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A novel route for grafting polymers via electropolymerization of a macro-reversible addition fragmentation chain-transfer (RAFT) agent onto a conducting surface is reported. The electro-deposition of the chain transfer agent (CTA) on the conducting surface was done using cyclic voltammetry (CV). The statistically exposed dithiobenzoate moieties served as a CTA for the polymerization of styrene on a matrix of an electrodeposited conjugated polymer. The polystyrene (PS)-modified substrate was then used as the macro-CTA for the synthesis of the second block of poly-tert-butyl acrylate (PTBA) on the surface. The polymerization from the surface was characterized by surface analytical methods including AFM, XPS, and contact angle measurements.

This work shows a new column arrangement to improve the utilization of the adsorbent in multi-column Pressure Swing Adsorption (PSA) processes. This cycle was specifically designed to increase the unit productivity for gas separations using adsorbents with slow diffusion kinetics where mass transfer zone (MTZ) inside the column is important. In this column arrangement, when the heavy (most adsorbed) gas breaks through one column, the exit of this column is connected to a second column (trim bed) where more heavy gas can be adsorbed. In this way, also more heavy gas will be adsorbed in the first (lead) column. The increase of process performance is directly related to the length of the MTZ: the larger the MTZ, the better will perform using the lead-trim beds concept. The cycle performance was tested for biogas upgrading to obtain high purity bio-methane (purity >98%) that can be used as renewable fuel. Two different adsorbents were employed in the process simulations: zeolites 13X (fast diffusion) and carbon molecular sieve (slow diffusion). Furthermore, the possibility of using less power in the purge step was considered. Using this process, it was possible to obtain unit productivity of 5.5 mol CH 4 per hour per kilogram of adsorbent.

The upgrading of biogas by pressure swing adsorption (PSA) was studied. Simulations of a process for binary separation of CH4−CO2 using zeolite 13X as selective adsorbent were carried out at 323 K. The results obtained with a two-column PSA process using a six-step cycle (pressurization, feed, depressurization, blowdown, purge, and pressure equalization) were compared with initial estimates by simulating the behavior of only one column. The recycle of highly contaminated streams was quantitatively evaluated in this paper. When recycled streams have purity lower than 99%, there is a significant decrease in the overall purity of biomethane. According to the simulations performed for a stream of biogas of 500 N m3/day, it is possible to obtain biomethane with a purity higher than 99% with a recovery of 85% and a power consumption of 0.12 kW/mol of produced methane.

INTRODUCTION Cell free tumor DNA (cftDNA) based targeted next generation sequencing (NGS) is a novel tool that enables accurate and minimally invasive tumor genotyping. MATERIAL AND METHODS Here we have performed cftDNA targeted NGS for the molecular diagnosis of a series of 92 peripheral blood samples obtained at diagnosis in patients included in a phase II randomized clinical trial comparing standard RCHOP versus BRCAP as first line treatment in patients with poor IPI (aaIPI2-3 or aaIPI1 with high b2m, age 18-71, NCT01848132). Centralized histopathological review of diagnostic tissue samples confirmed the diagnosis: 83 DLBCL (68%, 55/81 GCB, 32%, 26/81 non-GCB, according to Hans immunohistochemical algorithm), 4 TCHRBCL, 3 PMBCL, 1 concurrent DLBCL and FL3A, 1 FL 3B. 7 out of 83 cases had DLBCL morphology and DH by FISH (6 MYC/BCL2 and 1 MYC/BCL6, all GCB-type by IHC). A targeted NGS approach using amplicon-based chemistry (Truseq, Illumina) that interrogates exonic regions of 35 relevant genes in DLBCL (1458 amplicons analyzed) was used for library generation from plasma derived DNA. Germline DNA from peripheral blood granulocytes from 89 out of 92 patients was sequenced in parallel and used as control DNA for variant calling. Only somatic variants with a read depth above 100 and Variant Allele Frequency > 5% were considered. RESULTS cftDNA concentration (hGE/mL) was associated with LDH levels (U/mL) at diagnosis. Mean cftDNA concentration was lower in patients with low LDH (U Mann whitney p= 0.005). Somatic mutations were identified in 74% (68 out of 92) patient plasma samples. 242 somatic mutations were considered after filtering. Mean of 3.6 mutations per patient. 10 genes were mutated in >10% of the patients, including: FAT2 (19.6%), ARID1A (18%), NOTCH1 (17.4%), NOTCH2 (15.2%), KMT2D (14.13%), SMARCA4 (14%), ATM (13%), EP300 (13%), EZH2 (13%), PLCG2 (13%). Recurrent mutations were found in EZH2 (2 patients). Mutations in BCR/TLR pathway genes were found in less than 10% of the cases (CARD11, 7.6%; MYD88, 4.4%; CD79A, 5.4%; CD79B, 1%; BTK, 4.4%). NOTCH1 mutations were found preferentially in GCB type DLBCL (12/55 GCB vs 1/26 nonGCB, Chi square p value DISCUSSION cftDNA targeted NGS captures the mutational profile in a significant fraction of DLBCL patients and enables tumor genotyping in the clinical trial setting. In contrast with previously published data mutations in NOTCH pathway, including NOTCH1, NOTCH2 and SGK1 were relatively frequent in our series of poor IPI patients, outnumbering the frequency of mutations in BCR/TLR pathway. NOTCH pathway mutations were also preferentially found in GCB-type DLBCL-NOS, PMBCL and 1 case of TCHRBCL. In summary cftDNA genotyping based on targeted NGS can provide potentially useful information for therapy selection in DLBCL patients. Disclosures Martín: Roche: Consultancy, Honoraria, Other: Travel expenses; Celgene: Consultancy, Honoraria, Other: Travel expenses; Servier: Honoraria, Other: Travel expenses; Janssen: Honoraria, Other: Travel expenses. Gonzalez-Barca:Roche: Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Gilead: Consultancy; Celtrion: Consultancy. Montes-Moreno:TAKEDA: Consultancy; Roche: Consultancy.

In the title compound, C(17)H(32)O(2)S(3), the dodecyl chain and the trithiocarbonate unit adopt a nearly planar all-trans conformation, while the carboxyl group is synclinal to this chain direction. The molecules are linked by pairs of inversion-related O-H...O hydrogen bonds to form centrosymmetric dimers of R(2)(2)(8) type, and dimers related by translation are linked by C-H...O hydrogen bonds to form a chain of edge-fused rings, or a molecular ladder, containing alternating R(2)(2)(8) and R(4)(4)(20) rings.

Background: We gathered data from multiple institutions on the cetuximab regimen of patients with metastatic colorectal cancer. Methods: 126 patients from 19 centers were included from July 2006 to July 2007 in this prospective non-controlled study. Irinotecan-refractory metastatic colorectal cancer patients with Karnofsky ≧70 received cetuximab 500 mg/m2 every 2 weeks (q2w) in combination with irinotecan 180 mg/m2 q2w until disease progression or unacceptable toxicity. The primary endpoint was the progression-free rate at 12 weeks. Results: Median age was 65 years; 65.9% male; colon/rectum 64.3/34.1%; Karnofsky status ≤80/≧90% in 45.3/54.7% of the patients. The progression-free rate was 42.7 (95% CI 32.8–52.6) and 22.4% (95% CI 14.2–30.7) at 12 and 24 weeks, respectively. The main grade 3 or 4 toxicities were: diarrhea 13.5% and acne-like rash 10.3%. No grade 3 or 4 infusional or allergic reactions were reported. Conclusions: The progression-free rates confirm that cetuximab q2w in combination with irinotecan is an option, and is as active and safe as the standard weekly regimen.

A study was designed to assess the reliability of the serial detection of Aspergillus sp. DNA to diagnose invasive aspergillosis (IA) in patients with febrile neutropenia. Two blood and two serum samples were taken weekly from 83 patients. A total of 2,244 samples were analyzed by real-time quantitative PCR. Twelve (14.4%) patients were diagnosed with IA. Taking two consecutive positive results as the diagnostic criterion, PCR detected 11 cases, with 4 false positives, giving sensitivity, specificity, positive, and negative predictive values of 91.6%, 94.4%, 73.3%, and 98.5%, respectively. On analyzing in conjunction with high-resolution chest tomography (HRCT) and galactomannan (GM) testing, the combination of serial PCR and GM detected 100% of aspergillosis cases, with a positive predictive value of 75.1%. This diagnostic strategy presented, according to CART analysis, a receiver-operator curve with an area under the curve of 0.97 (95% confidence interval, 0.895 to 1.032; P < 0.01), with a relative risk of IA 6.92 times higher than the control population and with predictive success of 95.2%. As regards early diagnosis, the serial detection of Aspergillus DNA took on average 21 days less than HRCT and 68 days less than GM. The serial detection of Aspergillus DNA using real-time quantitative PCR has great diagnostic applicability, which increases when combined with GM quantification.

The aim of the project was to identify biological variables in high-clinical-risk patients with diffuse large B-cell lymphoma (DLBCL), treated with risk-adapted therapies. The study was performed in a series of high-clinical-risk patients with DLBCL treated with MegaCHOP or MegaCHOP + IFE followed by autologous stem-cell transplantation (ASCT). An initial reduced set of diagnostic tumoral samples was studied by gene expression profiling and gene-set-enrichment analysis. A set of potential biomarkers extracted from this study was then explored in tissue microarrays containing paraffin-diagnostic tissue from 50 patients. The statistical analysis identified 17 immunohistochemical markers associated with the clinical endpoints. A subsequent multivariate analysis identified FoxP3+ T-reg cells as an independent predictor of failure-free survival. Bcl6 expression, CG/ABC subclasses and IPI were found not to predict survival in this series. The increased presence of regulatory T-cells as a marker of adverse outcome highlights specific components of the tumoral microenvironment in the pathogenesis and treatment response prediction for high-clinical-risk patients with DLBCL.

