@article{OPUS4-22778, title = {Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials}, series = {Lancet Oncology}, volume = {19}, journal = {Lancet Oncology}, number = {1}, organization = {Early Breast Cancer Trialists' Collaborative Group (EBCTCG)}, doi = {10.1016/S1470-2045(17)30777-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227782}, pages = {27-39}, year = {2018}, abstract = {Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81\%] of 4756 women). More than two thirds (1349 [69\%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65\%] of 2320 treated with NACT vs 1135 [49\%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21.4\% for NACT versus 15.9\% for adjuvant chemotherapy (5.5\% increase [95\% CI 2.4-8.6]; rate ratio 1.37 [95\% CI 1.17-1.61]; p = 0.0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38.2\% for NACT vs 38.0\% for adjuvant chemotherapy; rate ratio 1.02 [95\% CI 0.92-1.14]; p = 0.66), breast cancer mortality (34.4\% vs 33.7\%; 1.06 [0.95-1.18]; p = 0.31), or death from any cause (40.9\% vs 41.2\%; 1.04 [0.94-1.15]; p = 0.45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. Copyright (c) The Author(s). Published by Elsevier Ltd.}, language = {en} } @article{RiceEikemaMarshetal.2019, author = {Rice, Carmel and Eikema, Dirk-Jan and Marsh, Judith C. W. and Knol, Cora and Hebert, Kyle and Putter, Hein and Peterson, Eefke and Deeg, H. Joachim and Halkes, Stijn and Pidala, Joseph and Anderlini, Paolo and Tischer, Johanna and Kroger, Nicolaus and McDonald, Andrew and Antin, Joseph H. and Schaap, Nicolaas P. and Hallek, Michael and Einsele, Herman and Mathews, Vikram and Kapoor, Neena and Boelens, Jaap-Jan and Mufti, Ghulam J. and Potter, Victoria and de la Tour, R{\´e}gis Pefault and Eapen, Mary and Dufour, Carlo}, title = {Allogeneic Hematopoietic Cell Transplantation in Patients Aged 50 Years or Older with Severe Aplastic Anemia}, series = {Biology of Blood and Marrow Transplantation}, volume = {25}, journal = {Biology of Blood and Marrow Transplantation}, number = {3}, doi = {10.1016/j.bbmt.2018.08.029}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225229}, pages = {488-495}, year = {2019}, abstract = {We report on 499 patients with severe aplastic anemia aged >= 50 years who underwent hematopoietic cell transplantation (HCT) from HLA-matched sibling (n = 275, 55\%) or HLA-matched (8/8) unrelated donors (n =187, 37\%) between 2005 and 2016. The median age at HCT was 57.8 years; 16\% of patients were 65 to 77 years old. Multivariable analysis confirmed higher mortality risks for patients with performance score less than 90\% (hazard ratio HR], 1.41; 95\% confidence interval [CI], 1.03 to 1.92; P= .03) and after unrelated donor transplantation (HR, 1.47; 95\% CI,1 to 2.16; P = .05). The 3-year probabilities of survival for patients with performance scores of 90 to 100 and less than 90 after HLA-matched sibling transplant were 66\% (range, 57\% to 75\%) and 57\% (range, 47\% to 76\%), respectively. The corresponding probabilities after HLA-matched unrelated donor transplantation were 57\% (range, 48\% to 67\%) and 48\% (range, 36\% to 59\%). Age at transplantation was not associated with survival, but grades II to IV acute graft-versus-host disease (GVHD) risks were higher for patients aged 65 years or older (subdistribution HR [sHR], 1.7; 95\% confidence interval, 1.07 to 2.72; P= .026). Chronic GVHD was lower with the GVHD prophylaxis regimens calcineurin inhibitor (CNI) + methotrexate (sHR, .52; 95\% CI, .33 to .81; P= .004) and CNI alone or with other agents (sHR, .27; 95\% CI, .14 to .53; P < .001) compared with CNI + mycophenolate. Although donor availability is modifiable only to a limited extent, choice of GVHD prophylaxis and selection of patients with good performance scores are key for improved outcomes. (C) 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.