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  • 101.
    Casulo, Carla
    et al.
    Univ Rochester, Wilmot Canc Inst, New York, NY USA.
    Friedberg, Jonathan W.
    Univ Rochester, Wilmot Canc Inst, New York, NY USA.
    Ahn, Kwang W.
    Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA;Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA.
    Flowers, Christopher
    Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Sch Med, Atlanta, GA 30322 USA.
    DiGilio, Alyssa
    Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA.
    Smith, Sonali M.
    Univ Chicago, Sect Hematol Oncol, Chicago, IL 60637 USA.
    Ahmed, Sairah
    Univ MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Div Canc Med, Houston, TX USA.
    Inwards, David
    Mayo Clin, Div Hematol, Rochester, MN USA.
    Aljurf, Mahmoud
    King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riydah, Saudi Arabia.
    Chen, Andy, I
    Oregon Hlth & Sci Univ, Blood & Marrow Transplant Program, Portland, OR 97201 USA.
    Choe, Hannah
    Weill Cornell Med Coll, Blood & Marrow Transplant Program, New York, NY USA.
    Cohen, Jonathon
    Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Sch Med, Atlanta, GA 30322 USA.
    Copelan, Edward
    Carolinas HealthCare Syst, Dept Hematol Oncol & Blood Disorders, Levine Canc Inst, Charlotte, NC USA.
    Farooq, Umar
    Univ Iowa, Dept Med, Iowa City, IA 52242 USA.
    Fenske, Timothy S.
    Med Coll Wisconsin, Dept Med, Div Hematol & Oncol, Milwaukee, WI 53226 USA.
    Freytes, Cesar
    Texas Transplant Inst, Blood & Marrow Transplant Program, San Antonio, TX USA.
    Gaballa, Sameh
    Thomas Jefferson Univ Hosp, Blood & Marrow Transplant Program, Philadelphia, PA 19107 USA.
    Ganguly, Siddhartha
    Univ Kansas, Div Hematol Malignancies & Cellular Therapeut, Med Ctr, Kansas City, KS 66103 USA.
    Jethava, Yogesh
    Univ Arkansas Med Sci, Blood & Marrow Transplant Program, Little Rock, AR 72205 USA.
    Kamble, Rammurti T.
    Baylor Coll Med, Ctr Cell & Gene Therapy, Div Hematol & Oncol, Houston, TX 77030 USA.
    Kenkre, Vaishalee P.
    Univ Wisconsin, Div Hematol & Oncol, Madison, WI USA.
    Lazarus, Hillard
    Univ Hosp Cleveland, Seidman Canc Ctr, Med Ctr, Cleveland, OH 44106 USA.
    Lazaryan, Aleksandr
    Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA.
    Olsson, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden.
    Rezvani, Andrew R.
    Stanford Hlth Care, Blood & Marrow Transplant Program, Stanford, CA USA.
    Rizzieri, David
    Duke Univ, Div Hematol Malignancies & Cellular Therapy, Durham, NC USA.
    Seo, Sachiko
    East Hosp, Natl Canc Res Ctr, Chiba, Japan.
    Shah, Gunjan L.
    Mem Sloan Kettering Canc Ctr, Blood & Marrow Transplant Program, 1275 York Ave, New York, NY 10021 USA.
    Shah, Nina
    Univ MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Div Canc Med, Houston, TX USA.
    Solh, Melham
    Northside Hosp, Blood & Marrow Transplant Grp Georgia, Atlanta, GA USA.
    Sureda, Anna
    Inst Catala Oncol Hosp, Hematol Dept, Barcelona, Spain.
    William, Basem
    Ohio State Med Ctr, James Canc Ctr, Columbus, OH USA.
    Cumpston, Aaron
    West Virginia Univ Hosp, Blood & Marrow Transplant Program, Morgantown, WV USA.
    Zelenetz, Andrew D.
    Mem Sloan Kettering Canc Ctr, Blood & Marrow Transplant Program, 1275 York Ave, New York, NY 10021 USA.
    Link, Brian K.
    Med Coll Wisconsin, Dept Med, Div Hematol & Oncol, Milwaukee, WI 53226 USA.
    Hamadani, Mehdi
    Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA.
    Autologous Transplantation in Follicular Lymphoma with Early Therapy Failure: A National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis2018Inngår i: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 24, nr 6, s. 1163-1171Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients with follicular lymphoma (FL) experiencing early therapy failure (ETF) within 2 years of frontline chemoimmunotherapy have poor overall survival (OS). We analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) and the National LymphoCare Study (NLCS) to determine whether autologous hematopoietic cell transplant (autoHCT) can improve outcomes in this high-risk FL subgroup. ETF was defined as failure to achieve at least partial response after frontline chemoimmunotherapy or lymphoma progression within 2 years of frontline chemoimmunotherapy. We identified 2 groups: the non-autoHCT cohort (patients from the NLCS with ETF not undergoing autoHCT) and the autoHCT cohort (CIBMTR patients with ETF undergoing autoHCT). All patients received rituximab-based chemotherapy as frontline treatment; 174 non-autoHCT patients and 175 autoHCT patients were identified and analyzed. There was no difference in 5-year OS between the 2 groups (60% versus 67%, respectively; P = .16). A planned subgroup analysis showed that patients with ETF receiving autoHCT soon after treatment failure (≤1 year of ETF; n = 123) had higher 5-year OS than those without autoHCT (73% versus 60%, P = .05). On multivariate analysis, early use of autoHCT was associated with significantly reduced mortality (hazard ratio, .63; 95% confidence interval, .42 to .94; P = .02). Patients with FL experiencing ETF after frontline chemoimmunotherapy lack optimal therapy. We demonstrate improved OS when receiving autoHCT within 1 year of treatment failure. Results from this unique collaboration between the NLCS and CIBMTR support consideration of early consolidation with autoHCT in select FL patients experiencing ETF.

  • 102.
    Cedervall, Jessica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hamidi, Anahita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Olsson, Anna-Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Platelets, NETs and cancer2018Inngår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 164, s. S148-S152Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In addition to the central role of platelets in hemostasis, they contribute to pathological conditions such as inflammation and tumor progression. Aberrant expression and/or exposure of pro-coagulant factors in the tumor microenvironment induce platelet activation and subsequent release of growth factors from platelet granules. Cancer patients are commonly affected by thrombotic events, as a result of tumor-induced platelet activation. A novel player potentially contributing to cancer-associated thrombosis is the formation of neutrophil extracellular traps (NETs). NETs are composed of externalized DNA of nuclear or mitochondrial origin, bound to histones and granular proteases such as neutrophil elastase (NE) and myeloperoxidase (MPO). These extracellular traps help neutrophils to catch and kill pathogens such as bacteria, virus and fungi. It is now clear that NETs form also under conditions of sterile inflammation such as cancer and autoimmunity and can promote thrombosis. Recent data show that platelets play a key role in determining when and where NETs should form. This review will highlight our current insight in the role of platelets as regulators of NET formation, both during infection and sterile inflammation.

  • 103.
    Cesaro, Simone
    et al.
    Azienda Osped Univ Integrata, Paediat Haematol & Oncol, Verona, Italy..
    de latour, Regis Peffault
    Univ Paris 07, Dept Haematol, BMT, Hop St Louis, Paris, France..
    Tridello, Gloria
    Azienda Osped Univ Integrata, Paediat Haematol & Oncol, Verona, Italy..
    Pillon, Marta
    Dipartimento Pediat, Clin Oncoematol Pediat, Padua, Italy..
    Carlson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Fagioli, Franca
    Regina Margherita Hosp, Paediat Haematol, Turin, Italy..
    Jouet, Jean-Pierre
    Hop Claude Huriez Serv Malad Sang, Lille, France..
    Koh, Mickey B. C.
    St George Hosp, Dept Haematol, London, England..
    Panizzolo, Irene Sara
    Azienda Osped Univ Integrata, Paediat Haematol & Oncol, Verona, Italy..
    Kyrcz-Krzemien, Slawomira
    Med Univ Silesia, Univ Dept Haematol, Katowice, Poland.;BMT, Katowice, Poland..
    Maertens, Johan
    Univ Hosp Gasthuisberg, Dept Haematol, Leuven, Belgium..
    Rambaldi, Alessandro
    Osped Riuniti Bergamo, Div Ematol, Bergamo, Italy..
    Strahm, Brigitte
    Univ Med Ctr, Dept Paediat & Adolescent Med, Paediat Haematol & Oncol, Freiburg, Germany..
    Blaise, Didier
    Inst Paoli Calmettes, Ctr Rech Cancerol Marseille, Programme Transplantat & Therapie Cellulaire, Marseille, France..
    Maschan, Alexei
    Fed Res Ctr Paediat Haematol Oncol & Immunol, Moscow, Russia..
    Marsh, Judith
    Kings Coll London, Kings Coll Hosp, Dept Haematol Med, London, England..
    Dufour, Carlo
    Inst G Gaslini, Paediat Haematol, Genoa, Italy..
    Second allogeneic stem cell transplant for aplastic anaemia: a retrospective study by the severe aplastic anaemia working party of the European society for blood and marrow transplantation2015Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 171, nr 4, s. 606-614Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We analysed the outcome of a second allogeneic haematopoietic stem cell transplant (alloHSCT) in 162 patients reported to the European Society for Blood and Marrow Transplantation between 1998 and 2009. Donor origin was a sibling in 110 and an unrelated donor in 52 transplants, respectively. The stem cell source was bone marrow in 31% and peripheral blood in 69% of transplants. The same donor as for the first alloHSCT was used in 81% of transplants whereas a change in the choice of stem cell source was reported in 56% of patients, mainly from bone marrow to peripheral blood. Neutrophil and platelet engraftment occurred in 85% and 72% of patients, after a median time of 15 and 17days, respectively. Grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 21% and 37% of patients, respectively. Graft failure (GF) occurred in 42 patients (26%). After a median follow-up of 3.5years, the 5-year overall survival (OS) was 60.7%. In multivariate analysis, the only factor significantly associated with a better outcome was a Karnofsky/Lansky score 80 (higher OS). We conclude that a second alloHSCT is feasible rescue option for GF in SAA, with a successful outcome in 60% of cases.

  • 104. Chaireti, R.
    et al.
    Lindahl, T. L.
    Bremme, K.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Inflammatory and endothelial markers and their relations to the haemostatic potential during the menstrual cycle2015Inngår i: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, nr S2, s. 614-614, artikkel-id PO292-TUEArtikkel i tidsskrift (Annet vitenskapelig)
  • 105.
    Chartomatsidou, Elisavet
    et al.
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece;Univ Ioannina, Dept Biol Applicat & Technol, Ioannina, Greece.
    Ntoufa, Stavroula
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece.
    Kotta, Konstantia
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece.
    Rovida, Alessandra
    Univ Vita Salute San Raffaele, Div Expt Oncol, Strateg Res Program CLL & B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Akritidou, Maria Anna
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece;Univ Ioannina, Dept Biol Applicat & Technol, Ioannina, Greece.
    Belloni, Daniela
    Univ Vita Salute San Raffaele, Div Expt Oncol, Strateg Res Program CLL & B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Ferrero, Elisabetta
    Univ Vita Salute San Raffaele, Div Expt Oncol, Strateg Res Program CLL & B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Trangas, Theoni
    Univ Ioannina, Dept Biol Applicat & Technol, Ioannina, Greece.
    Stavroyianni, Niki
    G Papanicolaou Hosp, BMT Unit, Dept Hematol, Thessaloniki, Greece.
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, BMT Unit, Dept Hematol, Thessaloniki, Greece.
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Div Expt Oncol, Strateg Res Program CLL & B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Papakonstantinou, Nikos
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece.
    Stamatopoulos, Kostas
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece.
    Inhibition of EZH2 and immune signaling exerts synergistic antitumor effects in chronic lymphocytic leukemia2019Inngår i: BLOOD ADVANCES, ISSN 2473-9529, Vol. 3, nr 12, s. 1891-1896Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Key Points:

    Microenvironmental stimuli affect EZH2 expression and function in CLL.Combined B-cell signaling and EZH2 inhibition showed synergistic effects on primary CLL cells.

