1,312 results on '"Hillmen P."'
Search Results
202. Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukemia
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Parker, H., Rose-Zerilli, M.J.J., Larrayoz, M., Clifford, R., Edelmann, J., Blakemore, S., Gibson, J., Wang, J., Ljungström, V., Wojdacz, T.K., Chaplin, T., Roghanian, A., Davis, Z., Parker, A., Tausch, E., Ntoufa, S., Ramos, S., Robbe, P., Alsolami, R., Steele, A.J., Packham, G., Rodriquez-Vicente, A.E., Brown, L., McNicholl, F., Forconi, F., Pettitt, A., Hillmen, P., Dyer, M., Cragg, M.S., Chelala, C., Oakes, C.C., Rosenquist, R., Stamatopoulos, K., Stilgenbauer, S., Knight, S., Schuh, A., Oscier, D.G., and Strefford, J.C.
- Abstract
Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and are disrupted at the genomic level in a spectrum of human tumors including haematological malignancies. Using high-resolution SNP-arrays, we identified recurrent deletions of the SETD2 locus in 3% (8/261) of chronic lymphocytic leukemia (CLL) patients. Further validation in two independent cohorts showed that SETD2 deletions were associated with loss of TP53, genomic complexity and chromothripsis. With next generation sequencing we detected mutations of SETD2 in an additional 3.8% of patients (23/602). In most cases, SETD2-deletions or mutations were often observed as a 56 clonal event and always as a mono-allelic lesion, leading to reduced mRNA expression in SETD2-disrupted cases. Patients with SETD2 abnormalities and wild-type TP53 and ATM from five clinical trials employing chemotherapy or chemo-immunotherapy, had reduced progression-free and overall survival compared to cases wild-type for all three genes. Consistent with its postulated role as a tumor suppressor, our data highlights SETD2 aberration as a recurrent, early loss-of-function event in CLL pathobiology linked to aggressive disease.
- Published
- 2016
203. FINAL RESULTS OF THE NCRI CLL210 TRIAL OF ALEMTUZUMAB, DEXAMETHASONE AND LENALIDOMIDE IN PATIENTS WITH HIGH-RISK CLL (ORIGINAL PROTOCOL)
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Pettitt, A. R., Polydoros, F., Dodd, J., Oates, M., Lin, K., Kalakonda, N., Mccarthy, H., Bloor, A., Schuh, A., Duncombe, A., Dearden, C., Fegan, C., Kennedy, B., Christina Yap, Coupland, S. E., and Hillmen, P.
- Published
- 2016
204. LINKING PROTEOME AND GENOME FOR BIOMARKER DISCOVERY IN CLL-ESTABLISHMENT OF A CLL PROTEIN DATABASE
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Gina Eagle, Zhuang, J., Jenkins, R., Kitteringham, N., Oates, M., Park, K., Schuh, A., Devereux, S., Hillmen, P., and Pettitt, A.
- Published
- 2016
205. Changing prognosis in paroxysmal nocturnal haemoglobinuria disease subcategories: an analysis of the International PNH Registry
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Socie, G., Schrezenmeier, H., Muus, P., Lisukov, I., Roth, A., Kulasekararaj, A., Lee, J.W., Araten, D., Hill, A., Brodsky, R., Urbano-Ispizua, A., Szer, J., Wilson, A., and Hillmen, P.
- Subjects
hemic and lymphatic diseases ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Medizin - Abstract
Item does not contain fulltext BACKGROUND: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare disease. Although much progress has been made in the understanding of the pathophysiology of the disease, far less is known with respect to the clinical outcomes of patients with PNH. Few retrospective studies provide survival estimates, and even fewer have explored the clinical heterogeneity of the disease. Haemolytic and aplastic anaemia (AA) forms of the disease have been recognised as main disease categories, with the haemolytic form being associated with the worst prognosis by the largest studied cohort some years ago. AIMS: To describe mortality and causes of death in PNH overall and by PNH classification and to evaluate risk factors associated with mortality. METHODS: We analysed data of 2356 patients enrolled in the International PNH Registry with multivariate analyses, using time-dependent covariates. Patients were classified into haemolytic, AA/PNH syndrome or intermediate PNH. RESULTS: Overall, 122 (5.2%) patients died after enrolment, the incidence according to subcategories being 5.1, 11.7, 2.0 and 4.8% for patients with haemolytic PNH, AA-PNH, intermediate and insufficient data respectively. Older age and decreased performance status also affected survival in multivariate analysis. Improved outcome of patients with haemolytic PNH suggests that eculizumab treatment in PNH may be associated with improved survival. CONCLUSION: A detailed analysis of clinical presentations and causes of death in patients with PNH, overall and by disease subcategories, provide evidence that in the current era, patients with haemolytic PNH are no longer those who harbour the worst prognosis. This finding differs sharply from what has been previously reported.
- Published
- 2016
206. Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia
- Author
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Parker, H, Rose Zerilli, M. J. J, Larrayoz, M, Clifford, R, Edelmann, J, Blakemore, S, Gibson, J, Wang, J, Ljungstr�m, V, Wojdacz, T. K, Chaplin, T, Roghanian, A, Davis, Z, Parker, A, Tausch, E, Ntoufa, S, Ramos, S, Robbe, P, Alsolami, R, Steele, A. J, Packham, G, Rodr�ez Vicente, A. E, Brown, L, Mcnicholl, F, Forconi, Francesco, Pettitt, A, Hillmen, P, Dyer, M, Cragg, M. S, Chelala, C, Oakes, C. C, Rosenquist, R, Stamatopoulos, K, Stilgenbauer, S, Knight, S, Schuh, A, Oscier, D. G, Strefford, J. C., Leukaemia & Lymphoma Research (UK), Royal Marsden NHS Foundation Trust, The Institute of Cancer Research (UK), Swedish Research Council, Swedish Cancer Society, Polysackaridforskning i Uppsala AB, German Research Foundation, Leukaemia Foundation, Wessex Medical Research, Kay Kendall Leukaemia Fund, and Cancer Research UK
- Subjects
Male ,Ataxia Telangiectasia Mutated Proteins ,Disease-Free Survival ,Humans ,Genes, Tumor Suppressor ,Hematologi ,Chronic ,Cancer och onkologi ,Leukemia ,B-Cell ,Genomics ,Histone-Lysine N-Methyltransferase ,Hematology ,Prognosis ,Leukemia, Lymphocytic, Chronic, B-Cell ,Lymphocytic ,Survival Rate ,Mutation ,Tumor Suppressor Protein p53 ,Genes ,Cancer and Oncology ,Histone Methyltransferases ,Female ,Original Article ,Tumor Suppressor - Abstract
Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and are disrupted at the genomic level in a spectrum of human tumours including haematological malignancies. Using high-resolution single nucleotide polymorphism (SNP) arrays, we identified recurrent deletions of the SETD2 locus in 3% (8/261) of chronic lymphocytic leukaemia (CLL) patients. Further validation in two independent cohorts showed that SETD2 deletions were associated with loss of TP53, genomic complexity and chromothripsis. With next-generation sequencing we detected mutations of SETD2 in an additional 3.8% of patients (23/602). In most cases, SETD2 deletions or mutations were often observed as a clonal event and always as a mono-allelic lesion, leading to reduced mRNA expression in SETD2-disrupted cases. Patients with SETD2 abnormalities and wild-type TP53 and ATM from five clinical trials employing chemotherapy or chemo-immunotherapy had reduced progression-free and overall survival compared with cases wild type for all three genes. Consistent with its postulated role as a tumour suppressor, our data highlight SETD2 aberration as a recurrent, early loss-of-function event in CLL pathobiology linked to aggressive disease., This work was funded by Bloodwise (11052, 12036), the Kay Kendall Leukaemia Fund (873), Cancer Research UK (C34999/A18087, ECMC C24563/A15581), Wessex Medical Research and the Bournemouth Leukaemia Fund. SS is supported by the Else Kröner-FreseniusStiftung (2012_A146) and Deutsche Forschungsgemeinschaft (SFB 1074 projects B1, B2). The LRF CLL4 trial was funded by a core grant from Leukaemia and Lymphoma Research. DG and DC acknowledge the support by The Royal Marsden Hospital and The Institute of Cancer Research National Institute of Health Research Biomedical Research Center. RR is supported by the Swedish Cancer Society, the Swedish Research Council, Science for Life Laboratory, Uppsala University, Uppsala University Hospital, and the Lion’s Cancer Research Foundation, Uppsala.
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- 2016
207. The european hematology association roadmap for european hematology research: A consensus document
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Engert, A. Balduini, C. Brand, A. Coiffier, B. Cordonnier, C. Döhner, H. De Wit, T.D. Eichinger, S. Fibbe, W. Green, T. De Haas, F. Iolascon, A. Jaffredo, T. Rodeghiero, F. Sall Es, G. Schuringa, J.J. André, M. Andre-Schmutz, I. Bacigalupo, A. Bochud, P.-Y. Den Boer, M. Bonini, C. Camaschella, C. Cant, A. Cappellini, M.D. Cazzola, M. Celso, C.L. Dimopoulos, M. Douay, L. Dzierzak, E. Einsele, H. Ferreri, A. De Franceschi, L. Gaulard, P. Gottgens, B. Greinacher, A. Gresele, P. Gribben, J. De Haan, G. Hansen, J.-B. Hochhaus, A. Kadir, R. Kaveri, S. Kouskoff, V. Kühne, T. Kyrle, P. Ljungman, P. Maschmeyer, G. Méndez-Ferrer, S. Milsom, M. Mummery, C. Ossenkoppele, G. Pecci, A. Peyvandi, F. Philipsen, S. Reitsma, P. Ribera, J.M. Risitano, A. Rivella, S. Ruf, W. Schroeder, T. Scully, M. Socie, G. Staal, F. Stanworth, S. Stauder, R. Stilgenbauer, S. Tamary, H. Theilgaard-Mönch, K. Thein, S.L. Tilly, H. Trneny, M. Vainchenker, W. Vannucchi, A.M. Viscoli, C. Vrielink, H. Zaaijer, H. Zanella, A. Zolla, L. Zwaginga, J.J. Martinez, P.A. Van Den Akker, E. Allard, S. Anagnou, N. Andolfo, I. Andrau, J.-C. Angelucci, E. Anstee, D. Aurer, I. Avet-Loiseau, H. Aydinok, Y. Bakchoul, T. Balduini, A. Barcellini, W. Baruch, D. Baruchel, A. Bayry, J. Bento, C. Van Den Berg, A. Bernardi, R. Bianchi, P. Bigas, A. Biondi, A. Bohonek, M. Bonnet, D. Borchmann, P. Borregaard, N. Brækkan, S. Van Den Brink, M. Brodin, E. Bullinger, L. Buske, C. Butzeck, B. Cammenga, J. Campo, E. Carbone, A. Cervantes, F. Cesaro, S. Charbord, P. Claas, F. Cohen, H. Conard, J. Coppo, P. Vives Corron, J.-L. Da Costa, L. Davi, F. Delwel, R. Dianzani, I. Domanović, D. Donnelly, P. Drnovšek, T.D. Dreyling, M. Du, M.-Q. Dufour, C. Durand, C. Efremov, D. Eleftheriou, A. Elion, J. Emonts, M. Engelhardt, M. Ezine, S. Falkenburg, F. Favier, R. Federico, M. Fenaux, P. Fitzgibbon, J. Flygare, J. Foà, R. Forrester, L. Galacteros, F. Garagiola, I. Gardiner, C. Garraud, O. Van Geet, C. Geiger, H. Geissler, J. Germing, U. Ghevaert, C. Girelli, D. Godeau, B. Gökbuget, N. Goldschmidt, H. Goodeve, A. Graf, T. Graziadei, G. Griesshammer, M. Gruel, Y. Guilhot, F. Von Gunten, S. Gyssens, I. Halter, J. Harrison, C. Harteveld, C. Hellström-Lindberg, E. Hermine, O. Higgs, D. Hillmen, P. Hirsch, H. Hoskin, P. Huls, G. Inati, A. Johnson, P. Kattamis, A. Kiefel, V. Kleanthous, M. Klump, H. Krause, D. Hovinga, J.K. Lacaud, G. Lacroix-Desmazes, S. Landman-Parker, J. Legouill, S. Lenz, G. Von Lilienfeld-Toal, M. Von Lindern, M. Lopez-Guillermo, A. Lopriore, E. Lozano, M. Macintyre, E. Makris, M. Mannhalter, C. Martens, J. Mathas, S. Matzdorff, A. Medvinsky, A. Menendez, P. Migliaccio, A.R. Miharada, K. Mikulska, M. Minard, V. Montalbán, C. De Montalembert, M. Montserrat, E. Morange, P.-E. Mountford, J. Muckenthaler, M. Müller-Tidow, C. Mumford, A. Nadel, B. Navarro, J.-T. El Nemer, W. Noizat-Pirenne, F. O’Mahony, B. Oldenburg, J. Olsson, M. Oostendorp, R. Palumbo, A. Passamonti, F. Patient, R. De Latour, R.P. Pflumio, F. Pierelli, L. Piga, A. Pollard, D. Raaijmakers, M. Radford, J. Rambach, R. Koneti Rao, A. Raslova, H. Rebulla, P. Rees, D. Ribrag, V. Rijneveld, A. Rinalducci, S. Robak, T. Roberts, I. Rodrigues, C. Rosendaal, F. Rosenwald, A. Rule, S. Russo, R. Saglio, G. Sanchez, M. Scharf, R.E. Schlenke, P. Semple, J. Sierra, J. So-Osman, C. Soria, J.M. Stamatopoulos, K. Stegmayr, B. Stunnenberg, H. Swinkels, D. Barata, J.P.T. Taghon, T. Taher, A. Terpos, E. Thachil, J. Tissot, J.D. Touw, I. Toye, A. Trappe, R. Traverse-Glehen, A. Unal, S. Vaulont, S. Viprakasit, V. Vitolo, U. Van Wijk, R. Wójtowicz, A. Zeerleder, S. Zieger, B. EHA Roadmap for European Hematology Research
- Abstract
The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at ∈ European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better fu treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. © 2016 Ferrata Storti Foundation.
