Letteratura scientifica selezionata sul tema "Wm 49 k92m 2006"

Abstract. We investigated the effect of the estrogen receptor (ESR) and ryanodine receptor (RYR1) genes on total number of born (TNB), number of born alive (NBA) and number of weaned (NW) piglets in Large White (LW), White Meaty (WM) and Landrace (L) sows from six Slovak breeding farms. We found a significant effect of ESR locus on NW (P≤0.01) in LW, however, we observed a negative effect of BB genotype on the trait. In WM, positive associations of B allele with TNB, NBA, NW were found but the differences were not confirmed statistically. A highly significant effect (P≤0.01) of ESR locus on TNB (+0.62±0.18 pigs per copy of B allele), NBA (+0.65±0.18) and NW (+0.51±0.16) was identified in L breed. With RYR1 gene we found significantly higher TNB and NBA in heterozygous WM sows (+1.01±0.36 in TNB; +0.87±0.32 in NBA; P≤0.01). NBA was also significant in LW (+0.41±0.19; P≤0.05).

Abstract. A four year record of MODIS spaceborne data provides a new measurement tool to assess the aerosol direct radiative effect at the top of the atmosphere. MODIS derives the aerosol optical thickness and microphysical properties from the scattered sunlight at 0.55–2.1 μm. The monthly MODIS data used here are accumulated measurements across a wide range of view and scattering angles and represent the aerosol's spectrally resolved angular properties. We use these data consistently to compute with estimated accuracy of ±0.6 Wm−2 the reflected sunlight by the aerosol over global oceans in cloud free conditions. The MODIS high spatial resolution (0.5 km) allows observation of the aerosol impact between clouds that can be missed by other sensors with larger footprints. We found that over the clear-sky global ocean the aerosol reflected 5.3±0.6 Wm−2 with an average radiative efficiency of −49±2 Wm−2 per unit optical thickness. The seasonal and regional distribution of the aerosol radiative effects are discussed. The analysis adds a new measurement perspective to a climate change problem dominated so far by models.

Abstract Nucleoside analogs (NA) are used alone or in combination in low grade B-cell lymphoproliferative disorders for 20 years. The incidence of disease transformation (Richter syndrome: RS) and development of MDS/AML among patients (pts) with indolent B-cell malignancies receiving NA are still controversial. We have reviewed the crude incidence of RS and MDS/AML in 165 WM patients treated with 3 F-based regimens. Results: Retrospective Study 1 (Leblond J Clin Oncol 1998): F (25mg/m2 iv D1–5) in 71 WM pts in relapse/refractory treated with alkylator, median time from diagnosis (dg) to tt: 5.9yrs, median prior tt: 2 (1–4). Randomized prospective study 2 (Leblond Blood 2001) in 92pts in first relapse after alkylator: Arm 1: F (25mg/m2 ivD1–D5) (45pts) vs Arm 2: CAP (doxorubicine 25mg/m2 IV D1, cyclophosphamide 750mg/m2 IV D1, Prednisone 40mg/m2 D1–5) (45pts), median time from dg to tt: 3.9yrs. Retrospective study N°3 (Tamburini Leukemia 2005) in first-line WM (14pts) or relapse WM (35pts): F 30mg/m2 D1–3 by oral route + Cyclophosphamide (C) 300mg/m2 D1–3 by oral route, median time from dg to tt: 2.1 yrs. The incidences of MDS/AML and RS are shown in Table 1 Discussion: the crude incidence of RS varied from 6,6% to 8% and was not statistically different in the randomized prospective study N°2 between the two groups. However, the incidence reported in pts treated with only alkylating-based regimens was lower: 3/167(1.8%) (Facon J Clin Oncol1993) and 3/217 (1.4%) (Garcia Sanz Br J Hematol 2001) and could be explained by a F use as salvage treatment in the CAP arm. The impact of fludarabine on RS needs to be confirmed in larger prospective studies. The crude incidence of MDS/AML varied from 1.4 to 8.9% in pts treated with fludarabine alone and was 6% in pts treated with F+C. The incidence reported in pts treated with alkylating based regimens varied from 1% (2/167, Facon 1993, 3/217 Garcia-Sanz 2001) to 6% (3/46, Kyle