}, language = {en} } @article{RuizHerediaSanchezVegaOnechaetal.2018, author = {Ruiz-Heredia, Yanira and S{\´a}nchez-Vega, Beatriz and Onecha, Esther and Barrio, Santiago and Alonso, Rafael and Carlos Mart{\´i}nez-Avila, Jose and Cuenca, Isabel and Agirre, Xabier and Braggio, Esteban and Hern{\´a}ndez, Miguel-T. and Mart{\´i}nez, Rafael and Rosi{\~n}ol, Laura and Gutierrez, Norma and Martin-Ramos, Marisa and Ocio, Enrique M. and Echeveste, Mar{\´i}a-Asunci{\´o}n and P{\´e}rez de Oteyza, Jaime and Oriol, Albert and Bargay, Joan and Gironella, Mercedes and Ayala, Rosa and Blad{\´e}, Joan and Mateos, Mar{\´i}a-Victoria and Kortum, Klaus M. and Stewart, Keith and Garc{\´i}a-Sanz, Ram{\´o}n and San Miguel, Jes{\´u}s and Jos{\´e} Lahuerta, Juan and Martinez-Lopez, Joaqu{\´i}n}, title = {Mutational screening of newly diagnosed multiple myeloma patients by deep targeted sequencing}, series = {Haematologica}, volume = {103}, journal = {Haematologica}, number = {11}, doi = {10.3324/haematol.2018.188839}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227151}, pages = {e544-e548}, year = {2018}, abstract = {no abstract available}, language = {en} } @article{RobindeWreedeWolschkeetal.2019, author = {Robin, Marie and de Wreede, Liesbeth C. and Wolschke, Christine and Schetelig, Johannes and Eikema, Diderik-Jan and Van Lint, Maria Teresa and Knelange, Nina Simone and Beelen, Dietrich and Brecht, Arne and Niederwieser, Dietger and Vitek, Antonin and Bethge, Wolfgang and Arnold, Renate and Finke, J{\"u}rgen and Volin, Liisa and Yakoub-Agha, Ibrahim and Nagler, Arnon and Poir{\´e}, Xavier and Einsele, Hermann and Chevallier, Patrice and Holler, Ernst and Ljungman, Per and Robinson, Stephen and Radujkovic, Alekxandar and McLornan, Donal and Chalandon, Yves and Kr{\"o}ger, Nicolaus}, title = {Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis}, series = {Haematologica}, volume = {104}, journal = {Haematologica}, number = {9}, doi = {10.3324/haematol.2018.205211}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226386}, pages = {1782-1788}, year = {2019}, abstract = {Allogeneic hematopoietic stem cell transplant remains the only curative treatment for myelofibrosis. Most post-transplantation events Aoccur during the first two years and hence we aimed to analyze the outcome of 2-year disease-free survivors. A total of 1055 patients with myelofibrosis transplanted between 1995 and 2014 and registered in the registry of the European Society for Blood and Marrow Transplantation were included. Survival was compared to the matched general population to determine excess mortality and the risk factors that are associated. In the 2-year survivors, disease-free survival was 64\% (60-68\%) and overall survival was 74\% (71-78\%) at ten years; results were better in younger individuals and in women. Excess mortality was 14\% (8-21\%) in patients aged <45 years and 33\% (13-53\%) in patients aged >= 65 years. The main cause of death was relapse of the primary disease. Graft-versus-host disease (GvHD) before two years decreased the risk of relapse. Multivariable analysis of excess mortality showed that age, male sex recipient, secondary myelofibrosis and no GvHD disease prior to the 2-year landmark increased the risk of excess mortality. This is the largest study to date analyzing long-term outcome in patients with myelofibrosis undergoing transplant. Overall it shows a good survival in patients alive and in remission at two years. However, the occurrence of late complications, including late relapses, infectious complications and secondary malignancies, highlights the importance of screening and monitoring of long-term survivors.}, subject = {Midollo-Osseo}, language = {en} } @article{SabelFleischhackTippeltetal.2016, author = {Sabel, Magnus and Fleischhack, Gudrun and Tippelt, Stephan and Gustafsson, G{\"o}ran and Doz, Fran{\c{c}}ois and Kortmann, Rolf and Massimino, Maura and Navajas, Aurora and von Hoff, Katja and Rutkowski, Stefan and Warmuth-Metz, Monika and Clifford, Steven C. and Pietsch, Torsten and Pizer, Barry and Linnering, Birgitta}, title = {Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study}, series = {Journal of Neurooncology}, volume = {129}, journal = {Journal of Neurooncology}, number = {3}, organization = {SIOP-E Brain Tumour Group}, doi = {10.1007/s11060-016-2202-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187498}, pages = {515-524}, year = {2016}, abstract = {The HIT-SIOP-PNET4 randomised trial for standard risk medulloblastoma (MB) (2001-2006) included 338 patients and compared hyperfractionated and conventional radiotherapy. We here report the long-term outcome after a median follow up of 7.8 years, including detailed information on relapse and the treatment of relapse. Data were extracted from the HIT Group Relapsed MB database and by way of a specific case report form. The event-free and overall (OS) survival at 10 years were 76 +/- 2 \% and 78 +/- 2 \% respectively with no significant difference between the treatment arms. Seventy-two relapses and three second malignant neoplasms were reported. Thirteen