BACKGROUND. It has been recognized that cure is possible for human immunodeficiency virus (HIV)-infected patients with Burkitt lymphoma/leukemia (BL) if appropriate chemotherapy is used. The introduction of rituximab in BL therapeutic schemes has been scarcely explored. The outcome and toxicity of HIV-positive patients with BL treated in a rituximab and intensive chemotherapy-based trial was evaluated. METHODS. Thirty-six consecutive patients, 15 to 55 years of age, diagnosed with advanced stage BL were recruited from July 2003 to August 2006, stratified according to HIV infection status and treated with 6 cycles of intensive chemotherapy including 8 doses of rituximab. RESULTS. Nineteen of the patients (53%) were HIV-infected. Their clinical characteristics were comparable to those of the HIV-negative patients. Complete remission (CR) rates were 88% and 84%, respectively, for HIV-negative and -positive patients. Twenty-seven patients (82% and 68%, respectively, for HIV-negative and -positive patients) completed the 6 protocol scheduled cycles. HIV-infected patients presented higher incidences of grade 3–4 mucositis (27% vs 7% of cycles, P = .0005) and severe infectious episodes (26% vs 8%, P = .0025). However, there were no statistically significant differences in 2-year overall survival (82%, 95% confidence interval [CI], 65%–99% and 73%, 95% CI, 54%–92%, respectively) or 2-year disease-free survival (93%, 95% CI, 82%–99% and 87%, 95% CI 72%–99%, respectively). CONCLUSIONS. Intensive immunochemotherapy can be administered safely to patients with HIV infection. Despite a higher incidence of severe mucositis and infections the remission and survival rates are comparable to those observed in HIV-negative patients. Cancer 2008. ©2008 American Cancer Society.

Part of this study has been reported as an oral presentation at the EHA Meeting in Vienna 2015., The introduction of Rituximab has improved the outcome and survival rates of Burkitt lymphoma (BL). However, early relapse and refractoriness are current limitations of BL treatment and new biological factors affecting the outcome of these patients have not been explored. This study aimed to identify the presence of genomic changes that could predict the response to new therapies in BL. Forty adolescent and adult BL patients treated with the Dose-Intensive Chemotherapy Including Rituximab (Burkimab) protocol (Spanish Programme for the Study and Treatment of Haematological Malignancies; PETHEMA) were analysed using array-based comparative genomic hybridization (CGH). In addition, the presence of TP53, TCF3 (E2A), ID3 and GNA13 mutations was assessed by next-generation sequencing (NGS). Ninety-seven per cent of the patients harboured genomic imbalances. Losses on 11q, 13q, 15q or 17p were associated with a poor response to Burkimab therapy (P = 0·038), shorter progression-free survival (PFS; P = 0·007) and overall survival (OS; P = 0·009). The integrative analysis of array-CGH and NGS showed that 26·3% (5/19) and 36·8% (7/19) of patients carried alterations in the TP53 and TCF3 genes, respectively. TP53 alterations were associated with shorter PFS (P = 0·011) while TCF3 alterations were associated with shorter OS (P = 0·032). Genetic studies could be used for risk stratification of BL patients treated with the Burkimab protocol., This work was supported in part by: grant no 306242-NGS-PTL from European Union’s Seventh Framework Programme (FP7/2007-2013), Fundacion-Castellano-Leonesa de Hematologia-y-Hemoterapia (FUCALHH 2013), Consejeria de Educacion, Junta de Castilla y León (HUS272U13), SACYL research projects: GRS1172/A/15, GRS 994/A/14, BIO/SA10/14, BIO/SA31/13. Fondo de Investigaciones Sanitarias FISPI09/01543, FIS-PI12/00281, PI14/01971, COST-ActionEuGESMA (BM0801), Fundacion Española de Hematologia y Hemoterapia (FEHH), and by grants RD12/0036/0069, RD12/ 0036/0029 and RD12/0036/0044 from the Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III (ISCIII), the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (ERDF) ‘Una manera de hacer Europa’ (Innocampus). NGS was performed as part of the IRON-II collaborative network of haematological laboratories. MFC was supported by study commission no 223-2011 granted by the UPTC, Colombia. MHS was supported by Junta de Castilla y Leon from the ERDF.

RESUMO – Visando fortalecer e aperfeicoar acoes para a implantacao da cultura Acrocomia aculeata (Jacq.) Lodd. ex Mart no cenario do agronegocio nacional, o presente trabalho vislumbra o aproveitamento dos oleos extraidos dos frutos da Macauba como materias-primas com valor agregado para a producao de alimentos. O trabalho apresenta uma revisao bibliografica que contempla propriedades fisicoquimicas e caracteristicas de qualidade de oleos vegetais produzidos com finalidade alimenticia – dentre os quais os extraidos da oliveira (Olea europaea) e do dende (Elaeis guineensis Jacq). Descricoes de regulamentos tecnicos, normas e metodologias preconizadas em orgaos e institutos nacionais e internacionais estao incluidos, contribuindo com a definicao de parâmetros de processamento da Macauba, tendo em vista a preservacao de caracteristicas nutricionais e funcionais naturais da oleaginosa. Finalmente, com base nas informacoes levantadas, o trabalho destaca o uso potencial dos oleos extraidos dos frutos da palmeira na elaboracao de um novo produto alimenticio, oleo de mesa, com apelos especiais.

Fundamento y objetivo La leucemia aguda linfoblastica (LAL) de fenotipo T incluye 4 subtipos inmunologicos: pro-T, pre-T, timica o cortical y madura. En algunos estudios, los subtipos LAL pro-T y maduro tienen un peor pronostico. El objetivo de este estudio ha sido describir las principales caracteristicas clinicas, los resultados del tratamiento y el pronostico de los subtipos inmunologicos de LAL-T en 81 pacientes adultos incluidos en 2 protocolos del grupo PETHEMA (LAL-96 y LAL-93). Pacientes y metodo Entre 1993 y 2003, se incluyo en 2 protocolos de PETHEMA a 81 pacientes adultos de 22 hospitales espanoles: LAL-96 para pacientes de riesgo estandar y LAL-93 para pacientes de alto riesgo. Se comparo los principales parametros clinicos y biologicos iniciales de cada subgrupo de LAL-T, asi como la rapidez en la respuesta al tratamiento, la tasa de remision completa, la supervivencia libre de enfermedad y la supervivencia global. Resultados De los 64 pacientes evaluables, la distribucion de los subtipos inmunologicos fue: 3 pro-T, 17 pre-T, 22 timica o cortical y 22 madura. Los pacientes con LAL-T madura presentaron afeccion inicial del sistema nervioso central y marcadores mieloides con mayor frecuencia que el resto de los pacientes. Los pacientes con LAL-T madura tuvieron una respuesta significativamente mas lenta al tratamiento que los que presentaban LAL-T pre-T y cortical, pero ello no se tradujo en diferencias significativas en la tasa de remision completa (el 77 frente al 94%) supervivencia libre de enfermedad (el 42 frente al 46%) y la supervivencia global (el 29 frente al 47%). Conclusiones Aunque los pacientes con LAL-T madura respondieron mas lentamente al tratamiento y su supervivencia tendio a ser mas corta, en el presente estudio no se encontraron diferencias estadisticamente significativas en el pronostico de los diferentes subtipos de LAL-T.

Introduccion En este estudio se describe un brote nosocomial de gripe en pacientes hematologicos de alto riesgo y su control mediante medidas preventivas y uso de zanamivir. Metodos Se evaluaron 15 pacientes que habian estado en contacto con un paciente con Influenza A. Se realizo cultivo viral del exudado nasofaringeo y se analizaron sus datos epidemiologicos, factores de riesgo y evolucion clinica. Se evaluo la eficacia de las medidas preventivas y del uso de zanamivir para profilaxis y tratamiento precoz de la infeccion gripal. Resultados Incluyendo el caso indice, 7 de 15 pacientes (46,6%) desarrollaron sintomas y en 5 de 7 (71,4%) se aislo el virus Influenza A. Los 8 pacientes restantes permanecieron asintomaticos y no se aislo virus Influenza del exudado nasofaringeo. Se realizo aislamiento de contacto y respiratorio y tratamiento precoz con zanamivir (10 mg/12 h por via inhalada, durante 5 dias) de los pacientes sintomaticos. Solo 1 de 7 pacientes sintomaticos desarrollo insuficiencia respiratoria; el resto tuvo un sindrome gripal de vias respiratorias superiores. No hubo mortalidad asociada. Se uso profilaxis con zanamivir en las mismas dosis en 3 pacientes asintomaticos de alto riesgo. La tolerancia al zanamivir fue buena en todos los pacientes. Desde que se iniciaron las medidas preventivas y el uso de zanamivir no se detectaron nuevos casos de gripe. Conclusion La tasa de ataque en un brote nosocomial de gripe en pacientes inmunodeprimidos puede ser muy elevada. La instauracion precoz de medidas de control junto con la profilaxis y tratamiento precoces con zanamivir permiten el control de estos brotes.