  • 106.
    Chatzilari, Elisavet
    et al.
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Baliakas, Panagiotis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Xochelli, Aliki
    Ctr Res & Technol Hellas, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Maronidis, Anastasios
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Vardi, Anna
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Larsson, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Douka, Vassiliki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Iskas, Michail
    George Papanicolaou Gen Hosp, Hematol BMT Unit, Thessaloniki, Greece..
    Karavalakis, George
    G Papanicolaou Hosp, BMT Unit, Dept Hematol, Thessaloniki, Greece..
    Papalexandri, Apostolia
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Niemann, Carsten
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Montillo, Marco
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Davi, Frederic
    Hop La Pitie Salpetriere, Dept Biol Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Ghia, Paolo
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Hadzidimitriou, Anastasia
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Nikolopoulos, Spiros
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Kompatsiaris, Yannis
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Personalized Modeling of Disease Evolution in CLL: Does Statistical Significance Translate into Predictive Accuracy?2015Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, nr 23Artikkel i tidsskrift (Annet vitenskapelig)
  • 107.
    Chen, Dongfeng
    et al.
    Univ Gothenburg, Dept Rheumatol & Inflammat Res, Box 480, SE-40530 Gothenburg, Sweden;Jiangsu Univ, Inst Life Sci, Zhenjiang, Peoples R China.
    Camponeschi, Alessandro
    Univ Gothenburg, Dept Rheumatol & Inflammat Res, Box 480, SE-40530 Gothenburg, Sweden.
    Wu, Qingqing
    Guizhou Med Univ, Affiliated Hosp, Cent Lab, Guiyang, Guizhou, Peoples R China.
    Gerasimcik, Natalija
    Univ Gothenburg, Dept Rheumatol & Inflammat Res, Box 480, SE-40530 Gothenburg, Sweden.
    Li, Huiqi
    Univ Gothenburg, Dept Occupat & Environm Med, Gothenburg, Sweden.
    Shen, Xue
    Guizhou Med Univ, Affiliated Hosp, Cent Lab, Guiyang, Guizhou, Peoples R China.
    Tan, Yujie
    Guizhou Med Univ, Affiliated Hosp, Cent Lab, Guiyang, Guizhou, Peoples R China.
    Sjögren, Helene
    Sahlgrens Univ Hosp, Dept Clin Chem, Gothenburg, Sweden.
    Nordlund, Jessica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lönnerholm, Gudmar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Abrahamsson, Jonas
    Sahlgrens Univ Hosp, Inst Clin Sci, Dept Paediat, Gothenburg, Sweden.
    Fogelstrand, Linda
    Sahlgrens Univ Hosp, Dept Clin Chem, Gothenburg, Sweden;Univ Gothenburg, Dept Clin Chem & Transfus Med, Gothenburg, Sweden.
    Mårtensson, Inga-Lill
    Univ Gothenburg, Dept Rheumatol & Inflammat Res, Box 480, SE-40530 Gothenburg, Sweden.
    CD99 expression is strongly associated with clinical outcome in children with B-cell precursor acute lymphoblastic leukaemia2019Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 184, nr 3, s. 418-423Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Our study aimed to determine the expression pattern and clinical relevance of CD99 in paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). Our findings demonstrate that high expression levels of CD99 are mainly found in high-risk BCP-ALL, e.g. BCR-ABL1 and CRLF2(,)(Re/Hi) and that high CD99 mRNA levels are strongly associated with a high frequency of relapse, high proportion of positive for minimal residual disease at day 29 and poor overall survival in paediatric cohorts, which indicate that CD99 is a potential biomarker for BCP-ALL.

  • 108.
    Chen, Robert
    et al.
    City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplant, 1500 E Duarte Rd, Duarte, CA 91010 USA.
    Zinzani, Pier Luigi
    Univ Bologna, Inst Hematol Seragnoli, Dept Expt Diagnost & Specialty Med, Bologna, Italy.
    Lee, Hun Ju
    Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA.
    Armand, Philippe
    Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
    Johnson, Nathalie A.
    Jewish Gen Hosp, Dept Hematol, Montreal, PQ, Canada.
    Brice, Pauline
    Hop St Louis, Dept Hematol Oncol, Paris, France.
    Radford, John
    Univ Manchester, Div Canc Sci, Manchester, Lancs, England;Christie NHS Fdn Trust, Manchester, Lancs, England.
    Ribrag, Vincent
    Inst Gustave Roussy, Dept Drug Dev & Hematol, Villejuif, France.
    Molin, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Vassilakopoulos, Theodoros P.
    Gen Hosp Athens, Dept Hematol & Bone Marrow Transplantat, Athens, Greece.
    Tomita, Akihiro
    Fujita Hlth Univ, Sch Med, Dept Hematol, Toyoake, Aichi, Japan.
    von Tresckow, Bastian
    Univ Cologne, Dept Internal Med, Cologne, Germany;Univ Hosp Cologne, Cologne, Germany.
    Shipp, Margaret A.
    Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
    Lin, Jianxin
    Merck & Co Inc, Med Oncol, Kenilworth, NJ USA.
    Kim, Eunhee
    Merck & Co Inc, Med Oncol, Kenilworth, NJ USA.
    Nahar, Akash
    Merck & Co Inc, Med Oncol, Kenilworth, NJ USA.
    Balakumaran, Arun
    Merck & Co Inc, Med Oncol, Kenilworth, NJ USA.
    Moskowitz, Craig H.
    Univ Miami, Dept Med, Sylvester Comprehens Canc Ctr, Miami, FL USA.
    Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-0872019Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 134, nr 14, s. 1144-1153Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Programmed death-1 inhibitors are approved for patients with relapsed or refractory classic Hodgkin lymphoma (RRcHL). We present the 2-year follow-up of the phase 2 KEYNOTE-087 study of pembrolizumab in 210 patients, based on HL progression after autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV; cohort 1); salvage chemotherapy and BV, with ineligibility for SCT owing to chemorefractory disease (cohort 2); and progression after SCT without BV (cohort 3). With a median follow-up of 27.6 months, the objective response rate (ORR) by blinded independent central review was 71.9% (95% CI, 65.3-77.9), the complete response rate (CRR) was 27.6%, and the partial response (PR) rate was 44.3%. Median duration of response was 16.5months (range, 0.0+ to 27.0+ [+, no progressive disease at last assessment]) in all patients, 22.1months in cohort 1, 11.1 months in cohort 2, and 24.4 months in cohort 3. Median progression-free survival was not reached in all patients with CR: 13.8 months (95% CI, 12.0-22.1) for patients with PR and 10.9 months (95% CI, 5.6-11.1) for patients with stable disease. Median overall survival was not reached in all patients or in any cohort. Treatment-related adverse events (TRAEs) of any grade occurred in 153 (72.9%) patients; grades 3 and 4 occurred in 25 (12.0%) patients; none resulted in death. Results confirmed effective antitumor activity, durability of response, and manageable safety of pembrolizumab monotherapy in RRcHL, regardless of prior treatment and including chemoresistant cHL.

  • 109.
    Chen, Y-B
    et al.
    Massachusetts Gen Hosp, Yawkey 9E 9052 55 Fruit St, Boston, MA 02114 USA..
    Wang, T.
    Med Coll Wisconsin, Ctr Int Blood, Marrow Transplant Res, Dept Med, Milwaukee, WI USA.;Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI USA..
    Hemmer, M. T.
    Med Coll Wisconsin, Ctr Int Blood, Marrow Transplant Res, Dept Med, Milwaukee, WI USA..
    Brady, C.
    Natl Marrow Donor Program Be Match, Ctr Int Blood, Marrow Transplant Res, Minneapolis, MN USA..
    Couriel, D. R.
    Marrow Transplant Program, Utah Blood, Salt Lake City, UT USA..
    Alousi, A.
    Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Stem Cell Transplantat, Houston, TX 77030 USA..
    Pidala, J.
    H Lee Moffitt Canc Ctr & Res Inst, Res Inst, Tampa, FL USA..
    Urbano-Ispizua, A.
    Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain.;Univ Barcelona, Inst Res Josep Carreras, Dept Hematol, Hosp Clin, Barcelona, Spain..
    Choi, S. W.
    Univ Michigan, Ann Arbor, MI 48109 USA..
    Nishihori, T.
    H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA..
    Teshima, T.
    Univ Hosp, Fukuoka, Japan..
    Inamoto, Y.
    Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, Tokyo, Japan..
    Wirk, B.
    Seattle Canc Care Alliance, Div Bone Marrow Transplant, Seattle, WA USA..
    Marks, D. I.
    Univ Hosp Bristol NHS Trust, Adult Bone Marrow Transplant, Bristol, Avon, England..
    Abdel-Azim, H.
    Univ So Calif, Keck Sch Med, Marrow Transplantat, Div Hematol Oncol & Blood, Los Angeles, CA 90033 USA..
    Lehmann, L.
    Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA..
    Yu, L.
    Louisiana State Univ, Med Ctr, Div Hematol Oncol, Childrens Hosp,Ctr Canc & Blood Disorders,HSC, New Orleans, LA USA..
    Bitan, M.
    Tel Aviv Sourasky Med Ctr, Tel Aviv, Dept Pediat Hematol Oncol, Tel Aviv, Israel..
    Cairo, M. S.
    New York Med Coll, Div Pediat Hematol Oncol, Stem Cell Transplantat, Dept Pediat, Valhalla, NY USA..
    Qayed, M.
    Emory Univ, Sch Med, Dept Pediat, Atlanta, GA, Australia..
    Salit, R.
    Fred Hutchinson Canc Res Ctr, Seattle, WA USA..
    Gale, R. P.
    Imperial Coll London, Hematol Res Ctr, Div Expt Med, Dept Med, London, England..
    Martino, R.
    Hosp Santa Creu St Pau, Div Clin Hematol, Barcelona, Spain..
    Jaglowski, S.
    Ohio State Univ, Med Ctr, Div Hematol, Columbus, OH 43210 USA..
    Bajel, A.
    Royal Melbourne Hosp City Campus, Melbourne, Australia..
    Savani, B.
    Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Dept Med, Nashville, TN USA..
    Frangoul, H.
    Vanderbilt Univ, Sch Med, Div Hematol Oncol, Dept Pediat, Nashville, TN USA..
    Lewis, I. D.
    Royal Adelaide Hosp, Haematol & Bone Marrow Transplant Unit, Adelaide, SA, Australia..
    Storek, J.
    Univ Calgary, Dept Med, Calgary, AB, Canada..
    Askar, M.
    Baylor Univ, Med Ctr, Dallas, TX USA..
    Kharfan-Dabaja, M. A.
    H Lee Mofitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA..
    Aljurf, M.
    King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riyadh, Saudi Arabia..
    Ringden, O.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Div Therapeut Immunol, Dept Lab Med, Stockholm, Sweden..
    Reshef, R.
    Columbia Univ, Med Ctr, Blood & Marrow Transplantat Program, Columbia Ctr Translat Immunol, New York, NY USA..
    Olsson, R. F.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Div Therapeut Immunol, Dept Lab Med, Stockholm, Sweden..
    Hashmi, S.
    Mayo Clin Rochester, Rochester, MN USA..
    Seo, S.
    Nat Canc Res Ctr, East Hosp, Kashiwa, Chiba, Japan..
    Spitzer, T. R.
    MacMillan, M. L.
    Univ Minnesota, Med Ctr, Minneapolis, MN USA..
    Lazaryan, A.
    Univ Minnesota, Med Ctr, Div Hematol Oncol, Dept Med, Minneapolis, MN USA..
    Spellman, S. R.
    Arora, M.
    Cutler, C. S.
    Dana Farber Canc Inst, Ctr Hematol Oncol, Dept Med Oncol, Boston, MA USA..
    GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes2017Inngår i: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 52, nr 3, s. 400-408Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord blood transplantation (UCBT) patients (single (>= 18 years) = 810, double (< 18 years) = 594) with acute leukemia to define the incidence of acute GvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD.

  • 110. Cherif, Honar
    et al.
    Greinacher, Andreas
    Lubenow, Norbert
    Patient was wrongly diagnosed and repeatedly treated for immune thrombocytopenia for 50 years2018Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, artikkel-id EY3IArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    We report on a patient with inherited macrothrombocytopenia, MYH9 related disease (MYH9-RD). The patient was wrongly diagnosed and repeatedly treated for immune thrombocytopenia (ITP) for nearly 50 years. Cases of misdiagnosed MYH9-RD and other hereditary thrombocytopenias have been described previously. Typical clinical features such as renal failure and/or progressive loss of hearing should give grounds to suspect hereditary thrombocytopenia. Initial laboratory diagnosis can start with a simple blood smear followed by immunohistochemistry and genotyping. Therapy with thrombopoietin receptor agonists may be beneficial in selected cases of MYH9-RD. ITP treatments including splenectomy are not indicated and may cause harm.

  • 111.
    Cherif, Honar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Karlsson, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Combination treatment with an erythropoiesis-stimulating agent and intravenous iron alleviates anaemia in patients with hereditary haemorrhagic telangiectasia2014Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, nr 4, s. 350-353Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Patients with hereditary haemorrhagic telangiectasia (HHT) suffer from recurrent epistaxis and bleeding from gastrointestinal telangiectasias that occur despite otherwise normal haemostasis and result in iron deficiency anaemia with increasing severity. In advanced disease, anaemia may be severe, be irresponsive to iron supplementation, and may lead to red blood cell transfusion dependency.