Br J Hematol 2000,) and was not different. In other low grade B-cell malignancies, a higher incidence of MDS/AML has been reported in pts treated with analog-alkylator combination compared to F or alkylator alone (Morrison J Clin Oncol 2002, Bowcock Br J Hematol 2006, Tam Hematologica 2006). In our study, the rate was the same in the two populations. The impact of late effects, particularly second malignancies, need to be better evaluated in prospective studies, especially in young patients and clinicians should discuss the risk when recommending such therapy to pts. MDS/AML and RS incidences in the three studies Study N°, pts Median survival time from study Median follow-up time from study MDS/AML (N,%) RS (N,%) N°1 71 pts 23 mo 34 mo 1/71 (1.4%) 5/71 (7%) N°2- 92 pts 41mo( arm1), 45 mo (arm2) 34mo 4/45 (8.9%, arm1), 2/45( 4.5%, arm2) 3/45 (6.6% arm1), 2/45 (4.5%, arm2) N°3-49pts 64% at 60 mo 42 mo 3/49 (6%) 4/49 (8%)

Abstract Introduction: Rituximab (R) is an integral component of therapy for B-cell lymphoid malignancies; bortezomib (Btz) has shown provocative single agent activity in Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL) and Waldenström’s Macroglobulinaemia (WM), providing the rationale for investigating the combination. Patients+Methods: Forty-five adult patients (pts.) (30 men, 15 women) with histologically confirmed recurrent CD20+ve FL, MCL or WM, median age 60 years (range 45-79), FL: 17, MCL: 18, WM: 10, stage III/IV 40 (93%), bone marrow (BM) infiltration 32 (73%), elevated LDH 22 (49%), performance status ≥1 22 (49%), were enrolled in a randomised trial comparing 2 schedules of Brz+R: Arm A (twice weekly) Btz: 1.3mg/m2 (on days 1, 4, 8, 11 of a 21-day cycle) and R: 375mg/m2 (on day 1) for 8 cycles, or Arm B (weekly) Btz: 1.6mg/m2 (on days 1, 8, 15, 22 of a 35-day cycle) and R: 375mg/m2 (on days 1, 8, 15, 22 of cycles 1 and 4) for 6 cycles (23 arm A, 22 arm B). The median number of previous treatments was 2 (range 1-7). Seventeen pts. had received a R-containing regimen, with response lasting >6 months, and 8 high-dose treatment. Response was evaluated using the IWR criteria (Cheson et al, JCO17: 1244, 1999) and the updated response criteria from the 3rd International Workshop on WM (Treon et al, Blood107: 3442, 2006) Results: Ability to deliver the therapy, toxicity and efficacy were equivalent in both arms. The median number of cycles given in arm A was 4 and 5 in arm B. Haematological toxicity (grade≥3: anaemia 0%, neutropenia 25%, thrombocytopenia 22%) was significantly influenced by the high percentage of pts. with BM infiltration and concomitant cytopenia on entry to the trial. The most common non-haematological adverse events were fatigue (76%), nausea (56%), diarrhoea (56%), lethargy (46%). Neurotoxicity occurred in 19 pts. (46%) (10 pts. grade 1, 7 pts. grade 2, 2 pts. grade 3). Btz dose was reduced in 7 pts.; 5 doses were omitted because of neuro or haematological toxicity. In 16 pts., treatment was delayed by 1-14 days and in 24 pts. treatment was stopped prematurely. The reasons for stopping treatment were: treatment-related toxicity 11 pts., progressive disease 9 pts., patient’s preference 3 pts., myocardial infarction 1 pt. One pt. was excluded having been found ineligible post randomisation. Thirty-nine pts. (21 arm A, 18 arm B) are evaluable for response so far, one having only received 1 cycle of therapy, which had to be discontinued because of excessive toxicity. 15/32 were in remission (CR, CRu, PR) at the completion of therapy, 7/7 at “mid-therapy” assessment, and 5 have yet to be evaluated. Thus the overall response rate (RR) presently is 22/39 (56%) (CR, CRu, PR), FL 44%, MCL 46%, WM 90%. Conclusions: The combination was active in pts. with recurrent NHL especially WM (RR 90%), despite multiple previous treatments, The weekly schedule is preferable being more convenient, as efficacious and no more toxic. Further investigation is warranted, despite not insignificant therapy compromising toxicity.