Introduction and objectives To analyze retrospectively the usefulness of cardiovascular magnetic resonance imaging in the assessment of patients with clinically suspected arrhythmogenic right ventricular dysplasia. Matherial and method We reviewed retrospectively findings from 46 consecutive patients (mean age, 42±19 years; 25 male) who were referred for investigation to rule out right ventricular dysplasia. Abnormal findings were classified according to the general diagnostic criteria established by the European Society of Cardiology. Results Evaluable images were available for all patients. Abnormal right ventricular findings were reported in 24 patients (52%), but only 5 were given a definite diagnosis of right ventricular dysplasia. Fatty infiltration was observed in 9 patients; it was an isolated finding in 6 but was associated with right ventricular contractile dysfunction in 3. These latter patients belonged to the group with confirmed dysplasia. None of the 22 patients (48%) with normal findings on magnetic resonance imaging was given a diagnosis of dysplasia. Conclusions Cardiovascular magnetic resonance imaging enabled the right ventricle to be assessed in all patients. In those with clinically suspected dysplasia, normal findings ruled out the diagnosis. However, only 21% of those with abnormal findings on magnetic resonance imaging were finally given a confirmed diagnosis of dysplasia. Fatty infiltration of the right ventricular wall does not imply dysplasia unless it is associated with other abnormalities in right ventricular morphology or contractility. Cardiovascular magnetic resonance imaging is useful in the work-up of patients with clinically suspected arrhythmogenic right ventricular dysplasia.

Introduccion y objetivos Revisar la utilidad practica de la cardiorresonancia magnetica en la evaluacion de pacientes con sospecha clinica de displasia arritmogenica ventricular derecha. Material y metodo Revisamos retrospectivamente los estudios de 46 pacientes (edad: 42 ± 19 anos, 25 varones) remitidos a nuestro centro con diagnostico de sospecha de displasia ventricular derecha. Clasificamos las alteraciones observadas segun los criterios diagnosticos generales, mayores y menores, establecidos por la Sociedad Europea de Cardiologia. Resultados Obtuvimos imagenes valorables en el 100% de los casos. Detectamos afeccion de ventriculo derecho en 24 pacientes (52%), entre los que solo 5 cumplieron criterios de displasia. Nueve pacientes mostraron infiltracion grasa, 6 como unico hallazgo y en 3 pacientes en asociacion con alteraciones de la contractilidad; estos ultimos pertenecian al grupo con criterios diagnosticos de displasia. Ninguno de los 22 pacientes con cardiorresonancia normal (48%) fue diagnosticado de displasia. Conclusiones La cardiorresonancia magnetica permitio estudiar el ventriculo derecho en el 100% de los casos. En la poblacion evaluada, un estudio normal permitio descartar el diagnostico de displasia. Entre el 52% de los estudios con hallazgos patologicos, el diagnostico se confirmo en una pequena proporcion (5/24). La presencia de infiltracion grasa no implico el diagnostico de displasia si no se acompanaba de otras alteraciones, morfologicas o de la contractilidad, del ventriculo derecho. La cardiorresonancia magnetica es una tecnica util, en la practica clinica, para el estudio de pacientes con sospecha de displasia arritmogenica ventricular derecha.

Aims and background Primary pulmonary lymphoma is an uncommon disease with a poorly defined management. We reviewed and followed the cases of primary pulmonary lymphoma in our institution to gather an estimation of this entity in our population. Design and methods We reviewed the records of all patients with biopsy-proven lymphoma of the lung. The main diagnostic criterion for primary pulmonary lymphoma was the absence of extrapulmonary involvement. Results We identified 6 cases of primary pulmonary lymphoma among 33 patients with biopsy-proven lymphoma of the lung evaluated in our center in a 12-year period. A radiological abnormality in an asymptomatic patient was the most common clinical presentation. Four cases were low-grade and two cases high-grade non-Hodgkin PPL. Histopathologic analyses of lung specimens obtained by transbronchial biopsy were sufficient for a diagnosis in 5 of the 6 cases and avoided invasive surgical maneuvers. Most patients followed an indolent course, but with a tendency to relapse. Conclusions Although clinical management of this entity is undefined, we feel bronchoscopic study, which is less aggressive than surgery, may be an adequate procedure for a diagnosis. Mono-chemotherapy using alkylating agents and careful clinical observation may be the best therapeutic approach for these patients, since most of them have favorable outcomes, whatever the treatment modalities.

Between 1994 and 1999, 88 multiple myeloma (MM) patients were included in a phase II study to evaluate a tandem autologous stem cell transplantation (ASCT) programme. The first was conditioned with melphalan 200 mg/m2 (MEL200-ASCT1), and the second with cyclophosphamide, etoposide and BCNU (CBV-ASCT2). All patients were in response after MEL200-ASCT1. A control group of MM patients with response to a single ASCT was selected to compare outcomes. After MEL200-ASCT1, 26 patients (30%) achieved complete remission (CR). Of the remaining 48 evaluable patients, 16 (33%) achieved CR with CBV-ASCT2. The final CR rate was 48%. The 5-year survival (OS) was 55%[95% confidence interval (CI) 43-67%] while the event-free survival (EFS) was 28% (95% CI 15-39%). CR status after CBV-ASCT2 was the most important prognostic factor for OS and EFS (P = 0.00001), although no differences in outcomes were detected when the patients in CR after MEL200-ASCT1 were compared with those who obtained CR after CBV-ASCT2. Univariate and multivariate analyses showed improved OS and EFS for the tandem series as compared with the control series treated with a single MEL200-ASCT. However, in a stratified comparison by response, there were no prognostic differences between tandem patients and control patients treated with a single ASCT. In summary, our study suggests that the benefit of a second high-dose therapy course depends on its capacity to result in CR for MM patients who have not attained CR after ASCT1.

Las remesas familiares en El Salvador son un fenómeno reciente cuya importancia ha venido aumentando en los últimos años.Aproximadamente hace diez años, en forma coincidente con el momento en que se derrumban los precios internacionales de nuestro principal producto de exportación: el café.Son resultado del peculiar proceso migratorio que acompaña la evolución de la economía en las últimas dos décadas.Se considera además que este fenómeno migratorio hacia el extranjero, especialmente a los Estados Unidos, aunque forma parte de un vasto movimiento de latinoamericanos hacia el país de las esperanzas, en nuestro caso especial es motivado por dos causas fundamentales: la falta de oportunidades de empleo y el enorme diferencial de salarios entre El Salvador y el principal país de destino, aunado a los diez años de guerra civil que afectó a muchas poblaciones de las zonas rurales, así como, a las zonas marginales de los centros urbanos.

After a previous analysis that did not detect clear differences in the results of three conditioning regimens used for autologous stem cell transplantation (ASCT) in patients from the Spanish Registry for Transplant in Multiple Myeloma (MM), we have updated the registry, including a larger number of cases and a fourth conditioning regimen with a longer follow-up. We evaluate 472 MM patients treated with 200 mg/m2 melphalan (MEL200), 135 patients treated with 140 mg/m2 melphalan plus total body irradiation [(MEL140 + TBI)], 186 patients treated with 12 mg/kg busulphan plus 140 mg/m2 melphalan (BUMEL) and 28 patients treated with 14 mg/kg busulphan followed by cyclophosphamide 120 mg/kg (BUCY). There were no significant differences in respect to either transplant related death or haematological recovery, regardless of growth factor use, between the four conditioning programs. Nevertheless, hospitalization time with MEL200 was less than with BUMEL when growth factors were used (19+/-9 vs. 25+/-9 days, P = 0.009) and less than with MEL140 + TBI without growth factors (20+/-8 days vs. 27+/-9 days, P = 0.002). In patients with measurable disease at ASCT (non-complete remission [CR]), BUMEL achieved a 51% CR vs. 43%-31% in the other groups (P = 0.007). The response rate for patients in partial remission (PR) at ASCT was 100% with BUMEL vs. 93%-86% in the other groups (P between 0.02 and 0.0007). The median overall survival (OS) for the BUMEL group was 57 months (95% confidence interval [CI]: 51-78) as compared to 45 (CI: 36-64) months for the MEL200 group and 39 (CI: 28-72) months for the MEL140 + TBI and BUCY groups. The median event free survival (EFS) was longer in the BUMEL group [30 (CI: 22-44) mo] than in the MEL200 [22 (CI: 18-26) mo], BUCY [23 (CI: 11-50) mo] or MEL140 + TBI groups [20 (CI: 15-29) mo]. Nevertheless, the differences in OS and EFS did not reach statistical significance in either the univariate analysis or the multivariate analysis adjusted with other high prognostic weight factors. As in the initial study, differences in regards to the anti-myeloma effect of the conditioning regimens are not conclusive. However, the better response rates associated with the favorable tendency in outcome achieved with BUMEL, continue to justify further prospective studies.

The molecules of the title compound, C(34)H(24)N(2)S(4), lie across centres of inversion in the space group P2(1)/n. The spacer unit linking the benzene rings and carbazole units is effectively planar, while the carbazole unit itself is slightly folded. Molecules are linked into sheets by a single C-H···π(arene) hydrogen bond and the hydrogen-bonded sheets are themselves linked into a three-dimensional framework structure by a single π-π stacking interaction.