    Methods

    We conducted a retrospective study at our Centre for Osler's Disease to evaluate the effectiveness of adding an erythropoiesis-stimulating agent (ESA) to intravenous iron supplementation in the management of anaemic HHT patients. Blood values and treatment parameters were collected for nine months before combination therapy (iron supplementation only) and 12 months during combination therapy (iron supplementation plus ESA).

    Results

    Four patients received intravenous iron and an ESA with mean weekly doses of 126 mg and 17,300 units (U), respectively. Mean haemoglobin improved significantly during combination therapy, from 106 g/L to 119 g/L (p < 0.001).

    Conclusion

    Anaemia can be alleviated in patients with HHT who are irresponsive to intravenous iron supplementation, by addition of an ESA. The proposed mechanism behind the iron irresponsiveness is that the anaemia is caused by a combination of recurrent haemorrhage and anaemia of chronic disease.

  • 112.
    Chhabra, Saurabh
    et al.
    Med Coll Wisconsin, Dept Med, Div Hematol Oncol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA.
    Ahn, Kwang Woo
    Med Coll Wisconsin, Inst Hlth & Soc, Dept Biostat, Milwaukee, WI 53226 USA;Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
    Hu, Zhen-Huan
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
    Jain, Sandeep
    Med Univ South Carolina, Dept Med, Div Hematol Oncol, Charleston, SC 29425 USA.
    Assal, Amer
    Columbia Univ, Med Ctr, New York, NY USA.
    Cerny, Jan
    UMass Mem Med Ctr, Worcester, MA USA.
    Copelan, Edward A.
    Carolinas HealthCare Syst, Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA.
    Daly, Andrew
    Tom Baker Canc Clin, Calgary, AB, Canada.
    DeFilipp, Zachariah
    Massachusetts Gen Hosp, Blood & Marrow Transplant Program, Boston, MA 02114 USA.
    Gadalla, Shahinaz M.
    NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, NIH, Rockville, MD USA.
    Gale, Robert Peter
    Imperial Coll London, Dept Med, Div Expt Med, Hematol Res Ctr, London, England.
    Ganguly, Siddhartha
    Univ Kansas, Med Ctr, Div Hematol & Oncol, Blood & Marrow Transplantat, Kansas City, KS 66103 USA.
    Hamilton, Betty K.
    Cleveland Clin Fdn, Dept Hematol & Med Oncol, 9500 Euclid Ave, Cleveland, OH 44195 USA.
    Hildebrandt, Gerhard Carl
    Univ Kentucky, Markey Canc Ctr, Lexington, KY USA.
    Hsu, Jack W.
    Shands HealthCare, Dept Med, Div Hematol & Oncol, Gainesville, FL USA;Univ Florida, Gainesville, FL USA.
    Inamoto, Yoshihiro
    Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, Tokyo, Japan.
    Kanate, Abraham S.
    West Virginia Univ, Osborn Hematopoiet Malignancy & Transplantat Prog, Morgantown, WV 26506 USA.
    Khoury, H. Jean
    Emory Univ Hosp, 1364 Clifton Rd NE, Atlanta, GA 30322 USA.
    Lazarus, Hillard M.
    Case Western Reserve Univ, Univ Hosp Cleveland, Med Ctr, Seidman Canc Ctr, Cleveland, OH 44106 USA.
    Litzow, Mark R.
    Mayo Clin Rochester, Div Hematol & Transplant Ctr, Rochester, MN USA.
    Nathan, Sunita
    Rush Univ, Med Ctr, Chicago, IL 60612 USA.
    Olsson, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden.
    Pawarode, Attaphol
    Univ Michigan, Dept Internal Med, Div Hematol Oncol, Med Sch,Blood & Marrow Transplantat Program, Ann Arbor, MI 48109 USA.
    Ringden, Olle
    Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden.
    Rowe, Jacob M.
    Shaare Zedek Med Ctr, Dept Hematol, Jerusalem, Israel.
    Saad, Ayman
    Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA.
    Savani, Bipin N.
    Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, 221 Kirkland Hall, Nashville, TN 37235 USA.
    Schouten, Harry C.
    Acad Ziekenhuis, Dept Hematol, Maastricht, Netherlands.
    Seo, Sachiko
    Natl Canc Res Ctr East, Dept Hematol & Oncol, Chiba, Japan.
    Shah, Nirav N.
    Med Coll Wisconsin, Dept Med, Div Hematol Oncol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA.
    Solh, Melhem
    Northside Hosp, Blood & Marrow Transplant Grp Georgia, Atlanta, GA USA.
    Stuart, Robert K.
    Med Univ South Carolina, Dept Med, Div Hematol Oncol, Charleston, SC 29425 USA.
    Ustun, Celalettin
    Univ Minnesota, Med Ctr, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA.
    Woolfrey, Ann E.
    Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
    Yared, Jean A.
    Univ Maryland, Greenebaum Canc Ctr, Div Hematol Oncol, Blood & Marrow Transplantat Program,Dept Med, Baltimore, MD 21201 USA.
    Alyea, Edwin P.
    Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA.
    Kalaycio, Matt E.
    Cleveland Clin Fdn, Dept Hematol & Med Oncol, 9500 Euclid Ave, Cleveland, OH 44195 USA.
    Popat, Uday
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Sobecks, Ronald M.
    Cleveland Clin Fdn, Dept Hematol & Med Oncol, 9500 Euclid Ave, Cleveland, OH 44195 USA.
    Saber, Wael
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
    Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia2018Inngår i: BLOOD ADVANCES, ISSN 2473-9529, Vol. 2, nr 21, s. 2922-2936Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era.

  • 113.
    Christensen, Kjeld
    et al.
    Orebro Univ Hosp, Dept Cardiol, Orebro, Sweden.;Linnaeus Univ, Linnaeus Ctr Biomat Chem, SE-39182 Kalmar, Sweden..
    Kozarcanin, Huda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Linnaeus Univ, Linnaeus Ctr Biomat Chem, SE-39182 Kalmar, Sweden..
    Ekdahl, Kristina N.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Linnaeus Univ, Linnaeus Ctr Biomat Chem, SE-39182 Kalmar, Sweden..
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Linnaeus Univ, Linnaeus Ctr Biomat Chem, SE-39182 Kalmar, Sweden..
    Evidence of contact activation in patients suffering from ST-elevation myocardial infarction2016Inngår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 141, s. 158-162Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Factor (F) XIIa is an attractive target for anticoagulation in arterial thrombosis. The aim of this study is to investigate the degree of involvement of the contact system in cardiac infarctions. Methods and patients: 165 patients suffering from ST-elevation myocardial infarction (STEMI) and 100 healthy controls were included in the study. Samples were drawn at admission before percutaneous intervention (PCI), 1-3 days post-percutaneous intervention (PCI) and, in one-third of the patients, 3 months after PCI. In order to investigate the degree of Factor XII (FXII) activation, changes in FXIIa/AT and FXIIa/C1INH complex levels were quantified by ELISA. Results: FXIIa/AT levels at admission (0.89 +/- 0.50; p < 0.01) were significantly higher than those in normal individuals (0.39 +/- 0.28), but the levels after 1-3 days (0.33 +/- 0.33; p < 0.05) were essentially normalized. In contrast, the FXII/C1INH levels at admission (1.40 +/- 0.72; p < 0.001) and after 1-3 days (0.83 +/- 0.59; p < 0.001) were both significantly higher than those in normal individuals (0.40 +/- 0.30). FXIIa/AT and FXIIa/C1INH complexes at admission (p < 0.001; p < 0.001) and after 1-3 days (p < 0.02; p < 0.001) were significantly different from those at 3 months. No significant differences were observed when the data were stratified for patency (open/closed culprit lesions). Conclusion: Both FXIIa/AT and FXIIa/C1INH complexes were significantly increased and reflected the activation of FXII in STEMI patients at admission. In particular, FXIIa/AT complex elevations support the hypothesis that clot propagation-mediated FXII activation had occurred, and this activation may be a target for anticoagulation in patients with cardiac infarction. Based on previous studies, the FXIIa/C1INH complex levels were primarily interpreted to reflex endothelial cell activation.

  • 114.
    Christersson, Christina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Jönelid, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Thulin, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    The change of the amount of circulating microparticles and their association to the general atherosclerotic burden after acute coronary syndrome2015Inngår i: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, nr S2, s. 214-214, artikkel-id OR312Artikkel i tidsskrift (Annet vitenskapelig)
  • 115.
    Christiansson, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Myeloid-Derived Suppressor Cells and Other Immune Escape Mechanisms in Chronic Leukemia2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Chronic myeloid leukemia (CML) is characterized by the Philadelphia chromosome, a minute chromosome that leads to the creation of the fusion gene BCR/ABL and the transcription of the fusion protein BCR/ABL in transformed cells. The constitutively active tyrosine kinase BCR/ABL confers enhanced proliferation and survival on leukemic cells. CML has in only a few decades gone from being a disease with very bad prognosis to being a disease that can be effectively treated with oral tyrosine kinase inhibitors (TKIs). TKIs are drugs inhibiting BCR/ABL as well as other tyrosine kinases. In this thesis, the focus has been on the immune system of CML patients, on immune escape mechanisms present in untreated patients and on how these are affected by TKI therapy. We have found that newly diagnosed, untreated CML patients exert different kinds of immune escape mechanisms. Patients belonging to the Sokal high-risk group had higher levels of myeloid-derived suppressor cells (MDSCs) as well as high levels of the programmed death receptor 1 (PD-1)-expressing cytotoxic T cells compared to control subjects. Moreover, CML patients had higher levels of myeloid cells expressing the ligand for PD-1, PD-L1. CML patients as well as patients with B cell malignacies had high levels of soluble CD25 in blood plasma. In B cell malignacies, sCD25 was found to be released from T regulatory cells (Tregs). Treatment with the TKIs imatinib or dasatinib decreased the levels of MDSCs in peripheral blood. Tregs on the other hand increased during TKI therapy. The immunostimulatory molecule CD40 as well as NK cells increased during therapy, indicating an immunostimulatory effect of TKIs. When evaluating immune responses, multiplex techniques for quantification of proteins such as cytokines and chemokines are becoming increasingly popular. With these techniques a lot of information can be gained from a small sample volume and complex networks can be more easily studied than when using for example the singleplex ELISA. When comparing different multiplex platforms we found that the absolute protein concentration measured by one platform rarely correlated with the absolute concentration measured by another platform. However, relative quantification was better correlated.