- Published
- 2016
208. Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL/SLL
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Brown, J R, primary, Hillmen, P, additional, O’Brien, S, additional, Barrientos, J C, additional, Reddy, N M, additional, Coutre, S E, additional, Tam, C S, additional, Mulligan, S P, additional, Jaeger, U, additional, Barr, P M, additional, Furman, R R, additional, Kipps, T J, additional, Cymbalista, F, additional, Thornton, P, additional, Caligaris-Cappio, F, additional, Delgado, J, additional, Montillo, M, additional, DeVos, S, additional, Moreno, C, additional, Pagel, J M, additional, Munir, T, additional, Burger, J A, additional, Chung, D, additional, Lin, J, additional, Gau, L, additional, Chang, B, additional, Cole, G, additional, Hsu, E, additional, James, D F, additional, and Byrd, J C, additional
- Published
- 2017
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- View/download PDF
209. INTEGRATED ANALYSIS: OUTCOMES OF IBRUTINIB-TREATED PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LEUKEMIA (CLL/SLL) WITH HIGH-RISK PROGNOSTIC FACTORS
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Kipps, T.J., primary, Fraser, G., additional, Coutre, S.E., additional, Brown, J.R., additional, Barrientos, J.C., additional, Barr, P.M., additional, Byrd, J.C., additional, O'Brien, S.M., additional, Dilhuydy, M., additional, Hillmen, P., additional, Jaeger, U., additional, Moreno, C., additional, Cramer, P., additional, Stilgenbauer, S., additional, Chanan-Khan, A.A., additional, Mahler, M., additional, Salman, M., additional, Cheng, M., additional, Londhe, A., additional, Ninomoto, J., additional, Howes, A., additional, James, D.F., additional, and Hallek, M., additional
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- 2017
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210. LONG-TERM EFFICACY AND SAFETY IN THE RESONATE STUDY: IBRUTINIB IN PATIENTS WITH PREVIOUSLY TREATED CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) WITH UP TO FOUR YEARS FOLLOW-UP
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Montillo, M., primary, Byrd, J.C., additional, Hillmen, P., additional, O'Brien, S., additional, Barrientos, J.C., additional, Reddy, N.M., additional, Coutre, S., additional, Tam, C.S., additional, Mulligan, S.P., additional, Jaeger, U., additional, Barr, P.M., additional, Furman, R.R., additional, Kipps, T.J., additional, Thornton, P., additional, Moreno, C., additional, Pagel, J.M., additional, Burger, J.A., additional, Jones, J., additional, Dai, S., additional, Vezan, R., additional, James, D.F., additional, and Brown, J.R., additional
- Published
- 2017
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211. EFFECT OF ADDING IDELALISIB TO FRONTLINE OFATUMUMAB PLUS EITHER CHLORAMBUCIL OR BENDAMUSTINE IN LESS FIT PATIENTS WITH CLL: PRELIMINARY RESULTS FROM THE NCRI RIALTO TRIAL.
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Pettitt, A.R., primary, Kalakonda, N., additional, Polydoros, F., additional, Bickerstaff, M., additional, Menon, G., additional, Coupland, S.E., additional, Oates, M., additional, Lin, K., additional, Pocock, C., additional, Jenkins, S., additional, Schuh, A., additional, Wandroo, F., additional, Rassam, S., additional, Duncombe, A.S., additional, Jenner, M., additional, Cervi, P., additional, Paneesha, S., additional, Aldouri, M., additional, Fox, C.P., additional, Knechtli, C., additional, Hamblin, M., additional, Turner, D., additional, and Hillmen, P., additional
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- 2017
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212. BONE MARROW IS MORE SENSITIVE THAN PERIPHERAL BLOOD FOR DETECTION OF MRD IN CLL AND PROVIDES A MORE RELIABLE PREDICTION OF OUTCOME ACROSS DIFFERENT TREATMENTS
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Rawstron, A, Cohen, D, de Tute, R, McParland, L, Collett, L, Phillips, D, Chalmers, A, Varghese, A, Munir, T, Gregory, W, and Hillmen, P
- Published
- 2015
213. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): A randomised, multicentre, open-label phase 3 trial
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Hillmen, P. Robak, T. Janssens, A. Babu, K.G. Kloczko, J. Grosicki, S. Doubek, M. Panagiotidis, P. Kimby, E. Schuh, A. Pettitt, A.R. Boyd, T. Montillo, M. Gupta, I.V. Wright, O. Dixon, I. Carey, J.L. Chang, C.-N. Lisby, S. McKeown, A. Offner, F.
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hemic and lymphatic diseases - Abstract
Background Treatment for patients with chronic lymphocytic leukaemia who are elderly or who have comorbidities is challenging because fludarabine-based chemoimmunotherapies are mostly not suitable. Chlorambucil remains the standard of care in many countries. We aimed to investigate whether the addition of ofatumumab to chlorambucil could lead to better clinical outcomes than does treatment with chlorambucil alone, while also being tolerable for patients who have few treatment options. Methods We carried out a randomised, open-label, phase 3 trial for treatment-naive patients with chronic lymphocytic leukaemia in 109 centres in 16 countries. We included patients who had active disease needing treatment, but in whom fludarabine-based treatment was not possible. We randomly assigned patients (1:1) to receive oral chlorambucil (10 mg/m2) on days 1-7 of a 28 day treatment course or to receive chlorambucil by this schedule plus intravenous ofatumumab (cycle 1: 300 mg on day 1 and 1000 mg on day 8; subsequent cycles: 1000 mg on day 1) for three to 12 cycles. Assignment was done with a randomisation list that was computer generated at GlaxoSmithKline, and was stratified, in a block size of two, by age, disease stage, and performance status. The primary endpoint was progression-free survival in the intention-to-treat population and assessment was done by an independent review committee that was masked to group assignment. The study is registered with ClinicalTrials.gov, number NCT00748189. Findings We enrolled 447 patients, median age 69 years (range 35-92). Between Dec 22, 2008, and May 26, 2011, we randomly assigned 221 patients to chlorambucil plus ofatumumab and 226 patients to chlorambucil alone. Median progression-free survival was 22·4 months (95% CI 19·0-25·2) in the group assigned to chlorambucil plus ofatumumab compared with 13·1 months (10·6-13·8) in the group assigned to chlorambucil only (hazard ratio 0·57, 95% CI 0·45-0·72; p
- Published
- 2015
214. Ofatumumab in poor-prognosis chronic lymphocytic leukemia: a Phase 4, non--interventional, observational study from the European Research Initiative on Chronic Lymphocytic Leukemia
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Moreno, C, Montillo, M, Panayiotidis, P, Dimou, M, Bloor, A, Dupuis, J, Schuh, A, Norin, S, Geisler, C, Hillmen, P, Doubek, M, Trněný, M, Obrtlikova, P, Laurenti, L, Stilgenbauer, S, Smolej, L, Ghia, P, Cymbalista, F, Jaeger, U, Stamatopoulos, K, Stavroyianni, N, Carrington, P, Zouabi, H, Leblond, V, Gomez Garcia JC, Rubio, M, Marasca, Roberto, Musuraca, G, Rigacci, L, Farina, L, Paolini, R, Pospisilova, S, Kimby, E, Bradley, C, and Montserrat, E.
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Treatment ,Poor Prognosis ,Chronic Lymphocytic Leukemia ,Ofatumumab - Published
- 2015
215. Ofatumumab in poor-prognosis chronic lymphocytic leukemia: A phase IV, non-interventional, observational study from the European research initiative on chronic lymphocytic leukemia
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Moreno, C. Montillo, M. Panayiotidis, P. Dimou, M. Bloor, A. Dupuis, J. Schuh, A. Norin, S. Geisler, C. Hillmen, P. Doubek, M. Trněný, M. Obrtlikova, P. Laurenti, L. Stilgenbauer, S. Smolej, L. Ghia, P. Cymbalista, F. Jaeger, U. Stamatopoulos, K. Stavroyianni, N. Carrington, P. Zouabi, H. Leblond, V. Gomez-Garcia, J.C. Rubio, M. Marasca, R. Musuraca, G. Rigacci, L. Farina, L. Paolini, R. Pospisilova, S. Kimby, E. Bradley, C. Montserrat, E.
- Abstract
We report the largest retrospective, phase IV non-interventional, observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia. Total number of patients was 103; median age was 65 years (range 39-85). Median number of prior lines of therapy was 4 (range 1-13), including, in most cases, rituximab-, fludarabine-and alemtuzumab-based regimens; 13 patients had been allografted. Of 113 adverse events, 28 (29%) were considered to be directly related to ofatumumab. Grade 3-4 toxicities included neutropenia (10%), thrombocytopenia (5%), anemia (3%), pneumonia (17%), and fever (3%). Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy. On an intention-to-treat analysis, the overall response rate was 22% (3 complete response, 1 incomplete complete response). Median progression-free and overall survival times were 5 and 11 months, respectively. This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia. The complete response rate, however, was low. Therefore, treatment with ofatumumab should be moved to earlier phases of the disease. Ideally, this should be done in combination with other agents, as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine. © 2015 Ferrata Storti Foundation.