The karyotype is a predictor of outcomes in adults with acute lymphoblastic leukemia (ALL). The unfavorable prognostic significance of complex karyotype (CK) has been reported, whereas the prognostic relevance of monosomal karyotype (MK) has not been consistently evaluated. We aimed to assess the prognostic value of CK and MK in adults with ALL treated with risk-adapted protocols of the Spanish PETHEMA Group.The karyotypes of 881 adult ALL patients treated according to the protocols of the PETHEMA Group between 1993 and 2012 were centrally reviewed. CK and MK were assessed according to Moorman's criteria, and Breem's criteria, respectively. Specific analyses according to the risk groups and to the presence of t(9:22) were performed.Of 364 evaluable patients 33 (9.2%) had CK, and 68 of 535 evaluable patients (12.8%) had MK. Complete remission rate, remission duration, and overall survival were not significantly different according to the presence of CK or MK in the whole series, according to the B or T lineage, in the high-risk group, or in patients with t(9;22), regardless of imatinib treatment, and in patients who received chemotherapy alone or chemotherapy followed by stem cell transplantationOur study shows that CK and MK were not associated with a worse prognosis in adult patients with ALL treated with risk-adapted or subtype-oriented protocols. In patients with Ph+ ALL, MK did not have an impact on prognosis irrespective of imatinib treatment.

We conducted a multicentre, phase II study of interim positron emission tomography (PET) as a guide to risk-adapted therapy in high-risk patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Patients achieving negative fluorodeoxyglucose (FDG)-PET after three courses of R-MegaCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) received three additional courses, whereas PET-positive patients received two courses of R-IFE (rituximab, ifosfamide, etoposide) followed by BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous stem-cell transplantation. The primary endpoint was progression-free survival (PFS). 71 patients (median age 55 years, range 25-69) were enrolled. With a median follow-up of 42·8 months (range 7·2-58·4), the estimated 4-year PFS and overall survival (OS) were 67% and 78%, respectively, for the global series. Patients in complete remission after interim PET (N = 36) had significantly better 3-year PFS than those with partial response (N = 30) [81% vs. 57%, Hazard ratio (HR) = 2·6, 95% confidence interval (CI) = 1·02-6·65] but not a statistically significant longer OS. A retrospective PET central review was done for 51 patients. According to semiquantitative analysis, 3-year PFS (81% vs. 33%; HR = 6·9, 95% CI = 2·35-20·6) and OS (95% vs. 33%, HR = 19·4, 95% CI = 3·89-97·0) were significantly better for negative than for positive interim PET patients. Early PET assessment is valuable for risk stratification in DLBCL; for this purpose semiquantitative evaluation is a better predictor than visual criteria.

Lymphoma patients with persistent disease undergoing autologous transplantation have a very poor prognosis in the rituximab era. The addition of radioimmunotherapy to the conditioning regimen may improve the outcome for these patients. In a prospective, phase 2 study, we evaluated the safety and efficacy of the addition of 90Y-ibritumomab tiuxetan to the conditioning chemotherapy in patients with refractory diffuse large B-cell lymphoma. Thirty patients with induction failure (primary refractory; n=18) or refractory to salvage immunochemotherapy at relapse (n=12) were included in the study. The median age of the patients was 53 years (range, 25–67). All patients were given 90Y-ibritumomab tiuxetan at a fixed dose of 0.4 mCi/kg (maximum dose 32 mCi) 14 days prior to the preparative chemotherapy regimen. Histological examination showed that 22 patients had de novo diffuse large B-cell lymphoma and eight had transformed diffuse large B-cell lymphoma. All patients had persistent disease at the time of transplantation, with 25 patients considered to be chemorefractory. The median time to neutrophil recovery (>500 white blood cells/μL) was 11 days (range, 9–21), while the median time to platelet recovery (>20,000 platelets/μL) was 13 days (range, 11–35). The overall response rate at day +100 was 70% (95% CI, 53.6–86.4) with 60% (95% CI, 42.5–77.5) of patients obtaining a complete response. After a median follow-up of 31 months for alive patients (range, 16–54), the estimated 3-year overall and progression-free survival rates are 63% (95% CI, 48–82) and 61% (95% CI, 45–80), respectively. We conclude that autologous transplantation with conditioning including 90Y-ibritumomab tiuxetan is safe and results in a very high response rate with promising survival in this group of patients with refractory diffuse large B-cell lymphoma with a very poor prognosis. Study registered at European Union Drug Regulating Authorities Clinical Trials (EudraCT) N. 2007-003198-22.

The results of intensive immunochemotherapy were analyzed in human immunodeficiency virus (HIV)-related Burkitt lymphoma/leukemia (BLL) in two cohorts (Spain and Germany). Alternating cycles of chemotherapy were administered, with dose reductions for patients over 55 years. Eighty percent of patients achieved remission, 11% died during induction, 9% failed and 7% died in remission. Four-year overall survival (OS) and progression-free survival (PFS) probabilities were 72% (95% confidence interval [CI]: 62-82%) and 71% (95% CI: 61-81%). CD4 T-cell count200/μL and bone marrow involvement were associated with poor OS (hazard ratio [HR] 3.2 [1.2-8.3] and HR 2.7 [1.1-6.6]) and PFS (HR 3.5 [1.3-9.1] and HR 2.4 [1-5.7]), bone marrow involvement with poor disease-free survival (DFS) (HR 14.4 [1.7-119.7] and Eastern Cooperative Oncology Group (ECOG) score2 (odds ratio [OR] 11.9 [1.4-99.9]) with induction death. In HIV-related BLL, intensive immunochemotherapy was feasible and effective, but toxic. Prognostic factors were performance status, CD4 T-cell count and bone marrow involvement.

Purpose Minimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Español de Tratamientos en Hematología (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia [LAL-AR/2003]) assigned adolescent and adult patients (age 15 to 60 years) with high-risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early cytologic response (day 14) and flow-MRD level after consolidation. Patients and Methods Patients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 × 10−4 at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level ≥ 5 × 10−4. Results Complete remission was attained in 282 (87%) of 326 patients, and 179 (76%) of 236 patients who completed early consolidation were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy (108). Five-year disease-free survival (DFS) and overall survival (OS) probabilities were 37% and 35% for the whole series, 32% and 37% for patients assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy. Multivariable analysis showed poor MRD clearance (≥ 1 × 10−3 after induction and ≥ 5 × 10−4 after early consolidation) as the only prognostic factor for DFS and OS. Conclusion Prognosis for Ph-negative HR-ALL in adolescents and adults with good early response to induction and low flow-MRD levels after consolidation is quite favorable when allo-HSCT is avoided. In this study, the pattern of MRD clearance was the only prognostic factor for DFS and OS.

Background: Survival of DLBCL patients with high IPI treated with RCHOP immunochemotherapy is poor. In this population, the combination of RCHOP with new drugs is an attractive approach, along with performing an evaluation with PET/CT after 2 to 4 cycles to change the therapy if an early complete response is not achieved. Methods : We performed a clinical trial comparing 6 cycles of RCHOP vs 6 cycles of BRCAP, a modified RCHOP regimen changing vincristine by bortezomib 1.3 mg/m2 sc days 1, 8, and 15 of a 21-day cycle. Pre-phase therapy was permitted for patients who could not wait the results of the screening procedures to start therapy due to the aggressiveness of the disease. (ClinicalTrials.gov Identifier: NCT01848132). Patients younger than 71 yrs diagnosed with DLBCL and an age-adjusted IPI (aaIPI) 2-3 or aaIPI 1 with increased beta2microglobulin were eligible. The primary endpoint was the proportion of patients who survives free of event at 2 years. Centralized anatomopathology review was performed in all cases; samples were classified as germinal center B-cell-like (GCB) vs non-GCB subtypes by immunohistochemistry according to the Hans algorithm. PET/CTs were performed baseline, after 2, 4 and 6 cycles (PET2, PET4, and PET6), and were reviewed at real time by at least 3 experts of a central panel. Response at the end of therapy was analyzed following the visual method with the Deauville scale, and response after PET2 and PET4 was evaluated using the semiquantitative method. Persistent disease at PET4 was considered as failure of therapy and these patients were removed from trial treatment. EFS was calculated from diagnosis until event defined as death from any cause, relapse, progression or need of salvage therapy (defined as PET4 or PET6 positive). Overall survival (OS) was calculated from diagnosis until death for any cause. We present here a preliminary analysis of results. Results: One hundred and twenty-one patients were included; data on 113 are presented (diagnosis not confirmed in 6, data missing in 2). Median age was 57.1 yrs (range 23-70), 57 (50.4%) were males. Characteristics at diagnosis were: non-GCB subtype 32/87 (36.8%), immunohistochemical co-expression of myc/bcl2 56/82 (77.8%), stage III-IV 107 (94.7%), ≥2 extranodal locations 55/76 (72.5%), ECOG 2-3 36 (32.1%), increased LDH 88 (77.9%), increased beta 2 microglobulin 73 (64.6%), aaIPI 3: 32 (28.3%). No differences were found between treatment arms. Fifty-five patients were treated in the experimental arm (EA) and 58 in the control arm (CA). Twenty-eight (28.3%) out of 99 patients required of pre-phase treatment. The mean relative dose intensity for bortezomib was 88.3%. Data about the most frequent toxicity are shown in table 1. Twenty-nine (30.2%) out of 96 patients who have finished 4 cycles had a positive PET4 according to central review and were withdrawn to receive salvage therapy. Complete remission (CR) at the end of therapy (PET4-/PET6-) was observed in 44 (45.8%) patients. After a median follow-up of 9 months, estimated 12-mo EFS was 36.6%, and 12-mo OS was 82.9% in the whole series. Data of the subgroup analysis according the immunohistochemistry subtypes by Hans algorithm are show in table 2. Conclusions: In the present preliminary analysis, no significant differences were found between RCHOP and BRCAP in terms of CR and EFS in this very high-risk population of young DLBCL patients. However, in the subgroup analysis of patients with non-GCB disease, we found a significantly better CR rate in patients treated with BRCAP. A longer follow-up is needed to evaluate the real impact of this therapy on survival. Disclosures González-Barca: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria. Martín:Sevier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees. Sancho:Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion, Inc: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. López-Jiménez:Abbvie: Membership on an entity's Board of Directors or advisory committees; Velgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; MundiPharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. López-Guillermo:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; MundiPharma: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Ramírez:Bristol-Myers-Squibb: Honoraria; Novartis: Honoraria; Roche: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees. Conde:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees.