relapses (18 \%) were isolated local relapses in the posterior fossa (PF) and 59 (82 \%) were craniospinal, metastatic relapses (isolated or multiple) with or without concurrent PF disease. Isolated PF relapse vs all other relapses occurred at mean/median of 38/35 and 28/26 months respectively (p = 0.24). Late relapse, i.e. > 5 years from diagnosis, occurred in six patients (8 \%). Relapse treatment consisted of combinations of surgery (25 \%), focal radiotherapy (RT 22 \%), high dose chemotherapy with stem cell rescue (HDSCR 21 \%) and conventional chemotherapy (90 \%). OS at 5 years after relapse was 6.0 +/- 4 \%. In multivariate analysis; isolated relapse in PF, and surgery were significantly associated with prolonged survival whereas RT and HDSCR were not. Survival after relapse was not related to biological factors and was very poor despite several patients receiving intensive treatments. Exploration of new drugs is warranted, preferably based on tumour biology from biopsy of the relapsed tumour.}, language = {en} } @article{JansenHeintelJordanetal.2019, author = {Jansen, Hendrik and Heintel, Timo M. and Jordan, Martin and Meffert, Rainer H. and Frey, Soenke P.}, title = {Survived traumatic hemipelvectomy with salvage of the limb in a 14  months old toddler}, series = {Trauma Case Reports}, volume = {22}, journal = {Trauma Case Reports}, doi = {10.1016/j.tcr.2019.100220}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202207}, pages = {100220}, year = {2019}, abstract = {We report on a 14 months old toddler who sustained a traumatic hemipelvectomy by being crushed between a car and a stone wall. After stabilization in the resuscitation room he was treated operatively by laparotomy, osteosynthesis of the pelvic ring, reconstruction of the both external iliac vessels and the urethra and reposition of the testicles. After 66 days he was discharged into rehabilitation. Implants were removed after eight months. 20 months after the injury, the leg was plegic, initial radiological signs of femoral head necrosis showed up but the infant was able to walk with an orthesis and a walker. Up to our knowledge, this is the youngest patient described in the literature with a survived traumatic hemipelvectomy and salvaged limb.}, language = {en} } @article{CarmelaVeglianteRoyoPalomeroetal.2011, author = {Carmela Vegliante, Maria and Royo, Cristina and Palomero, Jara and Salaverria, Itziar and Balint, Balazs and Martin-Guerrero, Idoia and Agirre, Xabier and Lujambio, Amaia and Richter, Julia and Xargay-Torrent, Silvia and Bea, Silvia and Hernandez, Luis and Enjuanes, Anna and Jose Calasanz, Maria and Rosenwald, Andreas and Ott, German and Roman-Gomez, Jose and Prosper, Felipe and Esteller, Manel and Jares, Pedro and Siebert, Reiner and Campo, Elias and Martin-Subero, Jose I. and Amador, Virginia}, title = {Epigenetic Activation of SOX11 in Lymphoid Neoplasms by Histone Modifications}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0021382}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135325}, pages = {e21382}, year = {2011}, abstract = {Recent studies have shown aberrant expression of SOX11 in various types of aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to such deregulation, we performed a comprehensive SOX11 gene expression and epigenetic study in stem cells, normal hematopoietic cells and different lymphoid neoplasms. We observed that SOX11 expression is associated with unmethylated DNA and presence of activating histone marks (H3K9/14Ac and H3K4me3) in embryonic stem cells and some aggressive B-cell neoplasms. In contrast, adult stem cells, normal hematopoietic cells and other lymphoid neoplasms do not express SOX11. Such repression was associated with silencing histone marks H3K9me2 and H3K27me3. The SOX11 promoter of non-malignant cells was consistently unmethylated whereas lymphoid neoplasms with silenced SOX11 tended to acquire DNA hypermethylation. SOX11 silencing in cell lines was reversed by the histone deacetylase inhibitor SAHA but not by the DNA methyltransferase inhibitor AZA. These data indicate that, although DNA hypermethylation of SOX11 is frequent in lymphoid neoplasms, it seems to be functionally inert, as SOX11 is already silenced in the hematopoietic system. In contrast, the pathogenic role of SOX11 is associated with its de novo expression in some aggressive lymphoid malignancies, which is mediated by a shift from inactivating to activating histone modifications.}, language = {en} }