Academic literature on the topic '621.32; 621.38; 621.382.2/.3'

SUMMARYThe aims were to assess the prevalence of HIV infection among young adult heroin users, including injecting heroin users (IHUs) and non-injecting heroin users (NIHUs), and to explore the differences by gender and other factors. The design was a cross-sectional cohort study between April 2001 and December 2003, which included 961 current heroin users (HU), aged 18–30 years: 422 in Madrid, 351 in Barcelona and 188 in Seville; 621 were IHUs and 340 were NIHUs. All were street-recruited by chain referral methods. Face-to-face interviews were conducted using a structured questionnaire with computer-assisted personal interviewing (CAPI). Samples for HIV testing (dried blood spot) were collected and tested with ELISA and Western Blot. Bivariate, logistic regression, and classification and regression tree analyses were performed. The overall prevalence of HIV infection among IHUs was 25·8% (95% CI 22·3–29·3) [32·4% (95% CI 26·6–38·1) in Madrid, 20·5% (95% CI 15·6–25·4) in Barcelona, and 20·6% (95% CI 9·8–31·4) in Seville], whereas in NIHUs it was 4·0% (95% CI 2·1–6·7), with no differences among cities. The prevalence was significantly higher in women than in men in NIHUs (10·9%, 95% CI 4·3–17·5 vs. 1·7%, 95% CI 0·5–4·2) and was non-significantly higher in IHUs (30·4%, 95% CI 23·0–37·8 vs. 24·1%, 95% CI 20·1–28·1). HIV prevalence in short-term IHUs was 12·9% (CI 8·8–17·02), with no differences among cities. In the logistic analysis, the variables associated with infection in IHUs were ever having injected with used syringes (OR 3·4, 95% CI 2·2–5·3), ever having been in prison (OR 2·6, 95% CI 1·6–4·0), and heroin as the first drug injected at least weekly (OR 2·3, 95% CI 1·1–4·5). Factors positively associated with HIV infection in NIHUs were female sex (OR 8·7, 95% CI 2·6–29·2) and age >25 years (OR 3·1, 95% CI 0·9–11·1), while primary educational level was inversely associated (OR 0·26, 95% CI 0·1–0·9). Although there are important geographic differences, HIV prevalence in IHUs remains high, even in short-term IHUs, whereas it was almost six times lower in NIHUs. The prevalence in women is higher than in men, particularly among NIHUs. A wide range of preventive strategies should be developed, aimed primarily at empowering women to negotiate safe sex.

Abstract Atrial fibrillation (AF) is the most common cardiac rhythm disorder. The prevalence is nearly 10 % in patients (pts) older than 75 years (yrs). Some authors are reluctant to give oral anticoagulant therapy for older pts based on their higher incidence of bleeding Objective : to compare characteristics, incidence of thrombosis and bleeding in 2 groups of pts with AF, under OA for at least 3 months. Methods: we retrospectively analyzed 184 pts below 75 yrs (Group A) and 133 pts with 75 yrs and older (Group B), between Jan 2002 and Aug 2007. Results: the mean follow-up was 514 pts/year for the A group and 382 pts/year for group B. The features of each group are listed in the table below: Group A Group B p Age (mean- range) 64,9 (33/74) 79,8 (75/91) Gender (M/F) 116/68 (1,7/1) 55/78 (0,7/1) Rheumatic AF 89/184 61/114 Non valvular AF 80/184 53/114 Previous thrombosis 21/184 (11.4%) 29/133 (21.8%) 0,01 Diabetes mellitus 28/184 (15.2%) 10/133 (7.5%) 0,05 Arterial Hypertension 78/184 (42.3 %) 53/133 (39.8%) Hyperthyroidism 29/184 (15.7%) 18/133 (13.5%) Left Mega Atrium 43/174 (24.7%) 32/110 (29%) Coronary Artery Disease 38/184 (20.6%) 31/133 (23.3%) Cardiomegaly 53/170 (31.1%) 41/122 (33.6%) Ejection Fraction ≤30% 26/175 (14,8%) 20/112 (17.8%) Creatinin ≥ 2 mg/dl 8/184 (4.3%) 8/133 (6.1%) Thromboses 4/184 (2.1%) 3/133 (2.2%) Bleeding minor 59/184 (32%} 49/133 (36.8%) major 5/184 (2.7%) 2/133 (1.5%) fatal 0 2/2 (100%) Controls with INR 2-3 61 % 60,5 % Conclusion: There was no difference in the incidence of major and minor bleeding/thrombotic complications between the groups. Group B disclosed a higher number of thromboses previous to OA therapy, and fewer pts with diabetes. In our experience, OA seemed to be equally safe and effective when we compared both populations. There was no difference in the incidence of major and minor bleeding/thrombotic complications between the groups.