Background:High dose therapy supported by autologous stem cell transplantation (HDT/ASCT) has been a treatment frequently indicated in follicular lymphoma (FL) patients and has contributed to modify the natural history of the disease. Secondary neoplasia is one of the concerns after HDT/ASCT, although its incidence after transplant-free treatments is considerable (RummelM et al. Lancet Oncol 2016; Sacchi S et al. Haematologica 2008). The high incidence of secondary neoplasia in some of the studies, together with the lack of OS advantage in transplanted patients compared to those treated with conventional Chemo/R, has led to abandon HDT/ASCT by many groups. However, its incidence is very variable among studies due in part to cohort different in terms of age, pre-ASCT treatments, used of TBI-based or TBI-free conditioning regimen or length of follow-up. Methods:The Incidence of secondary neoplasia, the factors associated with its development and the survival of 655 FL patients reported to the Spanish GELTAMO registry and intensified with HDT/ASCT between 1989 and 2007 with a median follow-up of 12.3 years from HDT/ASCT and 14.5 years from diagnosis were analyzed. Baseline characteristics and therapeutic-related data are listed in the table. Standardized Incidence Ratios (SIR) were calculated to assess the risk of a second malignancy by dividing the number of observed second malignancies with the number of expected sex matched incidence using the 2008 crudes rates in the Spanish population (J Farley et al. EJC 2013). Data were updated with a cut-off date of 31 June 2016. Results:Median OS were 21.3 years from HDT/ASCT and 22.6 years from the time of FL diagnosis. A total of 83 patients (12.75%) developed 85 second malignancies. There were 45 cases of solid tumors (51%), including 8 skin cancers; 34 cases of Acute Myeloid Leukemia or Myelodysplastic Syndromes (AML/MDS) (40%); 2 Acute Lymphoblastic Leukemia (ALL), 1 chronic myeloid leukemia (CML), 1 Hodgkin lymphoma (HL) and 2 cases of other cancers. The accumulated incidence at 5, 10 and 15 years were 6.7%, 12% and 17.8%, respectively. The incidence for solid tumors and AML/SMD were 2.1%, 4.1%, 9.5% and 3.1%,6.4% and 8,1% at 5, 10 and 15 years, respectively. Median time from HDT/AST to the diagnosis of the second malignancy was 5.5 years (IQR 3.2-9.6). Solid tumors and AML/SMD were documented with a median time of occurrence since HDT/ASCT 7.7 years (IQR 3.2-9.9) and 4.2 years (IQR 1.7-7.3), respectively. The SIR for second neoplasia was 2.8 (CI 95%: 2.6-2.9) and only 1.4 (CI 95% 1.3-16) in the case of solid tumors. Only male sex (P=.006) and the use of anthracycline at first line therapy in the case of solid tumors (P=.02) were associated with an increased number of second neoplasia. Older age and a status of disease before HDT/ASCT different to complete response showed a tendency. There were no differences according to the use of fludarabine or rituximab previously to HDT/ASCT, number of therapy lines before HDT/ASCT, time from diagnosis to HDT/ASCT or conditioning regimen. Median OS for patients with second neoplasia is 12 years from the time of FL diagnosis, 9.4 years from ASCT (fig 2)[14.5 y. for solid tumors and 8 y. for sMDS/sAML (P=.01)] and 1.5 years from the time of diagnosis of second neoplasia [2.3 y. for solid tumors and 1.25 y. for sMDS/sAML (P=.01)], respectively Conclusion: This very long follow-up study, that includes patients from the rituximab era, indicates that FL patients undergoing an ASCT are at an increased risk of developing a 2nd malignancy, especially AML-MDS. However, the incidence is not higher than the reported in other series without transplantation. Only male sex and the use of anthracyclines were associated with an increased risk of 2nd neoplasia. Given the favorable survival obtained by ASCT in FL, the risk of secondary neoplasia shouldn't preclude its application. However, once a neoplasia is diagnosed the prognosis is dismal. Thus, a carefully selection of patients candidates to HDT/ASCT is necessary. Table Table. Figure Figure. Disclosures Lopez-Jimenez: Abbvie: Membership on an entity's Board of Directors or advisory committees; Velgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; MundiPharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Martín:Sevier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria.

Background: Diffuse large B-cell lymphoma (DLBCL) patients with relapsed or refractory disease after rituximab-containing first-line therapy have poor outcomes with current salvage regimens. Accordingly, prospective studies incorporating new agents are needed for these patients. We conducted a phase 1b/2 trial to analyze the safety and efficacy of lenalidomide in combination with R-ESHAP (LR-ESHAP) in patients with relapsed or refractory DLBCL. The phase 1b part of the trial has been completed and lenalidomide 10 mg/day was identified as the maximum tolerated dose (MTD) (Martín et al, Br J Haematol 2016; 173: 245-52). Here we present the preliminary results of the phase 2 (ClinicalTrials.gov Identifier: NCT02340936). Patients and methods: Eligible patients must be refractory to, or have relapsed following first-line treatment with rituximab in combination with an anthracycline-containing regimen and be eligible for autologous stem-cell transplantation (ASCT). Subjects received 3 cycles of lenalidomide 10 mg given on days 1 to 14 of every 21-day cycle, in combination with R-ESHAP salvage chemotherapy at standard doses (rituximab 375 mg/m2 day 1, etoposide 40 mg/m2 days 1-4, cisplatin 25 mg/m2 days 1-4, cytarabine 2000 mg/m2 day 5, and methylprednisolone 500 mg days 1-5). Responding patients received BEAM followed by ASCT. The primary endpoint was overall response rate (ORR) after 3 cycles of therapy. Secondary endpoints were complete remission (CR) rate, stem-cell mobilization activity, progression-free and overall survival, and toxicity. Results: Patient characteristics: 46 patients were included in the phase 2 analysis, of whom 12 were enrolled between January 2012 and March 2013, and had been given the MTD during phase 1; 34 were enrolled between January 2015 and November 2015. Median age was 58 (23-69) years, and 56.5% were male. Evaluable population per-protocol consisted of 44 patients because 2 patients were excluded during the first cycle due to withdrawal of consent and centralized diagnosis at relapse of lymphoblastic lymphoma, respectively. First-line treatment consisted of R-CHOP or similar in 38 patients, R-EPOCH in 3, VR-CAP in 1, and Burkitt lymphoma protocols in 2. Disease status at LR-ESHAP was: primary refractory disease in 67% of patients (partial response [PR] after first-line, n=13; and stable or progressive disease [ Feasibility and efficacy: 40 out of 44 patients (91%) received the planned 3 cycles of treatment (2 without lenalidomide in the third cycle due to toxicity) and 2 patients two cycles (due to persistent hematological and renal toxicities, respectively). Two patients discontinued treatment during the first cycle due to grade 3 infections (fungal pulmonary infection and mastoiditis, respectively). ORR to LR-ESHAP in the per-protocol population (n=44) was 68% (41% CR). Patients with relapsed disease had significantly better ORR and CR rates (87% and 67%, respectively) than patients in PR (77% and 31%) or Toxicity: 42 serious adverse events (SAEs) have been reported during 128 cycles of treatment, including 14 episodes of febrile neutropenia (11%), 12 infections (9%), 2 renal disorders, 3 cardiac disorders, 3 thrombosis, and 8 other toxicities. All of them recovered except 1 case of colon adenocarcinoma in a patient with previous adenoma in the same location. There were no treatment-related deaths during LR-ESHAP cycles. Conclusions: LR-ESHAP is safe, feasible and associated with high response rates in rituximab-pretreated relapsed or refractory DLBCL patients. Longer follow-up is needed to perform survival analysis. Efficacy analysis according to COO is ongoing. Disclosures Martín: Janssen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sevier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. González-Barca:Sanofi: Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria. Lopez-Guillermo:Roche: Consultancy, Research Funding; Celgene: Consultancy; Gilead: Consultancy; Janssen: Consultancy; Mundipharma: Consultancy.