- Published
- 2015
216. Reproducible Diagnosis of Chronic Lymphocytic Leukemia (CLL) By Flow Cytometry: An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation Project
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Rawstron, Ac, Kreuzer, Ka, Soosapilla, A, Spacek, M, Gambell, P, McIver brown, N, Psarra, K, Arroz, M, Milani, R, de la Serna, J, Cedena, Mt, Jaksic, O, Nomdedeu, Jf, Moreno, C, Rigolin, Gian Matteo, Cuneo, Antonio, Johansen, P, Johnsen, He, Rosenquist, R, Niemann, Cu, Kern, W, Westerman, Da, Trneny, M, Mulligan, Sp, Hillmen, P, Oscier, Dg, Hallek, M, Ghia, P, and Montserrat, E.
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CLL, flow cytometry ,flow cytometry ,CLL ,NO - Published
- 2015
217. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up(aEuro)
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Eichhorst B, Robak T, Montserrat E, Ghia P, Hillmen P, Hallek M, Buske C, and CERVANTES A
- Published
- 2015
218. Acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia: updated phase 2 results
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Byrd, John C., Wierda, William G., Schuh, Anna, Devereux, Stephen, Chaves, Jorge M., Brown, Jennifer R., Hillmen, Peter, Martin, Peter, Awan, Farrukh T., Stephens, Deborah M., Ghia, Paolo, Barrientos, Jacqueline, Pagel, John M., Woyach, Jennifer A., Burke, Kathleen, Covey, Todd, Gulrajani, Michael, Hamdy, Ahmed, Izumi, Raquel, Frigault, Melanie M., Patel, Priti, Rothbaum, Wayne, Wang, Min Hui, O’Brien, Susan, and Furman, Richard R.
- Abstract
Therapeutic targeting of Bruton tyrosine kinase (BTK) has dramatically improved survival outcomes for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Acalabrutinib is an oral, highly selective BTK inhibitor that allows for twice-daily dosing due to its selectivity. In this phase 1b/2 study, 134 patients with relapsed/refractory CLL or SLL (median age, 66 years [range, 42-85 years]; median prior therapies, 2 [range, 1-13]) received acalabrutinib 100 mg twice daily for a median of 41 months (range, 0.2-58 months). Median trough BTK occupancy at steady state was 97%. Most adverse events (AEs) were mild or moderate, and were most commonly diarrhea (52%) and headache (51%). Grade =3 AEs (occurring in =5% of patients) were neutropenia (14%), pneumonia (11%), hypertension (7%), anemia (7%), and diarrhea (5%). Atrial fibrillation and major bleeding AEs (all grades) occurred in 7% and 5% of patients, respectively. Most patients (56%) remain on treatment; the primary reasons for discontinuation were progressive disease (21%) and AEs (11%). The overall response rate, including partial response with lymphocytosis, with acalabrutinib was 94%; responses were similar regardless of genomic features (presence of del(11)(q22.3), del(17)(p13.1), complex karyotype, or immunoglobulin variable region heavy chain mutation status). Median duration of response and progression-free survival (PFS) have not been reached; the estimated 45-month PFS was 62% (95% confidence interval, 51% to 71%). BTK mutation was detected in 6 of 9 patients (67%) at relapse. This updated and expanded study confirms the efficacy, durability of response, and long-term safety of acalabrutinib, justifying its further investigation in previously untreated and treated patients with CLL/SLL. This trial was registered at www.clinicaltrials.gov as #NCT02029443.
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- 2020
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219. Integrative analysis of spontaneous CLL regression highlights genetic and microenvironmental interdependency in CLL
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Kwok, Marwan, Oldreive, Ceri, Rawstron, Andy C., Goel, Anshita, Papatzikas, Grigorios, Jones, Rhiannon E., Drennan, Samantha, Agathanggelou, Angelo, Sharma-Oates, Archana, Evans, Paul, Smith, Edward, Dalal, Surita, Mao, Jingwen, Hollows, Robert, Gordon, Naheema, Hamada, Mayumi, Davies, Nicholas J., Parry, Helen, Beggs, Andrew D., Munir, Talha, Moreton, Paul, Paneesha, Shankara, Pratt, Guy, Taylor, A. Malcolm R., Forconi, Francesco, Baird, Duncan M., Cazier, Jean-Baptiste, Moss, Paul, Hillmen, Peter, and Stankovic, Tatjana
- Abstract
Spontaneous regression is a recognized phenomenon in chronic lymphocytic leukemia (CLL) but its biological basis remains unknown. We undertook a detailed investigation of the biological and clinical features of 20 spontaneous CLL regression cases incorporating phenotypic, functional, transcriptomic, and genomic studies at sequential time points. All spontaneously regressed tumors were IGHV-mutated with no restricted IGHVusage or B-cell receptor (BCR) stereotypy. They exhibited shortened telomeres similar to nonregressing CLL, indicating prior proliferation. They also displayed low Ki-67, CD49d, cell-surface immunoglobulin M (IgM) expression and IgM-signaling response but high CXCR4 expression, indicating low proliferative activity associated with poor migration to proliferation centers, with these features becoming increasingly marked during regression. Spontaneously regressed CLL displayed a transcriptome profile characterized by downregulation of metabolic processes as well as MYCand its downstream targets compared with nonregressing CLL. Moreover, spontaneous regression was associated with reversal of T-cell exhaustion features including reduced programmed cell death 1 expression and increased T-cell proliferation. Interestingly, archetypal CLL genomic aberrations including HIST1H1Band TP53mutations and del(13q14) were found in some spontaneously regressing tumors, but genetic composition remained stable during regression. Conversely, a single case of CLL relapse following spontaneous regression was associated with increased BCR signaling, CLL proliferation, and clonal evolution. These observations indicate that spontaneously regressing CLL appear to undergo a period of proliferation before entering a more quiescent state, and that a complex interaction between genomic alterations and the microenvironment determines disease course. Together, the findings provide novel insight into the biological processes underpinning spontaneous CLL regression, with implications for CLL treatment.
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- 2020
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220. Ibrutinib Plus Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia: The CLARITY Study.
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Hillmen, Peter, Rawstron, Andy C., Brock, Kristian, Muñoz-Vicente, Samuel, Yates, Francesca J., Bishop, Rebecca, Boucher, Rebecca, MacDonald, Donald, Fegan, Christopher, McCaig, Alison, Schuh, Anna, Pettitt, Andrew, Gribben, John G., Patten, Piers E.M., Devereux, Stephen, Bloor, Adrian, Fox, Christopher P., Forconi, Francesco, and Munir, Talha
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- 2019
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221. Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival: Post-Treatment Follow-Up of the MURANO Phase III Study.
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Kater, Arnon P, Seymour, John F, Hillmen, Peter, Eichhorst, Barbara, Langerak, Anton W, Owen, Carolyn, Verdugo, Maria, Wu, Jenny, Punnoose, Elizabeth A, Jiang, Yanwen, Wang, Jue, Boyer, Michelle, Humphrey, Kathryn, Mobasher, Mehrdad, and Kipps, Thomas J
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- 2019
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222. Plain language summary: treatment of paroxysmal nocturnal hemoglobinuria with pegcetacoplan for 48 weeks (PEGASUS study)
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de Latour, Régis Peffault, Szer, Jeff, Weitz, Ilene, Röth, Alexander, Höchsmann, Britta, Panse, Jens, Usuki, Kensuke, Griffin, Morag, Kiladjian, Jean-Jacques, Castro, Carlos de, Nishimori, Hisakazu, Al-Adhami, Mohammed, Deschatelets, Pascal, Francois, Cedric, Risitano, Antonio, and Hillmen, Peter
- Abstract
What is this summary about?Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, serious blood disease, characterized by uncontrolled activation of the complement system that causes hemolysis (destruction of red blood cells). The complement component 5 (C5) inhibitor eculizumab was the first approved treatment for PNH. The PEGASUS trial compared eculizumab with pegcetacoplan, a new complement component 3 (C3) inhibitor. Because C3 is activated before C5, blocking C3 would also block C5; thus, a C3 inhibitor might prevent hemolysis more completely than a C5 inhibitor in patients with PNH. During the first 16 weeks of PEGASUS, patients received either pegcetacoplan or eculizumab; results were published separately. This summary describes results of the following 32 weeks of PEGASUS, during which all patients received pegcetacoplan to evaluate if pegcetacoplan continued to be effective and safe for up to 48 weeks.What were the results?Pegcetacoplan continued to be effective in participants who received it throughout the study and improved symptoms in participants who switched from eculizumab. The most common adverse events (side effects) were skin irritation at the injection site, hemolysis, nasopharyngitis (runny nose and sore throat), and diarrhea. Adverse events were serious and related to pegcetacoplan in 4 of 77 (5%) patients; all patients recovered from these events.What do the results mean?Pegcetacoplan improved symptoms and was well tolerated for up to 48 weeks by most patients in PEGASUS, suggesting that adult patients with PNH may benefit from long-term pegcetacoplan treatment.
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- 2024
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223. Systematic review of purine analog treatment for chronic lymphocytic leukemia: lessons for future trials
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Bauduer, M., Gribben, J., Herrmann, R., Thiel, E., Rai, K., Larson, R., Ferrara, F., Barnard, J., Pearce, H., Taylor, C., Brillant, B., Steurer, M., Weingart, O., Flinn, W., Funkhouser, A., Nallman, M., Sun, Z., Jakšić, Branimir, Suciou, S., Chevret, S., Dighiero, G., Leporrier, M., Frankel, S.R., Sirard, C., Hillmen, P., Trehu, B., Felder, M., Busch, R., Eichorst, B., Mallek, M., Stilgenbauer, S., Pangalis, G., Bezares, R., van Oers, M.H.J., van Putten, W., Gobbi, M., Spriano, M., Mabed, M., Catovsky, D., Richards, S., Wade, R., Abdelhamid, T., Dearden, C., Knauf, W., Blonski, J., Jamroziak, K., Robak, T., Mauro, F., Hiddeman, W., Johnson, S.A., Longthorne, G., Rummel, M.J., Juliusson, G., Pulluqui, P., Zinzani, P.L., Pozzato, G., Reynolds, C, Furman, R.R., Durrant, J., Elphinstone, P., Evans, V., Gettins, .L, Hicks, C., James, S., Clarke, M., MacKinnon, L., McHugh, T.M., Morris, P., Read, S., Gregory, C., Pozzato, Gabriele, Bauduer M, Gribben J, Herrmann R, Thiel E, Rai K, Larson R, Ferrara F, Barnard J, Pearce H, Taylor C, Brillant C, Steurer M, Weingart O, Flinn IW, Funkhouser A, Tallman M, Sun Z, Jaksic B, Suciu S, Chevret S, Dighiero G, Leporrier M, Frankel SR, Sirard C, Hillmen P, Trehu B, Felder M, Busch R, Eichhorst B, Hallek M, Stilgenbauer S, Pangalis G, Bezares R, van Oers MH, van Putten W, Gobbi M, Spriano M, Mabed M, Catovsky D, Richards S, Wade R, Abdelhamid T, Dearden C, Knauf W, Blonski J, Jamroziak K, Robak T, Mauro F, Hiddeman W, Johnson SA, Longthorne G, Juliusson G, Pulluqi P, Zinzani PL, Pozzato G, Oncology US, Reynolds C, Furman RR, Durrant J, Elphinstone P, Evans V, Gettins L, Hicks C, James S, Clarke M, MacKinnon L, McHugh TM, Morris P, Read S, and Gregory C. CLL Trialists’ Collaborative Group
- Subjects
Oncology ,medicine.medical_specialty ,review ,Purine analogue ,chronic lymphocytic leukemia ,fludarabine ,clinical trial ,Pharmacology ,Disease-Free Survival ,combination therapy ,purine analog ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,Progression-free survival ,Cladribine ,Antineoplastic Agents, Alkylating ,Chlorambucil ,business.industry ,Hematology ,Odds ratio ,Leukemia, Lymphocytic, Chronic, B-Cell ,Fludarabine ,Clinical trial ,Treatment Outcome ,CLL ,cyclophosphamide ,Purines ,Original Articles and Brief Reports ,business ,Untreated Chronic Lymphocytic Leukemia ,medicine.drug - Abstract
Background. A systematic review of purine analogs revealed heterogeneity between trials in treatment effects on response and progression free survival, but not survival, perhaps partly due to variations in analysis methods. In addition, combination treatments required evaluation. Design and Methods. Individual patient data were sought for all randomized trials in untreated chronic lymphocytic leukemia which involved a purine analog, but not including antibody therapies. Results. Sixteen trials were found, addressing seven comparisons. Eight trials, with 2753 patients, showed that single agent purine analog improved progression free survival (Odds ratio = 0.71; 95% confidence interval =0.63-0.79). Heterogeneity remained substantial. Three trials, with 1403 patients, showed that progression free survival was further improved by the addition of cyclophosphamide (Odds ratio = 0.54; 0.47-0.62). Fewer data were available on the addition of other drugs to purine analog, and none showed clear benefit. Two trials, with 544 patients, suggested cladribine improved progression free survival compared to fludarabine (Odds ratio = 0.77; 0.63-0.95). No differences were seen in overall survival for any comparisons. Conclusions. Purine analogs, particularly combined with cyclophosphamide, significantly improve progression free survival but not survival. Some groups, such as the elderly, may not see the same benefits and maximising doses may be important for all treatments, including chlorambucil. Longer follow-up, consistent definitions and detailed reporting of trials should be encouraged.