Abstract Abstract 438 Between November 2002 and April 2006, 72 patients with Waldenstrom's Macroglobulinemia (WM) were enrolled in this multicenter trial of primary treatment with DRC which consisted of dexamethasone 20mg IV followed by rituximab 375 mg/m2 IV on day 1 and oral cyclophosphamide 100 mg/m2 bid on days 1 to 5 (total dose 1000 mg/m2). DRC courses were repeated every 21 days for six courses and then patients without progressive disease were observed without treatment. Patient characteristics, toxicity and response data have been reported previously (Dimopoulos et al, J Clin Oncol 2007;25:3344): 83% of patients achieved a response including 7% complete, 67% partial and 9% minor responses. In June 2012 we updated this study (minimum follow-up >6 years) in order to assess time to progression, time to next treatment, type and response of second-line treatment, overall survival (OS) and cause-specific survival (CSS) in which deaths unrelated to WM or complications of treatment were censored. Second line treatment was administered to patients who experienced progressive disease and also met criteria for treatment requirement based on consensus recommendations (Kyle et al, Sem Oncol 2003;30:116). The median time to progression was 35 months (95% Confidence Interval: 22–48 months) and the median time to next treatment requirement was 51 months. Among several factors who were analyzed for their possible correlation with shorter time to progression, only lymphadenopathy was significant (p=0.028). Among 40 patients who received second line treatment, 28 patients were retreated with either rituximab alone (n=7) with DRC (n=11) or with rituximab combined with other agents (n=10) and 23 patients (82%) achieved a minor response or better. The remaining 12 patients were treated with alkylating agents (n=5), with nucleoside analogues (n=4) with bortezomib (n=2) or with high dose therapy (n=1) and 8 patients achieved a minor response or better. So far 35 (49%) patients have died including 15 patients from unrelated causes (4 lung cancer, 1 bladder cancer, 1 melanoma, 1 gastric cancer, 1 pancreatic cancer, 4 complicated of heart diseases, 2 stroke and 1 pancreatitis). One patient, who received further therapy with fludarabine, developed myelodysplastic syndrome and 2 patients developed diffuse large-B cell lymphoma (one after DRC and one after multiple treatments which included alkylating agents and fludarabine). The probability for 5-year OS and CSS is 62% and 78%, respectively while median OS and CSS is 95 and 104 months respectively (figure). Post progression survival was 82 months and median survival after second line therapy was 82 months. The International Prognostic Staging System (IPSS) is predictive for OS. The probability for 5-year OS is 100%, 67% and 48% for patients with low-, intermediate- and high- risk WM (p=0.005). We conclude that this long-term follow-up analysis of the original phase II study showed that the DRC regimen is associated with a significant median time to progression of about 3 years and that most patients who develop disease progression respond again to rituximab-based regimens. So far, this regimen has not been associated with development of secondary myelodysplasia. The DRC regimen represents an active and safe treatment choice for patient with symptomatic WM. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Activating mutations in MYD88 and CXCR4 are present in 95-97% and 30-40% of patients with Waldenström Macroglobulinemia (WM), respectively. Gene expression and transcriptome studies have shown that BCL2 is highly expressed in WM cells, particularly in those patients with activating MYD88 mutations (Chng et al, Blood 2006; Hunter et al, Blood 2016). Use of the BCL2 inhibitor venetoclax triggered apoptosis of WM cells, including primary WM cells from ibrutinib-naïve and ibrutinib-treated patients. In a Phase I dose finding study, venetoclax showed efficacy in 4 WM patients (Davids et al, JCO 2017). We therefore initiated a phase II study to evaluate the safety and efficacy of venetoclax monotherapy in previously treated patients with WM (NCT02677324), and determined the impact of prior BTK-inhibitor (BTK-i) therapy and CXCR4 mutation status on treatment response. Methods: Venetoclax was administered as outpatient therapy, and followed a ramp-up of 200 mg daily on days 1-7, 400 mg daily on days 8-14, then 800 mg daily for maximum of 2 years. Dose reduction for adverse events (AEs) was permitted. Patients were closely monitored for tumor lysis syndrome (TLS) during the first 24 hours of each dose escalation. Response was assessed using modified IWWM-6 criteria. MYD88 and CXCR4 genotyping was performed as before (Xu et al, BJH 2016). Results: 30 patients with symptomatic WM were enrolled. Their median age was 66 years (range 39-80 years) and 17 (57%) were men. Indications for treatment included constitutional symptoms (52%), anemia (44%), peripheral neuropathy (15%), extramedullary disease (11%) and thrombocytopenia (7%). The median number of prior therapies was 2 (range 1-10), and 15 (50%) patients were previously treated with a BTK-i. All patients carried the MYD88L265P mutation, and 16 (53%) also had a CXCR4 mutation. At baseline, median serum IgM was 3,543 mg/dl (range 642-7,970 mg/dl), median bone marrow involvement was 35% (range 4-95%) and median hemoglobin was 10.6 g/dl (range 6.4-13.5 g/dl). All evaluable patients have completed 6 months of therapy, at a median follow-up of 12 months (range 1-23 months). All patients were successfully escalated to target dose of 800 mg. At 6 months, median serum IgM declined to 1,750 mg/dl (range 49-5,220 mg/dl), median bone marrow involvement declined to 5% (range 0-30%) and median hemoglobin increased to 12.4 g/dl (range 10-15.1 g/dl) (p<0.001 for all variables against baseline). At best response, very good partial response (VGPR) was attained in 5 patients (17%), partial response in 19 (63%), minor response in 2 (7%) and stable disease in 4 (13%), for an overall response rate of 87% and major response rate of 80%. Patients with prior refractory disease showed a lower major response rate versus those with relapsed disease (57% vs. 95%; p=0.01). Moreover, VGPR rates were lower in those with prior BTK-i exposure (7% vs. 27%; p=0.10), and CXCR4 mutations (6% vs. 29%; p=0.10). Median time to response (TTR) was 9 weeks and was slower in patients with prior BTK-i exposure (19 vs. 6 weeks; p=0.02). TTR was not impacted by relapsed vs. refractory disease status nor by CXCR4 mutation status. Two patients progressed at 8 and 10 months on therapy. Overall, treatment was well tolerated and no clinical TLS occurred. Laboratory TLS occurred in one patient with significant extramedullary disease. Grade 4 neutropenia occurred in 4 patients, who responded to G-CSF. Grade 3 AEs included neutropenia (n=7), anemia (n=2), back pain (n=1), constipation (n=1), diarrhea (n=1), headache (n=1), upper respiratory infection (n=1). Grade 2 AEs included anemia (n=5), nausea (n=4), neutropenia (n=3). Grade 1 AEs included nausea (n=9), diarrhea (n=6), rash (n=5). Dose reduction for AEs occurred in two patients (for neutropenia and diarrhea). No instances of IgM flare were observed, and there have been no deaths. Conclusion: The findings show that venetoclax is well tolerated, and produces high levels of response in patients with symptomatic, previously treated WM, including patients previously exposed to BTK-i. Prior BTK-i exposure and presence of CXCR4 mutations impacted VGPR response attainment. Figure. Figure. Disclosures Castillo: Beigene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Millennium: Research Funding; Genentech: Consultancy; Abbvie: Consultancy, Research Funding. Allan:Verastem: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy; Genentech: Membership on an entity's Board of Directors or advisory committees; Sunesis: Membership on an entity's Board of Directors or advisory committees. Furman:Loxo Oncology: Consultancy; TG Therapeutics: Consultancy; Verastem: Consultancy; Gilead: Consultancy; Incyte: Consultancy, Other: DSMB; AbbVie: Consultancy; Janssen: Consultancy; Sunesis: Consultancy; Genentech: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; Acerta: Consultancy, Research Funding. Siddiqi:Juno Therapeutics: Other: Steering committee. Advani:Kyowa: Other: Consulting/Advisory Role; Celgene: Other: Institutional Research Support; Merck: Other: Institutional Research Support; Bristol Myers Squibb: Other: Consultancy/Advisory role and Institutional Research Support; Janssen Pharmaceutical: Other: Institutional Research Support; Regeneron Pharmaceuticals, Inc.: Other: Institutional Research Support; Infinity: Other: Institutional Research Support; Forty Seven, Inc: Other: Institutional Research Support; Gilead/Kite: Other: Consultancy/Advisory Role; Millenium: Other: Institutional Research Support; Agensys: Other: Institutional Research Support; Kura: Other: Institutional Research Support; Roche/Genentech: Other: Consultancy/Advisory Role, Institutional Research Support; Takeda: Other: Consultancy/Advisory Role; Pharmacyclics: Other: Institutional Research Support; Bayer Healthcare Pharmaceuticals: Other: Consultancy/Advisory Role; Cell Medica: Other: Consultancy/Advisory Role; AstraZeneca: Other: Consultancy/Advisory Role; Autolus: Other: Consultancy/Advisory Role; Seattle Genetics: Other: Consultancy/Advisory role, Institutional Research Support. Hunter:Pharmacyclics: Consultancy. Davids:Roche: Consultancy; Surface Oncology: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; MEI Pharma: Consultancy, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Celgene: Consultancy; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy; Pharmacyclics: 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; MEI Pharma: Consultancy, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Surface Oncology: Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Surface Oncology: Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Merck: Consultancy; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Verastem: Consultancy, Research Funding; Celgene: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Membership on an entity's Board of Directors or advisory committees; Sunesis: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Consultancy, Research Funding. Treon:Janssen: Consultancy, Other: Travel, Accommodations, Expenses; Pharmacyclics: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Johnson & Johnson: Consultancy; BMS: Research Funding.

Abstract Introduction. Primary immune thrombocytopenia is a rare disease1. The incidence of ITP is not well estimated in Russia and worldwide. In adults it varies from 1,6 to 3,9/100 000 person-years2-3. The gender and age-associated results are discussed and differ in several investigations4-6. Study objectives: evaluation of the incidence of primary immune thrombocytopenia in adults in one region of Russia Patients and methods. The data source is the Registry of the patients with primary ITP in Russia. 272 adult patients: 77 males (28%) and 195 females (72%), age from 16 to 89 years (median 44 years) with ITP (ICD-10 code D69.3), newly diagnosed cases during the period from 12 Jan 2014 to 24 May 2016. Results. 221 (81%) cases were newly diagnosed in 12 regions of Russia in which registration was performed most actively - more than 5 cases for the duration of the study. But only one region was selected for the first evaluation of epidemiological characteristics because of the number of reasons. There is one hematological central clinic in this region in which diagnosis of ITP can be verified and patients with ITP are treated and monitored most properly. The early started and fully performed registration process can be regarded as covered most part of region population in this target region. 86 cases (27 male, 59 female) were registered in the target region. The gender-age distribution was following: male: age <41 = 10 (37%), age <41-60 = 7 (26%), age >60 = 10 (37%); female: age <29 = 10 (49%), age <41-60 = 15 (25%), age >60 = 15 (25%). The estimated incidence rate in the target region is shown in table 1. The estimated incidence rates in gender-age strata in the target region are demonstrated in table 2. Conclusion. Overall ITP incidence in one region of Russia is 3.20/100 000 person-years. It is compatible to the incidence in other European countries. Our data demonstrate the rise of incidence rate in males with age and its decrease with age in female population. Literature. 