    Delarbeid
    1. Increased Level of Myeloid-Derived Suppressor Cells, Programmed Death Receptor Ligand 1/Programmed Death Receptor 1, and Soluble CD25 in Sokal High Risk Chronic Myeloid Leukemia
    Åpne denne publikasjonen i ny fane eller vindu >>Increased Level of Myeloid-Derived Suppressor Cells, Programmed Death Receptor Ligand 1/Programmed Death Receptor 1, and Soluble CD25 in Sokal High Risk Chronic Myeloid Leukemia
    Vise andre…
    2013 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 1, s. e55818-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Immunotherapy (eg interferon α) in combination with tyrosine kinase inhibitors is currently in clinical trials for treatment of chronic myeloid leukemia (CML). Cancer patients commonly have problems with so called immune escape mechanisms that may hamper immunotherapy. Hence, to study the function of the immune system in CML is of interest. In the present paper we have identified immune escape mechanisms in CML with focus on those that directly hamper T cells since these cells are important to control tumor progression. CML patient samples were investigated for the presence of myeloid-derived suppressor cells (MDSCs), expression of programmed death receptor ligand 1/programmed death receptor 1 (PD-L1/PD-1), arginase 1 and soluble CD25. MDSC levels were increased in samples from Sokal high risk patients (p<0,05) and the cells were present on both CD34 negative and CD34 positive cell populations. Furthermore, expression of the MDSC-associated molecule arginase 1, known to inhibit T cells, was increased in the patients (p = 0,0079). Myeloid cells upregulated PD-L1 (p<0,05) and the receptor PD-1 was present on T cells. However, PD-L1 blockade did not increase T cell proliferation but upregulated IL-2 secretion. Finally, soluble CD25 was increased in high risk patients (p<0,0001). In conclusion T cells in CML patients may be under the control of different immune escape mechanisms that could hamper the use of immunotherapy in these patients. These escape mechanisms should be monitored in trials to understand their importance and how to overcome the immune suppression.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-196216 (URN)10.1371/journal.pone.0055818 (DOI)000314610600164 ()23383287 (PubMedID)
    Tilgjengelig fra: 2013-03-05 Laget: 2013-03-05 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    2. Imatinib or dasatinib treatment of chronic myeloid leukemia reduces circulating myeloid-derived suppressor cells but increases their CD40 expression
    Åpne denne publikasjonen i ny fane eller vindu >>Imatinib or dasatinib treatment of chronic myeloid leukemia reduces circulating myeloid-derived suppressor cells but increases their CD40 expression
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-197601 (URN)
    Tilgjengelig fra: 2013-03-30 Laget: 2013-03-30 Sist oppdatert: 2013-08-30
    3. A Comparison of Multiplex Platforms for Absolute and Relative Protein Quantification
    Åpne denne publikasjonen i ny fane eller vindu >>A Comparison of Multiplex Platforms for Absolute and Relative Protein Quantification
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-197603 (URN)
    Tilgjengelig fra: 2013-03-30 Laget: 2013-03-30 Sist oppdatert: 2013-08-30
    4. T regulatory cells control T-cell proliferation partly by the release of soluble CD25 in patients with B-cell malignancies
    Åpne denne publikasjonen i ny fane eller vindu >>T regulatory cells control T-cell proliferation partly by the release of soluble CD25 in patients with B-cell malignancies
    Vise andre…
    2010 (engelsk)Inngår i: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 131, nr 3, s. 371-376Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Interleukin-2 (IL-2) is one of the most studied cytokines driving T-cell proliferation, activation and survival. It binds to the IL-2 receptor consisting of three chains, the alpha (CD25), beta and common gamma (gammac). The binding of the CD25 chain to IL-2 is necessary to expose high-affinity binding sites for the beta and gammac chains, which, in turn, are responsible for downstream signalling. A high level of soluble CD25 (sCD25) has been associated with a poor prognosis in patients with non-Hodgkin's lymphoma. The function and source of origin of this soluble receptor is not well investigated. In the present study we hypothesized that T regulatory (Treg) cells may release CD25 to act as a decoy receptor for IL-2, thereby depriving T-effector cells of IL-2. Peripheral blood from patients with B-cell malignancies (n = 26) and healthy controls (n = 27) was investigated for the presence and function of FoxP3(+) Treg cells and sCD25 by multi-colour flow cytometry and enzyme-linked immunosorbent assay. Further, the proliferative capacity of T cells was evaluated with or without the presence of recombinant sCD25. The results demonstrate that Treg cells from patients had lower CD25 expression intensity and that they released CD25 in vitro. Further, high levels of Treg cells correlated with sCD25 plasma concentration. Recombinant sCD25 could suppress T-cell proliferation in vitro. In conclusion, the release of sCD25 by Treg cells may be a mechanism to deprive IL-2 and thereby inhibit anti-tumour T-cell responses.

    Emneord
    B-cell malignancy, CD25, interleukin-2 receptor α, immune escape mechanism, T regulatory cell
    HSV kategori
    Forskningsprogram
    Immunologi
    Identifikatorer
    urn:nbn:se:uu:diva-128828 (URN)10.1111/j.1365-2567.2010.03308.x (DOI)000282690500008 ()20518821 (PubMedID)
    Tilgjengelig fra: 2010-07-26 Laget: 2010-07-26 Sist oppdatert: 2017-12-12bibliografisk kontrollert
  • 116.
    Christiansson, Lisa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Söderlund, Stina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Mangsbo, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hjorth-Hansen, Henrik
    St Olavs Hosp, Dept Hematol, Trondheim, Norway.;Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, Trondheim, Norway..
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Markevarn, Berit
    Norrland Univ Hosp, Dept Hematol, Umea, Sweden..
    Richter, Johan
    Skane Univ Hosp, Dept Hematol & Coagulat, Lund, Sweden..
    Stenke, Leif
    Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Mustjoki, Satu
    Univ Helsinki, Dept Med, Div Hematol, Hematol Res Unit Helsinki, Helsinki, Finland.;Univ Helsinki.
    Loskog, Angelica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Olsson-Strömberg, Ulla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    The Tyrosine Kinase Inhibitors Imatinib and Dasatinib Reduce Myeloid Suppressor Cells and Release Effector Lymphocyte Responses2015Inngår i: Molecular Cancer Therapeutics, ISSN 1535-7163, E-ISSN 1538-8514, Vol. 14, nr 5, s. 1181-1191Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Immune escape mechanisms promote tumor progression and are hurdles of cancer immunotherapy. Removing immunosuppressive cells before treatment can enhance efficacy. Tyrosine kinase inhibitors (TKI) may be of interest to combine with immunotherapy, as it has been shown that the inhibitor sunitinib reduces myeloid suppressor cells in patients with renal cell carcinoma and dasatinib promotes expansion of natural killer-like lymphocytes in chronic myeloid leukemia (CML). In this study, the capacity of dasatinib and imatinib to reduce myeloid suppressor cells and to induce immunomodulation in vivo was investigated ex vivo. Samples from CML patients treated with imatinib (n = 18) or dasatinib (n = 14) within a Nordic clinical trial (clinicalTrials.gov identifier: NCT00852566) were investigated for the presence of CD11b(+)CD14(-)CD33(+) myeloid cells and inhibitorymolecules (arginase I, myeloperoxidase, IL10) as well as the presence of natural killer cells, T cells (naive/memory), and stimulatory cytokines (IL12, IFN gamma, MIG, IP10). Both imatinib and dasatinib decreased the presence of CD11b(+)CD14(-)CD33(+) myeloid cells as well as the inhibitory molecules and the remaining myeloid suppressor cells had an increased CD40 expression. Monocytes also increased CD40 after therapy. Moreover, increased levels of CD40, IL12, natural killer cells, and experienced T cells were noted after TKI initiation. The presence of experienced T cells was correlated to a higher IFNg and MIG plasma concentration. Taken together, the results demonstrate that both imatinib and dasatinib tilted the immunosuppressive CML tumor milieu towards promoting immune stimulation. Hence, imatinib and dasatinib may be of interest to combine with cancer immunotherapy. 

  • 117.
    Cornell, Robert F.
    et al.
    Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA..
    Bachanova, Veronika
    Univ Minnesota, Med Ctr, Bone & Marrow Transplant Program, Minneapolis, MN 55455 USA..
    D'Souza, Anita
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA..
    Woo-Ahn, Kwang
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.;Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA..
    Martens, Michael
    Med Coll Wisconsin, Dept Oncol, Milwaukee, WI 53226 USA..
    Huang, Jiaxing
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA..
    Al-Homsi, A. Samer
    Spectrum Hlth, Blood & Marrow Transplant, Grand Rapids, MI USA..
    Chhabra, Saurabh
    Med Univ South Carolina, Dept Med, Charleston, SC USA..
    Copelan, Edward
    Carolinas HealthCare Syst, Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA..
    Diaz, Miguel-Angel
    Hosp Infanta Univ Nino Jesus, Dept Hematol Oncol, Madrid, Spain..
    Freytes, Cesar O.
    Texas Transplant Inst, San Antonio, TX USA..
    Gale, Robert Peter
    Imperial Coll London, Dept Med, Div Expt Med, Hematol Res Ctr, London, England..
    Ganguly, Siddhartha
    Univ Kansas, Med Ctr, Blood & Marrow Transplantat, Div Hematol & Oncol, Kansas City, KS 66103 USA..
    Hamadani, Mehdi
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA..
    Hildebrandt, Gerhard
    Univ Kentucky, Div Hematol & Blood & Marrow Transplantat, Markey Canc Ctr, Lexington, KY USA..
    Kamble, Rammurti T.
    Baylor Coll Med, Div Hematol & Oncol, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Kharfan-Dabaja, Mohamed
    H Lee Moffitt Canc & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA..
    Kindwall-Keller, Tamila
    Univ Virginia Hlth Syst, Div Hematol Oncol, Charlottesville, VA USA..
    Lazarus, Hillard M.
    Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA..
    Marks, David I.
    Univ Hosp Bristol NHS Trust, Adult Bone Marrow Transplant, Bristol, Avon, England..
    Nishihori, Taiga
    H Lee Moffitt Canc & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA..
    Olsson, Richard F.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Div Therapeut Immunol, Dept Lab Med, Stockholm, Sweden..
    Saad, Ayman
    Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA..
    Usmani, Saad
    Carolinas HealthCare Syst, Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA..
    Vesole, David H.
    Hackensack UMC, John Theurer Canc Ctr, Hackensack, NJ USA..
    Yared, Jean
    Univ Maryland, Dept Med, Blood & Marrow Transplantat Program, Div Hematol Oncol,Greenebaum Canc Ctr, Baltimore, MD 21201 USA..
    Mark, Tomer
    Weill Cornell Med Coll, Dept Med, New York, NY USA..
    Nieto, Yago
    Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA..
    Hari, Parameswaran
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA..
    Allogeneic Transplantation for Relapsed Waldenström Macroglobulinemia and Lymphoplasmacytic Lymphoma2017Inngår i: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 23, nr 1, s. 60-66Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Waldenstrom macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) is characterized by lymphoplasmacytic proliferation, lymph node and spleen enlargement, bone marrow involvement, and IgM production. Treatment varies based on the extent and biology of disease. In some patients, the use of allogeneic hematopoietic cell transplantation (alloHCT) may have curative potential. We evaluated long-term outcomes of 144 patients who received adult alloHCT for WM/LPL. Data were obtained from the Center for International Blood and Marrow Transplant Research database (2001 to 2013). Patients received myeloablative (n = 67) or reduced-intensity conditioning (RIC; n = 67). Median age at alloHCT was 53 years, and median time from diagnosis to transplantation was 41 months. Thirteen percent (n = 18) failed prior autologous HCT. About half (n = 82, 57%) had chemosensitive disease at the time of transplantation, whereas 22% had progressive disease. Rates of progression-free survival, overall survival, relapse, and nonrelapse mortality at 5 years were 46%, 52%, 24%, and 30%, respectively. Patients with chemosensitive disease and better pretransplant disease status experienced significantly superior overall survival. There were no significant differences in progression-free survival based on conditioning (myeloablative, 50%, versus RIC, 41%) or graft source. Conditioning intensity did not impact treatment-related mortality or relapse. The most common causes of death were primary disease and graft-versus-host disease (GVHD). AlloHCT yielded durable survival in select patients with WM/LPL. Strategies to reduce mortality from GVHD and post-transplant relapse are necessary to improve this approach.

  • 118. Cornell, Robert F
    et al.
    D'Souza, Anita
    Kassim, Adetola A
    Costa, Luciano J
    Innis-Shelton, Racquel D
    Zhang, Mei-Jie
    Huang, Jiaxing
    Abidi, Muneer
    Aiello, Jack
    Akpek, Gorgun
    Bashey, Asad
    Bashir, Qaiser
    Cerny, Jan
    Comenzo, Raymond
    Diaz, Miguel Angel
    Freytes, César
    Gale, Robert Peter
    Ganguly, Siddhartha
    Hamadani, Mehdi
    Hashmi, Shahrukh
    Holmberg, Leona
    Hossain, Nasheed
    Kamble, Rammurti T
    Kharfan-Dabaja, Mohamed
    Kindwall-Keller, Tamila
    Kyle, Robert
    Kumar, Shaji
    Lazarus, Hillard
    Lee, Cindy
    Maiolino, Angelo
    Marks, David I
    Meehan, Kenneth
    Mikhael, Joe
    Nath, Rajneesh
    Nishihori, Taiga
    Olsson, Richard F.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Ramanathan, Muthalagu
    Saad, Ayman
    Seo, Sachiko
    Usmani, Saad
    Vesole, David
    Vij, Ravi
    Vogl, Dan
    Wirk, Baldeep M
    Yared, Jean
    Krishnan, Amrita
    Mark, Tomer
    Nieto, Yago
    Hari, Parameswaran
    Maintenance versus Induction Therapy Choice on Outcomes after Autologous Transplantation for Multiple Myeloma2017Inngår i: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 23, nr 2, s. 269-277Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bortezomib (V), lenalidomide (R), cyclophosphamide (C), and dexamethasone (D) are components of the most commonly used modern doublet (RD, VD) or triplet (VRD, CVD) initial induction regimens before autologous hematopoietic cell transplantation (AHCT) for multiple myeloma (MM) in the United States. In this study we evaluated 693 patients receiving "upfront" AHCT after initial induction therapy with modern doublet or triplet regimens using data reported to the Center for International Blood and Marrow Transplant Research from 2008 to 2013. Analysis was limited to those receiving a single AHCT after 1 line of induction therapy within 12 months from treatment initiation for MM. In multivariate analysis, progression-free survival (PFS) and overall survival were similar irrespective of induction regimen. However, high-risk cytogenetics and nonreceipt of post-transplant maintenance/consolidation therapy were associated with higher risk of relapse. Patients receiving post-transplant therapy had significantly improved 3-year PFS versus no post-transplant therapy (55% versus 39%, P = .0001). This benefit was most evident in patients not achieving at least a complete response post-AHCT (P = .005). In patients receiving upfront AHCT, the choice of induction regimen (doublet or triplet therapies) appears to be of lower impact than use of post-transplant therapy.