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- 2012
224. Paroxysmal Nocturnal Haemoglobinuria (PNH) Arising from Non-Canonical Mutations
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Pike, Alexandra, Richards, Stephen John, McKinley, Claire E, Arnold, Louise M, Varghese, Abraham Mullasseril, Munir, Talha, Muus, Petra, Hillmen, Peter, Griffin, Morag, Kelly, Richard J, and Newton, Darren
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Introduction
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- 2023
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225. Using Peripheral Blood (PB) Measurable Residual Disease (MRD) Levels to Predict <0.01% Bone Marrow Disease (BM uMRD4): Identification of Effective PB Targets for CLL Treatment Cessation in the Ibrutinib+Venetoclax Arm of the FLAIR Trial
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Rawstron, Andy, Webster, Nichola, Dalal, Surita, de Tute, Ruth M, Bell, Sue, Cairns, David Allan, Girvan, Sean, Greatorex, Natasha, Hockaday, Anna, Jackson, Sharon, Phillips, David, Stones, David, Allsup, David, Bloor, Adrian John Clifton, Sarma, Anita, Varghese, Abraham Mullasseril, Munir, Talha, and Hillmen, Peter
- Abstract
Time-limited treatments for CLL are under investigation but the optimal target for treatment cessation is not fully clear. Bone marrow (BM) measurable residual disease (MRD) is usually the most sensitive measure but would be too invasive to guide treatment in a routine setting. The iwCLL threshold of BM uMRD4 (<0.01%) has been demonstrated to be a powerful indicator of improved outcomes across multiple different trials and the aim of this analysis is to determine the feasibility of using PB MRD analysis to identify patients who have attained BM uMRD4.
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- 2023
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226. Telomere Length and DNA Methylation Epitype Both Provide Independent Prognostic Information in CLL Patients; Data from the UK CLL4, Arctic and Admire Clinical Trials
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Carr, Louise J., Norris, Kevin, Parker, Helen, Nilsson-Takeuchi, Anna, Bryant, Dean J., Amarasinghe, Harindra Eranthi, Kadalayil, Latha, Else, Monica, Wojdacz, Tomasz, Pettitt, Andrew, Hillmen, Peter, Schuh, Anna, Walewska, Renata, Baird, Duncan M., Oscier, David Graham, Oakes, Christopher C., Gibson, Jane, Pepper, Chris, and Strefford, Jonathan C.
- Abstract
The presence of TP53 aberrations ( TP53ab) and/or unmutated IGHV genes (U-CLL) helps select initial treatment for CLL patients (Hallek 2018 & Walewska 2022). However, many other biomarkers identified in recent years have failed to impact clinical decisions due to their coexistence with poor-risk indicators and uncertainty in their predictive abilities, often without suitable validation in long-term Phase II/III trials with comprehensive molecular analysis.
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- 2023
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227. Molecular Analysis at Relapse of Patients Treated on the Ibrutinib and Rituximab Arm of the National Multi-Centre Phase III FLAIR Study in Previously Untreated CLL Patients
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Sarma, Anita, Evans, Charlotte, Dalal, Surita, Webster, Nichola, Rawstron, Andy, Shingles, Jane, Newton, Darren, Cairns, David Allan, Glover, Paul, Grand, Thomas, Warren, Helen, Bell, Sue, Girvan, Sean, Greatorex, Natasha, Hockaday, Anna, Jackson, Sharon, Phillips, David, Stones, David, Allsup, David, Bloor, Adrian John Clifton, Varghese, Abraham Mullasseril, Munir, Talha, and Hillmen, Peter
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Background
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- 2023
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228. Sars-Cov-2 Antibody and T-Cell Responses in Patients with Paroxysmal Nocturnal Hemoglobinuria and Aplastic Anemia after Four COVID-19 Vaccinations
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Pike, Alexandra, Fox, Natalie, McKinley, Claire E, Arnold, Louise M, Harland, Mark, Clarke, Deborah, Forrest, Briony, Houghton, Nicola, Youngs, Nora, Charlton, Emily, Zhakata, Tapiwa, Barnfield, Catherine, Harvey, Ruth, Wu, Mary, Kavanagh, Caitlin, Richards, Stephen John, Payne, Daniel, Varghese, Abraham Mullasseril, Nagumantry, Sateesh, Munir, Talha, Muus, Petra, Griffin, Morag, Newton, Darren, Hillmen, Peter, and Kelly, Richard J
- Abstract
Introduction: There is limited data on SARS-CoV-2 vaccination responses in the rare hematological disorders paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia (AA). These patients were expected to have more severe COVID-19 infection and reduced vaccination responses due to their underlying disease and immunosuppressive treatment. We previously reported limited anti-spike IgA/G/M responses after first COVID-19 vaccination which improved following second vaccination (Pike et al, Lancet Haematology 2022). Here we report spike-specific IgG, in vitroviral neutralization and T-cell responses in 244 patients with PNH and/or AA and in 49 healthy volunteers, following the first four vaccinations.
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- 2023
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229. Assessment of human antihuman antibodies to eculizumab after long-term treatment in patients with paroxysmal nocturnal hemoglobinuria
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Hillmen, P., Muus, P., Szer, J., Hill, A., Hochsmann, B., Kulasekararaj, A., Risitano, A.M., Neste, E. van den, Liljeholm, M., Ebrahim, K.S., Bedrosian, C.L., Gao, X., Ames, D., Socie, G., Hillmen, P., Muus, P., Szer, J., Hill, A., Hochsmann, B., Kulasekararaj, A., Risitano, A.M., Neste, E. van den, Liljeholm, M., Ebrahim, K.S., Bedrosian, C.L., Gao, X., Ames, D., and Socie, G.
- Abstract
Item does not contain fulltext
- Published
- 2016
230. The European Hematology Association Roadmap for European Hematology Research: a consensus document.
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EHA Roadmap for European Hematology, Research, Engert, A., Balduini, C., Brand, A., Coiffier, B., Cordonnier, C., Döhner, H., de Wit TD., Eichinger, S., Fibbe, W., Green, T., de Haas, F., Iolascon, A., Jaffredo, T., Rodeghiero, F., Salles, G., Schuringa, JJ., André, M., Andre-Schmutz, I., Bacigalupo, A., Bochud, PY., Boer, Md., Bonini, C., Camaschella, C., Cant, A., Cappellini, MD., Cazzola, M., Celso, CL., Dimopoulos, M., Douay, L., Dzierzak, E., Einsele, H., Ferreri, A., De Franceschi, L., Gaulard, P., Gottgens, B., Greinacher, A., Gresele, P., Gribben, J., de Haan, G., Hansen, JB., Hochhaus, A., Kadir, R., Kaveri, S., Kouskoff, V., Kühne, T., Kyrle, P., Ljungman, P., Maschmeyer, G., Méndez-Ferrer£££Simón£££ S., Milsom, M., Mummery, C., Ossenkoppele, G., Pecci, A., Peyvandi, F., Philipsen, S., Reitsma, P., Ribera, JM., Risitano, A., Rivella, S., Ruf, W., Schroeder, T., Scully, M., Socie, G., Staal, F., Stanworth, S., Stauder, R., Stilgenbauer, S., Tamary, H., Theilgaard-Mönch, K., Thein, SL., Tilly, H., Trneny, M., Vainchenker, W., Vannucchi, AM., Viscoli, C., Vrielink, H., Zaaijer, H., Zanella, A., Zolla, L., Zwaginga, JJ., Martinez, PA., van den Akker, E., Allard, S., Anagnou, N., Andolfo, I., Andrau, JC., Angelucci, E., Anstee, D., Aurer, I., Avet-Loiseau, H., Aydinok, Y., Bakchoul, T., Balduini, A., Barcellini, W., Baruch, D., Baruchel, A., Bayry, J., Bento, C., van den Berg, A., Bernardi, R., Bianchi, P., Bigas, A., Biondi, A., Bohonek, M., Bonnet, D., Borchmann, P., Borregaard, N., Brækkan, S., van den Brink, M., Brodin, E., Bullinger, L., Buske, C., Butzeck, B., Cammenga, J., Campo, E., Carbone, A., Cervantes, F., Cesaro, S., Charbord, P., Claas, F., Cohen, H., Conard, J., Coppo, P., Corrons, JL., Costa, Ld., Davi, F., Delwel, R., Dianzani, I., Domanović, D., Donnelly, P., Drnov?ek£££Tadeja Dovč£££ TD., Dreyling, M., Du, MQ., Dufour, C., Durand, C., Efremov, D., Eleftheriou, A., Elion, J., Emonts, M., Engelhardt, M., Ezine, S., Falkenburg, F., Favier, R., Federico, M., Fenaux, P., Fitzgibbon, J., Flygare, J., Foà, R., Forrester, L., Galacteros, F., Garagiola, I., Gardiner, C., Garraud, O., van Geet, C., Geiger, H., Geissler, J., Germing, U., Ghevaert, C., Girelli, D., Godeau, B., Gökbuget, N., Goldschmidt, H., Goodeve, A., Graf, T., Graziadei, G., Griesshammer, M., Gruel, Y., Guilhot, F., von Gunten, S., Gyssens, I., Halter, J., Harrison, C., Harteveld, C., Hellström-Lindberg, E., Hermine, O., Higgs, D., Hillmen, P., Hirsch, H., Hoskin, P., Huls, G., Inati, A., Johnson, P., Kattamis, A., Kiefel, V., Kleanthous, M., Klump, H., Krause, D., Hovinga, JK., Lacaud, G., Lacroix-Desmazes, S., Landman-Parker, J., LeGouill, S., Lenz, G., von Lilienfeld-Toal, M., von Lindern, M., Lopez-Guillermo, A., Lopriore, E., Lozano, M., MacIntyre, E., Makris, M., Mannhalter, C., Martens, J., Mathas, S., Matzdorff, A., Medvinsky, A., Menendez, P., Migliaccio, AR., Miharada, K., Mikulska, M., Minard, V., Montalbán, C., de