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  • 1.
    Andersen, Christen L.
    et al.
    Dept Haematol, Roskilde Hosp, Roskilde, Denmark.; Dept Haematol, Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark.
    McMullin, Mary F.
    Dept Haematol, Queens Univ Belfast, Antrim, North Ireland.
    Ejerblad, Elisabeth
    Dept Haematol, Univ Uppsala Hosp, Uppsala, Sweden.
    Zweegman, Sonja
    Dept Haematol, Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
    Harrison, Claire
    Dept Haematol, Guys & St Thomas Hosp, London, England; NHS Foundation Trust, London, England.
    Fernandes, Savio
    Bareford, David
    Dept Haematol, Russells Hall Hosp, Dudley, England.
    Knapper, Steven
    Dept Haematol, Cardiff Univ, Cardiff, S Glam, UK.
    Samuelsson, Jan
    Dept Internal Med, Stockholm South Hosp, Stockholm, Sweden.
    Loefvenberg, Eva
    Haematol Ctr, Karolinska Univ Hosp, Stockholm, Sweden.
    Linder, Olle
    Andreasson, Bjorn
    Dept Haematol, NU Hosp Org, Uddevalla Hosp, Uddevalla, Sweden.
    Ahlstrand, Erik
    Örebro University Hospital.
    Jensen, Morten K.
    Dept Haematol, Herlev Hosp, Herlev, Denmark.
    Bjerrum, Ole W.
    Vestergaard, Hanne
    Dept Haematol, Odense Univ Hosp, Odense, Denmark.
    Larsen, Herdis
    Dept Internal Med, Dept Haematol, Viborg Hosp, Viborg, Denmark.
    Klausen, Tobias W.
    Mourits-Andersen, Torben
    Dept Haematol, Esbjerg Cent Hosp, Esbjerg, Denmark.
    Hasselbalch, Hans C.
    Dept Haematol, Roskilde Hosp, Roskilde, Denmark.
    A phase II study of vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia2013In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 162, no 4, p. 498-508Article in journal (Refereed)
    Abstract [en]

    Inhibition of histone deacetylases may be an important target in patients with myeloproliferative neoplasms. This investigator-initiated, non-randomized, open-label phase II multi-centre study included 63 patients (19 essential thrombocythaemia, 44 polycythaemia vera) from 15 centres. The primary objective was to evaluate if vorinostat was followed by a decline in clonal myeloproliferation as defined by European Leukaemia Net. Thirty patients (48%) completed the intervention period (24 weeks of therapy). An intention-to-treat response rate of 35% was identified. Pruritus was resolved [19% to 0% (P=0.06)] and the prevalence of splenomegaly was lowered from 50% to 27% (P=0.03). Sixty-five per cent of the patients experienced a decrease in JAK2 V617F allele burden (P=0.006). Thirty-three patients (52% of patients) discontinued study drug before end of intervention due to adverse events (28 patients) or lack of response (5 patients). In conclusion, vorinostat showed effectiveness by normalizing elevated leucocyte and platelet counts, resolving pruritus and significantly reducing splenomegaly. However, vorinostat was associated with significant side effects resulting in a high discontinuation rate. A lower dose of vorinostat in combination with conventional and/or novel targeted therapies may be warranted in future studies.

  • 2.
    Berggren, Daniel Moreno
    et al.
    Department of Medical Science, Section of Haematology, Uppsala University, Uppsala, Sweden.
    Folkvaljon, Yasin
    Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Engvall, Marie
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Sundberg, Johan
    Department of Medical Science, Section of Haematology, Uppsala University, Uppsala, Sweden.
    Lambe, Mats
    Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Antunovic, Petar
    Department of Haematology, Linköping University Hospital, Linköping, Sweden.
    Garelius, Hege
    Section for Haematology and Coagulation, Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Lorenz, Fryderyk
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Nilsson, Lars
    Department of Haematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.
    Rasmussen, Bengt
    Örebro University, School of Medical Sciences.
    Lehmann, Sören
    Department of Medical Science, Section of Haematology, Uppsala University, Uppsala, Sweden.
    Hellström-Lindberg, Eva
    Centre for Haematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Jädersten, Martin
    Centre for Haematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Ejerblad, Elisabeth
    Department of Medical Science, Section of Haematology, Uppsala University, Uppsala, Sweden.
    Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population-based setting: a report from the Swedish MDS register2018In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 181, no 5, p. 614-627Article in journal (Refereed)
    Abstract [en]