  • 119.
    Dahlberg, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Genetic Cartography at Massively Parallel Scale2018Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Massively parallel sequencing (MPS) is revolutionizing genomics. In this work we use, refine, and develop new tools for the discipline.

    MPS has led to the discovery of multiple novel subtypes in Acute Lymphoblastic Leukemia (ALL). In Study I we screen for fusion genes in 134 pediatric ALL patients, including patients without an assigned subtype. In approximately 80% of these patients we detect novel or known fusion gene families, most of which display distinct methylation and expression patterns. This shows the potential for improvements in the clinical stratification of ALL. Large sample sizes are important to detect recurrent somatic variation. In Study II we investigate if a non-index overlapping pooling schema can be used to increase sample size and detect somatic variation. We designed a schema for 172 ALL samples and show that it is possible to use this method to call somatic variants.

    Around the globe there are many ongoing and completed genome projects. In Study III we sequenced the genome of 1000 Swedes to create a reference data set for the Swedish population. We identified more than 10 million variants that were not present in publicly available databases, highlighting the need for population-specific resources. Data, and the tools developed during this study, have been made publicly available as a resource for genomics in Sweden and abroad.

    The increased amount of sequencing data has created a greater need for automation. In Study IV we present Arteria, a computational automation system for sequencing core facilities. This system has been adopted by multiple facilities and has been used to analyze thousands of samples. In Study V we developed CheckQC, a program that provides automated quality control of Illumina sequencing runs. These tools make scaling up MPS less labour intensive, a key to unlocking the full future potential of genomics.

    The tools, and data presented here are a valuable contribution to the scientific community. Collectively they showcase the power of MPS and genomics to bring about new knowledge of human health and disease.

    Delarbeid
    1. Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles
    Åpne denne publikasjonen i ny fane eller vindu >>Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles
    Vise andre…
    2017 (engelsk)Inngår i: Journal of Hematology & Oncology, ISSN 1756-8722, E-ISSN 1756-8722, Vol. 10, artikkel-id 148Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts. Methods: We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes. Results: We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations. Conclusion: Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.

    Emneord
    Pediatric acute lymphoblastic leukemia, RNA sequencing, Fusion genes, BCP-ALL, T-ALL, Translocation
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-332658 (URN)10.1186/s13045-017-0515-y (DOI)000408001300001 ()28806978 (PubMedID)
    Forskningsfinansiär
    Swedish Foundation for Strategic Research , RBc08-008Swedish Cancer Society, 130440, 160711Swedish Childhood Cancer Foundation, 11098Swedish Research Council, C0524801, 2016-03691_3
    Merknad

    De 2 sista författarna delar sistaförfattarskapet.

    Tilgjengelig fra: 2017-10-31 Laget: 2017-10-31 Sist oppdatert: 2019-10-23bibliografisk kontrollert
    2. Identification of somatic variants by targeted sequencing of pooled cancer samples
    Åpne denne publikasjonen i ny fane eller vindu >>Identification of somatic variants by targeted sequencing of pooled cancer samples
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Forskningsprogram
    Medicinsk genetik
    Identifikatorer
    urn:nbn:se:uu:diva-269752 (URN)
    Tilgjengelig fra: 2015-12-18 Laget: 2015-12-18 Sist oppdatert: 2018-08-27
    3. SweGen: a whole-genome data resource of genetic variability in a cross-section of the Swedish population
    Åpne denne publikasjonen i ny fane eller vindu >>SweGen: a whole-genome data resource of genetic variability in a cross-section of the Swedish population
    Vise andre…
    2017 (engelsk)Inngår i: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 25, nr 11, s. 1253-1260Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.

    sted, utgiver, år, opplag, sider
    NATURE PUBLISHING GROUP, 2017
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-337314 (URN)10.1038/ejhg.2017.130 (DOI)000412823800012 ()28832569 (PubMedID)
    Forskningsfinansiär
    Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceKnut and Alice Wallenberg Foundation, 2014.0272Swedish Research CouncilSwedish National Infrastructure for Computing (SNIC), sens2016003EU, European Research Council, 282330
    Tilgjengelig fra: 2018-01-08 Laget: 2018-01-08 Sist oppdatert: 2018-08-27bibliografisk kontrollert
    4. Arteria: An automation system for a sequencing core facility
    Åpne denne publikasjonen i ny fane eller vindu >>Arteria: An automation system for a sequencing core facility
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-357972 (URN)
    Tilgjengelig fra: 2018-08-23 Laget: 2018-08-23 Sist oppdatert: 2018-08-27
    5. CheckQC: Quick quality control of Illumina sequencing runs
    Åpne denne publikasjonen i ny fane eller vindu >>CheckQC: Quick quality control of Illumina sequencing runs
    2018 (engelsk)Inngår i: The Journal of Open Source Software, ISSN 2475-9066, Vol. 3, nr 22, artikkel-id 556Artikkel i tidsskrift (Fagfellevurdert) Published
    Emneord
    bioinformatics, sequencing
    HSV kategori
    Forskningsprogram
    Bioinformatik
    Identifikatorer
    urn:nbn:se:uu:diva-349255 (URN)10.21105/joss.00556 (DOI)
    Tilgjengelig fra: 2018-04-24 Laget: 2018-04-24 Sist oppdatert: 2018-08-27bibliografisk kontrollert
  • 120. Dahlen, Torsten
    et al.
    Edgren, Gustaf
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Lambe, Mats
    Bjorkholm, Magnus
    Sandin, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Sjalander, Anders
    Richter, Johan
    Ohm, Lotta
    Back, Magnus
    Stenke, Leif
    Increased Risk of Cardiovascular Events Associated with TKI Treatment in Chronic Phase Chronic Myeloid Leukemia. Data from Swedish Population-Based Registries2014Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, nr 21Artikkel i tidsskrift (Annet vitenskapelig)
  • 121.
    Dahlin, J. S.
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Stockholm, Sweden..
    Ungerstedt, J. S.
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden.;Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden..
    Grootens, J.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Stockholm, Sweden..
    Sander, B.
    Karolinska Inst, Karolinska Univ Hosp, Div Pathol, Dept Lab Med, Stockholm, Sweden..
    Guelen, T.
    Karolinska Univ, Huddinge Hosp, Dept Resp Dis & Allergy, Stockholm, Sweden..
    Hägglund, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi. Univ Uppsala Hosp, Sect Hematol, Uppsala, Sweden..
    Nilsson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi. Karolinska Inst, Karolinska Univ Hosp, Dept Med, Stockholm, Sweden..
    Detection of circulating mast cells in advanced systemic mastocytosis2016Inngår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 30, nr 9, s. 1954-+Artikkel i tidsskrift (Fagfellevurdert)
  • 122.
    Dahlin, Joakim S.
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Ekoff, Maria
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Grootens, Jennine
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Löf, Liza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Ungerstedt, Johanna S.
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden.;Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden..
    Olsson-Strömberg, Ulla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Nilsson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi. Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden.
    KIT signaling is dispensable for human mast cell progenitor development2017Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 130, nr 16, s. 1785-1794Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human hematopoietic progenitors are generally assumed to require stem cell factor (SCF) and KIT signaling during differentiation for the formation of mast cells. Imatinib treatment, which inhibits KIT signaling, depletes mast cells in vivo. Furthermore, the absence of SCF or imatinib treatment prevents progenitors from developing into mast cells in vitro. However, these observations do not mean that mast cell progenitors require SCF and KIT signaling throughout differentiation. Here, we demonstrate that circulating mast cell progenitors are present in patients undergoing imatinib treatment. In addition, we show that mast cell progenitors from peripheral blood survive, mature, and proliferate without SCF and KIT signaling in vitro. Contrary to the prevailing consensus, our results show that SCF and KIT signaling are dispensable for early mast cell development.

  • 123.
    Dahlin, Joakim S
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Malinovschi, Andrei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Öhrvik, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Sandelin, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Janson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Alving, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Hallgren, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Lineage- CD34hi CD117int/hi FcϵRI+ cells in human blood constitute a rare population of mast cell progenitors2016Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 127, nr 4, s. 383-391Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34(+) progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered. To our knowledge, this is the first report of human lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7 and developed a mast cell-like phenotype, although with a slow cell division capacity in vitro. Isolated lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) blood cells had an immature mast cell-like appearance and expressed high levels of many mast cell-related genes as compared with human blood basophils in whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A mRNA transcripts were detected by quantitative RT-PCR. Altogether, we propose that the lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) blood mast cell progenitors than asthmatics with normal lung function.

  • 124.
    Dantonello, Tobias M
    et al.
    Paediatrics 5 (oncology, hematology, immunology), Olgahospital Klinikum Stuttgart, Germany.
    Stark, Monika
    Paediatrics 5 (oncology, hematology, immunology), Olgahospital Klinikum Stuttgart, Germany.
    Timmermann, Beate
    Fuchs, Jörg
    Selle, Barbara
    Linderkamp, Christin
    Handgretinger, Rupert
    Hagen, Rudolf
    Feuchtgruber, Simone
    Kube, Stefanie
    Kosztyla, Daniel
    Kazanowska, Bernarda
    Ladenstein, Ruth
    Niggli, Felix
    Ljungman, Gustaf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Bielack, Stefan S
    Klingebiel, Thomas
    Koscielniak, Ewa
    Paediatrics 5 (oncology, hematology, immunology), Olgahospital Klinikum Stuttgart, Germany.
    Tumour volume reduction after neoadjuvant chemotherapy impacts outcome in localised embryonal rhabdomyosarcoma2015Inngår i: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 62, nr 1, s. 16-23Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Response (tumour volume reduction) to induction chemotherapy has been used to stratify secondary local and systemic treatment of Intergroup Rhabdomyosarcoma Study Group III (IRSG-III) embryonal rhabdomyosarcoma (RME) in consecutive CWS-trials. To evaluate its actual impact we studied response-related treatment and outcomes.

    PROCEDURE: Patients with IRSG-III RME <21 years and non-response (NR, <33% volume reduction) in five consecutive CWS-trials were analysed and compared with partial responders (PAR, ≥33% reduction). The NR was reviewed and sub-classified as Objective Response (OR, <0%-33% reduction) or Stable/Progressive Disease (SPD).

    RESULTS: Fifty-nine of 529 patients had NR (n = 34 OR, n = 25 SPD). Primary risk-factors including age, tumour size, and TN-classification did not differ between NR and PAR groups but NR had more patients with unfavourable sites comparatively (P = 0.04). There were no differences in primary risk-factors between OR and SPD. Significant factors associated with poor outcome in multivariate analysis were NR, TN-classification, age >10 years, tumour size >5 cm and therapy in older trials. After response assessment n = 24 NR continued to receive induction chemotherapy, n = 32 received other combinations and n = 3 no further chemotherapy. Forty-two non-responders were irradiated, and the tumours were completely resected in n = 20. After a median follow-up of 8 years, 34 NR are alive. Seventeen of 21 failures leading to disease-related deaths were locoregional. The five-year overall survival rate (OS) was 76 ± 4% for PAR, 79 ± 14% for OR, but only 40 ± 19% for SPD (P < 0.001).

    CONCLUSION: Response to induction chemotherapy appears to be an important surrogate marker of poor outcome in patients with SPD largely due to ineffective local control.

  • 125. Darzentas, N.
    et al.
    Hadzidimitriou, A.
    Murray, Fiona
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Hatzi, K.
    Josefsson, P.
    Laoutaris, N.
    Moreno, C.
    Anagnostopoulos, A.
    Jurlander, J.
    Tsaftaris, A.
    Chiorazzi, N.
    Belessi, C.
    Ghia, Paolo
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Davi, F.
    Stamatopoulos, K.
    A different ontogenesis for chronic lymphocytic leukemia cases carrying stereotyped antigen receptors: molecular and computational evidence2010Inngår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 24, nr 1, s. 125-132Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chronic lymphocytic leukemia (CLL) is uniquely characterized by the existence of subsets of cases with quasi-identical, 'stereotyped' B-cell receptors (BCRs). Herein we investigate this stereotypy in 2662 patients with CLL, the largest series yet, using purpose-built bioinformatics methods based on sequence pattern discovery. Besides improving the identification of 'stereotyped' cases, we demonstrate that CLL actually consists of two different categories, based on the BCR repertoire, with important biological and ontogenetic differences. The first ( approximately 30% of cases) shows a very restricted repertoire and is characterized by BCR stereotypy (clustered cases), whereas the second includes cases with heterogeneous BCRs (nonclustered cases). Eleven major CLL clusters were identified with antigen-binding sites defined by just a few critically positioned residues, regardless of the actual immunoglobulin (IG) variable gene used. This situation is closely reminiscent of the receptors expressed by cells participating in innate immune responses. On these grounds, we argue that whereas CLL cases with heterogeneous BCRs likely derive from the conventional B-cell pool, cases with stereotyped BCRs could derive from progenitor cells evolutionarily adapted to particular antigenic challenges, perhaps intermediate between a true innate immune system and the conventional adaptive B-cell immune system, functionally similar to what has been suggested previously for mouse B1 cells.

