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Barcelona, Spain

Passweg J.R.,University of Basel | Baldomero H.,University of Basel | Peters C.,BMT Unit | Gaspar H.B.,University College London | And 13 more authors.
Bone Marrow Transplantation | Year: 2014

In all, 661 of 680 centers in 48 countries reported 37 818 hematopoietic SCT (HSCT) in 33 678 patients (14 165 allogeneic (42%), 19 513 autologous (58%)) in the 2012 survey. Main indications were leukemias, 10 641 (32%; 95% allogeneic); lymphoid neoplasias, 19 336 (57%; 11% allogeneic); solid tumors, 1630 (5%; 3% allogeneic); and nonmalignant disorders, 1953 (6%; 90% allogeneic). There were more unrelated donors than HLA-identical sibling donors (54% versus 38% (8% being mismatched related donor HSCT)). Cord blood was almost exclusive in allogeneic transplants (5% of total). Since 2011, the highest increases in allogeneic HSCT were for AML in CR1 (12%) and for myeloproliferative neoplasm (15%). For autologous HSCT the main increases were for plasma cell disorders (7%), non-Hodgkin lymphoma (4%) and autoimmune disease (50%). There were 4097 pediatric patients <18 years of age receiving HSCT, 2902 received an allogeneic and 1195 an autologous HSCT. Overall, 69% of allogeneic and 64% of autologous HSCT were performed in dedicated pediatric centers and the remainder in combined adult and pediatric centers. Distributions of diseases, donor types and stem cell source for all patients and pediatric patients in particular are shown. A percentage of centers fulfilling the annual required criteria for patient numbers for JACIE accreditation are provided. © 2014 Macmillan Publishers Limited. All rights reserved.

Ruppen I.,Tumor Markers Group | Grau L.,Tumor Markers Group | Orenes-Pinero E.,Tumor Markers Group | Ashman K.,Spanish National Cancer Research Center | And 4 more authors.
Molecular and Cellular Proteomics | Year: 2010

KiSS-1 is a metastasis suppressor gene reported to be involved in the progression of several solid neoplasias. The loss of KiSS-1 gene expression has been shown to be inversely correlated with increasing tumor stage, distant metastases, and poor overall survival in bladder tumors. To identify the molecular pathways associated with the metastasis suppressor role of KiSS-1 in bladder cancer, we carried out a proteomics analysis of bladder cancer cells (EJ138) transiently transfected with a vector encompassing the full-length KiSS-1 gene using an iTRAQ (isobaric tags for relative and absolute quantitation) approach. Protein extracts collected after 24- and 48-h transfection were fractionated and cleaved with trypsin, and the resulting peptides were labeled with iTRAQ reagents. The labeled peptides were separated by strong cation exchange and reversed phase LC and analyzed by MALDI-TOF/TOF MS. Three software packages were utilized for data analysis: ProteinPilot for identification and quantification of differentially expressed proteins, Protein Center for gene ontology analysis, and Ingenuity Pathways Analysis to provide insight into biological networks. Comparative analysis among transfected, mock, and empty vector-exposed cells identified 1529 proteins with high confidence (>99%) showing high correlation rates among replicates (70%). The involvement of the identified proteins in biological networks served to characterize molecular pathways associated with KiSS-1 expression and to select critical candidates for verification analyses by Western blot using independent transfected replicates. As part of complementary clinical validation strategies, immunohistochemical analyses of proteins regulated by KiSS-1, such as Filamin A, were performed on bladder tumors spotted onto tissue microarrays (n = 280). In summary, our study not only served to uncover molecular mechanisms associated with the metastasis suppressor role of KiSS-1 in bladder cancer but also to reveal the biomarker role of Filamin A in bladder cancer progression and clinical outcome. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Cubilla A.L.,Institute Patologia e Investigacion | Lloveras B.,Institute cataladOncologia | Alejo M.,Johns Hopkins University | Clavero O.,Institute cataladOncologia | And 15 more authors.
American Journal of Surgical Pathology | Year: 2011

