving at least 4 cycles. There was no difference in OS between the 3 dosing schedules (11.7 months (7d) vs. 10.2 months (6d) vs. 12.0 months (5-2-2); p = .87; figure 1A), regional cancer centre vs. community (11.3 months vs. 11.7 months; p = .19; figure 1B) or by centre volume (11.4 months < 50 patients vs. 11.6 months > 50 patients; p = .38; figure 1C). On univariate analysis, the following were predictive of OS: blast percentage, number of cytopenias, karyotype, IPSS, WHO classification, TD, greater transfusion burden and secondary MDS. The multivariate model with the highest R2 (13.5%) included blast percentage (p < .0001), karyotype (p < .0001), cytopenias (p = .038), TD (p < .0001) and secondary MDS (p = .0006) as summarized in the table below. Conclusions: In our large real world evaluation of AZA use in higher-risk MDS/low blast count AML, we validated the expected overall response rates to AZA but demonstrated a lower than expected OS compared to the AZA-001 trial. Reassuringly, survival did not differ by dosing schedules, centre volumes or center type (regional cancer vs. community). OS was higher in the 2/3 of patients who received at least 4 cycles of treatment, reinforcing the necessity of sustained administration until therapeutic benefits are realized. This represents the largest real world evaluation of AZA in higher-risk MDS/low blast count AML and additional analyses are underway. Table Table. Figure 1 Figure 1. Disclosures Mozessohn: Celgene: Honoraria. Buckstein:Celgene: Honoraria, Research Funding; Novartis: Honoraria.

Abstract Background Meeting clinical requirements for platelets and plasma requires an understanding of usage, in order to plan for evolving demand and ensure supply in emergencies. Current strategies to ensure availability during increased demand or blood shortages include triaging by restricting supply to clinically urgent cases or deferring elective surgery. However, few data regarding urgency of need for different clinical indications are available. We developed a novel approach to clinical profiling of platelets and plasma to inform supply and contingency planning. Methods We conducted a random sample survey of platelet and plasma units in the Australian state of Victoria (population 5.3 million). The Australian Red Cross Blood Service produces and distributes all platelets and plasma for the state at a single site. Randomly selected units were tagged with a case report form (CRF) during production and distributed as usual. Institutional blood bank scientists completed the CRF when tagged units were issued for transfusion, reporting recipient demographics, clinical indication for transfusion, and transfusion urgency. Units were tagged over 12 months to minimize seasonal fluctuations. Results 1252 platelet units were tagged: 752 pooled (60%) and 500 apheresis units (39.9%). This represented 7.6% of issues during the study period (7.4% of pooled and 8.0% of all apheresis platelets). The fate of 1243 platelet units was determined (99.3%). Of these, 94 (7.6%) were discarded during production before issue and were excluded from analysis. 1885 plasma units were tagged, representing 9.6% of units issued. The fate of 1808 units was determined (95.9%). Transfusion rate for issued platelets was 72.2% (830 units); 71.2% of pooled and 73.7% of apheresis platelets were transfused. Common reasons for discard were expiry (300 units, 26.1%); recall (5, 0.4%), commonly for bacterial flags; and other (14, 1.2%). Transfusion rate for issued plasma was 87.8% (1587 units). Common reasons for discard were were expiry (48 units, 2.7%), recall (3, 0.2%) and other reasons including breakage and unit thawed but not used (170, 9.4%). Median age of platelets recipients was 58 years (range 0–99); 60.6% were male; for plasma recipients median age was 51 (0-98); 64.1% were male. For platelets, the clinical urgency of transfusion was reported to be acute (required within one hour) in 126 cases (15.2%); urgent (required within 24h) 527 (63.5%); semi-urgent (required within one week) 130 (15.7%); non-urgent 2 (0.2%); unreported 45 (5.4%). The most common indications for platelet transfusion were hematological and oncological, together 64% of cases (530 units), comprising acute leukemias 260 (31.3%); lymphoma 59 (7.1%); myeloma 35 (4.2%); non-hematologic malignancies 68 (8.2%). Surgical conditions followed: 25.1% (208) of cases, comprising cardiothoracic 91 (11.0%); urological 30 (3.6%); gastrointestinal 18 (2.2%) and solid organ transplantation 16 (1.9%). Clinical condition was not reported in 40 (4.8%). Only 66 platelet units (7.9%) were transfused to support elective surgery. For plasma, urgency was reported as acute in 566 (35.7%), urgent in 857 (54.0%); semi-urgent in 84 (5.3%) and non-urgent in 13 (0.8%) and unreported in 67 (4.2%). The most common indications for plasma transfusion were surgical: cardiothoracic 249 cases (15.7%); vascular 87 (5.5%); gastrointestinal 58 (3.7%); orthopedic 29 (1.8%). Others included hematology (234 cases, 14.7%), mainly to support TTP patients (139, 8.8% of total); gastroenterology (227, 14.3%), mainly to support chronic liver disease patients (114, 7.2% of total) and trauma (104, 6.6%). Across all areas, 168 plasma units (18.9%) were transfused to support elective surgery and 179 (11%) to reverse warfarin. Conclusions The high levels of urgent transfusion and low proportion of platelets and plasma used in elective surgery seen here suggest that in a shortage conventional triage strategies would have little impact on demand. Clinical platelet and plasma usage is highly concentrated in specialized areas, predominantly to support patients with hematologic and malignant disorders, those undergoing major non-elective surgery, and the critically ill. Changes in demand or clinical practice in these areas may have substantial effects on requirements. Additional strategies are required to ensure continued adequacy of supply during blood shortages or demand fluctuations. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Myelodysplastic syndrome (MDS) is a heterogeneous disease characterized by cytopenias and a propensity to progress into acute myeloid leukemia in a subset of patients. Clinical trials which led to FDA approval of hypomethylating agents (HMAs) stratified patient's risk status per the IPSS. In 2008, WHO further categorized patients into different groups and the IPSS was revised into the IPSS-R. Therefore, there is a paucity of data regarding the response rates and clinical outcomes of HMA therapy when stratified per WHO subtype and IPSS-R. Goal: We carried this review to assess whether WHO subtypes or IPSS-R had a differential response with corresponding impact on survival. Methods: After IRB approval, all MDS pts who received hypomethylating agents (HMA) (azacitidine or decitabine) with available response data (2000-2014) were included. Clinical characteristics were obtained retrospectively. IPSS-R (Greenberg 2012) was used for risk stratification. Response assessment was based on IWGR 2006 criteria. Statistical comparisons were performed with the χ2 test for categorical variables and the Wilcoxon test for continuous variables. Survival analysis was based on the Kaplan-Meier method and log rank test. For all analyses, P ≤ 0.05 was considered statistically significant. Results: We identified 823 pt in our MDS database; among those that received HMA therapy 70 patients (pts) had evaluable response data. The median age at diagnosis was 67 years (31-85) and 49 (70%) were males. MDS subtypes per WHO 2008 classification