  • 126.
    De Caterina, Raffaele
    et al.
    Univ G DAnnunzio, Chieti, Italy.;Fdn Toscana G Monasterio, Pisa, Italy..
    Husted, Steen
    Univ Aarhus, Aarhus, Denmark..
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Andreotti, Felicita
    Univ Cattolica Sacro Cuore, I-00168 Rome, Italy..
    Arnesen, Harald
    Oslo Univ Hosp Ulleval, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Bachmann, Fedor
    Univ Lausanne, Lausanne, Switzerland..
    Baigent, Colin
    Univ Oxford, Oxford, England..
    Collet, Jean-Philippe
    Grp Hosp Pitie Salpetriere, INSERM, UMRS ICAN 1166, F-75634 Paris, France..
    Halvorsen, Sigrun
    Oslo Univ Hosp Ulleval, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Huber, Kurt
    Wilhelminenhosp, Vienna, Austria..
    Jespersen, Jorgen
    Univ Southern Denmark, Esbjerg, Denmark..
    Kristensen, Steen Dalby
    Aarhus Univ Hosp, DK-8000 Aarhus, Denmark..
    Lip, Gregory Y. H.
    Univ Birmingham, City Hosp, Inst Cardiovasc Sci, Birmingham, W Midlands, England..
    Morais, Joao
    Hosp Santo Andre, Leiria, Portugal..
    Rasmussen, Lars Hvilsted
    Aalborg Univ, Aalborg, Denmark..
    Ricci, Fabrizio
    Univ G DAnnunzio, Chieti, Italy.;Fdn Toscana G Monasterio, Pisa, Italy..
    Sibbing, Dirk
    Univ Munich, Klinikum Univ Munchen, Med Klin & Poliklin 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Storey, Robert F.
    Univ Sheffield, Sheffield, S Yorkshire, England..
    ten Berg, Jurrien
    St Antonius Hosp, Nieuwegein, Netherlands..
    Verheugt, Freek W. A.
    Onze Lieve Vrouw Hosp, Amsterdam, Netherlands..
    Weitz, Jeffrey I.
    McMaster Univ, Hamilton, ON, Canada.;Thrombosis & Atherosclerosis Res Inst, Hamilton, ON, Canada..
    Oral anticoagulants in coronary heart disease (Section IV) Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease2016Inngår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 115, nr 4, s. 685-711Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Until recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice.

  • 127.
    de Laval, Philip
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Mobarrez, Fariborz
    Karolinska Univ Hosp, Karolinska Inst, Unit Rheumatol, Dept Med, Solna, Sweden.
    Almquist, Tora
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Nephrol, Stockholm, Sweden.
    Vassil, Liina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Soveri, Inga
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Acute effects of haemodialysis on circulating microparticles2019Inngår i: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 12, nr 3, s. 456-462Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Microparticles (MPs) are small cell membrane-derived vesicles regarded as both biomarkers and mediators of biological effects. Elevated levels of MPs have previously been associated with endothelial dysfunction and predict cardiovascular death in patients with end-stage renal disease. The objective of this study was to measure change in MP concentrations in contemporary haemodialysis (HD).

    Methods. Blood was sampled from 20 consecutive HD patients before and 1h into the HD session. MPs were measured by flow cytometry and phenotyped based on surface markers.

    Results. Concentrations of platelet (CD41(+)) (P = 0.039), endothelial (CD62E(+)) (P = 0.004) andmonocyte-derived MPs (CD14(+)) (P<0.001) significantly increased during HD. Similarly, endothelial-(P = 0.007) and monocyte-derived MPs (P = 0.001) expressing tissue factor (TF) significantly increased as well as MPs expressing Klotho (P = 0.003) and receptor for advanced glycation end products (RAGE) (P = 0.009). Furthermore, MPs expressing platelet activationmarkers P-selectin (P = 0.009) and CD40L (P = 0.045) also significantly increased. The increase of endothelial (P = 0.034), monocyte (P = 0.014) and RAGE(+) MPs (P = 0.032) as well as TF+ platelet-derived MPs (P = 0.043) was significantly higher in patients treated with low-flux compared with high-flux dialysers.

    Conclusion. Dialysis triggers release of MPs of various origins with marked differences between high-flux and low-flux dialysers. The MPs carry surface molecules that could possibly influence coagulation, inflammation, oxidative stress and endothelial dysfunction. The clinical impact of these findings remains to be established in future studies.

  • 128. de Miranda, Noel F. C. C.
    et al.
    Georgiou, Konstantinos
    Chen, Longyun
    Wu, Chenglin
    Gao, Zhibo
    Zaravinos, Apostolos
    Lisboa, Susana
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Teixeira, Manuel R.
    Zeng, Yixin
    Peng, Roujun
    Pan-Hammarstrom, Qiang
    Exome sequencing reveals novel mutation targets in diffuse large B-cell lymphomas derived from Chinese patients2014Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, nr 16, s. 2544-2553Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Next-generation sequencing studies on diffuse large B-cell lymphomas (DLBCLs) have revealed novel targets of genetic aberrations but also high intercohort heterogeneity. Previous studies have suggested that the prevalence of disease subgroups and cytogenetic profiles differ between Western and Asian patients. To characterize the coding genome of Chinese DLBCL, we performed whole-exome sequencing of DNA derived from 31 tumors and respective peripheral blood samples. The mutation prevalence of B2M, CD70, DTX1, LYN, TMSB4X, and UBE2A was investigated in an additional 105 tumor samples. We discovered 11 novel targets of recurrent mutations in DLBCL that included functionally relevant genes such as LYN and TMSB4X. Additional genes were found mutated at high frequency (>= 10%) in the Chinese cohort including DTX1, which was the most prevalent mutation target in the Notch pathway. We furthermore demonstrated that mutations in DTX1 impair its function as a negative regulator of Notch. Novel and previous unappreciated targets of somatic mutations in DLBCL identified in this study support the existence of additional/alternative tumorigenic pathways in these tumors. The observed differences with previous reports might be explained by the genetic heterogeneity of DLBCL, the germline genetic makeup of Chinese individuals, and/or exposure to distinct etiological agents.

  • 129.
    Del Giudice, I.
    et al.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Visentin, A.
    Univ Padua, Hematol & Clin Immunol Unit, Dept Med, Padua, Italy.
    Trentin, L.
    Univ Padua, Hematol & Clin Immunol Unit, Dept Med, Padua, Italy.
    Flogegard, M.
    Falun Cent Hosp, Hematol, Med Clin, Falun, Sweden.
    Cavalloni, C.
    Policlin San Matteo, IRCCS, Pavia, Italy.
    Orlandi, E.
    Policlin San Matteo, IRCCS, Pavia, Italy.
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Raponi, S.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Ilari, C.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Cafforio, L.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    De Propris, M. S.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Della Starza, I.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Peragine, N.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Mariglia, P.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Semenzato, G.
    Univ Padua, Hematol & Clin Immunol Unit, Dept Med, Padua, Italy.
    Guarini, A.
    Sapienza Univ, Dept Mol Med, Rome, Italy.
    Montserrat, E.
    Univ Barcelona, Dept Hematol, Hosp Clin, Barcelona, Spain.
    Foa, R.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Spontaneous Clinical Regression In Chronic Lymphocytic Leukemia: Clinical And Biologic Features Of 9 Cases From The ERIC Registry2017Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, nr Suppl. 3, s. 121-122, artikkel-id P177Artikkel i tidsskrift (Annet vitenskapelig)
  • 130.
    Del Giudice, I.
    et al.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Visentin, A.
    Univ Padua, Hematol & Clin Immunol Unit, Dept Med, Padua, Italy.
    Trentin, L.
    Univ Padua, Hematol & Clin Immunol Unit, Dept Med, Padua, Italy.
    Flogegard, M.
    Falun Cent Hosp, Hematol, Med Clin, Falun, Sweden.
    Cavalloni, C.
    Policlin San Matteo, IRCCS, Pavia, Italy.
    Orlandi, E.
    Policlin San Matteo, IRCCS, Pavia, Italy.
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Raponi, S.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Ilari, C.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Cafforio, L.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    De Propris, M. S.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Della Starza, I.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Peragine, N.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Mariglia, P.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Semenzato, G.
    Univ Padua, Hematol & Clin Immunol Unit, Dept Med, Padua, Italy.
    Guarini, A.
    Sapienza Univ, Dept Mol Med, Rome, Italy.
    Montserrat, E.
    Univ Barcelona, Dept Hematol, Hosp Clin, Barcelona, Spain.
    Foa, R.
    Sapienza Univ, Dept Cellular Biotechnol & Hematol, Hematol, Rome, Italy.
    Spontaneous Clinical Regression In Chronic Lymphocytic Leukemia: Clinical And Biologic Features Of 9 Cases From The ERIC Registry2017Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, nr Suppl. 2, s. 714-714, artikkel-id PB1779Artikkel i tidsskrift (Annet vitenskapelig)
  • 131.
    Deneberg, Stefan
    et al.
    Karolinska Univ Hosp, Ctr Hematol, Stockholm, Sweden.;Karolinska Inst, Inst Med, Stockholm, Sweden..
    Lundin, Ebba
    Karolinska Univ Hosp, Ctr Hematol, Stockholm, Sweden..
    Lazarevic, Vladimir
    Skane Univ Hosp, Dept Hematol, Lund, Sweden..
    Benson, Lina
    Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden..
    Uggla, Bertil
    Orebro Univ Hosp, Med, Orebro, Sweden..
    Antunovic, Petar
    Linkoping Univ Hosp, Hematol, S-58185 Linkoping, Sweden..
    Mollgard, Lars
    Sahlgrens Univ Hosp, Dept Hematol, Gothenbourg, Sweden..
    Lehmann, Sören
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Juliusson, Gunnar
    Skane Univ Hosp, Dept Hematol, Lund, Sweden..
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Derolf, Asa Rangert
    Karolinska Univ Hosp, Dept Med, Div Hematol, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Reasons for Decreasing Early Mortality in Acute Myeloid Leukemia: An Epidemiological Study from the Swedish Acute Leukemia Registry2015Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, nr 23Artikkel i tidsskrift (Annet vitenskapelig)
  • 132.
    Deol, Abhinav
    et al.
    Wayne State Univ, Karmanos Canc Inst, Dept Oncol, 4100 John R,4 HWCRC, Detroit, MI 48201 USA..
    Sengsayadeth, Salyka
    Vanderbilt Univ, Med Ctr, Nashville, TN USA..
    Ahn, Kwang Woo
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.;Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA..
    Wang, Hai-Lin
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA..
    Aljurf, Mahmoud
    King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riyadh, Saudi Arabia..
    Antin, Joseph Harry
    Dana Farber Canc Inst, Dept Med Oncol, Ctr Hematol Oncol, Boston, MA 02115 USA..
    Battiwalla, Minoo
    NHLBI, Hematol Branch, Bethesda, MD 20892 USA..
    Bornhauser, Martin
    Carl Gustav Carus Univ Hosp, Dresden, Germany..
    Cahn, Jean-Yves
    Univ Hosp, Dept Hematol, Grenoble, France..
    Camitta, Bruce
    Med Coll Wisconsin, Midwest Ctr Canc & Blood Disorders, Milwaukee, WI 53226 USA.;Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA..
    Chen, Yi-Bin
    Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA..
    Cutler, Corey S.
    Dana Farber Canc Inst, Dept Med Oncol, Ctr Hematol Oncol, Boston, MA 02115 USA..
    Gale, Robert Peter
    Imperial Coll London, Dept Med, Div Expt Med, Hematol Res Ctr, London, England..
    Ganguly, Siddhartha
    Univ Kansas, Med Ctr, Div Hematol & Oncol, Blood & Marrow Transplantat, Kansas City, KS 66103 USA..
    Hamadani, Mehdi
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA..
    Inamoto, Yoshihiro
    Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, Tokyo, Japan..
    Jagasia, Madan
    Vanderbilt Univ, Med Ctr, Nashville, TN USA..
    Kamble, Rammurti
    Baylor Coll Med, Ctr Cell & Gene Therapy, Div Hematol & Oncol, Houston, TX 77030 USA..
    Koreth, John
    Dana Farber Canc Inst, Dept Med Oncol, Ctr Hematol Oncol, Boston, MA 02115 USA..
    Lazarus, Hillard M.
    Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA..
    Liesveld, Jane
    Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA..
    Litzow, Mark R.
    Mayo Clin, Div Hematol, Rochester, NY USA.;Mayo Clin, Transplant Ctr, Rochester, NY USA..
    Marks, David I.
    Univ Hosp Bristol Natl Hlth Serv Trust, Pediat Bone Marrow Transplant, Bristol, Avon, England..
    Nishihori, Taiga
    H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA..
    Olsson, Richard F.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Div Therapeut Immunol, Dept Lab Med, Stockholm, Sweden..
    Reshef, Ran
    Columbia Univ, Med Ctr, Blood & Marrow Transplantat Program, New York, NY USA.;Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY USA..
    Rowe, Jacob M.
    Shaare Zedek Med Ctr, Dept Hematol, Jerusalem, Israel..
    Saad, Ayman A.
    Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA..
    Sabloff, Mitchell
    Univ Ottawa, Dept Med, Div Hematol, Ottawa, ON, Canada.;Ottawa Hosp, Res Inst, Ottawa, ON, Canada..
    Schouten, Harry C.
    Acad Hosp Maastricht, Dept Hematol, Maastricht, Netherlands..
    Shea, Thomas C.
    Univ North Carolina Hlth Care, Dept Med, Div Hematol & Oncol, Chapel Hill, NC USA..
    Soiffer, Robert J.
    Dana Farber Canc Inst, Dept Med Oncol, Ctr Hematol Oncol, Boston, MA 02115 USA..
    Uy, Geoffrey L.
    Washington Univ, Sch Med, Div Oncol, St Louis, MO USA..
    Waller, Edmond K.
    Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA..
    Wiernik, Peter H.
    Our Lady Mercy Med Ctr, Bronx, NY USA..
    Wirk, Badeep
    Seattle Canc Care Alliance, Div Bone Marrow Transplant, Seattle, WA USA..
    Woolfrey, Ann E.
    Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA..
    Bunjes, Donald
    Ulm Univ Hosp, Dept Internal Med 3, Ulm, Germany..
    Devine, Steven
    Ohio State Univ, Dept Internal Med, Comprehens Canc Ctr James, Columbus, OH 43210 USA..
    de Lima, Marcos
    Univ Hosp Case Med Ctr, Seidman Canc Ctr, Dept Med, Cleveland, OH USA..
    Sandmaier, Brenda M.
    Univ Washington, Div Med Oncol, Seattle, WA 98195 USA.;Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA..
    Weisdorf, Dan
    Natl Marrow Donor Program Be Match, Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA..
    Khoury, Hanna Jean
    Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA..
    Saber, Wael
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA..
    Does FLT3 Mutation Impact Survival After Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia?: A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis2016Inngår i: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 122, nr 19, s. 3005-3014Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Patients with FMS like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT). METHODS: Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes. RESULTS: In total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild-type (WT) group (38% [95% confidence interval (CI), 30%-45%] vs 28% [95% CI, 24%-33%]; P = .04; relative risk, 1.60 [95% CI, 1.15-2.22]; P = .0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia-free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3-year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%-57%; WT group: 55%, 95% CI, 50%-60%; P = .20). CONCLUSIONS: The current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long-term survivors.