    The myelodysplastic syndromes (MDS) have highly variable outcomes and prognostic scoring systems are important tools for risk assessment and to guide therapeutic decisions. However, few population-based studies have compared the value of the different scoring systems. With data from the nationwide Swedish population-based MDS register we validated the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) and the World Health Organization (WHO) Classification-based Prognostic Scoring System (WPSS). We also present population-based data on incidence, clinical characteristics including detailed cytogenetics and outcome from the register. The study encompassed 1329 patients reported to the register between 2009 and 2013, 14% of these had therapy-related MDS (t-MDS). Based on the MDS register, the yearly crude incidence of MDS in Sweden was 2<bold></bold>9 per 100000 inhabitants. IPSS-R had a significantly better prognostic power than IPSS (P<0<bold></bold>001). There was a trend for better prognostic power of IPSS-R compared to WPSS (P=0<bold></bold>05) and for WPSS compared to IPSS (P=0<bold></bold>07). IPSS-R was superior to both IPSS and WPSS for patients aged 70years. Patients with t-MDS had a worse outcome compared to de novo MDS (d-MDS), however, the validity of the prognostic scoring systems was comparable for d-MDS and t-MDS. In conclusion, population-based studies are important to validate prognostic scores in a real-world' setting. In our nationwide cohort, the IPSS-R showed the best predictive power.

  • 3.
    Ludvigsson, Jonas F.
    et al.
    Örebro University, School of Health and Medical Sciences.
    Welander, Adina
    Lassila, Riitta
    Ekbom, Anders
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Risk of thromboembolism in 14,000 individuals with coeliac disease2007In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 139, no 1, p. 121-127Article in journal (Refereed)
    Abstract [en]

    The risk of venous thromboembolism (VTE) was examined in individuals with coeliac disease (CD). The Swedish national inpatient register was used to identify 14 207 individuals with a diagnosis of CD (1964–2003). These individuals were matched for age, sex, calendar year and county with 69 048 reference individuals. Cox regression was used to estimate hazard ratios (HRs) for subsequent thromboembolism in individuals with more than 1 year of follow-up and no prior VTE. CD was associated with an increased risk of subsequent VTE (HR = 1·86; 95% confidence interval (CI) 1·54–2·24). The risk increase was restricted to individuals with CD diagnosed in adulthood. Risk estimates were not affected by the presence of diabetes mellitus or concomitant surgery. Compared with inpatients as reference individuals, CD individuals remained at increased risk of subsequent VTE (adjusted HR = 1·27; 95% CI = 1·06–1·52). In conclusion, this study found a statistically significantly positive association between CD and VTE. This modest association might be explained by a combination of surveillance bias and chronic inflammation

  • 4.
    Osterborg, Anders
    et al.
    Dept Haematol, Karolinska Univ Hosp, Stockholm, Sweden.
    Wierda, William G.
    M D Anderson Canc Ctr, Univ Texas, Houston TX, USA; Canc Therapy Res Ctr, San Antonio TX, USA.
    Mayer, Jiri
    Fac Hosp Brno, Dept Internal Med Haematooncol, University Hospital, Brno, Czech Republic.
    Hess, Georg
    Johannes Gutenberg Univ, Mainz, Germany.
    Hillmen, Peter
    Leeds Teaching Hosp, Leeds, England.
    Schetelig, Johannes
    Univ Klinickum Carl Gustav Carus, Dresden, Germany.
    Schuh, Anna
    Churchill Hosp, Oxford, England.
    Smolej, Lukas
    Fac Med Hradec Kralove, Univ Hosp, Hradec Kralove, Czech Republic; Charles Univ Prague, Hradec Kralove, Czech Republic.
    Beck, Christian
    Haematol Onkolog Inst, Moenchengladbach, Germany.
    Dreyfus, Brigitte
    Hop Jean Bernanrd, Poitiers, France.
    Hellman, Andrzej
    Akad Med Gdansku, Gdansk, Poland.
    Kozlowski, Piotr
    Örebro University Hospital.
    Pfreundschuh, Michael
    Univ Saarlandes Kliniken, Homburg, Germany.
    Rizzi, Rita
    Azienda ospedaliero-universitaria consorziale policlinico, Bari, Italy.
    Spacek, Martin
    Fak Nemocnice, Prague, Czech Republic..
    Phillips, Jennifer L.
    GlaxoSmithKline, Collegeville PA, USA.
    Gupta, Ira V.
    Williams, Vanessa
    Glaxo SmithKline, Durham NC, USA.
    Jewell, Roxanne C.
    Glaxo SmithKline, Durham NC ,USA..
    Nebot, Noelia
    Glaxo SmithKline, Durham NC, USA.
    Lisby, Steen
    Genmab AS, Copenhagen, Denmark.
    Dyer, Martin J. S.
    Ernest & Helen Scott Haematol Res Inst, Univ Leicester, Leicester, England.
    Ofatumumab retreatment and maintenance in fludarabine-refractory chronic lymphocytic leukaemia patients2015In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 170, no 1, p. 40-49Article in journal (Refereed)
    Abstract [en]