were 31(44%) RAEB1/2, 26(37%) RCMD, 10(14%) MDS-U, 2(3%) RARS, and 1(1%) MDS 5q. Fifteen (33%) patients had secondary MDS. 23(32%) developed AML, and median time to leukemic transformation was 14 months (7.8-21). Median time to start HMA was 2.7 months (0-77). Median follow up from initial diagnosis was 20 months (3-118) at which time 22(31%) deaths were documented. A. Patient characteristics: Prior to HMA therapy median laboratory values included; Hemoglobin 9.6 g/dL (6.6-14.8), ANC 1.1 x1010 (0.01-16), Platelet 66 x1010 (4-937), peripheral blast % 0 (0-18), and bone marrow blast % 5 (0-17). IPSS-R for our cohort was as the following, 15(27%) Very high, 14(25%) high, 10(18%) intermediate 12(21%) low, and 5(9%) very low risk. B. HMA Response rates based on WHO subtype: We observed no significant difference in response (p = 0.6) when comparing response rate among different groups. Response rates per WHO subtype were as follows: i. RAEB: 7 (22%) pts achieved CR/Marrow CR, 1(3%) had HI/PR, 17(55%), and 6(20%) had stable disease (SD) and progressive disease (PD), respectively. ii. RCMD: 2 (8%) pts achieved CR/Marrow CR, 4(16%) had HI/PR, 12(46%), and 8(30%) had SD and PD, respectively. iii. MDS-U: 1 (10%) pt achieved CR/Marrow CR, 1(10%) had HI/PR, 6(60%), and 2(20%) had SD and PD, respectively. iv. MDS 5q/RARS: 1(33%) had SD, and the remaining three pts had PD. C. HMA Response rates based on IPSS-R: i. Very low: 1(20%) had HI/PR, 3(60%), and 1(20%) had SD. ii. Low: 2(17%) pts achieved CR/Marrow CR, 3(25%) had HI/PR, 4(33%), and 3(25%) had SD and PD, respectively. iii. Intermediate: 2 (20%) pts achieved CR/Marrow CR, 5(50%), and 3(30%) had SD and PD, respectively. iv. High: 2(14%) pts achieved CR/Marrow CR, 2(14%) had HI/PR, 7(50%), and 3(21%) had SD and PD, respectively. v. Very high: 1(7%) pts achieved CR/Marrow CR, 9(60%), and 5(33%) had SD and PD, respectively. Comparing responses among IPSS-R risk stratification groups, was not statistically significant (p = 0.49). We did not observe a difference in response rate when we further classified pts into low risk (very low, low & intermediate), and high risk (high, very high) (p = 0.27). D. Response effect on Survival: Overall survival was not statistically different among responders (CR/Marrow CR/HI &PR) and non-responder (SD & PD); 22.3 vs 14.7 months respectively (p = 0.21) (Figure1). Conclusion: Using contemporary MDS risk stratification and WHO classification was not predictive of response to hypomethylating agents. Responders did not seem to benefit from prolongation of survival. Given the small sample size in this cohort, this should be further explored in larger groups to identify if there are any potential subgroups that would benefit more from such therapy. Figure 1. Figure 1. Disclosures Al-Kali: Celgene: Research Funding.

Abstract Background Hematologic toxicity is a common treatment complication of chronic hepatitis C virus (HCV) infection, especially when interferon (IFN) and ribavirin are used. The side effects of treatment are often augmented in cancer patients due to baseline cytopenias. These adverse events often lead to dose reduction or discontinuation of antivirals. Hematopoietic growth factors (GF) and blood transfusions are used to counteract toxicities allowing patients to complete treatment. We aimed to evaluate the incidence and management of hematological toxicity associated with different types of HCV treatment in cancer patients. Methods Medical records of cancer patients treated for HCV infection at MD Anderson Cancer Center between 2009 and 2014 were reviewed. Those seen from 8/2009 to 10/2012 were analyzed retrospectively, whereas those seen from 11/2012 to 7/2014 were prospectively studied. Patients who received combination treatment with peg-IFN and ribavirin (PR), telaprevir or boceprevir plus PR (TBPR), sofosbuvir plus PR (SPR), sofosbuvir with simeprevir (SS) and sofosbuvir with ribavirin (SR) were included in the study. Data regarding treatment interventions (dose reductions and/or discontinuation of antivirals), use of GFs or blood transfusions in the management hematological side effects were analyzed. Categorical variables were analyzed using the χ2 or Fischer's exact test. Results Sixty-five patients were identified (Table). The need for treatment interventions, GFs or blood transfusions was comparable between patients with hematologic malignancies and solid tumors. Seventeen (81%) of the PR group, 13 (93%) of the TBPR group, 6 (67%) of the SPR group, 9 (64%) of the SR group and 0 of the SS group required treatment interventions (p <0.001) (Figure). Twelve (57%) of the PR group, 9 (64%) of the TBPR group, 3 (33%) of the SPR group, 2 (14%) of the SR group and 0 of SS group required the use of GFs (p <0.01). Six (29%) patients of the PR group, 9 (64%) from the TBPR group, 1 (11%) from the SPR group, 1 (7%) from the SR group and 0 from the SS group received blood transfusions (p <0.01). From patients who received GFs (N=26), 2 received epoetin alfa, 11 darbepoetin alfa, 2 filgrastim, 17 pegfilgrastim, 4 eltrombopag and 1 romiplostim. Ten of them (39%) required multiple GFs, with darbepoetin alfa and pegfilgrastim being the most common combination. Combined use of GFs was only needed in those receiving TBPR (56%), PR (33%) or SPR (33%). Overall, 82% of the patients who received treatment interventions, 77% of those who received GFs and 47% of those who received blood transfusions were able to complete HCV treatment. Thirteen patients (62%) from the PR group, 12 (86%) from the TBPR group, 3 (33%) from the SPR group, 2 (14%) from the SR group and 0 from the SS group developed grade 3 or 4 hematologic toxicities (p <0.001). One (25%) of 4 patients receiving eltrombopag developed portal vein thrombosis. No other patients developed side effects attributed to GF support. Conclusions Hematologic toxicity during HCV treatment in cancer patients is common. The use of GFs helps manage such toxicity, allowing completion of antiviral therapy. The newer HCV direct-acting antiviral agents are associated with less hematological toxicity, requiring fewer interventions, GFs and blood transfusions. No hematologic side effects were seen with the IFN-free, ribavirin-free combination of SS. Abstract 4126. Table Characteristics of HCV-infected cancer patients treated with different antiviral regimens PR (N=21)% TBPR (N=14)% SPR (N=9)% SR (N=14)% SS (N=7)% Age, median (range) 54.3 (45-68) 59.7 (49-69) 54.7 (35-75) 62.7 (33-82) 60.9 (46-64) Male gender 13 (62) 6 (43) 4 (44) 8 (57) 4 (57) Type of cancer Solid Hematologic 16 (76)5 (24) 10 (71)4 (29) 4 (44)5 (56) 6 (43)8 (57) 4 (57)3 (43) Cirrhosis 5 (24) 7 (50) 2 (22) 3 (21) 6 (86) Baseline labs, median (range) Hemoglobin (g/dL) Platelets (x1,000 K/uL) Absolute Neutrophil count (K/uL) 12.8 (10-15.9)165 (83-408)1385 (940-6120) 13.5 (9.6-16.3)112 (52-397)2360 (800-4900) 13.8 (8.8-14.2)183 (121-268)2680 (1650-5810) 13.1 (9.8-15.5)179 (57-390)2490 (1040-4040) 13.8 (12.3-16.1)141 (59-239)3000 (1390-5030) FDA-recommended duration of antiviral treatment, weeks 24-48 24-48 12 12-24 12 Duration of antiviral treatment, median (range) 24 (2-48) 19 (3-52) 12 (1-12)* 12 (3-24)* 6 (3-12)* *Patients may still be on treatment. Figure Management of hematologic toxicity during HCV treatment of cancer patients Figure. Management of hematologic toxicity during HCV treatment of cancer patients Disclosures Torres: Genentech,: Consultancy; Vertex Pharmaceuticals: Consultancy, Research Funding; Merck & Co., Inc. : Consultancy, Research Funding; Gilead Sciences: Consultancy.