1) Rodeghiero F., Stasi R., Gernsheimer T., Michel M., Provan D., Arnold D.M., et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from international working group. Blood. 2009; 113(11): 2386--93. doi: 10.1182/blood-2008-07-162503. 2) Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN. The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports. Am J Hematol. 2010; 85(3): 174-180. 3) Moulis G, Palmaro A, Montastruc J-L, Godeau B, Lapeyre-Mestre M, Sailler L. Epidemiology of incident immune thrombocytopenia: a natiowide population-based study in France. Blood. 2014; 124(22): 3308-3315. 4) Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data. J Thromb Haemost 2006; 4: 2377-83 5) Schoonen WM, Kucera G, Coelson J, et al. Epidemiology of immune thrombocytopenic purpura in the General Practise Research Database. Br J Haematol 2009; 145(2): 235-244. 6) Lisukov I.A., Maschan A.A., Shamardina A.V., Chagorova T.V., Davydkin I.L., Sycheva T.M., et al. Immune thrombocytopenia: clinical manifestations and response to therapy. Intermediate analysis of data of the Russian register of patients with primary immune thrombocytopenia and review of literature. Oncogematologiya. 2013; 2: 61--9]. Disclosures No relevant conflicts of interest to declare.

Abstract Introduction Today’s diagnostic tests for multiple myeloma reflect the criteria of the updated WHO classification based on biological, morphological and clinical heterogeneity. It has been the concept behind the present study to extend our current biological classification and provide a new tool to generate insight into the stage of clonal differentiation and oncogenesis. The goal of the present study was to generate B-cell subset associated gene signatures (BAGS) from the BM hierarchy used to assign individual phenotypic cell of origin (pCOO) subtypes in patients and validate its pathogenetic impact by prognostic evaluation. Methods Bone marrows (BM, n=7) were harvested from sternum during cardiac surgery. B-cell subsets were phenotyped by Euroflow standard for multiparametric flow cytometry and FACS-sorted for microarray analysis on the Human Exon 1.0 ST Arrays platform. This combination allowed us to generate five BAGS for PreBI, PreBII, immature (Im), naïve (N), memory (M) B-cells, and plasma cells (PC) of normal BM. The BAGS classifier was based on all median-centred probe sets from the data set by regularized multinomial regression with 6 discrete outcomes corresponding to each B-cell subset and the elastic net penalty using the algorithm implemented in the R-package glmnet24. Each clinical data set was probe-set-wise adjusted to have a zero median and the same variance as in the BM data set. The associated cell of origin subset for each patient in each data set was predicted by the BAGS classifier by assigning the class with the highest predicted probability score above 0.45 and otherwise UC. All statistical analyses were done with R version 3.0.2. Survival analysis was performed by the Kaplan-Meier method and log-rank tests. Clinical data sets were from University of Arkansas for Medical Sciences UAMS (n=559), the Dana Farber Cancer Institute DFCI (n=170) both available on the GEO website. Results First, we verified the quality of the sampled B-cell subsets based on the expression patterns of differentiation marker genes. Next, we constructed the BAGS-classifier provided by 38-68 gene probe sets (n), capable of assigning samples to each of the six subtypes of PreBI (n=38), PreBII (n=82), Im (n=71), N (n=68), M (n=52) and PC (n=43). Second, we assigned individual myeloma cases in the 2 patient cohorts including a total of 729 myeloma patients. The resultant assignments generated patient BAGS subtypes with diagnostic frequencies of 0,5-0,6 % preBI, 7-8 % preBII, 27-30 % Im, 8-9 % N, 36-37 % M, 1-5 % PC and 15-16 % UC subtypes. The frequencies were not different between the cohorts. Third, the BAGS subtypes was associated significantly with