Montalembert, M., Montserrat, E., Morange, PE., Mountford, J., Muckenthaler, M., Müller-Tidow, C., Mumford, A., Nadel, B., Navarro, JT., Nemer, We., Noizat-Pirenne, F., O'Mahony, B., Oldenburg, J., Olsson, M., Oostendorp, R., Palumbo, A., Passamonti, F., Patient, R., Peffault, R., Pflumio, F., Pierelli, L., Piga, A., Pollard, D., Raaijmakers, M., Radford, J., Rambach, R., Rao, AK., Raslova, H., Rebulla, P., Rees, D., Ribrag, V., Rijneveld, A., Rinalducci, S., Robak, T., Roberts, I., Rodrigues, C., Rosendaal, F., Rosenwald, A., Rule, S., Russo, R., Saglio, G., Sanchez, M., Scharf, RE., Schlenke, P., Semple, J., Sierra, J., So-Osman, C., Soria, JM., Stamatopoulos, K., Stegmayr, B., Stunnenberg, H., Swinkels, D., Barata£££João Pedro Taborda£££ JP., Taghon, T., Taher, A., Terpos, E., Thachil, J., Tissot, JD., Touw, I., Toye, A., Trappe, R., Traverse-Glehen, A., Unal, S., Vaulont, S., Viprakasit, V., Vitolo, U., van Wijk, R., Wójtowicz, A., Zeerleder, S., Zieger, B., de Wit, T.D., Schuringa, J.J., EHA Roadmap for European Hematology, Research, Engert, A., Balduini, C., Brand, A., Coiffier, B., Cordonnier, C., Döhner, H., de Wit TD., Eichinger, S., Fibbe, W., Green, T., de Haas, F., Iolascon, A., Jaffredo, T., Rodeghiero, F., Salles, G., Schuringa, JJ., André, M., Andre-Schmutz, I., Bacigalupo, A., Bochud, PY., Boer, Md., Bonini, C., Camaschella, C., Cant, A., Cappellini, MD., Cazzola, M., Celso, CL., Dimopoulos, M., Douay, L., Dzierzak, E., Einsele, H., Ferreri, A., De Franceschi, L., Gaulard, P., Gottgens, B., Greinacher, A., Gresele, P., Gribben, J., de Haan, G., Hansen, JB., Hochhaus, A., Kadir, R., Kaveri, S., Kouskoff, V., Kühne, T., Kyrle, P., Ljungman, P., Maschmeyer, G., Méndez-Ferrer£££Simón£££ S., Milsom, M., Mummery, C., Ossenkoppele, G., Pecci, A., Peyvandi, F., Philipsen, S., Reitsma, P., Ribera, JM., Risitano, A., Rivella, S., Ruf, W., Schroeder, T., Scully, M., Socie, G., Staal, F., Stanworth, S., Stauder, R., Stilgenbauer, S., Tamary, H., Theilgaard-Mönch, K., Thein, SL., Tilly, H., Trneny, M., Vainchenker, W., Vannucchi, AM., Viscoli, C., Vrielink, H., Zaaijer, H., Zanella, A., Zolla, L., Zwaginga, JJ., Martinez, PA., van den Akker, E., Allard, S., Anagnou, N., Andolfo, I., Andrau, JC., Angelucci, E., Anstee, D., Aurer, I., Avet-Loiseau, H., Aydinok, Y., Bakchoul, T., Balduini, A., Barcellini, W., Baruch, D., Baruchel, A., Bayry, J., Bento, C., van den Berg, A., Bernardi, R., Bianchi, P., Bigas, A., Biondi, A., Bohonek, M., Bonnet, D., Borchmann, P., Borregaard, N., Brækkan, S., van den Brink, M., Brodin, E., Bullinger, L., Buske, C., Butzeck, B., Cammenga, J., Campo, E., Carbone, A., Cervantes, F., Cesaro, S., Charbord, P., Claas, F., Cohen, H., Conard, J., Coppo, P., Corrons, JL., Costa, Ld., Davi, F., Delwel, R., Dianzani, I., Domanović, D., Donnelly, P., Drnov?ek£££Tadeja Dovč£££ TD., Dreyling, M., Du, MQ., Dufour, C., Durand, C., Efremov, D., Eleftheriou, A., Elion, J., Emonts, M., Engelhardt, M., Ezine, S., Falkenburg, F., Favier, R., Federico, M., Fenaux, P., Fitzgibbon, J., Flygare, J., Foà, R., Forrester, L., Galacteros, F., Garagiola, I., Gardiner, C., Garraud, O., van Geet, C., Geiger, H., Geissler, J., Germing, U., Ghevaert, C., Girelli, D., Godeau, B., Gökbuget, N., Goldschmidt, H., Goodeve, A., Graf, T., Graziadei, G., Griesshammer, M., Gruel, Y., Guilhot, F., von Gunten, S., Gyssens, I., Halter, J., Harrison, C., Harteveld, C., Hellström-Lindberg, E., Hermine, O., Higgs, D., Hillmen, P., Hirsch, H., Hoskin, P., Huls, G., Inati, A., Johnson, P., Kattamis, A., Kiefel, V., Kleanthous, M., Klump, H., Krause, D., Hovinga, JK., Lacaud, G., Lacroix-Desmazes, S., Landman-Parker, J., LeGouill, S., Lenz, G., von Lilienfeld-Toal, M., von Lindern, M., Lopez-Guillermo, A., Lopriore, E., Lozano, M., MacIntyre, E., Makris, M., Mannhalter, C., Martens, J., Mathas, S., Matzdorff, A., Medvinsky, A., Menendez, P., Migliaccio, AR., Miharada, K., Mikulska, M., Minard, V., Montalbán, C., de Montalembert, M., Montserrat, E., Morange, PE., Mountford, J., Muckenthaler, M., Müller-Tidow, C., Mumford, A., Nadel, B., Navarro, JT., Nemer, We., Noizat-Pirenne, F., O'Mahony, B., Oldenburg, J., Olsson, M., Oostendorp, R., Palumbo, A., Passamonti, F., Patient, R., Peffault, R., Pflumio, F., Pierelli, L., Piga, A., Pollard, D., Raaijmakers, M., Radford, J., Rambach, R., Rao, AK., Raslova, H., Rebulla, P., Rees, D., Ribrag, V., Rijneveld, A., Rinalducci, S., Robak, T., Roberts, I., Rodrigues, C., Rosendaal, F., Rosenwald, A., Rule, S., Russo, R., Saglio, G., Sanchez, M., Scharf, RE., Schlenke, P., Semple, J., Sierra, J., So-Osman, C., Soria, JM., Stamatopoulos, K., Stegmayr, B., Stunnenberg, H., Swinkels, D., Barata£££João Pedro Taborda£££ JP., Taghon, T., Taher, A., Terpos, E., Thachil, J., Tissot, JD., Touw, I., Toye, A., Trappe, R., Traverse-Glehen, A., Unal, S., Vaulont, S., Viprakasit, V., Vitolo, U., van Wijk, R., Wójtowicz, A., Zeerleder, S., Zieger, B., de Wit, T.D., and Schuringa, J.J.
- Abstract
The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at euro23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap.The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders.The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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- 2016
231. The european hematology association roadmap for european hematology research: A consensus document
- Author
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Engert, A, Balduini, C, Brand, A, Coiffier, B, Cordonnier, C, Döhner, H, De Wit, T, Eichinger, S, Fibbe, W, Green, T, De Haas, F, Iolascon, A, Jaffredo, T, Rodeghiero, F, Sall Es, G, Schuringa, J, André, M, Andre Schmutz, I, Bacigalupo, A, Bochud, P, Den Boer, M, Bonini, C, Camaschella, C, Cant, A, Cappellini, M, Cazzola, M, Celso, C, Dimopoulos, M, Douay, L, Dzierzak, E, Einsele, H, Ferreri, A, De Franceschi, L, Gaulard, P, Gottgens, B, Greinacher, A, Gresele, P, Gribben, J, De Haan, G, Hansen, J, Hochhaus, A, Kadir, R, Kaveri, S, Kouskoff, V, Kühne, T, Kyrle, P, Ljungman, P, Maschmeyer, G, Méndez Ferrer, S, Milsom, M, Mummery, C, Ossenkoppele, G, Pecci, A, Peyvandi, F, Philipsen, S, Reitsma, P, Ribera, J, Risitano, A, Rivella, S, Ruf, W, Schroeder, T, Scully, M, Socie, G, Staal, F, Stanworth, S, Stauder, R, Stilgenbauer, S, Tamary, H, Theilgaard Mönch, K, Thein, S, Tilly, H, Trneny, M, Vainchenker, W, Vannucchi, A, Viscoli, C, Vrielink, H, Zaaijer, H, Zanella, A, Zolla, L, Zwaginga, J, Martinez, P, Van Den Akker, E, Allard, S, Anagnou, N, Andolfo, I, Andrau, J, Angelucci, E, Anstee, D, Aurer, I, Avet Loiseau, H, Aydinok, Y, Bakchoul, T, Balduini, A, Barcellini, W, Baruch, D, Baruchel, A, Bayry, J, Bento, C, Van Den Berg, A, Bernardi, R, Bianchi, P, Bigas, A, Biondi, A, Bohonek, M, Bonnet, D, Borchmann, P, Borregaard, N, Brækkan, S, Van Den Brink, M, Brodin, E, Bullinger, L, Buske, C, Butzeck, B, Cammenga, J, Campo, E, Carbone, A, Cervantes, F, Cesaro, S, Charbord, P, Claas, F, Cohen, H, Conard, J, Coppo, P, Vives Corron, J, Da Costa, L, Davi, F, Delwel, R, Dianzani, I, Domanović, D, Donnelly, P, Drnovšek, T, Dreyling, M, Du, M, Dufour, C, Durand, C, Efremov, D, Eleftheriou, A, Elion, J, Emonts, M, Engelhardt, M, Ezine, S, Falkenburg, F, Favier, R, Federico, M, Fenaux, P, Fitzgibbon, J, Flygare, J, Foà, R, Forrester, L, Galacteros, F, Garagiola, I, Gardiner, C, Garraud, O, Van Geet, C, Geiger, H, Geissler, J, Germing, U, Ghevaert, C, Girelli, D, Godeau, B, Gökbuget, N, Goldschmidt, H, Goodeve, A, Graf, T, Graziadei, G, Griesshammer, M, Gruel, Y, Guilhot, F, Von Gunten, S, Gyssens, I, Halter, J, Harrison, C, Harteveld, C, Hellström Lindberg, E, Hermine, O, Higgs, D, Hillmen, P, Hirsch, H, Hoskin, P, Huls, G, Inati, A, Johnson, P, Kattamis, A, Kiefel, V, Kleanthous, M, Klump, H, Krause, D, Hovinga, J, Lacaud, G, Lacroix Desmazes, S, Landman Parker, J, Legouill, S, Lenz, G, Von Lilienfeld Toal, M, Von Lindern, M, Lopez Guillermo, A, Lopriore, E, Lozano, M, Macintyre, E, Makris, M, Mannhalter, C, Martens, J, Mathas, S, Matzdorff, A, Medvinsky, A, Menendez, P, Migliaccio, A, Miharada, K, Mikulska, M, Minard, V, Montalbán, C, De Montalembert, M, Montserrat, E, Morange, P, Mountford, J, Muckenthaler, M, Müller Tidow, C, Mumford, A, Nadel, B, Navarro, J, El Nemer, W, Noizat Pirenne, F, O’Mahony, B, Oldenburg, J, Olsson, M, Oostendorp, R, Palumbo, A, Passamonti, F, Patient, R, De Latour, R, Pflumio, F, Pierelli, L, Piga, A, Pollard, D, Raaijmakers, M, Radford, J, Rambach, R, Koneti Rao, A, Raslova, H, Rebulla, P, Rees, D, Ribrag, V, Rijneveld, A, Rinalducci, S, Robak, T, Roberts, I, Rodrigues, C, Rosendaal, F, Rosenwald, A, Rule, S, Russo, R, Saglio, G, Sanchez, M, Scharf, R, Schlenke, P, Semple, J, Sierra, J, So Osman, C, Soria, J, Stamatopoulos, K, Stegmayr, B, Stunnenberg, H, Swinkels, D, Barata, J, Taghon, T, Taher, A, Terpos, E, Thachil, J, Tissot, J, Touw, I, Toye, A, Trappe, R, Traverse