    There are limited data on retreatment with monoclonal antibodies (mAb) in patients with chronic lymphocytic leukaemia (CLL). In a pivotal study, ofatumumab (human anti-CD20 mAb) monotherapy demonstrated a 47% objective response rate (ORR) in fludarabine refractory CLL patients. From this study, a subset of 29 patients who had at least stable disease and then progressed were retreated with eight weekly ofatumumab infusions (induction treatment period), followed by monthly infusions for up to 2years (maintenance treatment period). The ORR after 8weeks of induction retreatment was 45% and 24% had continued disease control after maintenance at 52weeks. Efficacy and safety of the retreated patients were compared with their initial results in the pivotal study. Response duration was 241months vs. 68months; time to next therapy was 148months vs. 123months; and progression-free survival was 74months vs. 79months (medians). Upon retreatment, 72% had infusion reactions, mostly Grade 1-2. Three patients had fatal infections. In summary, ofatumumab retreatment and maintenance therapy was feasible in patients with heavily pretreated CLL and appeared to result in more durable disease control than initial ofatumumab treatment in this subset of patients who may have a more favourable disease profile.

  • 5.
    Roehle, Anja
    et al.
    Institute for Pathology, University Clinic Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
    Hoefig, Kai P
    Clinic Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
    Repsilber, Dirk
    Research Institute for the Biology of Farm Animals FBN, Dummerstorf, Germany.
    Thorns, Christoph
    Clinic Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
    Ziepert, Marita
    Institute for Medical Informatics, Statistics and Epidemiology, IMISE, University Leipzig, Leipzig, Germany.
    Wesche, Kai O
    Institute for Pathology, University Clinic Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
    Thiere, Marlen
    Institute for Pathology, University Clinic Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
    Loeffler, Markus
    Institute for Medical Informatics, Statistics and Epidemiology, IMISE, University Leipzig, Leipzig, Germany.
    Klapper, Wolfram
    Institute for Pathology, University Clinic Schleswig-Holstein, Campus Kiel, Kiel, Germany.
    Pfreundschuh, Michael
    Department of Internal Medicine I, University Clinic Saarland, Homburg/Saar, Germany.
    Matolcsy, András
    1st Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
    Bernd, Heinz-Wolfram
    Institute for Pathology, University Clinic Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
    Reiniger, Lila
    Institute for Pathology, University Clinic Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
    Merz, Hartmut
    Institute for Pathology, University Clinic Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
    Feller, Alfred C
    MicroRNA signatures characterize diffuse large B-cell lymphomas and follicular lymphomas2008In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 142, no 5, p. 732-44Article in journal (Refereed)
    Abstract [en]

    MicroRNAs (miRNA, miR) are negative regulators of gene expression that play an important role in diverse biological processes such as development, cell growth, apoptosis and haematopoiesis, suggesting their association with cancer. Here we analysed the expression signatures of 157 miRNAs in 58 diffuse large B-cell lymphoma (DLBCL), 46 follicular lymphoma (FL) and seven non-neoplastic lymph nodes (LN). Comparison of the possible combinations of DLBCL-, FL- and LN resulted in specific DLBCL- and FL-signatures, which include miRNAs with previously published function in haematopoiesis (MIRN150 and MIRN155) or tumour development (MIRN210, MIRN10A, MIRN17-5P and MIRN145). As compared to LN, some miRNAs are differentially regulated in both lymphoma types (MIRN155, MIRN210, MIRN106A, MIRN149 and MIRN139). Conversely, some miRNAs show lymphoma-specific aberrant expression, such as MIRN9/9*, MIRN301, MIRN338 and MIRN213 in FL and MIRN150, MIRN17-5P, MIRN145, MIRN328 and others in DLBCL. A classification tree was computed using four miRNAs (MIRN330, MIRN17-5P, MIRN106a and MIRN210) to correctly identify 98% of all 111 cases that were analysed in this study. Finally, eight miRNAs were found to correlate with event-free and overall survival in DLBCL including known tumour suppressors (MIRN21, MIRN127 and MIRN34a) and oncogenes (MIRN195 and MIRNLET7G).

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