Abstract Background: The StiL Study NHL 7-2008 investigates the role of maintenance duration with rituximab after induction with bendamustine-rituximab (B-R) for first-line treatment of advanced follicular (FL), other indolent lymphoma, or mantle cell lymphoma. Methods: Patients (pts) with FL were treated with a maximum of 6 cycles of B-R (bendamustine 90 mg/m2 [days 1+2], rituximab 375 mg/m2) administered every 28 days plus 2 additional cycles of rituximab every 4 weeks. All responding pts (complete response [CR] or partial response [PR]) were then eligible for rituximab maintenance treatment and a subsequent randomization: all responding pts with FL received 2 years rituximab maintenance (375 mg/m2) administered every two months. Pts with an ongoing response were then randomized 1:1 to observation (no further treatment) or to 2 more years of rituximab maintenance (i.e. B-R plus 2 years vs 4 years rituximab maintenance). Here we report on the response to B-R and tolerability and safety of B-R followed by 2 years of rituximab maintenance in pts with FL only. Patient Characteristics: To date, 612 pts (319 women and 293 men) with FL have been registered (first patient in April 2009, last patient registered July 2012). Median age was 61 years (range, 24-81); 352 (58%) pts had stage IV; median number of nodal areas was 5; bone marrow involvement was found in 322 (52%) pts; and 175 pts (28%) presented with splenomegaly. The median LDH was 210 U/l, with 197 pts (32%) having an LDH > 240 U/l. Median FLIPI was 3 and the median CD4 count was 491 per mm3at induction. Results: To date, 546 pts of 612 are evaluable for response and safety. The overall response rate (ORR) was 93.6% with 511 pts achieving a remission after B-R induction therapy. The CR rate was 39.6%; nine pts (1.6%) had stable disease; and 27 (4.9%) did not respond to B-R and had progressive disease. Of these 511 pts achieving remission, 291 (56.9%) received the full planned 2 years rituximab maintenance treatment, and 281 pts were then randomized to observation only (n=140) or 2 additional years of rituximab maintenance (n=141). Seventy nine pts are still undergoing treatment with the planned 2-year standard rituximab maintenance and are not yet randomized. Reasons for not receiving the full 2-year course of rituximab maintenance (n=141) included: death (n=6); relapse or progressive disease (n=50); transformation into aggressive lymphoma (n=4); infection during rituximab maintenance (n=4); infection during B-R induction (n=1); toxicity (e.g. neutropenia) (n=19); secondary malignancies during induction or during rituximab maintenance (n=3 and n=6, respectively); reactivated hepatits B (n=1); rituximab intolerance (n=3); removal of the patient from the trial by the investigator for any reason (n=16); withdrawal of patient consent during induction with B-R (n=2) and during the 2-year rituximab maintenance (n=14); non-compliance (n=2); lost to follow up (n=6); severe comorbidity (dementia) (n=1); and other reasons (n=3). No unexpected toxicity and no progressive multifocal encephalopathy were observed. To date, 35/612 pts developed 38 secondary malignancies. Conclusions: Results of this study confirm the efficacy of B-R in pts with previously untreated advanced FL. These results are in line with those of other studies such as StiL NHL 1-2003(1) or the “BRIGHT”-Study(2). Rituximab standard maintenance over 2 years for FL appears safe, with no new or unexpected toxicities. 1. Rummel et al. Lancet 2013;381:1203-10. 2. Flinn et al. Blood 2014;123:2944-52. Disclosures Off Label Use: Indication and dosage of bendamustine.