  • 133.
    Derolf, Åsa
    et al.
    Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden;Karolinska Inst, Dept Internal Med, Stockholm, Sweden.
    Juliusson, Gunnar
    Skane Univ Hosp, Dept Hematol Oncol & Radiat Phys, Lund, Sweden.
    Benson, Lina
    Epidemiol & Reg Oncol Ctr Stockholm, Stockholm, Sweden.
    Flöisand, Yngvar
    Oslo Univ Hosp, Dept Hematol, Oslo, Norway.
    Lazarevic, Vladimir
    Skane Univ Hosp, Dept Hematol Oncol & Radiat Phys, Lund, Sweden.
    Antunovic, Petar
    Linkoping Univ Hosp, Dept Hematol, Linkoping, Sweden.
    Möllgård, Lars
    Sahlgrens Univ Hosp, Dept Med, Gothenburg, Sweden.
    Lehmann, Sören
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Uggla, Bertil
    Orebro Univ Hosp, Sch Hlth & Med Sci, Dept Med, Orebro, Sweden.
    Wahlin, Anders
    Umea Univ, Dept Radiat Sci, Umea, Sweden.
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Deneberg, Stefan
    Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden;Karolinska Inst, Dept Internal Med, Stockholm, Sweden.
    Decreasing early mortality in acute myeloid leukaemia in Sweden 1997-2014: improving performance status is a major contributing factor2020Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 188, nr 1, s. 187-191Artikkel i tidsskrift (Fagfellevurdert)
  • 134.
    Dhanraj, Santhosh
    et al.
    Univ Toronto, Inst Med Sci, Toronto, ON, Canada.;Hosp Sick Children, Genet & Genome Biol Program, Toronto, ON, Canada..
    Gunja, Sethu Madhava Rao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Kemisk biologi.
    Deveau, Adam P.
    IWK Hlth Ctr, Dept Pediat, Halifax, NS, Canada..
    Nissbeck, Mikael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Kemisk biologi.
    Boonyawat, Boonchai
    Hosp Sick Children, Genet & Genome Biol Program, Toronto, ON, Canada..
    Coombs, Andrew J.
    IWK Hlth Ctr, Dept Pediat, Halifax, NS, Canada..
    Renieri, Alessandra
    Univ Siena, Med Genet, I-53100 Siena, Italy..
    Mucciolo, Mafalda
    Univ Siena, Med Genet, I-53100 Siena, Italy..
    Marozza, Annabella
    Univ Siena, Med Genet, I-53100 Siena, Italy..
    Buoni, Sabrina
    Univ Siena, Pediat Neurol, Siena, Italy..
    Turner, Lesley
    Mem Univ Newfoundland, Discipline Genet, St John, NF, Canada..
    Li, Hongbing
    Hosp Sick Children, Genet & Genome Biol Program, Toronto, ON, Canada..
    Jarrar, Ameer
    IWK Hlth Ctr, Dept Pediat, Halifax, NS, Canada..
    Sabanayagam, Mathura
    Hosp Sick Children, Genet & Genome Biol Program, Toronto, ON, Canada..
    Kirby, Melanie
    Hosp Sick Children, Dept Pediat, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada..
    Shago, Mary
    Hosp Sick Children, Dept Paediat, Lab Med, Cytogenet Lab, Toronto, ON, Canada..
    Pinto, Dalila
    Mt Sinai Sch Med, Mindich Child Hlth & Dev Inst, Seaver Autism Ctr, Dept Psychiat, New York, NY USA.;Mt Sinai Sch Med, Mindich Child Hlth & Dev Inst, Seaver Autism Ctr, Dept Genet & Genom Sci, New York, NY USA..
    Berman, Jason N.
    Dalhousie Univ, IWK Hlth Ctr, Pediat, Microbiol & Immunol, Halifax, NS, Canada..
    Scherer, Stephen W.
    Hosp Sick Children, Genet & Genome Biol Program, Toronto, ON, Canada..
    Virtanen, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Kemisk biologi.
    Dror, Yigal
    Univ Toronto, Inst Med Sci, Toronto, ON, Canada.;Hosp Sick Children, Genet & Genome Biol Program, Toronto, ON, Canada.;Hosp Sick Children, Dept Pediat, Div Hematol Oncol, Marrow Failure & Myelodysplasia Program, Toronto, ON M5G 1X8, Canada..
    Bone Marrow Failure and Developmental Delay Caused By Mutations in Poly(A)-Specific Ribonuclease2015Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, nr 23Artikkel i tidsskrift (Annet vitenskapelig)
  • 135.
    Dickinson, Michael
    et al.
    Peter MacCallum Canc Ctr, Clin Haematol, Melbourne, Vic 3000, Australia;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.
    Cherif, Honar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Fenaux, Pierre
    Univ Paris XIII, Hop Avicenne, AP HP, Bobigny, France.
    Mittelman, Moshe
    Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel.
    Verma, Amit
    Albert Einstein Coll Med, Dept Med, Div Med Oncol, New York, NY USA.
    Portella, Maria Socorro O.
    Novartis Pharmaceut, E Hanover, NJ USA.
    Burgess, Paul
    Novartis Pharma AG, Basel, Switzerland.
    Ramos, Pedro Marques
    Novartis Pharma AG, Basel, Switzerland.
    Choi, Jeea
    Novartis Pharmaceut, E Hanover, NJ USA.
    Platzbecker, Uwe
    Univ Leipzig, Univ Hosp Leipzig, Med Clin & Policlin 1, Leipzig, Germany.
    Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia2018Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 132, nr 25, s. 2629-2638Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Azacitidine treatment of myelodysplastic syndromes (MDSs) generally exacerbates thrombocytopenia during the first treatment cycles. A Study of Eltrombopag in Myelodysplastic Syndromes Receiving Azacitidine (SUPPORT), a phase 3, randomized, double-blind, placebo-controlled study, investigated the platelet supportive effects of eltrombopag given concomitantly with azacitidine. International Prognostic Scoring System intermediate-1, intermediate-2, or high-risk MDS patients with baseline platelets <75 3 10(9)/L were randomized 1: 1 to eltrombopag (start, 200 mg/d [East Asians, 100 mg/d], maximum, 300 mg/d [East Asians, 150 mg/d]) or placebo, plus azacitidine (75 mg/m2 subcutaneously once daily for 7 days every 28 days). The primary end point was the proportion of patients platelet transfusion-free during cycles 1 through 4 of azacitidine therapy. Based on planned interim analyses, an independent data monitoring committee recommended stopping the study prematurely because efficacy outcomes crossed the predefined futility threshold and for safety reasons. At termination, 28/179 (16%) eltrombopag and 55/177 (31%) placebo patients met the primary end point. Overall response (International Working Group criteria; complete, marrow, or partial response) occurred in 20% and 35% of eltrombopag and placebo patients, respectively, by investigator assessment. There was no difference in hematologic improvement in any cell lineage between the 2 arms. There was no improvement in overall or progression-free survival. Adverse events with >= 10% occurrence in the eltrombopag vs placebo arm were febrile neutropenia and diarrhea. Compared with azacitidine alone, eltrombopag plus azacitidine worsened platelet recovery, with lower response rates and a trend toward increased progression to acute myeloid leukemia. This trial was registered at www.clinicaltrials.govas# NCT02158936.