We have retrospectively analysed 344 multiple myeloma (MM) patients (202 de novo patients) treated in a non-uniform way in whom high-dose therapy and autologous stem cell transplantation (ASCT) response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF). Patients in complete remission (CR) by EP were further subclassified as CR1 when IF was negative and CR2 when it remained positive. Partial responders (PR) were also subclassified as PR1 (very good PR, > 90% reduction in M-component) or PR2 (50-90% reduction). CR1 patients showed a significantly better event-free survival (EFS) [35% at 5 years, 95% confidence interval (CI) 17-53, median 46 months] and overall survival (OS) (72% at 5 years, CI 57-86, median not reached) compared with any other response group (univariate comparison P < 0.00000 to P = 0. 004). In contrast, comparison of CR2 with PR1 and with PR2 did not define different prognostic subgroups (median EFS 30, 30 and 26 months respectively, P = 0.6; median survival 56, 44 and 42 months respectively, P = 0.5). The non-responding patients had the worst outcome (5-year OS 8%, median 7 months). Multivariate analysis confirmed both the absence of differences among CR2, PR1 and PR2 and the highly discriminatory prognostic capacity of a three-category classification: (i) CR1 (ii) CR2 + PR1 + PR2, and (iii) non-response (EFS P < 0.00000; OS P < 0.00000; both Cox models P < 0.00000). In the logistic regression analysis, the factors significantly associated with failure to achieve CR1 were the use of two or more up-front chemotherapy lines, status of non-response pre-ASCT and inclusion of total body irradiation (TBI) in the preparative regimen. Tandem transplants or the use of multiple agents (busulphan and melphalan) in the preparative regimen resulted in a higher CR1 level; none of the biological factors explored influenced the possibility of achieving CR1. These results confirm that, in MM patients undergoing ASCT, achieving a negative IF identifies the patient subset with the best prognosis; accordingly, therapeutic strategies should be specifically designed to achieve negative IF.

High-dose chemoradiotherapy conditioning regimens for autologous stem cell transplantation (ASCT) are generally held to give similar results in multiple myeloma (MM), but no specific comparative study has been published. We addressed this issue by comparing the main high-dose chemoradiotherapy regimens used in the Spanish Registry. Patient cohorts included 315 cases treated with 200 mg/m2 melphalan (MEL200), 127 patients with 140 mg/m2 melphalan plus total body irradiation (MEL140 + TBI) and 121 cases with 12 mg/kg busulphan plus 140 mg/m2 melphalan (BUMEL). After ASCT, granulocyte and platelet recovery time was similar in all conditioning groups. There were no differences in transplant-related mortality. All regimens yielded a similar response in reference to pre-ASCT MM status, although BUMEL produced a slightly better overall response when compared with the other regimens (97% vs. 89% and 92%, P = 0.003). The 5-year overall survival (OS) with BUMEL was 47% [95% confidence interval (CI) 26-68] compared with 43% (CI 31-54) for MEL140 + TBI and 37% (CI: 18-56) for MEL200. The median survival for the BUMEL group was 64 months compared with 45 and 37 months for the MEL200 and MEL140 + TBI groups respectively. These differences were non-significant (P = 0.2). The median event-free survival (EFS) was better for BUMEL (32 months) than for MEL200 (22 months) or for MEL140 + TBI (20 months). The differences in EFS between BUMEL and the other conditioning regimens reached statistical significance (P = 0.01). Nevertheless, the adjusted multivariate analysis for OS and EFS revealed that the conditioning regimens had no independent prognostic value. We concluded that three different conditioning regimens, commonly used for ASCT in MM, have a similar antimyeloma effect. However, the trend for better results observed in our series with BUMEL requires a prospective trial.

Doubly cyclometallated binuclear platinum-(II) and -(IV) complexes, as well as their non-cyclometallated platinum(II) precursors, were prepared from the reactions of [Pt2Me4(µ-SMe2)2] with imine ligands derived from terephthalaldehyde. All compounds were characterized by NMR and UV/VIS spectroscopy and the reactivities of the cyclometallated platinum complexes towards phosphines were studied. Electrochemical and spectroelectrochemical (UV/VIS/NIR and EPR) studies were carried out and indicated that while the oxidation of the platinum(II) complexes leads to unstable platinum(III) species, the reduction of the platinum compounds leads to an uptake of an electron into a MO mainly centred on the bridging ligand and is followed by either scission of the bridging ligand for the platinum(II) compounds or scission of the axial ligands for the platinum(IV) compounds.

Purpose: To evaluate initial results in patients with epiphora secondary to obstruction of the nasolacrimal duct treated by placement of a polyurethane stent, and to discuss the technical problems and complications arising during the procedure, with visualization of the anatomy of the drainage apparatus using computed tomography (CT). Methods: We inserted 20 polyurethane Song stents under fluoroscopic guidance after dacryocystography in 19 patients with grade 3–4 epiphora caused by idiopathic obstruction of the nasolacrimal duct. CT scans were obtained following stent placement in all patients. Results: We focus on the technical problems and complications that arose during these procedures. During negotiation of the guidewire past the obstruction at the level of the junction of the duct with the lacrimal sac, the guidewire created a false passage in a posterior suborbital direction in two cases and towards the posterior midline in another. In all cases the guidewire was withdrawn and reinserted through the proper anatomic route without further difficulty or complications. In two cases the stent was improperly positioned wholly or partially outside the nasolacrimal system (one medially, one posteriorly). In one case the stent was removed and reinserted; in the other it remains in place and functional. CT was performed in all these cases to ensure proper anatomic alignment and determine what had gone wrong. The epiphora was completely resolved in 13 cases and partially relieved in four; there were three cases of stent obstruction. Epistaxis of short duration (1 hr) occurred in seven patients and headache in one. Conclusions: Treatment of epiphora with polyurethane stents is a technique that is well tolerated by patients and achieves a high success rate, yet problems in placement may be encountered. Though no major consequences for patients are involved, cognizance of such difficulties is important to avoid incorrect positioning of stents.

The reactions of [Pt 2 Me 4 ( μ -SMe 2 ) 2 ] ( 1 ) with chlorinated ligands Me 2 NCH 2 CH 2 NCHAr (Ar=C 6 Cl 5 ( 2a ); 2,3,6-C 6 H 2 Cl 3 ( 2b ); 2,3,5-C 6 H 2 Cl 3 ( 2c ); 2,4-C 6 H 3 Cl 2 ( 2d ); 3,5-C 6 H 3 Cl 2 ( 2e ) and 3-C 6 H 4 Cl ( 2f )) yield either cyclometallated [C,N,N′] platinum(IV) complexes [PtMe 2 Cl(Me 2 NCH 2 CH 2 NCHR–C, N , N ′)], arising from C–Cl bond activation, or cyclometallated [C,N,N′] platinum(II) complexes [PtMe(Me 2 NCH 2 CH 2 NCHR– C , N , N ′)], arising from C–H bond activation, followed by methane elimination. These processes occur at room temperature except for the formation of compound [PtMe{Me 2 NCH 2 CH 2 NCH(3,5-C 6 H 2 Cl 2 )}] ( 4e ) which is produced in refluxing toluene, since at room temperature cyclometallation of ligand 2e is not achieved. Compound [PtMe 2 {Me 2 NCH 2 CH 2 NCH(3,5-C 6 H 3 Cl 2 )– N , N ′)}] ( 3e ), arising from coordination of the ligand to the platinum center, is obtained at room temperature. The reactions of 1 with ligands PhCH 2 NCHAr (Ar=2,3,6-C 6 H 2 Cl 3 ( 2g ) and 2,3,5-C 6 H 2 Cl 3 ( 2h )) produce cyclometallated [C,N] platinum(IV) complexes. The reactivities of the platinum complexes towards phosphines and methyl iodide have been studied. All complexes have been characterized by NMR spectroscopy and the X-ray crystal structure of [PtMe 2 Cl{Me 2 NCH 2 CH 2 NCH(3,5-C 6 H 2 Cl 2 )– C , N , N ′}] ( 4c ) has been determined. The electrochemical properties of the compounds based on cyclic voltammetry have also been studied. While the first reduction step is nearly reversible for cyclometallated platinum(II) compounds, coordination complex 3e and cyclometallated platinum(IV) compounds exhibit an irreversible reduction wave. In all cases oxidation occurs in an irreversible manner. The processes involved and the influence of the chlorine substituents are discussed.

The prognosis for fit patients with mantle cell lymphoma has improved with intensive strategies. Currently, the role of maintenance/consolidation approaches is being tested as relapses continue to appear. In this trial we evaluated the feasibility, safety and efficacy of rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine followed by consolidation with 90Y-ibritumomab tiuxetan. Patients received six cycles followed by a single dose of 90Y-ibritumomab tiuxetan. Thirty patients were enrolled; their median age was 59 years. Twenty-four patients finished the induction treatment, 23 achieved complete remission (77%, 95% confidence interval 60–93) and one patient had progressive disease (3%). Eighteen patients (60%), all in complete remission, received consolidation therapy. In the intent-to-treat population, failure-free, progression-free and overall survival rates at 4 years were 40% (95% confidence interval 20.4–59.6), 52% (95% confidence interval 32.4–71.6) and 81% (95% confidence interval 67.28–94.72), respectively. For patients who received consolidation, failure-free and overall survival rates were 55% (95% confidence interval 31.48–78.52) and 87% (95% confidence interval 70–100), respectively. Hematologic toxicity was significant during induction and responsible for one death (3.3%). After consolidation, grade 3–4 neutropenia and thrombocytopenia were observed in 72% and 83% of patients, with a median duration of 5 and 12 weeks, respectively. Six (20%) patients died, three due to secondary malignancies (myelodysplastic syndrome and bladder and rectum carcinomas). In conclusion, in our experience, rituximab-hyperCVAD alternated with rituximab-methotrexate-cytarabine and followed by consolidation with 90Y-ibritumomab tiuxetan was efficacious although less feasible than expected. The unacceptable toxicity observed, especially secondary malignancies, advise against the use of this strategy. Trial registration: clinical.gov identifier: NCT2005-004400-37