2602 Background: A CLIA-certified organoid based drug sensitivity assay (a cancer organogram) has been developed for all solid tumors. An actionable report of organogram sensitivities to endocrine, chemotherapy and targeted agents, produced a drug sensitivity score as a tool to inform therapy decision making. Objectives: To evaluate the success rate of organoid derivation, the organogram drug responses across cancer types and to analyze the impact of the organogram report on therapeutic decision making. Methods: From 2016 to 2020, 628 cancer organograms were performed, with 513 tumor samples from 419 cancer patients. Within 48 hours of collection, fresh samples of tumor cells obtained from core biopsies, surgical excisions, or fluids were cultured, the majority as 3D organoids. Drug screens were performed with a library of up to 220 drugs, and dose-response was evaluated across a range of concentrations for each drug. Organogram sensitivity was ranked as response in five categories based on SPM Score: Exceptional (SPM15/14), Good (13/12), Moderate to Low (11/9), and None( < 9). 118 drugs on average were tested per screen (range: 68-152), so in a total of 628 organograms, more than 70,000 individual drug trials have been performed. The median turnaround time was 28 days (range: 19.5-51.5). Results: Of the 513 collected samples, 314 were fresh specimens: 96 core biopsies, 151 surgical specimens, and 67 fluids (pleural effusions or ascites), with an organoid derivation success rate of 58.3%, 78%, and 88%, respectively. Overall success rate in organoid derivation was 70.2%. Samples with poor viability and low tumor cell count (22%) were rejected. The primary cancer types tested were ovarian (n = 92, 17.9%), breast (n = 73, 14.2%), colorectal (n = 70, 13.6%), pancreatic (n = 51, 9.9%), cholangiocarcinoma (n = 42, 8.1%), and other solid tumors (n = 185, 36%). Median age of patients was 56 years old (range: 5-83), most of them heavily pretreated. 20.45% of drugs screened had exceptional and good responses (SPM score 15-12) (SD: 17.92%). We reviewed genomic data from 374 third-party genomic reports. The most frequent genomic alterations found were TP53 (n = 143, 38.2%), BRCA1 and BRCA2 (n = 47, 12.5%) CDKN2A (n = 42, 11.2%), FGFR1/2/3/4 (n = 41, 10.9%), and PIK3CA (n = 38, 10.1%). Post-test treatment information is available for a subset of 61 patients. The treating physician made an organogram-guided therapeutic decision in 32/44 patients with post test treatment drugs scored (72%). Conclusions: The cancer organogram test has a high rate of success in generating an actionable report that identifies therapies for patients with limited therapeutic options, including those with no known genomic biomarkers. The organogram guided selection of therapeutics for a significant subset of patients, nearly 4 times the rate reported with genomic testing alone.

18509 Background: Elderly patients (pts) are more likely to develop haematological toxicity with anthracycline based regimen. There are no sufficient data available on toxicities especially in elderly pts who are treated by taxane containing regimen. Methods: Four prospective randomised trials in the treatment of primary breast cancer have been combined retrospectively to evaluate the toxicity in pts ≥ 60 treated by a taxane. Pts received either 1: docetaxel/adriamycin/cyclophosphamide (TAC 75/50/600 mg/m2), 2: adriamycin(epirubicin)/cyclophosphamide (A(E)/C: 60(90)/600 mgm2) followed by docetaxel (T: 100 mg/m2) or paclitaxel (P: 175mg/m2), or 3: dose-dense adriamycin/docetaxel (AT dd: 50/75 mg/m2) or 4: epirubicin-paclitaxel in sequence (E-P dd: 90–175 mg/m2). A descriptive analysis was performed in regards to pts and per cycles. In the sequential regimen cycles without taxanes were not considered evaluable. Results: 917 pts median age of 64 (range 60–80) years were included in this pooled analysis. 59 were older than 70 years. In total 3852 cycles of a taxane containing chemotherapy were administered. 378 pts (41.2%) received therapy 1, 332 (36.2%) therapy 2, 121 (13.2%) therapy 3, and 86 (9.4%) therapy 4. A total of 16 % of the pts did not complete treatment. Grade 3–4 neutropenia occurred in 46.2% and febrile neutropenia in 6.1% of the pts, severe anemia (0.8%) and thrombopenia (1.1%) was infrequent. Main non hematological toxicities were (% pts with grade I-IV): fatigue 86; loss of appetite 74; nausea and vomiting 68; mucositis 60; sensory neuropathy; conjunctivitis 45; skin 38; nail 39; fluid retention 36; dyspnea 32. Conclusion: Toxicity of taxanes in pts older than 60 years does not significantly differ from younger pts. Therefore, taxanes as adjuvant or neoadjuvant treatment for primary breast cancer could also be considered in otherwise fit pts in the age group of 60–70. [Table: see text]