Introduction: Up to 40% of patients (pts) with previously untreated diffuse large B-cell lymphoma (DLBCL) fail to achieve remission, or relapse, with standard-of-care rituximab (R) plus CHOP (R-CHOP). Atezolizumab (atezo) is a fully humanized anti-programmed death-ligand 1 (PD-L1) antibody with a complementary mode of action to R. We present updated data from an ongoing Phase I/II study (NCT02596971) evaluating the safety and efficacy of atezo combined with R-CHOP (R-CHOP-atezo) in pts with previously untreated DLBCL. This is an updated analysis performed at the end of consolidation (EOC). Methods: This open-label, multicenter study enrolled adults with previously untreated advanced DLBCL (ECOG performance status 0-2). Pts received induction treatment with R-CHOP-atezo (8 x 21-day cycles of R [375mg/m2 i.v. on Day 1 (Cycles 1-8)] and atezo [1200mg i.v. on Day 1 (Cycles 2−8)], and 6 or 8 cycles of CHOP, as determined by the investigator [INV]). Pts who had a complete response (CR) at end of induction (EOI) received consolidation treatment with atezo 1200mg i.v. on Day 1 of Cycles 9─25, every 21 days for 12 months. Pts are followed for 12 months after EOC. Primary endpoints were safety and efficacy as determined by CR rate at EOI by an independent review committee (IRC) using Lugano 2014 criteria (modified to include required confirmation of CR at EOI by biopsy in cases with bone marrow involvement at baseline, and confirmation of a PET-based partial response [PR] by CT-based CR or PR). Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results: As of May 2019, 42 pts had enrolled and received treatment. Of these, 7 pts discontinued study treatment prior to EOI (protocol violation [n=1], adverse event [AE; n=4], progressive disease [PD; n=1] and withdrawn consent [n=1]); 5 more pts discontinued at EOI (PD [n=2] and PR [n=3]). Of 30 pts initiating consolidation treatment, 15 discontinued (AE [n=9], PD [n=3] and withdrawn consent [n=3]). Median observation time was 21.3 (0.7-29.2) months. Key baseline characteristics included: median age, 65 years; International Prognostic Index (IPI) score ≥3, 69%; cell of origin (COO; Nanostring): ABC (34%), GCB (53%), unclassified (12.5%). Among the 40 pts who received at least one dose of atezo, and were therefore evaluable for efficacy at EOI, 31 (77.5%) had a CR and 4 (10%) had a PR by IRC; PD occurred in 2 (5%) pts; 3 (7.5%) were not evaluable. At 6, 12, 18 (EOC) and 24 months, Kaplan-Meier estimates (95% CI) of INV-assessed PFS were 97.4% (82.8, 99.6), 83.6% (67.0, 92.3), 80.6% (63.5, 90.3) and 74.9% (54.3, 87.2), respectively, and those for OS were 100% (not evaluable), 97.5% (83.6, 99.6), 89.8% (75.1, 96.1) and 86.4% (70.0, 94.2), respectively. Kaplan-Meier survival curves for PFS and OS are shown in the Figure. All 42 pts in the safety population experienced ≥1 AE of any grade, with neutropenia (52.4%), constipation (42.9%) and fatigue (40.5%) the most common. Grade 3-4 AEs occurred in 28/42 (67%) pts during induction and 15/30 (50%) pts during consolidation. Hematologic events were the most common grade 3-4 AEs (Table). One fatal AE (unconfirmed progressive multifocal leukoencephalopathy) was reported during follow-up. Overall, 24% of pts had an AE of special interest (AESI). The most common AESIs during induction were lipase increased (n=1), hyperthyroidism (n=1) and amylase increased (n=1), and those during consolidation were lipase increased (n=2), pancreatitis (n=2) and hepatitis (n=2). These events were generally well managed by atezo discontinuation and steroid treatment, and were largely reversible. AEs led to discontinuation of any treatment in 15 (36%) pts. AEs that led to discontinuation of any treatment in ≥1 pt were neutropenia (n=3), lipase increased (n=3) and amylase increased (n=2). Despite a relatively high number of discontinuations due to AEs during consolidation, events were generally manageable and reversible and all pts maintained response at the time of the analysis. Exploratory biomarker data and minimal residual disease data will be presented. Conclusions: The EOI PET-CR response rate and preliminary PFS with R-CHOP-atezo are encouraging and at least comparable to those previously reported for R-CHOP. The overall safety profile of R-CHOP-atezo appears manageable and as expected, with no new safety signals reported with consolidation and no overall increase in toxicity other than immune-mediated events. Disclosures Younes: BMS: Research Funding; Epizyme: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; HCM: Consultancy; Genentech: Research Funding; Syndax: Research Funding; Xynomics: Consultancy; Biopath: Consultancy; Takeda: Honoraria; Abbvie: Honoraria; Roche: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Curis: Honoraria, Research Funding; Merck: Honoraria, Research Funding; AstraZeneca: Research Funding; Pharmacyclics: Research Funding. Burke:Celgene: Consultancy; Roche/Genentech: Consultancy; Gilead: Consultancy. Cheson:Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trillium: Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding; Portola: Research Funding; Kite: Research Funding; Gilead: Research Funding; Epizyme: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; Symbios: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Diefenbach:Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding; Genentech: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding; MEI: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Millenium/Takeda: Research Funding; Trillium: Research Funding. Hahn:Roche: Other: Roche paid airfare and accommodation for attendance at ASH 3 years ago . 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Lossos:NIH: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Janssen Scientific: Membership on an entity's Board of Directors or advisory committees. Vitolo:F. Hoffmann-La Roche: Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees. Yuen:Seattle Genetics, Inc.: Other: Travel expenses, Research Funding. Raval:Roche: Employment, Equity Ownership. Shivhare:F. Hoffmann-La Roche Ltd: Employment. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Sellam:Roche: Employment, Equity Ownership. Sharman:AstraZeneca: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria, Research Funding. OffLabel Disclosure: Atezolizumab (atezo) is a programmed death-ligand 1 (PD-L1) blocking antibody. In the United States, atezo is approved for treatment of pts with locally advanced or metastatic urothelial carcinoma who are: not eligible for cisplatin-containing chemotherapy (chemo) and whose tumors express PDL-1, or are not eligible for any platinum-containing chemo regardless of PD L1 status; or have disease progression during or following any platinum-containing chemo, or within 12 months of neoadjuvant or adjuvant chemo. Atezo is also approved: in combination with bevacizumab, paclitaxel and carboplatin for first-line treatment of pts with metastatic non-squamous non-small-cell lung carcinoma (NSCLC) with no EGFR or ALK genomic tumor aberrations, and for pts with metastatic NSCLC who have disease progression during or following platinum-containing chemo; in combination with paclitaxel protein-bound for the treatment of adults with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1; and in combination with carboplatin and etoposide, for the first-line treatment of adults with extensive-stage small cell lung cancer. Atezo is not approved for treatment of pts with multiple myeloma.