O presente trabalho apresenta um estudo acerca da extração alcalina de proteínas dos farelos de polpa e amêndoa de macaúba. A fim de avaliar a influência dos parâmetros de processo, a saber, concentração de NaCl da solução de extração, razão sólido:solução, temperatura e pH da solução de extração, sobre o rendimento de extração das proteínas dos farelos, um planejamento experimental fatorial (24) foi conduzido. Os parâmetros foram avaliados em 2 níveis, além do ponto central. Para o farelo de amêndoa, a avaliação estatística dos efeitos dos parâmetros para a maximização do rendimento de extração, ao nível de significância de 95%, indicam que o pH e a razão sólido:solução são estatisticamente significativos. No entanto, para o farelo da polpa, os parâmetros que influenciam de forma significativa o rendimento do processo de extração, dentro das faixas investigadas, são a concentração de NaCl, a razão sólido: solução e o pH da solução de extração. Os resultados apontam que para ambos os farelos, a temperatura de extração, dentro da faixa investigada, não exerce influência sobre o rendimento. De um modo geral, o processo de extração alcalina de proteínas dos farelos de macaúba mostra-se promissor, sendo atingidos rendimentos de extração de até 99% e 92%, respectivamente. Mesmo na pior condição experimental de extração, para ambos os farelos, um rendimento acima de 50% foi obtido. Os resultados apresentados são de fundamental importância para futuros estudos que visam otimizar os parâmetros de processo para maximização do rendimento de extração de proteínas, inclusive em escala industrial. AbstractThis work presents a study about alkaline extraction of proteins from macaúba bran. In order to evaluate the influences of the process parameters, namely, the concentration of NaCl solution, ratio solid:solution, temperature and the pH of extraction solution, on protein extraction yield from macaúba bran, an experimental factorial design (24) was conducted. The parameters were evaluated in 2 levels, in addition to the central point. For the kernel bran of macaúba, the statistical evaluation of process parameter effects for the maximization of protein extraction yield, at a significance level of 95%, indicates that the pH and the ratio solid:solution are statistically significant. For the pulp bran of macaúba the parameters that influence significantly the extraction yield of proteins, within ranges investigated, are the concentration of NaCl solution, the ratio solid:solution and the pH of the extraction solution. For both types of bran, the extraction temperature, within range investigated, does not exercise influence, at a significance level of 95%, on the protein extraction yield. In general, the alkaline extraction of proteins from the pulp and the kernel bran of macaúba show to be promising, being achieved extraction yields of up to 99% and 92%, respectively. Even in the worst experimental condition of extraction, for both types of bran, a yield above 50% was obtained. The results obtained and presented are important for future studies aiming industrial application and so to optimize the process parameters of extraction for maximization of protein yield.

BACKGROUND: The use of rituximab together with intensive chemotherapy in Burkitt's lymphoma or leukemia (BL) has been scarcely explored. This study prospectively evaluated and compared the outcome and toxicity of human immunodeficiency virus (HIV)-positive and HIV-negative patients with BL who were treated in an intensive immunochemotherapy-based and age-adapted trial. METHODS: A total of 118 adult patients (80 HIV-negative and 38 HIV-positive) aged 15 to 83 years were treated with 4 (nonbulky stages I-II) or 6 (stages II bulky, III-IV) cycles of intensive chemotherapy combined with rituximab. Reduction in chemotherapy doses and modification of the cycle schedules was performed in patients older than 55 years. RESULTS: The clinical characteristics of HIV-positive patients were comparable with those who were HIV-negative. Complete remission rates were 82% and 87%, respectively, and 9 patients died in induction, 9 died in remission, and 7 relapsed. After a median follow-up of 2.5 years, nonsignificant differences were observed in the 4-year disease-free survival and overall survival (OS) probabilities (77% and 63% for HIV-positive and 80% and 78% for HIV-negative patients, respectively). Young HIV-infected patients presented higher incidences of grade 3 or 4 mucositis and severe infectious episodes. Poor general status and bone marrow involvement, but not advanced age, were associated with a shorter OS, allowing the definition of 3 prognostic groups, with the OS ranging from 50% to 92%. CONCLUSIONS: Age-adapted intensive immunochemotherapy is highly effective in both HIV-negative and HIV-positive patients, with a higher toxicity in the latter group. Poor general status and bone marrow involvement had a negative impact on survival. Cancer 2013. © 2013 American Cancer Society.

Objective The combination of oxaliplatin and oral capecitabine (XELOX) has shown to be an active regimen in metastatic colorectal cancer (MCRC). However, the experience with XELOX in elderly patients is limited. This study aimed to evaluate the efficacy and safety of XELOX as first-line treatment in elderly patients with MCRC. Patients and Methods Patients aged ≥70years with previously untreated MCRC received oxaliplatin 85mg/m 2 on day 1, every 2weeks plus capecitabine 1000mg/m 2 (or capecitabine 750mg/m 2 if creatinine clearance was 30–50mL/min) twice daily on days 1–7, every 2weeks. Treatment was continued until progression, intolerable toxicity, or for a maximum of 12cycles. Results Thirty-five patients were enrolled. Median age was 78years (range, 70–83). Patients received a median of 11cycles of treatment. The objective response rate (ORR) was 49% and the tumor control rate was 86%. Median time to progression and overall survival were 8.6 (95% CI: 5.5–11.7) and 15.5 (95% CI: 9.6–21.3) months, respectively. Toxicities were generally mild to moderate. Major grade 1–2 toxicities were asthenia (40%), nausea (43%), and diarrhea (40%). No grade 4 toxicity was detected and grade 3 toxicities were reported in 17% of patients. There was no treatment-related death. Conclusion Our findings show that the biweekly XELOX regimen represents an effective and tolerable first-line treatment option for elderly patients with MCRC.

An instance of severe damage to wind turbines due to Sub-Synchronous Control Interaction (SSCI) has been observed in the case of an interconnection of a wind farm to a series compensated transmission system. This paper presents the methodology to be followed to perform a SSCI study. The frequency-domain impedance scanning and the time-domain simulation approach are used to identify and verify the SSCI. It is necessary to perform transient simulations utilizing a detailed model of the Wind Turbine Generator (WTG). Typical fault types and disturbances that could trigger an unstable SSCI response of the WTG are simulated. The studies are performed on the IEEE Second Benchmark Model. The study compares the time-domain response of a wind farm comprised of Type 3 Doubly Fed Induction Generator (DFIG) WTGs with that of a wind farm comprised of Type 4 (Full converter) WTGs as far as SSCI is considered.

Background: Positron emission tomography / computed tomography with fluorodeoxyglucose (FDG-PET/CT) is widely accepted for staging and for end treatment assessment in patients with DLBCL, and has demonstrated to have prognostic impact when used to evaluate early response to chemotherapy (CT) in this group of patients. In the last years, many changes in the way of interpreting PET/CT have been proposed, both for interim and for end of treatment (Barrington SG, J Clin Oncol 2014;32:3048-3058) We present preliminary data of the first Spanish centralized PET/CT review in a Phase 2 randomized trial in young patients with poor prognosis diffuse large B-cell lymphoma (DLBCL), which compares 6 cycles of RCHOP versus 6 cycles of a modified RCHOP regimen, Bortezomid-R CAP (BRCAP). ClinicalTrials.gov Identifier: NCT01848132. The main objective is to evaluate concordance between reviewers in interim and final PET, in order to stablish the best criteria for PET/CT assessment. PET2 ability to predict PET4 result is also analyzed. Methods: A blinded, prospective, centralized review in real time of PET/CT images was realized by the GELTAMO PET network. For each patient, images of basal (PET0), interim PET2 and PET4 and final PET after completion of chemotherapy (PET 6) were sent to a central platform, and then analysed by the review panel composed of seven expert nuclear medicine physicians. PET2 and PET4 were interpreted visually based on Deauville criteria (considering scores 4 and 5 as positive), and also semiquantitavely (considering a positive PET2 when ΔSUVmax≤66% and a positive PET4 when ΔSUVmax≤70%). PET6 was interpreted following Deauville criteria. Final result of every PET/CT was defined as positive or negative by the central review panel. When discordance between visual and semiquantitative analysis was found in interim PET, semiquantitative method was determinant of final result. A positive PET4 result determined dropped out from trial. Concordance between all readers was analysed using Cohen's kappa coefficient. Results: Of the first 76 patients that underwent PET/CT, 64 patients completed PET0, PET2 and PET4; 34 patients underwent PET0, PET2, PET4 and PET6. In the central review, 44/64 patients (69%) were PET2(-) and 20/64 (31%) were PET2(+); 44/64 (69%) were PET4(-) and 20/64 (31%) PET4(+); 21/34 (62%) were PET6(-) and 13/34 (38%) were PET6(+). We found 43 patients with negative PET2 and PET4, 19 patients with positive PET2 and PET4, 1 patient with positive PET2 and negative PET4, and 1 patient with negative PET2 and positive PET4. PET2 result was predictive of PET4 (p Concordance between reviewers for PET2 using visual assessment was good (median kappa=0,74) and very good using semiquantitative analysis (median kappa: 0,83). Concordance between reviewers for PET4 using visual assessment was good (kappa=0,72) and very good when semiquantitative analysis was used (median kappa=0,87). For PET6, concordance between readers was moderate (kappa=0.45). Conclusion: In this homogeneus group of patients, a centralized semiquantitative analysis of interim PET after 2 and 4 cycles of chemotherapy improves concordance between readers in comparison with visual analysis. When semiquantitative method is used, PET2 is predictive of PET4 result. In the same way, visual analysis of PET6 using Deauville criteria seems to have a worse concordance between readers, but more patients need to be analyzed to confirm this result. Disclosures No relevant conflicts of interest to declare.