Abstract BACKGROUND Adding pertuzumab to trastuzumab in patients (pts) with HER2+ breast cancer improves pathological complete response (pCR) rates. Pertuzumab + trastuzumab + chemotherapy is approved in Australia as neoadjuvant therapy in early stage (&gt;2 cm or node positive), locally advanced and inflammatory HER2+ breast cancer. This study captured real-world data on the safety and effectiveness of pertuzumab in the neoadjuvant setting. METHODS PeRSIA (ML39622) is a secondary data use non-interventional study of pts initiating neoadjuvant pertuzumab treatment for non-metastatic HER2+ breast cancer. The primary objective is to assess the effectiveness and safety of neoadjuvant pertuzumab when added to trastuzumab in the real-world setting. Deidentified data obtained from the pts’ medical notes were captured using REDCaP, hosted at the Walter and Eliza Hall Institute of Medical Research. This analysis reports the co-primary endpoints of breast pCR (bpCR) with or without in situ disease (ypT0/is or ypT0), total pCR (tpCR) with or without in situ disease (ypT0/is ypN0 or ypT0 ypN0), and the incidence of adverse events (AEs) related to pertuzumab. Secondary objectives include describing rates of breast and nodal surgery, relapse free survival (RFS) and overall survival (OS). RESULTS Ninety five pts receiving neoadjuvant pertuzumab were enrolled between March 2018 and July 2019, with data available for all pts. HER2-targeted neoadjuvant treatment was completed in 91 pts (95.8%) with a median number of 4 cycles [range 1-6] of pertuzumab and 5 cycles [range 1-6] of trastuzumab. Four pts did not complete the planned neoadjuvant therapy due to early CR (n=1), and pertuzumab-related AEs (n=3). The most common neoadjuvant chemotherapy regimens were sequential anthracyclines + taxanes (n=59, 62.1%) and single agent taxane (n=29, 30.5%). Surgery was performed in 92 pts (96.8%). Three pts did not proceed to surgery due to patient decision (n=1), physician decision (n=1), and development of a new non-breast cancer which resulted in death (n=1). Of those pts that underwent surgery, 65/92 (70.7%) had a bpCR and 59/92 (64.1%) had a tpCR. All pts who did not achieve a pCR obtained a partial response (33/92, 35.9%). Total pCR was seen in 27/34 (79.4%) pts with hormone receptor-negative and 32/58 (55.2%) pts with hormone receptor-positive cancers. 27/95 (28.4%) pts experienced an AE related to pertuzumab; diarrhea (21.1%) and rash (4.2%) were the most common AEs. Three pts (3.2%) discontinued pertuzumab due to an AE: cardiac toxicity, diarrhea and rash (n=1), cardiac toxicity (n=1), and diarrhea and sepsis (n=1). Following surgery, 93/95 (97.9%) patients received adjuvant HER2-directed therapy, and 4/95 (4.2%) received adjuvant chemotherapy. After a median follow-up from diagnosis of 21.2 [14.0-83.9] months, the RFS and OS were 92.6% and 99.0% respectively. Disease recurrence occurred in 6 pts (distant n=4, contralateral n=2). CONCLUSIONS This is the first multicenter, observational study of neoadjuvant therapy based on dual blockade with pertuzumab and trastuzumab for HER2+ non-metastatic breast cancer in Australia. The pCR rates achieved were numerically higher than previously reported in clinical trials. There were no significant safety findings outside of the expected safety profile for pertuzumab. Acknowledgments: Study sponsored by Roche Products, Pty. Limited. Theresa Wade (WriteSource Medical) provided medical writing. Table: Baseline Characteristics (n=95)CharacteristicNumber (%)Age, median (range)50.3 (24.4 -82.1)Charlson Comorbidity Index- 077 (81.1)- 19 (9.5)- 2 +9 (9.5)Tumour Size12 (12.6)- T156 (59.0)- T225 (26.3)- T3- Unreported2 (2.1)Tumour Grade- 10 (0)- 231 (32.6)- 362 (65.3)- Unreported2 (2.1)Nodal status- Positive63 (66.3)- Negative32 (33.7)Hormone Receptor Status- HR+60 (63.2)- HR-35 (36.8)Median baseline left ventricular ejection fraction (range)65.0% (35-79)Cardiac risk factors- 053 (55.8)- 122 (23.2)- 2+20 (21.1) Citation Format: Sheau Wen Lok, Richard De Boer, Sallt Baron-Hay, Peter Button, Bianca Devitt, Benjamin Forster, Peter Fox, Michael Harold, Sahisha Ketheeswaran, Ganessan Kichenadasse, Belinda E Kiely, Gavin Marx, Louise Nott, Laura Pellegrini, Ali Tafreshi, Peter GIbbs. Pertuzumab study for HER2-positive non-metastatic breast cancer in the neoadjuvant setting in Australia [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-38.