Background: One third to one half of penile squamous cell carcinomas (SCCs) are related to human papillomavirus (HPV) infection. Viral detection is usually carried out by polymerase chain reaction (PCR) or other molecular methods. In this study, we evaluated p16 immunohistochemical expression, which is simpler and less costly, as a potential marker of high-risk HPV (HR-HPV) infection in penile SCC. DESIGN AND METHODS: We pathologically classified 202 invasive penile carcinomas and performed HPV genotyping by short PCR fragment (SPF)10 PCR and p16 immunohistochemistry. We also evaluated HPV and p16 according to the histologic subtypes of penile SCC. Tumors depicting continuous p16 immunostain in all neoplastic cells were considered positive. HPV and p16 status were compared using classifier performances and concordance indexes. RESULTS: Evidence of HPV (low-risk and high-risk genotypes) was found in 63 cases (31%) by PCR. Fifty-three p16-positive cases were identified (26%). Overexpression of p16 had a sensitivity of 67% and a specificity of 91% for defining the HPV status. Concordance indexes between p16 and HPV status were high (≥78%) in general cases and in all histologic subtypes of penile SCC. The stain was useful in the differential diagnosis of basaloid and low-grade warty carcinomas. Low-risk HPV genotypes were found in 5 tumors, 4 of which were p16 negative. Basaloid and nonbasaloid high-grade (grade 3) SCCs were more likely to be HR-HPV positive when compared with grades 1 to 2 tumors (P<0.000001 and 0.0417, respectively). Conclusions: p16 overexpression was found to be a reliable marker for HR-HPV and a helpful tool in the differential diagnosis of low-grade verruciform and high-grade solid penile tumors. SCC variants depicting basaloid features were more likely to be HPV and p16 positive than low-grade, keratinizing lesions. We also observed a tendency toward HPV positivity in high-grade nonbasaloid tumors. Our results indicated a concordance between HPV and p16 status and this observation may have diagnostic and prognostic implications. Copyright © 2011 by Lippincott Williams & Wilkins.

Kopetz S.,University of Houston | Tabernero J.,Autonomous University of Barcelona | Rosenberg R.,Ludwig Maximilians University of Munich | Jiang Z.-Q.,University of Houston | And 9 more authors.
Oncologist | Year: 2015

Background. Approximately 20% of patients with stage II colorectal cancer will experience a relapse. Current clinicalpathologic stratification factors do not allowclear identification of these high-risk patients. ColoPrint (Agendia, Amsterdam, The Netherlands, http://www.agendia.com) is a gene expression classifier that distinguishes patients with low or high risk of disease relapse. Methods. ColoPrint was developed using whole-genome expression data and validated in several independent validation cohorts. Stage II patients from these studieswere pooled (n5416), and ColoPrint was compared with clinical risk factors described in the National Comprehensive Cancer Network (NCCN) 2013 Guidelines for Colon Cancer. Median follow-up was 81 months. Most patients (70%) did not receive adjuvant chemotherapy. Risk of relapse (ROR) was defined as survival until first event of recurrence or death fromcancer. Results. In the pooled stage II data set, ColoPrint identified 63% of patients as low risk with a 5-year ROR of 10%, whereas high-risk patients (37%) had a 5-yearRORof 21%, with a hazard ratio (HR) of 2.16 (p =.004). This remained significant in a multivariate model that included number of lymph nodes retrieved and microsatellite instability. In the T3 microsatellitestable subgroup (n5301), ColoPrint classified 59% of patients as low risk with a 5-year ROR of 9.9%. High-risk patients (31%) had a 22.4% ROR (HR: 2.41; p =.005). In contrast, the NCCN clinical high-risk factors were unable to distinguish high-and low-risk patients (15% vs. 13% ROR; p =.55). Conclusion. ColoPrint significantly improved prognostic accuracy independent of microsatellite status or clinical variables, facilitating the identification of patients at higher risk who might be considered for additional treatment. © AlphaMed Press 2015.

Graus F.,Service of Neurology | Bruna J.,Service of Neurology | Pardo J.,Hospital Universitari Of Bellvitge | Escudero D.,Hospital Universitari Germans Trias i Pujol | And 29 more authors.
Neuro-Oncology | Year: 2013

BackgroundTo assess management patterns and outcome in patients with glioblastoma multiforme (GBM) treated during 2008-2010 in Spain. MethodsRetrospective analysis of clinical, therapeutic, and survival data collected through filled questionnaires from patients with histologically confirmed GBM diagnosed in 19 Spanish hospitals.ResultsWe identified 834 patients (23% aged >70 years). Surgical resection was achieved in 66% of patients, although the extent of surgery was confirmed by postoperative MRI in only 41%. There were major postoperative complications in 14% of patients, and age was the only independent predictor (Odds ratio [OR], 1.03; 95% confidence interval [CI],1.01-1.05; P =. 006). After surgery, 57% received radiotherapy (RT) with concomitant and adjuvant temozolomide, 21% received other regimens, and 22% were not further treated. In patients treated with surgical resection, RT, and chemotherapy (n = 396), initiation of RT ≤42 days was associated with longer progression-free survival (hazard ratio [HR], 0.8; 95% CI, 0.64-0.99; P =. 042) but not with overall survival (HR, 0.79; 95% CI, 0.62-1.00; P =. 055). Only 32% of patients older than 70 years received RT with concomitant and adjuvant temozolomide. The median survival in this group was 10.8 months (95% CI, 6.8-14.9 months), compared with 17.0 months (95% CI, 15.5-18.4 months; P =. 034) among younger patients with GBM treated with the same regimen.ConclusionsIn a community setting, 57% of all patients with GBM and only 32% of older patients received RT with concomitant and adjuvant temozolomide. In patients with surgical resection who were eligible for chemoradiation, initiation of RT ≤42 days was associated with better progression-free survival. © 2013 The Author(s).

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