The aim of this paper was to identify which psycholinguistic variables are better predictors of performance for healthy participants in a picture naming task and in a picture categorization task. A correlation analysis and a Path analysis were carried out. The correlation analysis showed that naming accuracy and naming latency are significant and positively correlated with lexical frequency and conceptual familiarity variables, whereas they are negatively correlated with H index. Reaction times in the categorization task were negatively correlated with lexical frequency and conceptual familiarity variables and positively correlated with visual complexity variable. The Path analysis showed that subjective lexical frequency and H index are the better predictors for picture naming task. In picture categorization task, for reaction times, the better predictor variables were subjective lexical frequency, conceptual familiarity and visual complexity. 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Seven spot ladybird beetle, (Coccinella septempunctata) is a widely distributed natural enemy of soft-bodied insect pests especially aphids worldwide. Both the adult and larvae of this coccinellid beetle are voracious feeders and serve as a commercially available biological control agent around the globe. Different techniques are adopted to enhance the mass rearing and storage of this natural enemy by taking advantage of its natural ability to withstand under extremely low temperatures and entering diapause under unfavorable low temperature conditions. The key objective of this study was to develop a cost effective technique for enhancing the storage life and predatory potential of the larvae of C. septempunctata through cold storage in conjunction with the use of nuclear techniques, gamma radiations. Results showed that the host eating potential of larvae was enhanced as the cold storage duration was increased. Gamma irradiation further enhanced the feeding potential of larvae that were kept under cold storage. Different irradiation doses also affected the development time of C. septempuntata larvae significantly. Without cold storage, the lower radiation doses (10 and 25 GY) prolonged the developmental time as compared to un-irradiated larvae. Furthermore, the higher dose of radiation (50GY) increased the developmental time after removal from cold storage. This study first time paves the way to use radiation in conjunction with cold storage as an effective technique in implementation of different biological control approaches as a part of any IPM programs.Key wordGamma irradiations; cold storage, Coccinella septempunctata larvae; predatory potential; integrated pest management programme.INTRODUCTIONNuclear techniques such as gamma radiations have a vast application in different programmes of biological control including continuous supply of sterilized host and improved rearing techniques (Greany and Carpenter, 2000; Cai et al., 2017). Similarly irradiation can be used for sentinel-host eggs and larvae for monitoring survival and distribution of parasitoids (Jordão-paranhos et al., 2003; Hendrichs et al., 2009; Tunçbilek et al., 2009; Zapater et al., 2009; Van Lenteren, 2012). Also, at the production level, such technique may facilitate the management of host rearing, improve quality and expedite transport of product (Fatima et al., 2009; Hamed et al., 2009; Wang et al., 2009). Gamma irradiations can also be used to stop insect’s development to enhance host suitability for their use in different mass rearing programs (Celmer-Warda, 2004; Hendrichs et al., 2009; Seth et al., 2009). Development and survival of all insects have a direct connection with temperatures which in turn affect the physical, functional and behavioral adaptations (Ramløy, 2000). Many insects living in moderate regions can survive at low temperature by process of diapause. A temperature between 0 to 10oC may cause some insects to become sluggish and they only become active when the temperature is suitable. Such insects show greater adaptations to flexible temperature regimes for better survival. Many studies have reported this concept of cold-hardiness in insects in general (Bale, 2002; Danks, 2006) and specifically in coccinellid beetles over past years (Watanabe, 2002; Koch et al., 2004; Pervez and Omkar, 2006; Labrie et al., 2008; Berkvens et al., 2010). Using this cold hardiness phenomenon, many coccinellids have been studied for the effect of cold storage such as Coccinella undecimpunctata (Abdel‐Salam and Abdel‐Baky, 2000), Coleomegilla maculata (Gagné and Coderre, 2001) and Harmonia axyridis (Watanabe, 2002). This natural phenomenon, therefore, can be a helpful tool in developing low temperature stockpiling for improving mass-rearing procedures (Mousapour et al., 2014). It may provide a significant output in terms of providing natural enemies as and when required during pest infestation peaks (Venkatesan et al., 2000). Use of irradiation in conjunction with cold storage proves to be an effective technique in implementation of different biological control approaches as a part of any IPM programme. A study reported that the pupate of house fly, Musca domestica irradiated at dose of 500 Gy and can stored up to 2 months at 6°C for future use for a parasitoid wasp Spalangia endius rearing (Zapater et al., 2009). Similarly, when irradiated at 20 GY, parasitic wasps Cotesia flavipes were stored safely up to two months without deterioration of their parasitic potential (Fatima et al., 2009). Similarly, bio-control program of sugarcane shoot borer Chilo infescatellus proved successful through the use of irradiation combined with cold storage of its egg and larval parasitoids Trichogramma chilonis and C. flavipes (Fatima et al., 2009). Less mobile life stages such as larvae are of significance in any IPM strategy because they remain on target site for more time period as compared to adults. Therefore, use of predatory larvae is very promising in different biological control approaches because of their immediate attack on pests and more resistance to unfavorable environmental conditions than delicate egg stage. In addition, with their augmentation into fields, larval stage shows their presence for longer time than adult stage and their feeding potential is also satisfactory as that of adults. For the best utilization of these predators in the field and maximum impact of 3rd and 4th larval instars on prey, we should encourage late 2nd second instar larvae of predatory beetles in the fields as these instars have more feeding capacity due to increased size and ability to handle larger preys.In spite of higher significance, there is little information available about the effect of cold storage on the survival of larval instars of different ladybird beetles and its effect on their predatory potential. Very few studies report the use of cold storage for non-diapausing larval stage like for Semiadalia undecimnotata and only one study reported the short-term storage (up to two weeks) of 2nd and 3rd instar coccinellid, C. maculate, without any loss in feeding voracity of larvae after storage (Gagné and Coderre, 2001). The survival of 3rd and 4th larval instars of C. undecimpunctata for 7 days after storage at 5oC was reported in a study but the survival rate declined after 15-60 days of storage (Abdel‐Salam and Abdel‐Baky, 2000). As C. septempunctata is considered one of the voracious predators (Afroz, 2001; Jandial and Malik, 2006; Bilashini and Singh, 2009; Xia et al., 2018) and diapause is a prominent feature of this beetle and it may undergo facultative diapause under suitable laboratory conditions (Suleman, 2015). No information is available to date about the combined effect of cold storage and irradiation on the larval instars of this species.OBJECTIVES The objective of this study was to devise a cost effective technique for the cold storage and its effect on the subsequent predatory potential of the seven spotted ladybird beetle larvae in conjunction with the use