Abstract We have analysed the influence of age on survival after a tandem hematopoietic stem cell transplantation prospective protocol (GEM-2000) in patients diagnosed of multiple myeloma (MM). From 870 patients with symptomatic MM aged < 70 years and prospectively included in the GEM-2000 protocol, we have analysed the outcome of a group of 637 patients [351 males, median age of 59 (range, 32 – 70) years] and treated with at least one autologous stem cell transplantation (ASCT). Sixteen patients (2.5%) were between 31 and 40 years of age (group A), 96 patients (15%) between 41 and 50 years (group B), 244 patients (38%) between 51 and 60 years (group C) and the remaining 281 patients (44.5%), between 61 and 70 years (group D). In 325 patients the M component at diagnosis was an IgG (51%). Fifty three patients (8%) had stage I at diagnosis, 232 patients (37%) stage II and 352 patients (55%), stage III. One hundred and one patients (16%) presented with renal insufficiency at diagnosis. Significantly lower levels of serum albumin at diagnosis were observed in the older group of patients (3.88 g/L vs 4.46 g/L, p = 0.05). Most of the patients (612, 96%) were initially treated with the alternating protocol VBCMP/VBAD. The response rate to the first line therapy was of 84% (n = 533), without differences between group D and the rest of the groups. The BUMEL protocol (busulfan 10 mg/kg po plus melphalan 140 mg/m2 iv) and MEL200 (melphalan 200 mg/m2 iv) were the two conditioning regimens used for the first intensive procedure. Although the proportion of older patients (group D) who received MEL200 was higher than in the younger groups of patients (groups A – C) (35% vs 44%), these differences did not reach a statistical significance. At three months after the first ASCT, 30% of the patients had reached a complete remission with negative immunofixation (CR IF-); this percentage was significantly superior in the younger group of patients (groups A – C) with respect to group D (32% vs 27%, p = 0.02). Transplant related mortality (TRM) was also significantly superior in group D (8% vs 3%, p = 0.01). At the time of follow-up, 124 patients (19%) have received a second transplantation; a second intensive procedure was more frequently performed in the younger group with respect to group D (25% vs 12%, p = 0.0001). This second transplant was an ASCT in 73% of the patients (65% in groups A – C vs 94% in group D, p = 0.04). With a median follow-up of 24 months, 508 patients are alive. Actuarial 2-year overall survival (OS) and event free survival (EFS) for the whole population of patients are 75%±2% and 57%±2%, respectively, with statistically significant differences between groups A - C and group D (77%±3% vs 72%±3%, p = 0.05 and 62%±3% vs 52%±4%, p = 0.02, respectively). The overall benefit of the intensification procedure seems to be less in the older group of MM patients (61 – 70 years) included in the GEM-2000 protocol. These results could be related to the achievement of a significant lower rate of CR IF- after the first ASCT and a higher TRM in this older population of patients.

Abstract Background: Total lymphocyte count (TLC) has been shown to correlate with outcomes in patients (pts) with acute leukemia. The clinical correlation to TLC in pts with chronic myeloid leukemia in chronic phase (CML-CP) who were treated with a tyrosine-kinase inhibitor (TKI) is unclear. Methods: Lymphocyte data in pts with newly diagnosed CML-CP who were enrolled in consecutive or parallel clinical trials with front-line imatinib (IM), nilotinib (Nilo), or dasatinib (Dasa) were collected at the time of diagnosis, and 3 and 6 months (M) after the start of TKI. Relative lymphocytrosis (RLC) was defined as lymphocyte >150% at 3 or 6M compared with baseline at diagnosis. Absolute lymphocytosis (ALC) was defined as lymphocyte > 4,000 /µL at 3 or 6M after the start of TKI. Pts were assessed for response, overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS) based on ALC and RLC. The Kaplan-Meier method was used to calculate OS, EFS, TFS, and FFS. A log-rank test and Cox regression were used for univariate (UVA) and multivariate analysis (MVA), respectively. Results: A total of 483 pts were enrolled in this study: 271 in IM, 105 in Nilo, and 107 in Dasa. Patient characteristics and outcomes are summarized in Table 1. Median age at diagnosis was 48 years, and median follow-up was 85M and ongoing (5-154+). Time from diagnosis to start of TKI, Sokal risk score, and ALC at baseline between groups did not differ clinically. Of 481 pts, 93 (19%) developed RLC at 3 or 6M; IM, 38 (14%); Nilo, 23 (22%); Dasa, 32 (30%) (p= .001). ALC at 3 or 6M was observed in 15 (3%); IM, 3 (1%); Nilo, 1 (1%); Dasa, 11 (10%) (p<.001). Overall, cumulative incidence of complete cytogenetic response (CCyR) at 6M, major molecular response (MMR) at 12M, molecular response with 4.5 log reduction by IS (MR4.5) at 24M did not differ significantly between RLC and non-RLC (3 or 6M), or between ALC and non-ALC (3 or 6M). 