overall survival (P = 8.6 x 10-5) for high dose melphalan and autologous stem cell transplanted UAMS patients1, as illustrated in Figure 1. The most significant impact was observed within the PreB-II (light blue) and M (acid green) subtypes conferred with significant inferior prognosis compared to the Im (amethyst), N (apple green) and PC (blue) subtypes. The PreB-II and M subtypes in the UAMS cohort were correlated to the ISS stage I-III with 33%, 49% and 69% of the cases, respectively. Fourth, we compared the BAGS subtypes and the TC classification2 with no observed correlations (results not shown). Conclusions Our data support a new COO defined BAGS classification based on the normal BM B-cell subset phenotypes with impact on staging and prognosis in multiple myeloma and a new diagnostic platform, which may result in more effective disease management. References 1) Zhan F, Huang Y, Colla S et al. The molecular classification of multiple myeloma. Blood. 2006 Sep 15;108(6):2020-8. 2) Bergsagel PL, Kuehl WM, Zhan F, Sawyer J, Barlogie B, Shaughnessy J Jr. Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood. 2005 Jul 1;106(1):296-303. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

O clareamento dental tem sido uma opção conservadora para o tratamento estético dos dentes. A procura pelo procedimento tornou-se popular, sendo considerado ainda um procedimento minimamente invasivo, seguro e eficaz quando feito corretamente e acompanhado por um profissional habilitado. Esse procedimento poderá mudar significativamente a aparência dos dentes, tornando-a agradável. O propósito deste estudo foi avaliar o efeito do clareamento de consultório do esmalte dental sobre sua alteração de cor e a rugosidade superficial após o envelhecimento artificial embebidas fitness. 100 dentes bovinos foram submetidos a uma análise cromática inicial, por meio de um Espectrofotômetro de Reflexão Ultravioleta Visível*,Modelo* VITA Easyshade® Compact, com a avaliação de cor calculada através do Sistema CIE L*a*b*. A análise de rugosidade superficial (Ra) dos blocos de esmalte foi realizada em rugosímetro HommelEtamic W10 (JENOPTIK Industrial Metrology Germany GmbH). Após as análises iniciais os dentes foram divididos em10 grupos de estudo (n=10)- 50 amostras clareadas e 50 amostras não clareadas (3sessões-1/semana)-sendo imersas em sucos detox de açai (DTXAc), rosa (DTXRs), verde (DTXV), amarelo (DTXAm) e água mineral(A) por 1 hora/ dia. A alteração de cor (ΔE) e rugosidade (Ra) foram calculados.Não foi observada diferença estatisticamente significante na porcentagem de aumento da rugosidade das amostras. Apresentaram maior alteração de cor, as amostras clareadas que foram submetidas a envelhecimento artificial em DTXAm e DTXRs. Entre os grupos que não foram clareados, os Sucos DTXRs, de DTXAc e DTXV apresentaram maior alteração de cor. O uso de Sucos DTXRs e DTXAm entre as sessões de clareamento de consultório resultou em maior alteração de cor.Descritores: Esmalte Dentário; Clareamento Dental; Clareadores Dentários.ReferênciasAttia ML, Gomes ACO, César ICR, Munin E, Aguiar FHB, Liporoni PCS. Avaliação da eficácia de clareamento e da susceptibilidade ao manchamento de blocos dentais humanos e bovinos submetidos a dois agentes pigmentantes. In: Anais do IX Encontro Latino Americano de Iniciação Científica e V Encontro Latino Americano de Pós-Graduação. João Pessoa: Universidade do Vale do Paraíba; 2005.Ramos APB, Cesar ICR, Alves GL, Alves LP, Munin E, Rego MA, Liporoni PC. Avaliação do clareamento dental com peróxido de carbamida a 16%, submetidos a diferentes pigmentos, através de análise de fotorreflectância e rugosidade. In: Anais do X Encontro Latino Americano de Iniciação Científica e VI Encontro Latino Americano de Pós-Graduação – Universidade do Vale do Paraíba. João Pessoa: Universidade do Vale do Paraíba; 2005.Souto CMC. Avaliação da influência de ingestão de bebidas corantes em diferentes tempos na estabilidade do clareamento dental: análise de fotorreflectância. [dissertação]. Taubaté: Universidade de Taubaté; 2006.Sundfeld RH. 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