of gamma radiations. Hypothesis of the study was that an optimum length of low temperature treatment for storage purpose would not affect the predation capacity of C. septempunctata larvae and their developmental parameters including survival and pupation will remain unaffected. Furthermore, use of gamma irradiation will have some additional effects on survival and feeding capacity of irradiated C. septempunctata larvae. Such techniques can be utilized in different biocontrol programs where short term storage is required. So these larvae can be successfully imparted in different IPM programs against sucking complex of insect pests as a component of biological control strategyMATERIALS AND METHODSPlant materials: Collection and rearing of C. septempunctata: Adult C. septempunctata were collected from the wheat crop (in NIAB vicinity and farm area) in the month of March during late winter and early in spring season 2016-2017. They were kept in plastic jars and were fed with brassica aphids. Under controlled laboratory conditions (25+2oC, 16h: 8h L:D and 65+5% R.H.), eggs of C. septempuctata were obtained and after hatching, larvae were also given brassica aphids as dietary source. Larvae of second instar were selected for this experiment (as the first instar is generally very weak and vulnerable to mortality under low temperatures). As the larvae approached second instar, they were separated for the experimentation. Irradiation of larvae at different doses: Irradiation of larvae was carried out by the irradiation source 137CS at Radiation laboratory, and the larvae were then brought back to the IPM laboratory, Plant Protection Division, Nuclear Institute for Agriculture and Biology (NIAB) Faisalabad. Radiation doses of 10 GY (Grey), 25 GY and 50 GY were used to treat the second instar larvae. There were three replicates for each treatment and five larvae per replicate were used. Control treatment was left un-irradiated.Cold storage of irradiated larvae: In present work, second instar C. septempunctata larvae were studied for storage at low temperature of 8oC. The larvae were kept at 8oC for 0, I and II weeks where week 0 depicts no cold treatment and this set of larvae was left under laboratory conditions for feeding and to complete their development. For larvae that were kept under cold storage for one week at 8°C, the term week I was devised. Similarly, week II denotes the larvae that remained under cold conditions (8°C) for two continuous weeks. Larvae were removed from cold storage in their respective week i.e., after week I and week II and were left under laboratory conditions to complete their development by feeding on aphids. Data collection: For recording the predatory potential of C. septempunctata larvae, 100 aphids were provided per larva per replicate on a daily basis until pupation as this number was more than their feeding capacity to make sure that they were not starved (personal observation). Observations were recorded for survival rate, developmental time and feeding potential. Data analysis: Data were statistically analysed by Statistical Software SPSS (Version 16.0). The data were subjected to normality check through the One-sample Kolmogorov-Smirnov test. Non normal data were transformed to normal data which were then used for all parametric variance tests. One-way and two-way analyses of variance were used. For comparison between variables, LSD test at α 0.05 was applied.RESULTSFeeding potential of irradiated larvae after removal from cold storage: Results showed an increase in the feeding potential of C. septempunctata larvae with increased cold storage duration. The feeding potential was significantly higher for the larvae that spent maximum length of time (week II) under cold storage conditions followed by week I and week 0. Gamma irradiations further enhanced the feeding potential of larvae that were kept under cold storage. When larvae were irradiated at 10 GY, the eating capacity of larvae increased significantly with the duration of cold storage. Similarly, larvae that were irradiated at 25 GY, showed increase in feeding potential on aphids as the time period of cold storage increased. The feeding potential of larvae that were irradiated at 50 GY, was again significantly increased with increase of cold storage duration. When different radiation doses were compared to week 0 of storage, there was a significant difference in feeding potential and larvae irradiated at 50 GY consumed the maximum numbers of aphids when no cold storage was done followed by larvae irradiated at 10 and 25 GY. With the other treatment, where larvae were kept under cold storage for one week (week I) the larvae irradiated at 50GY again showed the highest feeding potential. The feeding potential of irradiated larvae was again significantly higher than the un-irradiated larvae that were kept for two weeks (week II) under cold storage (table 1).Two-way ANOVA was performed to check the interaction between the different radiation doses and different lengths of storage durations for feeding potential of C. septempunctata larvae on aphids. The feeding potential of larvae irradiated at different doses and subjected to variable durations of cold storage were significantly different for both the radiation doses and cold storage intervals. Furthermore, the interaction between the radiation doses and storage duration was also significant meaning that the larvae irradiated at different doses with different length of cold storage were having significant variations in feeding levels (table 2).Developmental time of irradiated larvae after removal from cold storage: Significant difference was found in the development time of the larvae of C. septempunctata when irradiated at different doses at week 0 (without cold storage). The larvae irradiated at 10 GY took the maximum time for development and with the increase in irradiation dosage, from 25 to 50 GY, the time of development was shortened. The larvae irradiated at 50 GY had the same development time as the un-irradiated ones. When, the irradiated larvae were subjected to cold storage of one week duration (week I), their development time after removal from storage condition varied significantly. The larvae irradiated at 25 GY took the maximum time for development followed by larvae irradiated at 50 GY and 10 GY. There was an indication that the development time was extended for irradiated larvae as compared to un-irradiated larvae.Results also depicted a significant difference in the time taken by irradiated larvae to complete their development after taken out from cold storage of two weeks duration (week II). As the storage time of irradiated larvae increased, the development time was prolonged. Results showed that the larvae that were irradiated at 25 and 50 GY, took the maximum time to complete their development. With the prolonged duration of cold storage up to two weeks (week II), this difference of development time was less evident at lower doses (10 GY). The larvae irradiated at 10 GY showed a significant difference in their developmental duration after being taken out of cold storage conditions of the week 0, I and II. There was no difference in the developmental duration of larvae that were un-irradiated and subjected to different regimes of storage. Un-irradiated larvae were least affected by the duration of storage. With the increase in the storage time, a decrease in the developmental time was recorded. Larvae that were irradiated at 10 GY, took the maximum period to complete their development when no cold storage was done (week 0) followed by week I and II of cold storage. When the larvae irradiated at 25 GY were compared for their development time, there was again significant difference for week 0, I and II of storage duration. Maximum time was taken by the larvae for their complete development when removed from cold storage after one week (week I). With the increase in storage duration the time taken by larvae to complete their development after removal from cold storage