5-y TFS, EFS and OS in ALC group were significantly worse than those in non-ALC group (p= .002, p=.016, p=.008, respectively). By UVA and MVA related to OS, age [p <.001; Hazard ratio (HR), 1.062; 95% confidence interval (95%CI), 1.036-1.089], presence of ALC at 3 or 6M [p = .028; HR, 10.948; 95%CI, 1.297-92.415], absence of MMR at 24M [p=.016; HR, 2.263; 95%CI, 1.165-4.393] were identified as adverse prognostic factors for OS. Conclusion: The presence of ALC ≥4,000/µL at 3 or 6M of TKI therapies is rare but is adversely associated with overall survival. Table 1. Patient Characteristics and Outcomes (N=483)a Overall [n= 481] IM [n= 271] Nilo [n= 105] Dasa [n= 107] Age, (year) 48 (15-85) 48 (15-85) 49 (17-82) 48 (16-83) Sokal Risk, No. (%) Low 334 (69) 175 (65) 79 (75) 80 (75) Intermediate 114 (24) 74 (27) 18 (17) 22 (21) High 32 (7) 20 (7) 8 (8) 4 (4) Time from diagnosis to start of TKI, (M) 0.9 (0-12.6) 1.0 (0-12.6) 0.5 (0-5.6) 0.7 (0.1-7.8) ALC at baseline, (/109L) 2.5 (0-86.6) 2.4 (0-16.7) 2.6 (0.4-9.2) 2.7 (0.3-86.6) Incidence of Relative Lymphocytosis, No. (%) At 3M 65 (14) 25 (9) 16 (15) 24 (22) At 6M 76 (16) 32 (12) 20 (19) 24 (22) Overall 93 (19) 38 (14) 23 (22) 32 (30) Incidence of Absolute Lymphocytosis, No. (%) At 3M 8 (2) 1 (0) 0 7 (7) At 6M 11 (2) 3 (1) 1 (1) 7 (7) Overall 15 (3) 3 (1) 1 (1) 11 (10) Outcomes of RLC and ALC at any time in each group, +/- (%/%) (p) <10% BCR-ABL/ABL at 3M RLC 36/40 (.596) 22/44 (.213) 50/37 (.280) 31/38 (.537) ALC 38/39 (.952) 0/42 (.394) 100/39 (.214) 36/35 (.952) Cumulative CCyR at 6M RLC 75/75 (.288) 50/66 (.063) 96/90 (.413) 90/87 (.628) ALC 67/75 (.711) 33/64 (.276) 0/92 (.001) 82/89 (.599) Cumulative MMR at 12M RLC 67/74 (.406) 53/70 (.030) 83/82 (.921) 72/74 (.903) ALC 60/73 (.488) 33/68 (.197) 0/83 (.033) 73/74 (.745) Cumulative MR4.5 at 24M RLC 46/52 (.564) 37/50 (.139) 57/55 (.889) 50/57 (.729) ALC 33/52 (.332) 33/48 (.610) 0/56 (.264) 36/57 (.252) 5-y FFS RLC 61/71 (.133) 56/69 (.167) 62/70 (.710) 61/74 (.285) ALC 50/69 (.076) 0/68 (<.001) 0/70 (<.001) 71/70 (.974) 5-y TFS RLC 90/93 (.369) 88/93 (.597) 91/88 (.115) 91/99 (.213) ALC 72/93 (.002) 67/93 (.014) 0/90 (<.001) 80/97 (.121) 5-y EFS RLC 80/86 (.213) 71/83 (.154) 84/87 (.450) 86/93 (.486) ALC 64/85 (.016) 33/82 (<.001) 0/87 (<.001) 80/92 (.574) 5-y OS RLC 89/93 (.068) 81/94 (.007) 100/84 (.126) 96/99 (.207) ALC 82/93 (.008) 67/93 (.001) 100/88 (.847) 83/99 (.040) a Two in IM and 1 in Dasa were not evaluable due to lack of differential data at 3 and 6M. Figure 1. OS in Pts with ALC Figure 1. OS in Pts with ALC Disclosures O'Brien: Amgen, Celgene, GSK: Consultancy; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Emergent, Genentech, Gilead, Infinity, Pharmacyclics, Spectrum: Consultancy, Research Funding; MorphoSys, Acerta, TG Therapeutics: Research Funding.

Abstract Background: PTLD comprises a diverse spectrum of hematological conditions, ranging from early lesions, characterized by reactive-like proliferations, to monomorphic lesions, resembling overt lymphoma. Â In most cases, the lesions are believed to arise as the result of reduced immune surveillance secondary to the use of immunosuppressive drugs post-transplant. This view is supported by the observation that PTLDs, particularly those characterized by early or polymorphic lesions, may regress spontaneously upon reduction of the immunosuppressive treatment. Studies in sporadic lymphomas have identified distinct microenvironmental characteristics, predictive of the clinical behavior, but data is scarce in the immunocompromised setting. Therefore, the aim of this study was to investigate the tumor microenvironment in a population-based cohort of PTLD. Methods: We identified 108 PTLD patients diagnosed in the period 1994-2011. Of these, 62 cases had adequate tissue for tissue microarray construction. All biopsies were reviewed and classified according to the WHO 2008 criteria. Immunohistochemically stained sections were digitally quantified using Tissuemorph (Visiopharm Integrator System 4.0.3.0, Visiopharm, Denmark). Determination of optimal cut-off values of the area fraction (AF) was established by a ROC-curve. ROC analyses were performed in every disease entity and used for endpoint analyses. Results: Themedian age was 45 yrs (range 2-77 yrs) with a M/F