Glehen, A, Unal, S, Vaulont, S, Viprakasit, V, Vitolo, U, Van Wijk, R, Wójtowicz, A, Zeerleder, S, Zieger, B, Zieger, B., ZANELLA, ALBERTO, BIONDI, ANDREA, Engert, A, Balduini, C, Brand, A, Coiffier, B, Cordonnier, C, Döhner, H, De Wit, T, Eichinger, S, Fibbe, W, Green, T, De Haas, F, Iolascon, A, Jaffredo, T, Rodeghiero, F, Sall Es, G, Schuringa, J, André, M, Andre Schmutz, I, Bacigalupo, A, Bochud, P, Den Boer, M, Bonini, C, Camaschella, C, Cant, A, Cappellini, M, Cazzola, M, Celso, C, Dimopoulos, M, Douay, L, Dzierzak, E, Einsele, H, Ferreri, A, De Franceschi, L, Gaulard, P, Gottgens, B, Greinacher, A, Gresele, P, Gribben, J, De Haan, G, Hansen, J, Hochhaus, A, Kadir, R, Kaveri, S, Kouskoff, V, Kühne, T, Kyrle, P, Ljungman, P, Maschmeyer, G, Méndez Ferrer, S, Milsom, M, Mummery, C, Ossenkoppele, G, Pecci, A, Peyvandi, F, Philipsen, S, Reitsma, P, Ribera, J, Risitano, A, Rivella, S, Ruf, W, Schroeder, T, Scully, M, Socie, G, Staal, F, Stanworth, S, Stauder, R, Stilgenbauer, S, Tamary, H, Theilgaard Mönch, K, Thein, S, Tilly, H, Trneny, M, Vainchenker, W, Vannucchi, A, Viscoli, C, Vrielink, H, Zaaijer, H, Zanella, A, Zolla, L, Zwaginga, J, Martinez, P, Van Den Akker, E, Allard, S, Anagnou, N, Andolfo, I, Andrau, J, Angelucci, E, Anstee, D, Aurer, I, Avet Loiseau, H, Aydinok, Y, Bakchoul, T, Balduini, A, Barcellini, W, Baruch, D, Baruchel, A, Bayry, J, Bento, C, Van Den Berg, A, Bernardi, R, Bianchi, P, Bigas, A, Biondi, A, Bohonek, M, Bonnet, D, Borchmann, P, Borregaard, N, Brækkan, S, Van Den Brink, M, Brodin, E, Bullinger, L, Buske, C, Butzeck, B, Cammenga, J, Campo, E, Carbone, A, Cervantes, F, Cesaro, S, Charbord, P, Claas, F, Cohen, H, Conard, J, Coppo, P, Vives Corron, J, Da Costa, L, Davi, F, Delwel, R, Dianzani, I, Domanović, D, Donnelly, P, Drnovšek, T, Dreyling, M, Du, M, Dufour, C, Durand, C, Efremov, D, Eleftheriou, A, Elion, J, Emonts, M, Engelhardt, M, Ezine, S, Falkenburg, F, Favier, R, Federico, M, Fenaux, P, Fitzgibbon, J, Flygare, J, Foà, R, Forrester, L, Galacteros, F, Garagiola, I, Gardiner, C, Garraud, O, Van Geet, C, Geiger, H, Geissler, J, Germing, U, Ghevaert, C, Girelli, D, Godeau, B, Gökbuget, N, Goldschmidt, H, Goodeve, A, Graf, T, Graziadei, G, Griesshammer, M, Gruel, Y, Guilhot, F, Von Gunten, S, Gyssens, I, Halter, J, Harrison, C, Harteveld, C, Hellström Lindberg, E, Hermine, O, Higgs, D, Hillmen, P, Hirsch, H, Hoskin, P, Huls, G, Inati, A, Johnson, P, Kattamis, A, Kiefel, V, Kleanthous, M, Klump, H, Krause, D, Hovinga, J, Lacaud, G, Lacroix Desmazes, S, Landman Parker, J, Legouill, S, Lenz, G, Von Lilienfeld Toal, M, Von Lindern, M, Lopez Guillermo, A, Lopriore, E, Lozano, M, Macintyre, E, Makris, M, Mannhalter, C, Martens, J, Mathas, S, Matzdorff, A, Medvinsky, A, Menendez, P, Migliaccio, A, Miharada, K, Mikulska, M, Minard, V, Montalbán, C, De Montalembert, M, Montserrat, E, Morange, P, Mountford, J, Muckenthaler, M, Müller Tidow, C, Mumford, A, Nadel, B, Navarro, J, El Nemer, W, Noizat Pirenne, F, O’Mahony, B, Oldenburg, J, Olsson, M, Oostendorp, R, Palumbo, A, Passamonti, F, Patient, R, De Latour, R, Pflumio, F, Pierelli, L, Piga, A, Pollard, D, Raaijmakers, M, Radford, J, Rambach, R, Koneti Rao, A, Raslova, H, Rebulla, P, Rees, D, Ribrag, V, Rijneveld, A, Rinalducci, S, Robak, T, Roberts, I, Rodrigues, C, Rosendaal, F, Rosenwald, A, Rule, S, Russo, R, Saglio, G, Sanchez, M, Scharf, R, Schlenke, P, Semple, J, Sierra, J, So Osman, C, Soria, J, Stamatopoulos, K, Stegmayr, B, Stunnenberg, H, Swinkels, D, Barata, J, Taghon, T, Taher, A, Terpos, E, Thachil, J, Tissot, J, Touw, I, Toye, A, Trappe, R, Traverse Glehen, A, Unal, S, Vaulont, S, Viprakasit, V, Vitolo, U, Van Wijk, R, Wójtowicz, A, Zeerleder, S, Zieger, B, Zieger, B., ZANELLA, ALBERTO, and BIONDI, ANDREA
- Abstract
The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at ∈ European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better fu treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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- 2016
232. Lenalidomide treatment and prognostic markers in relapsed or refractory chronic lymphocytic leukemia: data from the prospective, multicenter phase-II CLL-009 trial
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Buehler, A., Wendtner, C-M, Kipps, T. J., Rassenti, L., Fraser, G. A. M., Michallet, A-S, Hillmen, P., Duerig, J., Gregory, S. A., Kalaycio, M., Aurran-Schleinitz, T., Trentin, L., Gribben, J. G., Chanan-Khan, A., Purse, B., Zhang, J., De Bedout, S., Mei, J., Hallek, M., Stilgenbauer, S., Buehler, A., Wendtner, C-M, Kipps, T. J., Rassenti, L., Fraser, G. A. M., Michallet, A-S, Hillmen, P., Duerig, J., Gregory, S. A., Kalaycio, M., Aurran-Schleinitz, T., Trentin, L., Gribben, J. G., Chanan-Khan, A., Purse, B., Zhang, J., De Bedout, S., Mei, J., Hallek, M., and Stilgenbauer, S.
- Abstract
Efficacy of lenalidomide was investigated in 103 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) treated on the prospective, multicenter randomized phase-II CLL-009 trial. Interphase cytogenetic and mutational analyses identified TP53 mutations, unmutated IGHV, or del(17p) in 36/96 (37.5%), 68/88 (77.3%) or 22/92 (23.9%) patients. The overall response rate (ORR) was 40.4% (42/104). ORRs were similar irrespective of TP53 mutation (36.1% (13/36) vs 43.3% (26/60) for patients with vs without mutation) or IGHV mutation status (45.0% (9/20) vs 39.1% (27/68)); however, patients with del(17p) had lower ORRs than those without del(17p) (21.7% (5/22) vs 47.1% (33/70); P = 0.049). No significant differences in progression-free survival and overall survival (OS) were observed when comparing subgroups defined by the presence or absence of high-risk genetic characteristics. In multivariate analyses, only multiple prior therapies (>= 3 lines) significantly impacted outcomes (median OS: 21.2 months vs not reached; P = 0.019). This analysis indicates that lenalidomide is active in patients with relapsed/refractory CLL with unfavorable genetic profiles, including TP53 inactivation or unmutated IGHV.
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- 2016
233. A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study
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Rawstron, A. C., Fazi, C., Agathangelidis, A., Villamor, N., Letestu, R., Nomdedeu, J., Palacio, C., Stehlikova, O., Kreuzer, K-A, Liptrot, S., O'Brien, D., de Tute, R. M., Marinov, I., Hauwel, M., Spacek, M., Dobber, J., Kater, A. P., Gambell, P., Soosapilla, A., Lozanski, G., Brachtl, G., Lin, K., Boysen, J., Hanson, C., Jorgensen, J. L., Stetler-Stevenson, M., Yuan, C., Broome, H. E., Rassenti, L., Craig, F., Delgado, J., Moreno, C., Bosch, F., Egle, A., Doubek, M., Pospisilova, S., Mulligan, S., Westerman, D., Sanders, C. M., Emerson, R., Robins, H. S., Kirsch, I., Shanafelt, T., Pettitt, A., Kipps, T. J., Wierda, W. G., Cymbalista, F., Hallek, M., Hillmen, P., Montserrat, E., Ghia, P., Rawstron, A. C., Fazi, C., Agathangelidis, A., Villamor, N., Letestu, R., Nomdedeu, J., Palacio, C., Stehlikova, O., Kreuzer, K-A, Liptrot, S., O'Brien, D., de Tute, R. M., Marinov, I., Hauwel, M., Spacek, M., Dobber, J., Kater, A. P., Gambell, P., Soosapilla, A., Lozanski, G., Brachtl, G., Lin, K., Boysen, J., Hanson, C., Jorgensen, J. L., Stetler-Stevenson, M., Yuan, C., Broome, H. E., Rassenti, L., Craig, F., Delgado, J., Moreno, C., Bosch, F., Egle, A., Doubek, M., Pospisilova, S., Mulligan, S., Westerman, D., Sanders, C. M., Emerson, R., Robins, H. S., Kirsch, I., Shanafelt, T., Pettitt, A., Kipps, T. J., Wierda, W. G., Cymbalista, F., Hallek, M., Hillmen, P., Montserrat, E., and Ghia, P.
- Abstract
In chronic lymphocytic leukemia (CLL) the level of minimal residual disease (MRD) after therapy is an independent predictor of outcome. Given the increasing number of new agents being explored for CLL therapy, using MRD as a surrogate could greatly reduce the time necessary to assess their efficacy. In this European Research Initiative on CLL (ERIC) project we have identified and validated a flow-cytometric approach to reliably quantitate CLL cells to the level of 0.0010% (10(-5)). The assay comprises a core panel of six markers (i.e. CD19, CD20, CD5, CD43, CD79b and CD81) with a component specification independent of instrument and reagents, which can be locally re-validated using normal peripheral blood. This method is directly comparable to previous ERIC-designed assays and also provides a backbone for investigation of new markers. A parallel analysis of high-throughput sequencing using the ClonoSEQ assay showed good concordance with flow cytometry results at the 0.010% (10(-4)) level, the MRD threshold defined in the 2008 International Workshop on CLL guidelines, but it also provides good linearity to a detection limit of 1 in a million (10(-6)). The combination of both technologies would permit a highly sensitive approach to MRD detection while providing a reproducible and broadly accessible method to quantify residual disease and optimize treatment in CLL.