reduced.When the larvae were removed after different lengths of cold storage duration i.e., week 0, week I and week II, there was a significant difference in the developmental time afterwards. Results have shown that the higher dose of radiation, increased the developmental time after removal from cold storage. The larvae irradiated at 50 GY took the longest time to complete their development after removal from cold storage (week I and week II) as compared the larvae that were not kept under cold storage conditions (week 0) (table 3).Interaction between the different radiation doses and different lengths of storage durations for development time of larvae were checked by two-way ANOVA. The development time of larvae irradiated at different doses and subjected to variable durations of cold storage were significantly different for both the doses and cold storage intervals. Furthermore, the interaction between the radiation doses and storage duration was also significant meaning that the larvae irradiated at different doses with different length of cold storage were having significant variations in development times (table 4). DISCUSSIONThe present research work indicates the possibility of keeping the larval instars of C. septempunctata under cold storage conditions of 8oC for a short duration of around 14 days without affecting its further development and feeding potential. Furthermore, irradiation can enhance the feeding potential and increase the development time of larval instars. This in turn could be a useful technique in mass rearing and field release programmes for biological control through larval instars. Usually temperature range of 8-10oC is an optimal selection of low temperature for storage as reported earlier for eggs two spotted ladybird beetle, Adalia bipunctata and the eggs of C. septempunctata (Hamalainen and Markkula, 1977), Trichogramma species (Jalali and Singh, 1992) and fairyfly, Gonatocerus ashmeadi (Hymenoptra; Mymaridae) (Leopold and Chen, 2007). However, a study reported more than 80% survival rate for the coccinellid beetle, Harmonia axyridis for up to 150 days at moderately low temperature of 3-6oC (Ruan et al., 2012). So there is great flexibility in coccinellid adults and larvae for tolerating low temperature conditions. After removal from cold storage, larvae showed better feeding potential with consumption of more aphids when compared to normal larvae that were not placed under low temperature conditions. This indicates that when the adult or immature insect stages are subjected to low temperature environment, they tend to reduce their metabolic activity for keeping them alive on the reserves of their body fats and sustain themselves for a substantial length of time under such cold environment. Hereafter, the larval instars that were in cold storage were behaving as if starved for a certain length of time and showed more hunger. This behavior of improved or higher feeding potential of stored larvae has been reported previously (Chapman, 1998). Hence, the feeding potential of C. septempunctata larvae significantly increased after cold storage. Gagné and Coderre (2001) reported higher predatory efficacy in larvae of C. maculata when stored at the same temperature as in the present study i.e., 8oC. Similarly, Ruan et al. (2012) showed that the multicolored Asian ladybug, H. axyridis, when stored under cold conditions, had more eating capacity towards aphids Aphis craccivora Koch than the individuals that were not stored. Such studies indicate that the higher feeding potential in insects after being subjected to low temperature environmental conditions could be due to the maintenance of their metabolism rate to a certain level while utilizing their energy reserves to the maximum extent (Watanabe, 2002).The individuals coming out from cold storage are therefore capable of consuming more pray as they were in a condition of starvation and they have to regain their energy loss through enhanced consumption. Furthermore, the starvation in C. septempunctata has previously been reported to affect their feeding potential (Suleman et al., 2017). In the present study, the larval development was delayed after returning to normal laboratory conditions. Cold storage affects the life cycle of many insects other than coccinellids. The cold storage of green bug aphid parasitoid, Lysiphlebus testaceipes Cresson (Hymenoptra; Braconidae) mummies increased the life cycle 3-4 times. Nevertheless, in current study the development process of stored larvae resumed quickly after taking them out and larvae completed their development up to adult stage. Similar kinds of results were reported for resumption of larval development after removal from cold storage conditions. Such studies only report satisfactory survival rates and development for a short duration of cold storage but as the length of storage is increased, it could become harmful to certain insects. Gagné and Coderre (2001) reported that cold storage for longer period (three weeks) proved fatal for almost 40% of larvae of C. maculata. Furthermore, in the same study, the feeding potential of C. maculata larvae was also affected beyond two weeks of cold storage due to the loss of mobility after a long storage period. Many studies have reported that longer durations of low temperature conditions can either damage the metabolic pathways of body cells or may increase the levels of toxins within the bodies of insects. Also, low temperature exposure for longer duration may cause specific interruptions in the insect body especially neuro-hormones responsible for insect development, which could be dangerous or even life threatening.Chen et al. (2004) also reported that the biological qualities of parasitized Bemisia tabaci pupae on population quality of Encarsia formosa were affected negatively with increase in cold storage duration. Similarly, the egg hatchability of green lacewing Chrysoperla carnea Stephen was lost completely beyond 18 days of cold storage (Sohail et al., 2019). However, in the present study the cold storage was done for maximum two weeks and it is to be regarded as a short term storage hence the survival rate was satisfactory. Longer periods of cold storage for larvae are not considered safe due to their vulnerable state as compared to adults which are hardier. Also 2nd instar larvae used in the present study for cold storage for being bigger in size and physical stronger than 1st instar. Abdel‐Salam and Abdel‐Baky (2000) reported that in C. undecimpunctata the cold storage of 3rd and 4th larval instars was higher and considered safer than early larval instars. The same study showed sharp decline in survival rate after two weeks and there was no survival beyond 30-60 days of cold storage. The present study showed that short term storage of the larvae of C. septempunctata could be done without any loss of their feeding potential or development so the quality of predator remained unaffected. Similar kind of work for many other insects had been reported previously where cold storage technique proved useful without deteriorating the fitness of stored insects. For example, the flight ability of reared codling moth Cydia pomonella Linnaeus remained unaffected after removal from cold storage (Matveev et al., 2017). Moreover, a sturdy reported that pupae of a parasitoid wasp Trichogramma nerudai (Hymenoptera; Trichogrammatidae) could be safely put in cold storage for above than 50 days (Tezze and Botto, 2004). Similarly, a technique of cold storage of non-diapausing eggs of black fly Simulium ornaturm Meigen was developed at 1oC. Another study reported safe storage of a predatory bug insidious flower bug Orius insidiosus for more than 10 days at 8°C (Bueno et al., 2014).In present study without cold storage, the lower doses of 10 and 25 GY prolonged the developmental time as compared to un-irradiated larvae and higher doses of irradiations in conjunction with cold storage again significantly prolonged the developmental time of larvae when returned to the