ratio of 3:1. The majority presented in stage I-II (61%), and B symptoms and extranodal disease were common features (40% and 42%, respectively). Most tissue samples were EBV-positive (85%). The EBV latency pattern was predominantly latency II (41%) or III (43%). The AF of galectin-1 (gal-1) positive cells was clearly correlated to latency type (p=0.0001), whereas FOXP3 and programmed death-1 (PD-1) did not show such correlation (fig 1). Overall survival (OS) was significantly higher in cases with high levels of PD-1 expression, with 5-yrs OS of 39% (23-55%) and 69% (47-83%) for low and high levels, respectively (p=0.01). Expression levels of FOXP3 and gal-1 had no impact on OS in the total cohort (fig 1). In the monomorphic setting, a low AF of FOXP3 positive cells was associated with an increased risk of progression (OR 6.1; 95% CI: 1.4-26.0). This did not, however, translate into an inferior OS (p=0.163). To specifically characterize the tumor microenvironmental features of DLBCL-type PTLD with respect to cell of origin (COO), 30 evaluable cases were analyzed according to the Hans classifier; 10 (33%) were germinal center (GC) type and 20 (67%) of non-GC type. Cases of non-GC subtype had a significantly shorter time to PTLD of 1.16 yrs (CI: 0.64- 2.11), than those of GC-subtype (3.66 yrs; CI: 1.64- 8.16) (p=0.023) and a lower AF of gal-1 positive cells (p=0.042). The 5-yrs OS was 58% (32-77%) and 0% for non-GC versus GC-tumors, respectively (p=0.075). High levels of FOXP3 expression were associated with superior OS in the non-GC sub-group (p=0.04); gal-1 and PD-1 had no influence in the COO setting. Conclusion: The present study is one of the few attempts to describe tumor microenvironmental features in PTLD and relate them to outcome. In a population-based PTLD cohort, we found that specific immune cell subsets were variably expressed in different PTLD subtypes, and that high expression of PD-1 (whole cohort) and FOXP3 (non-GC DLBCL only) correlated with significantly better outcome. Â N(%) pts in TMA Organ tx(%) Kidney Heart Lung 47(75.8) 9(14.5) 6(9.7) Type PTLD(%) Early/polymorphic lesions Monomorphic PTLD Diffuse large B-cell lymphomaPeripheral T-cel lymphomal, NOS*T-Anaplastic large cell lymphomaBurkitt lymphomaHodgkin lymphoma-type PTLD Marginal zone lymphoma 18(29.0) 38(61.2) 32(51.6) 1(1.6) 3(4.8) 2(3.2) 4(6.5) 2(3.2) Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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AT III deficiency is associated with a high risk of venous thromboembolism, particularly in pregnancy. As prophylactic treatment it has been recommended to normalize plasma levels of AT in by use of AT III concentrates, besides giving heparin.We report on the prophylactic treatment of three sisters (age 21, 25, 32 years) with congenital AT in deficiency (38-53%, normal: 80-120%) as well as a reduced inducible fibrinolytic activity (1.2, 5.8, 7.9%, normal: >8.5%), who already had suffered from severe thromboembolism. During pregnancy prophylactic measures were taken individually, depending on the plasma level of 3-throm-boglobulin (BTG) determined every 2-3 weeks. At the time of the first increase of BTG (around 10th week of gestation) prophylaxis with s. c.heparin 2x7'500IU/d was started, leading to normalization of BTG. When BTG was again elevated, the dose of heparin was successively increased up to 2x15'000IU/d; thereby, functional AT IH levels remained in the range of 28-50%. Two patients received only heparin throughout the pregnancy. However, in one patient BTG levels could not be normalized by heparin alone (60-130ng/ml, normal: <43ng/ml). Injections of AT in concentrate, 11000IU, led to reduction of BTG within 2 hrs (60 → 42, 220 → 61 ng/ml). Therefore, AT m was given from the 25th week of gestation in increasing amounts up to 5'000IU/week (funct. AT m in plasma: 51 -72%) in addition to heparin (2x12'500IU/d), resulting in BTG levels of 33-51 ng/ml. From the onset of labour, all patients received AT IU concentrates (two patients l'OOOIU every second day, one patient 1'0001U daily) together with i. v. heparin 20'000-27'500IU/d, until the oral anticoagulant treatment started after delivery had reached therapeutic levels. The amount of AT m concentrate totally administered was 5'000IU in two patients and 66'000IU in one patient. None of the patients showed ever signs of venous thrombosis.Our observations demonstrate that instead of an AT in substitution with the aim to normalize its plasma level, an effective thrombosis prophylaxis - monitored by plasma levels of BTG - may be achieved with heparin alone or combined with low amounts of AT in concentrate.