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- 2016
234. PATTERNS OF IDELALISIB TREATMENT-EMERGENT LYMPHOCYTOSIS IN PATIENTS WITH CLL OR SLL
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Ghia, P., Cheson, B. D., Furman, R. R., Hallek, M., Hillmen, P., O'Brien, S. M., Sharman, J. P., Dubowy, R. L., Velasco, B., Waldapfel, C. C., Zelenetz, A. D., Brown, J. R., Ghia, P., Cheson, B. D., Furman, R. R., Hallek, M., Hillmen, P., O'Brien, S. M., Sharman, J. P., Dubowy, R. L., Velasco, B., Waldapfel, C. C., Zelenetz, A. D., and Brown, J. R.
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- 2016
235. Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia
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Leukaemia & Lymphoma Research (UK), Royal Marsden NHS Foundation Trust, The Institute of Cancer Research (UK), Swedish Research Council, Swedish Cancer Society, Polysackaridforskning i Uppsala AB, German Research Foundation, Leukaemia Foundation, Wessex Medical Research, Kay Kendall Leukaemia Fund, Cancer Research UK, Parker, H., Rose-Zerilli, M. J. J., Larráyoz, María José, Clifford, R., Edelmann, J., Blakemore, S., Gibson, J., Wang, J., Ljungström, V., Wojdacz, T. K., Chaplin, T., Roghanian, A., Davis, Z., Parker, Antón, Tausch, E., Ntoufa, S., Ramos, S., Robbe, P., Alsolami, R., Steele, A. J., Packham, G., Rodríguez-Vicente, Ana Eugenia, Brown, L., McNicholl, F., Forconi, F., Pettitt, A., Hillmen, P., Dyer, M., Cragg, M. S., Chelala, C., Oakes, C. C., Rosenquist, Richard, Stamatopoulos, Kostas, Stilgenbauer, S., Knight, S., Schuh, A., Oscier, David G., Strefford, Jonathan C., Leukaemia & Lymphoma Research (UK), Royal Marsden NHS Foundation Trust, The Institute of Cancer Research (UK), Swedish Research Council, Swedish Cancer Society, Polysackaridforskning i Uppsala AB, German Research Foundation, Leukaemia Foundation, Wessex Medical Research, Kay Kendall Leukaemia Fund, Cancer Research UK, Parker, H., Rose-Zerilli, M. J. J., Larráyoz, María José, Clifford, R., Edelmann, J., Blakemore, S., Gibson, J., Wang, J., Ljungström, V., Wojdacz, T. K., Chaplin, T., Roghanian, A., Davis, Z., Parker, Antón, Tausch, E., Ntoufa, S., Ramos, S., Robbe, P., Alsolami, R., Steele, A. J., Packham, G., Rodríguez-Vicente, Ana Eugenia, Brown, L., McNicholl, F., Forconi, F., Pettitt, A., Hillmen, P., Dyer, M., Cragg, M. S., Chelala, C., Oakes, C. C., Rosenquist, Richard, Stamatopoulos, Kostas, Stilgenbauer, S., Knight, S., Schuh, A., Oscier, David G., and Strefford, Jonathan C.
- Abstract
Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and are disrupted at the genomic level in a spectrum of human tumours including haematological malignancies. Using high-resolution single nucleotide polymorphism (SNP) arrays, we identified recurrent deletions of the SETD2 locus in 3% (8/261) of chronic lymphocytic leukaemia (CLL) patients. Further validation in two independent cohorts showed that SETD2 deletions were associated with loss of TP53, genomic complexity and chromothripsis. With next-generation sequencing we detected mutations of SETD2 in an additional 3.8% of patients (23/602). In most cases, SETD2 deletions or mutations were often observed as a clonal event and always as a mono-allelic lesion, leading to reduced mRNA expression in SETD2-disrupted cases. Patients with SETD2 abnormalities and wild-type TP53 and ATM from five clinical trials employing chemotherapy or chemo-immunotherapy had reduced progression-free and overall survival compared with cases wild type for all three genes. Consistent with its postulated role as a tumour suppressor, our data highlight SETD2 aberration as a recurrent, early loss-of-function event in CLL pathobiology linked to aggressive disease.
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- 2016
236. Paroxysmal nocturnal hemoglobinuria--hemolysis before and after eculizumab
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RISITANO, ANTONIO MARIA, Notaro R, Luzzatto L, Hill A, Kelly R, Hillmen P., Risitano, ANTONIO MARIA, Notaro, R, Luzzatto, L, Hill, A, Kelly, R, and Hillmen, P.
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- 2010
237. The Management of Pregnancy in Paroxysmal Nocturnal Hemoglobinuria on Long Term Eculizumab
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Kelly R, Arnold L, Richards S, Hill A, Bomken C, Hanley J, Loughney A, Khursigara G, Rother RP, Chalmers E, Fyfe A, Fitzsimons E, Nakamura R, Gaya A, Schubert J, Norfolk D, Simpson N, Hillmen P., RISITANO, ANTONIO MARIA, Kelly, R, Arnold, L, Richards, S, Hill, A, Bomken, C, Hanley, J, Loughney, A, Khursigara, G, Rother, Rp, Chalmers, E, Fyfe, A, Fitzsimons, E, Nakamura, R, Gaya, A, Risitano, ANTONIO MARIA, Schubert, J, Norfolk, D, Simpson, N, and Hillmen, P.
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- 2010
238. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia
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Byrd, Jc, Brown, Jr, O'Brien, S, Barrientos, Jc, Kay, Ne, Reddy, Nm, Coutre, S, Tam, Cs, Mulligan, Sp, Jaeger, U, Devereux, S, Barr, Pm, Furman, Rr, Kipps, Tj, Cymbalista, F, Pocock, C, Thornton, P, Caligaris Cappio, F, Robak, T, Delgado, J, Schuster, Sj, Montillo, M, Schuh, A, de Vos, S, Gill, D, Bloor, A, Dearden, C, Moreno, C, Jones, Jj, Chu, Ad, Fardis, M, Mcgreivy, J, Clow, F, James, Df, Hillmen, P, and Semenzato, GIANPIETRO CARLO
- Subjects
Male ,Oncology ,Lymphoma ,Medical and Health Sciences ,chemistry.chemical_compound ,Piperidines ,Recurrence ,Obinutuzumab ,Monoclonal ,80 and over ,Agammaglobulinaemia Tyrosine Kinase ,Chronic ,Humanized ,Fatigue ,Cancer ,Aged, 80 and over ,Leukemia ,Hazard ratio ,Antibodies, Monoclonal ,Hematology ,General Medicine ,Middle Aged ,Protein-Tyrosine Kinases ,Duvelisib ,Lymphocytic ,Survival Rate ,6.1 Pharmaceuticals ,Ibrutinib ,Acalabrutinib ,Female ,Diarrhea ,Adult ,medicine.medical_specialty ,Antibodies, Monoclonal, Humanized ,Ofatumumab ,Antibodies ,Disease-Free Survival ,Rare Diseases ,Clinical Research ,General & Internal Medicine ,Internal medicine ,medicine ,Humans ,Survival rate ,Aged ,Venetoclax ,business.industry ,Adenine ,B-Cell ,Evaluation of treatments and therapeutic interventions ,Leukemia, Lymphocytic, Chronic, B-Cell ,Pyrimidines ,Orphan Drug ,Cough ,chemistry ,Immunology ,Pyrazoles ,business ,RESONATE Investigators ,Follow-Up Studies - Abstract
Background In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, in patients at risk for a poor outcome. Methods In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. Results At a median follow-up of 9.4 months, ibrutinib significantly improved progression-free survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P
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- 2014
239. Multicenter phase III study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria
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Brodsky RA, Young NS, Antonioli E, Schrezenmeier H, Schubert J, Valls AG, Coyle L, de Castro C, Fu CL, Maciejewski JP, Bessler M, Kroon HA, Rother RP, Hillmen P., RISITANO, ANTONIO MARIA, Brodsky, Ra, Young, N, Antonioli, E, Risitano, ANTONIO MARIA, Schrezenmeier, H, Schubert, J, Valls, Ag, Coyle, L, de Castro, C, Fu, Cl, Maciejewski, Jp, Bessler, M, Kroon, Ha, Rother, Rp, and Hillmen, P.
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- 2008
240. appendix 6: Chronic lymphocytic leukaemia: eUpdate published online September 2016 (http://www.esmo.org/Guidelines/Haematological-Malignancies)
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Eichhorst, B., primary, Robak, T., additional, Montserrat, E., additional, Ghia, P., additional, Hillmen, P., additional, Hallek, M., additional, and Buske, C., additional
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- 2016
- Full Text
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241. Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia
- Author
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Parker, H, primary, Rose-Zerilli, M J J, additional, Larrayoz, M, additional, Clifford, R, additional, Edelmann, J, additional, Blakemore, S, additional, Gibson, J, additional, Wang, J, additional, Ljungström, V, additional, Wojdacz, T K, additional, Chaplin, T, additional, Roghanian, A, additional, Davis, Z, additional, Parker, A, additional, Tausch, E, additional, Ntoufa, S, additional, Ramos, S, additional, Robbe, P, additional, Alsolami, R, additional, Steele, A J, additional, Packham, G, additional, Rodríguez-Vicente, A E, additional, Brown, L, additional, McNicholl, F, additional, Forconi, F, additional, Pettitt, A, additional, Hillmen, P, additional, Dyer, M, additional, Cragg, M S, additional, Chelala, C, additional, Oakes, C C, additional, Rosenquist, R, additional, Stamatopoulos, K, additional, Stilgenbauer, S, additional, Knight, S, additional, Schuh, A, additional, Oscier, D G, additional, and Strefford, J C, additional
- Published
- 2016
- Full Text
- View/download PDF
242. An ultra-deep sequencing strategy to detect sub-clonal TP53 mutations in presentation chronic lymphocytic leukaemia cases using multiple polymerases
- Author
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Worrillow, L, primary, Baskaran, P, additional, Care, M A, additional, Varghese, A, additional, Munir, T, additional, Evans, P A, additional, O'Connor, S J, additional, Rawstron, A, additional, Hazelwood, L, additional, Tooze, R M, additional, Hillmen, P, additional, and Newton, D J, additional
- Published
- 2016
- Full Text
- View/download PDF
243. Lenalidomide treatment and prognostic markers in relapsed or refractory chronic lymphocytic leukemia: data from the prospective, multicenter phase-II CLL-009 trial
- Author
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Bühler, A, primary, Wendtner, C-M, additional, Kipps, T J, additional, Rassenti, L, additional, Fraser, G A M, additional, Michallet, A-S, additional, Hillmen, P, additional, Dürig, J, additional, Gregory, S A, additional, Kalaycio, M, additional, Aurran-Schleinitz, T, additional, Trentin, L, additional, Gribben, J G, additional, Chanan-Khan, A, additional, Purse, B, additional, Zhang, J, additional, De Bedout, S, additional, Mei, J, additional, Hallek, M, additional, and Stilgenbauer, S, additional