Background: survival of young patients with high IPI DLBCL treated with RCHOP chemotherapy needs to be improved. In this poor risk population the combination of RCHOP with new drugs is an attractive approach, along with performing an early evaluation with PET/CT after 2 to 4 cycles and change induction therapy if a complete response is not achieved. Bortezomib has been combined with RCHOP [1]. We present preliminary data of patients treated in a clinical trial comparing 6 cycles of RCHOP vs 6 cycles of BRCAP, a modified RCHOP regimen changing vincristine by bortezomib at a dose of 1.3 mg/m2 sc days 1, 8, and 15 of every 21 days cycle (NCT01848132). Methods: patients younger than 70 yrs diagnosed of DLBCL with aIPI 2-3 or aIPI 1 with elevated beta2microglobulin were eligible. The main objective was to evaluate the proportion of patients who survives free of event at 2 years. Central pathology review was performed in all cases, and samples were classified as GC vs non-GC subtypes by IHC (Hans algorithm). PET/CTs were performed at diagnosis, after 2, 4 and 6 cycles (PET2, PET4 , and PET6), and were reviewed by at least 3 experts of a central panel at real time. Response was analyzed following the visual method with the Deauville scale, and for PET2 and PET4 the semiquantitative method was used. Patients with persistent disease after 4 cycles were considered a failure of therapy and were dropped out from the trial. Results: data from the first 76 patients were analyzed. Diagnosis of DLBCL was confirmed in all except 3 pts, 36 pts were treated in the experimental arm and 37 in the control arm. Median age was 58.2 yo (range 23-70), 37 (50.7%) were males. Characteristics at diagnosis were: non-GC subtype 18/46 (39.1%), C-myc expression 35/43 (81.4%), bcl2 expression 43/49 (87.7%), double expression cmyc/bcl2 30/42 (71%), stage III-IV 64 (87.6%), ≥2 extranodal locations 27 (42.2%), ECOG 2-3 24 (33%), elevated LDH 43 (62.3%), elevated beta 2 microglobulin 47 (75.8%), aIPI 2: 42 (57.5%), aIPI 3: 21 (28.8%). Among 160 cycles of BRCAP chemotherapy, 5 (3.1%) on day 8, and 22 (13.7%) on day 15, were given without bortezomib due to a neutrophil count below 0.5 /L. The most common toxicities are shown in table 1 without significant differences between both arms. Twenty-one (32.8%) out of 64 patients had a positive PET2. Fifteen (26.8%) out of 56 patients who have finished the 4 cycles had a positive PET4 according to central review and were withdrawn of the trial. Table 1. Episodes of treatment-related adverse events Control arm: RCHOP n=166 Experimental arm: BRCAP n=160 Any grade Grade 3-4 Any grade Grade 3-4 Anemia 6 0 22 9 ( 5.6%) Neutropenia 31 26 (15.6%) 47 37 (23.1%) Thrombocytopenia 9 4 ( 2.4%) 16 5 ( 3.1%) Febrile neutropenia - 6 ( 3.6%) - 10 ( 6.2%) Fever 8 1 ( 0.6%) 8 0 Infection 4 1 ( 0.6%) 7 1 ( 0.6%) Nausea/vomiting 12 0 19 0 Peripheral neuropathy 7 1 ( 0.6%) 7 1 ( 0.6%) Diarrhea 4 0 8 0 Constipation 7 0 4 0 Hepatotoxicity 6 0 6 0 Conclusions: BRCAP regimen with bortezomib sc d1, 8, and 15 is feasible. Its main toxicity is hematological, and some patients cannot receive some doses of bortezomib due to neutropenia. Grade 3-4 non-hematological toxicity is rare, including peripheral neuropathy, and do not differ from RCHOP toxicity. 1.Ruan J et al, JCO 2011;29:690-7 Disclosures Sancho: CELLTRION, Inc.: Research Funding. Lopez-Guillermo:Roche, Celgene, Mundipharma, Gilead, Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

INTRODUCTION Follicular lymphoma (FL) may, over time, transform into an aggressive lymphoma, usually diffuse large B-cell lymphoma (DLBCL). Transformed follicular lymphomas (tFL) have a worse prognosis due to poorer response to treatment than primary DLBCL. The incidence of transformation is estimated in ~3% per year, although it varies largely between different studies (24%-70% overall). These differences are mainly due to different criteria to define tFL, to lack of evidence of tFL by biopsy, absence of clonality studies discarding secondary de novo NHL, studies performed in the pre-Rituximab era, or different follow-up times among studies. With all this pitfalls, the actual incidence of transformation remains an open question. The aim of the present study is to analyse the incidence and prognostic impact of transformation in patients with FL in a large retrospective series of the Spanish group of Lymphomas (GELTAMO). PATIENTS&METHODS A total of 1763 patients from 19 Spanish centres diagnosed of FL between 2000 and 2011 were recruited in the study. Data were obtained from the database of centres willing to participate in this study. True tFL (FL to DLBCL) were recorded. From the original cohort, FL IIIb, composite FL+DLBCL, discordant FL (FL in bone marrow and DLBCL in adenopathy or viceversa), and downgrading tFL (DLBCL at diagnosis and relapse of FL) were excluded. Patients with inadequate follow-up were not considered. Therefore, 1611 patients (grade I, II, and IIIa) were finally included. This study was approved by the Salamanca University Hospital Ethic Committee. RESULTS One hundred and ten patients (median follow up of 6 years) were transformed to DLBCL. Cumulative incidence of transformation at 5, 10, and 15 years was of 5%, 9%, and 14%, respectively. With a median follow up of 75.9 months (2 to 179), median time to transformation was 66 months, ranged 1-179. Considering survival from diagnosis of FL, tFL patients had a shorter OS than non-transformed (19% vs. 69%, p2 (p=0.002, HR: 2,1 95% CI: 1.3-3.4). In the multivariate analysis, factors predicting decreased OS after transformation included non-achievement of CR after first line therapy (p We analyzed separately the role of autologous stem cell transplantation (ASCT) in transformed FL patients. Patients that received ASCT were significantly younger ( CONCLUSIONS In this series, one of the largest reported in the rituximab era, high risk FLIPI (>=2) and non-response to FL first line therapy were associated with a higher risk of transformation.Only non-response to transformed FL treatment therapy and a high LDH at transformation were associated with a worse OS after transformation in the multivariate analysis. Autologous transplantation in transformed patients could have a benefit in terms of OS after transformation, but after the introduction of immunochemotherapy strategies, perhaps patients responding to treatment after transformation do not beneficiate from this strategy. *Equal contribution; ‡Equal senior contribution Disclosures Sancho: CELLTRION, Inc.: Research Funding.

Introduction: At present, determining OS (Overall Survival) remains the gold standard in clinical trial endpoints which evaluate the role of ASCT in FL. However, in the context of a disease characterized by very long median survivals with a continuous pattern of relapse, and still more with the advent of novel treatments, OS assessments seem elusive. In fact, PFS (Progression Free Survival) is the standard endpoint for new drug approvals in first-line FL, and some other earlier endpoints such 2-year PFS (Casulo et al , JCO 2015) or CR30 (Sargent, 2015) have been recently proposed as potential surrogates and as alternatives to PFS or OS as primary end-points in FL patients treated with 1st line chemoinmunoterapy. Objective: To assess if 2-year PFS and CR30 are feasible surrogates of OS in the setting of a very long follow-up series of FL patients treated with ASCT. Material and Methods: A total of 626 chemosensitive FL patients (mean age 47 years, male 49%) reported to the Spanish GELTAMO registry and intensified with ASCT between 1989 and 2007 were analyzed. The status of the disease at the moment of ASCT was either in 1st response [203 in 1st CR, 43% of them needing more than one therapy line to reach the CR, and 140 in 1st Partial Response (PR)] or in response after salvage therapy (174 in 2nd CR, 28 in 3rd CR and 81 in 2nd or 3rd PR). In 615 patients the status of the disease was evaluable after ASCT: 569 cases (92%) in CR, 27 cases (4%) in PR and 19 cases (3%) progressed or died. To assess 2-year PFS, two groups were defined: patients with progression of disease (POD) within 2 years from ASCT (early POD) and patients without progression within 2 years from ASCT. Cox model analysis was used to evaluate the association between early POD and OS from a risk - defining event, which is survival from time of POD for early progressors or from 2 years after ASCT for the reference group (Casulo et al, JCO 2015.Appendix). To asses CR30, two groups were defined: patients with and patients without CR at 30 months from ASCT. Cox model analysis was used to evaluate the association between being or not in CR at 30 months from ASCT. Results: Median follow-up is 12.2 years from ASCT and 14.2 years from diagnosis. Of the assessable patients, 31% were in the high-risk FLIPI group and 40% in the high-risk FLIPI 2 group. 30% of patients received rituximab prior to ASCT. Globally median PFS and median OS are 11 and 21 years, respectively. Patients transplanted in PR (n=221; 35%) had a worse OS than those transplanted in CR (n=405, 65%): HR 2.45 (95% CI, 2.2-2.7; P10-5), fig. 3. Conclusion: 2-year PFS and CR30 could be used as subrogates for OS and as primary end points, not only in FL patients treated with 1st line chemoinmunoterapy, but also in FL intensified with an ASCT. To our knowledge this is the first study to establish that early relapse after ASCT is predictive of poor survival in FL patients; in both, patients treated or not with rituximab previously to the ASCT. This finding is even more evident in patients transplanted in CR. Likewise, best response achieved before ASCT is a robust prognostic factor for OS in FL patients. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.