To determine a role of platelet membrane components on the interaction of platelet-collagen-von Willebrand factor(vWF), several experimental approaches were used. The adhesion of human fixed washed platelets(FWP) to collagen was decreased after the treatment with Serratia marcescens protease(100 ug/ml), but the collagen cofactor activity(COo) of vWF that enhances the adhesion of FWP to collagen was still present after the digestion. Although the platelet adhesion in the absence of normal plasma was not changed by the addition of monoclonal antibody(M-ab) against platelet membrane glycoprotein(GP) IIb/lIIa(1 0E5, BS Coller), the adhesion was decreased by 30-50% after the treatment of the platelets with 10-100 ug/ml anti-GPIb(6D1, BS Coller). The adhesion of FWP to collagen was inhibited by lectins;the adhesion was 58-75% in the presence of 100-400 ug/ml L. culinaris lectin or weat germ agglutinin and the adhesion was nil in the presence of 100 ug/ml Ricinus communis agglutinin I or 200 ug/ml concanavalin A. By the crossed aff ino-immunoelectrophoresis, the binding of GP Ilb/lIIa in Triton-solubilized platelet supernatant to the collagen spacer gel was observed. When CHAPSO solubilized platelet was applied to the collagen column and the fractions containing adhesion inhibitor were eluated by 0.3M NaCl, Mr of 240K, 220K, 21 OK, 116K, 61K, 54K, 50K and 45K proteins were identified besides the proteins which correspond to thrombospondin, GPIb, GP lib or Ilia by SDS-PAGE(7.5% gel, silver stain). GOo in normal plasma was not changed by anti-GPIIb/lIIa but was decreased to 32-38%by anti-GPIb. M-ab against vWF, CLB-RAg 35(van Mourik), that inhibits the binding of vWF to platelet by ristocetin decreased COo in normal plasma by 70% and CLB-RAg 201 (van Mourik) that inhibits the binding of vWF to collagen did completely inhibit the COo in normal plasma. In conclusion, our data suggest that (1) GPIb is partly involved in the platelet adhesion to collagen; (2) the binding of vWF to collagen is required for the expression of CCo; (3) CCo of vWF is partly mediated though GPIb; and (4) several platelet membrane protein(s) besides GPIb or GPIIb/lIIa may be also involved in both the adhesion of platelets to collagen and CCo of vWF.

Ovarian cancers tend to recur in 15-70% cases. CA-125 - is a tumor marker used for monitoring therapeutic response, and in surveillance, for recurrent disease. However, it has a limited role as a persistent high level can signify either recurrence or persistence of residual tumor. Metastases from ovarian cancer primarily involve the peritoneum rather than parenchymal sites; thus, the presence of small-volume recurrence or metastatic deposits on the visceral surfaces poses a challenge for interpretation of CT and MR images. PET/CT utilizes its property of higher accumulation in malignant cells to provide both anatomic and functional information for diagnosing malignant tumors. Objectives: The objectives of the study were to find the correlation between PET/CT findings and final histopathological diagnosis after a secondary cytoreductive surgery in suspected ovarian cancer recurrences. Materials and Methods: PET/CT was done in cases with rising or above normal CA-125 and no radiological findings. These patients with abnormal PET/CT findings were taken up for a secondary cytoreductive surgery and histopathological proven were taken as the standard against which PET/CT positive findings was compared. Results: The mean age in our group of patients with suspected recurrence was 53 years (Range 39-74 years). Of the 52 patients with suspected recurrence, 40 patietnts with a PET-CT scan with findings suggestive of an avid uptake underwent surgery. 22 patients had serous histology, 12 mucinous and 8 had clear cell carcinoma. Stage-wise distribution at the time of primary surgery is as follows stage I-3, stage II-7, stage III-26, stage IV-4. Of the 40 patients who underwent a second look surgery 32 had histopathologically confirmed recurrence. PET-CT detected a total of 86 lesions in the 40 patients who underwent surgery. Of these, 38 were in the lymph nodes 28 in para-aortic and 10 in pelvic, 32 were peritoneal lesions and 14 were pelvic, 2 were metastatic in the parenchyma of liver. Detection of the lesion on PET-CT was size dependant, of the 9 lesions were missed on PET-CT, 7 were less than 0.5 cm. The mean diameter of the lesions detected was 2.2 cm (range 0.3-6.2 cm). PET-CT accurately identified 62 of 70 histopathologically proven lesions. The overall lesion-based sensitivity of PET-CT is 88.6%, specificity 56.2%, Positive predictive value being 72.1%, negative predictive value of 69.2%. Accuracy of detecting lesions greater than 1 cm is 78.6% (44 of 56 lesions). Conclusions: Corelation between PET/CT and histopathologicaldisease: k (cohen value) = 0.81 which suggests excellent correlation. For selected patients with ovarian cancer recurrence may benefit from a comprehensive radiographic imaging survey (PET-CT) at the time of even no or minimal CA-125 elevation in early detection and successful cytoreductive surgical resection and an increase in overall survival.