laboratory conditions. Salem et al. (2014) also reported that Gamma irradiations significantly increased the duration of developmental stages (larvae and pupae) in cutworm, Agrotis ipsilon (Hufnagel). In another study, where endoparasitic wasps Glyptapanteles liparidis were evaluated with irradiated and non-irradiated gypsy moth Lymantria dispar larvae for oviposition, it was found that non-irradiated larvae had a shorter time to reach the adult stage as compared to irradiated larvae (Novotny et al., 2003). Both for higher doses with cold storage and lower doses without cold storage extended the larval duration of C. septempunctata. In another study when the parasitoid wasp Habrobracon hebetor was irradiated at the dose of 10 GY, it resulted in prolonged longevity (Genchev et al., 2008). In the same study, when another parasitoid Ventruria canescens was irradiated at lower doses of 4GY and 3 GY, it resulted in increased emergence from the host larvae, while gamma irradiations at the dose of 1 GY and 2 GY significantly stimulated the rate of parasitism (Genchev et al., 2008). The current study also indicated higher rates of predation in the form of increased feeding potential of larvae as a result of irradiations at lower doses.CONCLUSIONThe outcome of the current study shows that storage of 2nd instar C. septempunctata at low temperature of 8oC for a short duration of about 14 days is completely safe and could have broader application in different biocontrol programs. Such flexibility in storage duration can also assist in different mass rearing techniques and commercial uses. The combination of gamma radiation with low temperature cold storage could be a useful tool in developing different biological pest management programs against sucking insect pests. Incidence of periodic occurrence of both the target insect pests with their predatory ladybird beetles in synchrony is an important aspect that could be further strengthened by cold storage techniques. Therefore, short or long term bulk cold storage of useful commercial biocontrol agents and then reactivating them at appropriate time of pest infestation is a simple but an advantageous method in mass rearing programs. Increased feeding capacity of stored larvae is another edge and hence such larvae may prove more beneficial as compared to unstored larvae. Both cold storage and improved feeding of the C. septempuctata larvae can be utilized for implementation of IPM for many sucking insect pests of various crops, fruits and vegetables. Due to some constraints this study could not be continued beyond two weeks but for future directions, higher doses and longer duration periods could further elaborate the understanding and better application of such useful techniques in future IPM programmes on a wider scale. Also, some other predatory coccinellid beetle species can be tested with similar doses and cold storage treatments to see how effective this technique is on other species as well.ACKNOWLEDGMENTS We acknowledge the Sugarcane Research and Development Board for providing a research grant (No. SRDB/P/4/16) to carry out this research work. 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Abstract Funding Acknowledgements Abbott Introduction SyncAV has been shown to improve electrical synchronization by automatically adjusting atrioventricular delay (AVD) according to the intrinsic atrioventricular conduction time. Additional incremental electrical synchronization may be gained by the addition of second left ventricular (LV) pulse with MultiPoint Pacing (MPP). While the electrical synchronization benefits of SyncAV have been previously explored, there has been no assessment of the acute hemodynamic impact of SyncAV with or without MPP. Objective Evaluate the acute LV hemodynamic impact of SyncAV with and without MPP. Methods Heart failure patients with LBBB and QRS duration (QRSd) &gt; 140 ms undergoing CRT-P/D implant with a quadripolar LV lead were enrolled in this prospective study. A guidewire or catheter with pressure transducer was placed in the LV chamber and the maximum pressure change (dP/dtmax) was recorded during the following pacing modes: intrinsic conduction, conventional biventricular pacing with SyncAV (BiV + SyncAV), and MPP with SyncAV (MPP + SyncAV). Twelve-lead surface ECG was used to determine the patient-tailored SyncAV offset that minimized QRSd. Results Twenty-seven patients (67% male, 44% ischemic, 30 ± 7% ejection fraction) completed the acute recordings. Relative to the intrinsic QRSd of 163 ms, BiV + SyncAV reduced QRSd by 21.5% to 124 ms (p &lt; 0.001 vs. intrinsic) and MPP + SyncAV reduced QRSd by 26.6% to 120 ms (p &lt; 0.05 vs. BiV + SyncAV). Beyond electrical synchronization, SyncAV significantly improved acute hemodynamics. Relative to the intrinsic dP/dtmax of 842 mmHg/s, BiV + SyncAV elevated dP/dtmax by 6.3% to 900 mmHg/s (p &lt; 0.001 vs. intrinsic) and MPP + SyncAV elevated dP/dtmax by 8.8% to 926 mmHg/s (p &lt; 0.005 vs. BiV + SyncAV). Despite both QRSd and dP/dtmax improvement with SyncAV and MPP, correlation between electrical and hemodynamic measurements was poor (R2 = 0.0 for BiV + SyncAV, R2 = 0.1 for MPP + SyncAV). Conclusion SyncAV may significantly improve acute LV hemodynamics in addition to electrical synchrony in LBBB patients. Further incremental improvement was achieved by combining SyncAV with MPP. Abstract Figure.

Abstract Purpose To provide a comprehensive review of rituximab use for the treatment of non-infectious uveitis and scleritis. Methods Review of literature through December 2020. Results Individual data was available for 229 patients with refractory non-infectious uveitis (n = 108) or scleritis (n = 121) who received treatment with rituximab (RTX). Rituximab was generally utilized as third-line or later treatment (uveitis: 67/90, 74.4%; scleritis: 90/96, 93.8%) at a mean of 33.5 months following the diagnosis of uveitis (range = 0 to 168.0 months; median = 24.0 months) and 39.4 months after diagnosis of scleritis (range = 1.0 to 168.0 months; median = 21.0 months). Patients with non-infectious uveitis and scleritis either received prior treatment with corticosteroids only (uveitis: 18/90, 20%; scleritis: 4/94, 4.3%), or with one (uveitis: 19/90, 21.1%; scleritis: 30/94, 31.9%), two (uveitis: 11/90, 12.2%; scleritis 27/94, 28.7%), or three or more (uveitis: 37/90, 41.1%; scleritis: 31/94, 33.0%) corticosteroid-sparing immunosuppressive agents with or without corticosteroids before initiation of RTX treatment. The rheumatologic protocol (two infusions of 1 gram of RTX separated by 14 days) was utilized most frequently (uveitis: 45/87, 51.7%; scleritis: 87/114, 76.3%), followed by the Foster protocol (eight weekly infusions of 375 mg/m2 RTX; uveitis: 18/87, 20.7%; scleritis: 10/114, 8.8%), and the oncologic protocol (four weekly infusions of 375 mg/m2 RTX; uveitis: 5/87, 5.7%; scleritis: 6/114, 5.3%). Various other off-label regimens were used infrequently (uveitis: 19/87, 21.8%; scleritis 11/114, 9.6%). Rituximab treatments resulted in a positive therapeutic response for the majority of patients with non-infectious uveitis (81/97, 83.5%). Commonly treated uveitic diagnoses included non-paraneoplastic autoimmune retinopathy (30/107, 28.0%), juvenile idiopathic arthritis (21/107, 19.6%), Vogt-Koyanagi-Harada disease (12/107, 11.2%), and Behçet disease (11/107, 10.3%). Cases of non-infectious scleritis were most commonly attributed to granulomatosis with polyangiitis (75/121, 62.0%) and rheumatoid arthritis (15/121, 12.4%), and showed an even greater rate of positive therapeutic response (112/120, 93.3%) following RTX treatment. No side effects were reported in 76.3% (74/97) of uveitis and 85.5% (71/83) scleritis cases. Of those cases associated with RTX-induced adverse events, the most common were infusion reactions of various severity (11/35, 31.4%). Conclusions Overall, RTX appeared to be both effective and well-tolerated as second or third-line therapy for patients with non-infectious uveitis and scleritis.