- Published
- 2016
- Full Text
- View/download PDF
244. A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia.
- Author
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Deshmukh C.D., Offner F., Van Den Neste E.W., Wu K.L., Van Hoof A., Maiolino A., Pinczowski H., Zanichelli M.A., Pereira J., Larratt L., Spaner D., Howson-Jan K., Chen C.I., Cantin G., Fernandez L.A., Fraser G., Mayer J., Trneny M., Jebavy L., Bordessoule D., Lamy T., Milpied N., Truchan-Graczyk M., Eghbali H., Karsenti J.-M., Celigny P.S., Mans L., Cazin B., Gyan E., Lepretre S., Bergmann L., Tsionos K., Lokeshwar N.M., Agarwal M.B., Ross C.R., Narayanan G., Raina V., Bondarde S.A., Shah B.A., Bairey O., Tikva P., Shvidel L., Ambrosetti A., Rossi P.G.B., Angelucci E., Carella A.M., Massaia M., Zinzani P.L., Caligaris-Cappio F., Foa R., Gaidano G., della Carita A.O.M., Leone G., Santoro A., Griskevicius L., Jurgutis R., Baker B.W., Hawkins T., Corbett G.M., Ganly P., D'Souza A.B., Deptala A., Holowiecki J., Kloczko J., Skotnicki A., Zdziarska B., Kyrcz-Krzemien S., Dmoszynska A., Moreira I., Pereira A.P., Colita A., Moicean A.D., Vasilica M., Danaila C., Gheorghita E., Pavlov V.V., Rossiev V.A., Konstantinova T., Samoilova O.S., Novgorod N., Shelekhova T., Zaritsky A.Y., Abdulkadyrov K.M., Zyuzgin I.S., Pristupa A.S., Loscertales J., Vidal J.B., de Mallorca P., Gonzalez M., Ortuno F., Giraldo P., Nathwani A., Agrawal S.G., Rule S., Dearden C.E., Bloor A.J., Haynes A., Singer C., Boclek R.G., Bosserman L.D., Chan D., Davidson S.J., Dichmann R.A., Farber C., Hart L., Hermann R., Hu E., Janakiraman N., Jonas W., Liem K.D., Mcintyre R.E., O'Brien S., Patel G., Rado T., Schilder R., Smith S.E., Stock W., Turturro F., Venugopal P., Anderson T.C., Berry W., Boyd T.E., Byrd J., Cooper M., Flinn I., Gersh R., Gordon D., Guzley G.J., Wilks S.T., Klein A., Krauss J.C., Lister J., Mandell L., Molina A., Cooper B., Pendergrass K.B., Reeder C., Savin M.A., Spitzer G., Tuscano J.M., vanDeventer H., Eradat H.A., Masood A., Mena R., Awan F.T., Hillmen P., Hellmann A., Robak T., Hughes S.G., Trone D., Shannon M., Flinn I.W., Byrd J.C., Riveros D., Pavlovsky S., Iastrebner C.M., Carney D.A., Deveridge S., Durrant S., Hahn U.H., Hertzberg M., Leahy M.F., Ma D., Marlton P., Mulligan S., Opat S.S., Tiley C., Wickham N.W., Cannell P., Gatalano J., Catalano J., Cull G., To L.B., Hopfinger G., Jager U., Linkesch W., Petzer A., Schwarzmeier J., Steurer M., Greil R., Bememan Z., Bosly A., Bron D., Janssens A., Deshmukh C.D., Offner F., Van Den Neste E.W., Wu K.L., Van Hoof A., Maiolino A., Pinczowski H., Zanichelli M.A., Pereira J., Larratt L., Spaner D., Howson-Jan K., Chen C.I., Cantin G., Fernandez L.A., Fraser G., Mayer J., Trneny M., Jebavy L., Bordessoule D., Lamy T., Milpied N., Truchan-Graczyk M., Eghbali H., Karsenti J.-M., Celigny P.S., Mans L., Cazin B., Gyan E., Lepretre S., Bergmann L., Tsionos K., Lokeshwar N.M., Agarwal M.B., Ross C.R., Narayanan G., Raina V., Bondarde S.A., Shah B.A., Bairey O., Tikva P., Shvidel L., Ambrosetti A., Rossi P.G.B., Angelucci E., Carella A.M., Massaia M., Zinzani P.L., Caligaris-Cappio F., Foa R., Gaidano G., della Carita A.O.M., Leone G., Santoro A., Griskevicius L., Jurgutis R., Baker B.W., Hawkins T., Corbett G.M., Ganly P., D'Souza A.B., Deptala A., Holowiecki J., Kloczko J., Skotnicki A., Zdziarska B., Kyrcz-Krzemien S., Dmoszynska A., Moreira I., Pereira A.P., Colita A., Moicean A.D., Vasilica M., Danaila C., Gheorghita E., Pavlov V.V., Rossiev V.A., Konstantinova T., Samoilova O.S., Novgorod N., Shelekhova T., Zaritsky A.Y., Abdulkadyrov K.M., Zyuzgin I.S., Pristupa A.S., Loscertales J., Vidal J.B., de Mallorca P., Gonzalez M., Ortuno F., Giraldo P., Nathwani A., Agrawal S.G., Rule S., Dearden C.E., Bloor A.J., Haynes A., Singer C., Boclek R.G., Bosserman L.D., Chan D., Davidson S.J., Dichmann R.A., Farber C., Hart L., Hermann R., Hu E., Janakiraman N., Jonas W., Liem K.D., Mcintyre R.E., O'Brien S., Patel G., Rado T., Schilder R., Smith S.E., Stock W., Turturro F., Venugopal P., Anderson T.C., Berry W., Boyd T.E., Byrd J., Cooper M., Flinn I., Gersh R., Gordon D., Guzley G.J., Wilks S.T., Klein A., Krauss J.C., Lister J., Mandell L., Molina A., Cooper B., Pendergrass K.B., Reeder C., Savin M.A., Spitzer G., Tuscano J.M., vanDeventer H., Eradat H.A., Masood A., Mena R., Awan F.T., Hillmen P., Hellmann A., Robak T., Hughes S.G., Trone D., Shannon M., Flinn I.W., Byrd J.C., Riveros D., Pavlovsky S., Iastrebner C.M., Carney D.A., Deveridge S., Durrant S., Hahn U.H., Hertzberg M., Leahy M.F., Ma D., Marlton P., Mulligan S., Opat S.S., Tiley C., Wickham N.W., Cannell P., Gatalano J., Catalano J., Cull G., To L.B., Hopfinger G., Jager U., Linkesch W., Petzer A., Schwarzmeier J., Steurer M., Greil R., Bememan Z., Bosly A., Bron D., and Janssens A.
- Abstract
Summary: Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.Copyright © 2014 John Wiley & Sons Ltd.
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- 2015
245. Health-related quality of life impact of idelalisib in patients with relapsed chronic lymphocytic leukemia (CLL): phase 3 results
- Author
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Munir, T., Hillmen, P., Eradat, H., Ghia, P., O'Brien, S., Furman, R., Coutre, S., Sharman, J., Cheson, B., Pagel, J., Barrientos, J., Zelenetz, A., Kipps, T., Flinn, I., Lamanna, N., Hallek, M., Coiffier, B., Pettitt, A., Kim, Y., Jahn, T., Wagner, L., Munir, T., Hillmen, P., Eradat, H., Ghia, P., O'Brien, S., Furman, R., Coutre, S., Sharman, J., Cheson, B., Pagel, J., Barrientos, J., Zelenetz, A., Kipps, T., Flinn, I., Lamanna, N., Hallek, M., Coiffier, B., Pettitt, A., Kim, Y., Jahn, T., and Wagner, L.
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- 2015
246. Second interim analysis of a phase 3 study of idelalisib plus rituximab (R) for relapsed chronic lymphocytic leukaemia (CLL): efficacy analysis in patient subpopulations with Del(17p) and other adverse prognostic factors
- Author
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Munir, T., Hillmen, P., Sharman, J., Coutre, S., Furman, R., Cheson, B., Pagel, J., Barrientos, J., Zelenetz, A., Kipps, T., Flinn, I., Ghia, P., Hallek, M., Coiffier, B., O'Brien, S., Tausch, E., Kreuzer, K., Jiang, W., Lazarov, M., Li, D., Jahn, T., Stilgenbauer, S., Munir, T., Hillmen, P., Sharman, J., Coutre, S., Furman, R., Cheson, B., Pagel, J., Barrientos, J., Zelenetz, A., Kipps, T., Flinn, I., Ghia, P., Hallek, M., Coiffier, B., O'Brien, S., Tausch, E., Kreuzer, K., Jiang, W., Lazarov, M., Li, D., Jahn, T., and Stilgenbauer, S.
- Published
- 2015
247. Results from the phase 2 RESONATE (TM)-17 Trial: Efficacy and safety of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic leukaemia with 17p deletion
- Author
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Munir, T., O'Brien, S., Jones, J. A., Coutre, S. E., Mato, A. R., Hillmen, P., Tam, C., Osterborg, A., Siddiqi, T., Thirman, M. J., Furman, R. R., Ilhan, O., Keating, M., Call, T. G., Brown, J. R., Stevens-Brogan, M., Li, Y., Clow, F., James, D., Chu, A., Hallek, M., Stilgenbauer, S., Munir, T., O'Brien, S., Jones, J. A., Coutre, S. E., Mato, A. R., Hillmen, P., Tam, C., Osterborg, A., Siddiqi, T., Thirman, M. J., Furman, R. R., Ilhan, O., Keating, M., Call, T. G., Brown, J. R., Stevens-Brogan, M., Li, Y., Clow, F., James, D., Chu, A., Hallek, M., and Stilgenbauer, S.
- Published
- 2015
248. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up(aEuro)
- Author
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Eichhorst, B., Robak, T., Montserrat, E., Ghia, P., Hillmen, P., Hallek, M., Buske, C., Eichhorst, B., Robak, T., Montserrat, E., Ghia, P., Hillmen, P., Hallek, M., and Buske, C.
- Published
- 2015
249. Results from the phase 2 RESONATE (TM)-17 trial: Efficacy and safety of Ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma with Del17p
- Author
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Stilgenbauer, S., Jones, J. A., Coutre, S. E., Mato, A. R., Hillmen, P., Tam, C., Osterborg, A., Siddiqi, T., Thirman, M. J., Furman, R. R., Ilhan, O., Keating, M., Call, T. G., Brown, J. R., Stevens-Brogan, M., Li, Y., Clow, F., James, D. F., Chu, A. D., Hallek, M., O'Brien, S., Stilgenbauer, S., Jones, J. A., Coutre, S. E., Mato, A. R., Hillmen, P., Tam, C., Osterborg, A., Siddiqi, T., Thirman, M. J., Furman, R. R., Ilhan, O., Keating, M., Call, T. G., Brown, J. R., Stevens-Brogan, M., Li, Y., Clow, F., James, D. F., Chu, A. D., Hallek, M., and O'Brien, S.
- Published
- 2015
250. Ofatumumab in poor-prognosis chronic lymphocytic leukemia: a phase IV, non-interventional, observational study from the European Research Initiative on Chronic Lymphocytic Leukemia.
- Author
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Moreno, C, Montillo, M, Panayiotidis, P, Dimou, M, Bloor, A, Dupuis, J, Schuh, A, Norin, S, Geisler, C, Hillmen, P, Doubek, M, Trněný, M, Obrtlikova, P, Laurenti, Luca, Stilgenbauer, S, Smolej, L, Ghia, P, Cymbalista, F, Jaeger, U, Stamatopoulos, K, Stavroyianni, N, Carrington, P, Zouabi, H, Leblond, V, Gomez-Garcia, Jc, Rubio, M, Marasca, R, Musuraca, G, Rigacci, L, Farina, L, Paolini, R, Pospisilova, S, Kimby, E, Bradley, C, Montserrat, E., Laurenti L (ORCID:0000-0002-8327-1396), Moreno, C, Montillo, M, Panayiotidis, P, Dimou, M, Bloor, A, Dupuis, J, Schuh, A, Norin, S, Geisler, C, Hillmen, P, Doubek, M, Trněný, M, Obrtlikova, P, Laurenti, Luca, Stilgenbauer, S, Smolej, L, Ghia, P, Cymbalista, F, Jaeger, U, Stamatopoulos, K, Stavroyianni, N, Carrington, P, Zouabi, H, Leblond, V, Gomez-Garcia, Jc, Rubio, M, Marasca, R, Musuraca, G, Rigacci, L, Farina, L, Paolini, R, Pospisilova, S, Kimby, E, Bradley, C, Montserrat, E., and Laurenti L (ORCID:0000-0002-8327-1396)
- Abstract
X
- Published
- 2015
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