Abstract Background Adverse Left Ventricular (LV) remodeling (ALVR) following ST-segment Elevation Myocardial Infarction (STEMI) is the result of numerous mechanical, neurohormonal, micro and macrovascular factors, and remains a major clinical problem. Cardiac Magnetic Resonance (CMR) is a multimodality technique that provides comprehensive functional and tissue characterization of infarcted and non-infarcted myocardium. Whether changes in the extracellular matrix in the remote myocardium in patients following a STEMI are associated with adverse LV remodeling has been a topic of debate. Aim We explored the additive value of native T1 variation (ΔnT1) and derived-extracellular volume (ECV) fraction in the remote non-infarcted myocardium as predictors of adverse LV remodeling following STEMI. Methods A total of 99 subjects (83% male) with their first mechanically reperfused STEMI underwent CMR within 2 weeks and at 6 months, including T1 mapping prior and 15 to 20 minutes following a bolus of gadolinium (0.2 mmol/kg), with a MOLLI sequence. ECV and nT1 values were computed by averaging co-registered ROIs in three distinct segments in the remote non-infarcted myocardium. Results Baseline nT1 but not ECV correlated with infarct size (r=0.349, P&lt;0.001 and r=0.162, P=0.096 respectively). In addition, ΔnT1 but not ΔECV correlated with an increase in LV end-diastolic volume index (LVEDVi) (r=0.268, P&lt;0.01 and r=0.113, P=0.285). ALVR, defined as Δ&gt;20% inLVEDVi, occurred in 21 cases, despite optimal medical therapy. Subjects with ALVR showed greater ΔnT1 (13.2±44.1 vs −5.2±30.2 ms, P&lt;0.05) but no significant differences in ΔECV (1.27±2.77 vs 0.72±2.45%, P=0.401). Also, subjects with ALVR were more likely hypertensive (67 vs 33%, P&lt;0.05), had more segments with microvascular obstruction (2.1±2.2 vs 0.8±1.7, P&lt;0.01) and lower baseline EF (39.8±8.8 vs 44.6±9.6%, P&lt;0.05). Infarct size was not significantly larger in ALVR subjects (20.7±13.4 vs 17.5±13.0% LV mass, P=0.322). A multivariate analysis including all these factors, showed the extent of microvascular obstruction (ExpoB: 1.35 [1.05–1.73], P=0.019) and remote ΔnT1 (ExpoB: 1.02 [1.00–1.03], P=0.026) to be the independent predictors of ALVR. Conclusions The nT1 variation in remote non-infarcted myocardium and the extent of microvascular obstruction are superior to ECV changes and infarct size in predicting ALVR following STEMI. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Fundaciό La Maratό TV3 2015 30 31 32. Fondos FEDER

Abstract Background introduction Many patients, especially those at very high cardiovascular (CV) risk, do not reach low-density lipoprotein cholesterol (LDL-C) targets for at least 2 reasons: they may not receive a sufficiently intensive regimen, and/or they may not adhere to their medication. Purpose Describe demographic, clinical characteristics and treatment intensity and adherence in patients on lipid lowering therapies (LLT) following an Acute Coronary Syndrome (ACS) in France. Methods Retrospective cohort study on the PGRx (the Pharmacoepidemiologic General Research eXtension program)-ACS dataset in France, with data collected retrospective and prospectively via physicians, prescription records and patient interviews. Patients were accrued prospectively and/or retrospectively by centres from the PGRx Cardiology and General Practitioners networks. We included adult patients (≥18 years) suffering an ACS between 2013 and 2016 who received LLT at or within 92 days of their ACS hospital discharge. Follow-up was censored at time of new CV event, death, lost to follow-up or interview date (mean duration 12.4 months). Outcomes of interest included LLT intensity (high, moderate and low intensity statins with or without ezetimibe) and adherence measured as proportion of days covered (PDC). Results 2695 eligible patients were included (77% men); mean age (SD) 63.1 (12.8), 18% had diabetes mellitus, mean (SD) LDL-C 112.1 (46.4) mg/dl. Treatment with LLT at discharge is summarised in table below. Age and baseline LDL-C were drivers of treatment intensity with higher proportion of patients on high intensity statins in younger patients and in those with higher baseline LDL-C. Overall 70% of patients were adherent (PDC≥80%). Patients on moderate intensity were more adherent (76%) than those on low (63%) or high intensity statins (67%). Treatment patterns with LLT after an ACS LLT following ACS N (%) PDC at 1 year, Mean (SD) Adherent, N (%) Not Adherent, N (%) Ezetimibe 34 (1.3%) 82.8% (31.3%) 26 (76.5%) 8 (23.5%) Low intensity statins 64 (2.4%) 74.8% (33.8%) 40 (62.5%) 24 (37.5%) Moderate intensity statins 993 (37.1%) 82.0% (30.9%) 751 (75.6%) 242 (24.4%) High intensity statins 1515 (56.6%) 74.6% (36.2%) 1007 (66.5%) 508 (33.5%) Statin + ezetimibe 59 (2.2%) 75.9% (34.7%) 40 (67.8%) 19 (32.2%) Overall 2695 (100%) 77.6% (34.3%) 1871 (69.9%) 807 (30.1%) Conclusion(s) Our data show a substantial proportion of patients in France are not treated with high intensity statins after an ACS despite guidelines recommendation. Adherence to LLT is acceptable in patients after an ACS although it appears to worsen when high intense statins are used Acknowledgement/Funding Study has been funded by Amgen GmbH

This article studies whether firm-level and country-level factors affect to the corporation's debt maturity in case of Vietnam or not. The paper adopts the balance panel data of 267 listed companies on two trading board HOSE and HNX in the period from 2008 to 2015, estimated by FEM, REM, 2SLS and GMM method. To intrinsic factors, research results show that financial leverage and default risk control have high positive statistical significance with the debt maturity, but tangible assets are lower than those factors. In addition, growth opportunities and company quality have negative impacts to the debt maturity. To external factors, the results point out that economic growth, stock market development and governmental regulation's efficiency demonstrate the positive relationship to the debt maturity with fairly low correlation levels. 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