  • 136. Dignass, Axel U
    et al.
    Gasche, Christoph
    Bettenworth, Dominik
    Birgegård, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Danese, Silvio
    Gisbert, Javier P
    Gomollon, Fernando
    Iqbal, Tariq
    Katsanos, Konstantinos
    Koutroubakis, Ioannis
    Magro, Fernando
    Savoye, Guillaume
    Stein, Jürgen
    Vavricka, Stephan
    European Consensus on the Diagnosis and Management of Iron Deficiency and Anaemia in Inflammatory Bowel Diseases2015Inngår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 9, nr 3, s. 211-222Artikkel i tidsskrift (Fagfellevurdert)
  • 137.
    Dolinska, Monika
    et al.
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden..
    Klang, Johannis
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden..
    Xiao, Pingnan
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden..
    Durgaryan, Andranik
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden..
    Sandhow, Lakshmi
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden..
    Johansson, Anne-Sofie
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden..
    Kondo, Makoto
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden..
    Deneberg, Stefan
    Karolinska Univ Hosp, Ctr Hematol, Stockholm, Sweden..
    Ungerstedt, Johanna
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden.;Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden..
    Le Blanc, Katarina
    Karolinska Inst, Lab Med Clin Immunol, Stockholm, Sweden..
    Stenke, Leif
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Ekblom, Marja
    Skane Univ Hosp, Dept Hematol & Vasc Disorders, Lund, Sweden..
    Strömberg, Ulla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Mustjoki, Satu
    Univ Helsinki, Dept Hematol, HRUH, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Ctr Comprehens Canc, Helsinki, Finland..
    Lehmann, Soren
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden..
    Qian, Hong
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden..
    Phenotypic and Functional Alterations of Bone Marrow Mesenchymal Stem and Progenitor Cells in Chronic Myeloid Leukemia2015Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, nr 23Artikkel i tidsskrift (Annet vitenskapelig)
  • 138.
    Dolinska, Monika
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, SE-14186 Stockholm, Sweden..
    Piccini, Alexandre
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, SE-14186 Stockholm, Sweden..
    Wong, Wan Man
    Lund Univ, Dept Lab Med, Lund, Sweden..
    Gelali, Eleni
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, SE-14186 Stockholm, Sweden..
    Johansson, Anne-Sofie
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, SE-14186 Stockholm, Sweden..
    Klang, Johannis
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, SE-14186 Stockholm, Sweden..
    Xiao, Pingnan
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, SE-14186 Stockholm, Sweden..
    Yektaei-Karin, Elham
    Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Strömberg, Ulla Ohlsson
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Mustjoki, Satu
    Univ Helsinki, Dept Clin Chem & Hematol, Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Helsinki, Finland..
    Stenke, Leif
    Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Ekblom, Marja
    Lund Univ, Dept Lab Med, Lund, Sweden..
    Qian, Hong
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, SE-14186 Stockholm, Sweden..
    Leukotriene signaling via ALOX5 and cysteinyl leukotriene receptor 1 is dispensable for in vitro growth of CD34 (+)CD38(-) stem and progenitor cells in chronic myeloid leukemia2017Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 490, nr 2, s. 378-384Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tyrosine kinase inhibitors targeting the BCR-ABL oncoprotein in chronic myeloid leukemia (CML) are remarkably effective inducing deep molecular remission in most patients. However, they are less effective to eradicate the leukemic stem cells (LSC), resulting in disease persistence. Therefore, there is great need to develop novel therapeutic strategies to specifically target the LSC. In an experimental mouse CML model system, the leukotriene pathway, and specifically, the expression ALOX5, encoding 5-lipoxygenase (5-LO), has been reported as a critical regulator of the LSC. Based on these results, the 5-LO inhibitor zileuton has been introduced in clinical trials as a therapeutic option to target the LSC although its effect on primary human CML LSC has not been studied. We have here by using multiplex single cell PCR analyzed the expression of the mediators of the leukotriene pathway in bone marrow (BM) BCR-ABL(+)CD34(+)CD38(-) cells at diagnosis, and found low or undetectable expression of ALOX5. In line with this, zileuton did not exert significant overall growth inhibition in the long-term culture-initiating cell (LTC-IC) and colony (CFU-C) assays of BM CD34(+)CD38(-) cells from 7 CML patients. The majority of the single leukemic BCR-ABL(+)CD34(+)CD38(-) cells expressed cysteinyl leukotriene receptors CYSLTI and CYSLT2. However, montelukast, an inhibitor of CYSLTI, also failed to significantly suppress CFU-C and LTC-IC growth. These findings indicate that targeting ALOX5 or CYSLTI signaling with leukotriene antagonists, introduced into the clinical practice primarily as prophylaxis and treatment for asthma, may not be a promising pharmacological strategy to eradicate persisting LSC in CML patients. (C) 2017 The Author(s). Published by Elsevier Inc.

  • 139.
    Domanovic, Dragoslav
    et al.
    European Ctr Dis Prevent & Control ECDC, Stockholm, Sweden.
    Ushiro-Lumb, Ines
    NHS Blood & Transplant, Natl Transfus Microbiol Reference Lab, London, England;Publ Hlth England, London, England.
    Compernolle, Veerle
    Belgian Red Cross Flanders, Transfus Res Ctr, Ghent, Belgium.
    Brusin, Sergio
    European Ctr Dis Prevent & Control ECDC, Stockholm, Sweden.
    Funk, Markus
    Paul Ehrlich Inst, Fed Inst Vaccines & Biomed, Pharmacovigilance 2, Langen, Germany.
    Gallian, Pierre
    Etab Francais Sang Provence Alpes Cote dAzur & Co, Marseille, France.
    Georgsen, Jorgen
    Odense Univ Hosp, Dept Clin Immunol, South Danish Transfus Serv, Odense, Denmark.
    Janssen, Mart
    Sanquin Res, Transfus Technol Assessment, Dept Donor Med Res, Amsterdam, Netherlands.
    Jimenez-Marco, Teresa
    Balearic Isl Blood & Tissue Bank Fdn, Palma De Mallorca, Spain.
    Knutson, Folke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Liumbruno, Giancarlo M.
    Natl Inst Hlth, Italian Natl Blood Ctr, Rome, Italy.
    Mali, Polonca
    Blood Transfus Ctr Slovenia, Ljubljana, Slovenia.
    Marano, Giuseppe
    Natl Inst Hlth, Italian Natl Blood Ctr, Rome, Italy.
    Maryuningsih, Yuyun
    WHO, Geneva, Switzerland.
    Niederhauser, Christoph
    Interreg Blood Transfus Swiss Red Cross, Lab Diagnost, Bern, Switzerland.
    Politis, Constantina
    Hellen Natl Publ Hlth Org, Hellen Coordinating Hemovigilance Ctr, Athens, Greece.
    Pupella, Simonetta
    Natl Inst Hlth, Italian Natl Blood Ctr, Rome, Italy.
    Rautmann, Guy
    European Directorate Qual Med & HealthCare, Strasbourg, France.
    Saadat, Karmin
    Austrian Agcy Hlth & Food Safety, Vienna, Austria.
    Sandid, Imad
    French Natl Agcy Med & Hlth Prod Safety ANSM, St Denis, France.
    Sousa, Ana P.
    Portuguese Blood & Transplantat Ctr, Lisbon, Portugal.
    Vaglio, Stefania
    Natl Inst Hlth, Italian Natl Blood Ctr, Rome, Italy.
    Velati, Claudio
    Natl Inst Hlth, Italian Natl Blood Ctr, Rome, Italy.
    Verdun, Nicole
    US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
    Vesga, Miguel
    Spanish Sci Comm Transfus Safety, Basque Ctr Transfus & Human Tissues, Galdakao, Spain.
    Rebulla, Paolo
    IRCCS Fdn Ca Granda Maggiore Policlin Hosp, Milan, Italy.
    Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting2019Inngår i: Blood Transfusion, ISSN 1723-2007, Vol. 17, nr 6, s. 433-448Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pathogen reduction (PR) of selected blood components is a technology that has been adopted in practice in various ways. Although they offer great advantages in improving the safety of the blood supply, these technologies have limitations which hinder their broader use, e.g. increased costs. In this context, the European Centre for Disease Prevention and Control (ECDC), in co-operation with the Italian National Blood Centre, organised an expert consultation meeting to discuss the potential role of pathogen reduction technologies (PRT) as a blood safety intervention during outbreaks of infectious diseases for which (in most cases) laboratory screening of blood donations is not available. The meeting brought together 26 experts and representatives of national competent authorities for blood from thirteen European Union and European Economic Area (EU/EEA) Member States (MS), Switzerland, the World Health Organization, the European Directorate for the Quality of Medicines and Health Care of the Council of Europe, the US Food and Drug Administration, and the ECDC. During the meeting, the current use of PRTs in the EU/EEA MS and Switzerland was verified, with particular reference to emerging infectious diseases (see Appendix). In this article, we also present expert discussions and a common view on the potential use of PRT as a part of both preparedness and response to threats posed to blood safety by outbreaks of infectious disease.

  • 140. Douketis, J.
    et al.
    Healey, J. S.
    Brueckmann, M.
    Fraessdorf, M.
    Spyropoulos, A.
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Oldgren, J.
    Reilly, P.
    Ezekowitz, M.
    Connolly, S.
    Yusuf, S.
    Bleeding and thromboembolic outcomes in warfarin-and dabigatran-treated patients in the RE-LY trial who required an urgent surgery or procedure2015Inngår i: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, nr S2, s. 393-394, artikkel-id PO362-MONArtikkel i tidsskrift (Annet vitenskapelig)
  • 141.
    Drott, Kristina
    et al.
    Skane Univ Hosp, Dept Oncol, Lasarettsg 23 A, SE-22185 Lund, Sweden.
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Papworth, Karin
    Norrland Univ Hosp, Dept Oncol, Umea, Sweden.
    Relander, Thomas
    Skane Univ Hosp, Dept Oncol, Lasarettsg 23 A, SE-22185 Lund, Sweden.
    Jerkeman, Mats
    Skane Univ Hosp, Dept Oncol, Lasarettsg 23 A, SE-22185 Lund, Sweden.
    Valproate in combination with rituximab and CHOP as first-line therapy in diffuse large B-cell lymphoma (VALFRID)2018Inngår i: BLOOD ADVANCES, ISSN 2473-9529, Vol. 2, nr 12, s. 1386-1392Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aims of the present study were to establish the maximally tolerated dose (MTD) of the histone deacetylase inhibitor valproate together with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with diffuse large B-cell lymphoma (DLBCL). A phase 1 dose escalation study of valproate together with R-CHOP followed by a dose expansion study using the established MTD of valproate was performed. MTD of valproate together with R-CHOP was established at 60 mg/kg per day, as higher doses resulted in auditory adverse events (AEs). In the study population, 2-year progression-free survival was 84.7% (95% confidence interval [CI], 73.2%-98%). The 2-year overall survival (OS) was 96.8% (n = 31; 95% CI, 90.8%-100%). These data were compared with 2 risk-factor matched populations of R-CHOP-treated patients from the Swedish Lymphoma Registry (cohort A, n = 330 and B, n = 165). As compared with the matched cohorts, we observed a statistically significant (P = .034 and 0.028, respectively) beneficial effect of the addition of valproate to R-CHOP on the OS in the studied population. In conclusion, addition of valproate to R-CHOP is a feasible strategy in first-line treatment of DLBCL. The proposed phase 2 dose is 60 mg/kg per day together with prednisone. Auditory AEs were unexpected and warrant close monitoring. Our findings suggest that drugs that target histone deacetylation may add benefit and are tolerable when combined with standard R-CHOP in DLBCL.

  • 142.
    Drott, Kristina
    et al.
    Lund Univ, Dept Oncol, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Relander, Thomas
    Lund Univ, Dept Oncol, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Graffman, Cecilia
    Lund Univ, Dept Oncol, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Drott, Johan
    Respiratorius AB, Lund, Sweden..
    Jerkeman, Mats
    Lund Univ, Dept Oncol, Skane Univ Hosp, Lund, Sweden..
    Valproate in Combination with Rituximab and CHOP As First Line Therapy in Diffuse Large B-Cell Lymphoma (VALFRID): Preliminary Results from a Phase I Trial with a Dose Expansion Cohort2015Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, nr 23Artikkel i tidsskrift (Annet vitenskapelig)
  • 143. Eckerle, S.
    et al.
    Brune, V.
    Döring, C.
    Tiacci, E.
    Bohle, V.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Kodet, R.
    Paulli, M.
    Falini, B.
    Klapper, W.
    Chaubert, A. B.
    Willenbrock, K.
    Metzler, D.
    Bräuninger, A.
    Küppers, Ralf
    Hansmann, M-L.
    Gene expression profiling of isolated tumour cells from anaplastic large cell lymphomas: insights into its cellular origin, pathogenesis and relation to Hodgkin lymphoma2009Inngår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 23, nr 11, s. 2129-2138Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Anaplastic large cell lymphoma (ALCL) is a main type of T-cell lymphomas and comprises three distinct entities: systemic anaplastic lymphoma kinase (ALK) positive, systemic ALK(-) and cutaneous ALK(-) ALCL (cALCL). Little is known about their pathogenesis and their cellular origin, and morphological and immunophenotypical overlap exists between ALK(-) ALCL and classical Hodgkin lymphoma (cHL). We conducted gene expression profiling of microdissected lymphoma cells of five ALK(+) and four ALK(-) systemic ALCL, seven cALCL and sixteen cHL, and of eight subsets of normal T and NK cells. The analysis supports a derivation of ALCL from activated T cells, but the lymphoma cells acquired a gene expression pattern hampering an assignment to a CD4(+), CD8(+) or CD30(+) T-cell origin. Indeed, ALCL display a down-modulation of many T-cell characteristic molecules. All ALCL types show significant expression of NFkappaB target genes and upregulation of genes involved in oncogenesis (e.g. EZH2). Surprisingly, few genes are differentially expressed between systemic and cALCL despite their different clinical behaviour, and between ALK(-) ALCL and cHL despite their different cellular origin. ALK(+) ALCL are characterized by expression of genes regulated by pathways constitutively activated by ALK. This study provides multiple novel insights into the molecular biology and pathogenesis of ALCL.

  • 144.
    Edgren, G.
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, SE-17177 Stockholm, Sweden;Soder Sjukhuset, Dept Cardiol, Stockholm, Sweden.
    Hjalgrim, H.
    Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark;Copenhagen Univ Hosp, Dept Hematol, Copenhagen, Denmark.
    Rostgaard, K.
    Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark.
    Dahl, V.
    Publ Hlth Agcy Sweden, Dept Monitoring & Evaluat, Stockholm, Sweden.
    Titlestad, K.
    Odense Univ Hosp, Dept Clin Immunol, Odense, Denmark.
    Erikstrup, C.
    Aarhus Univ Hosp, Dept Clin Immunol, Aarhus, Denmark.
    Wikman, A.
    Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden;Karolinska Inst, Dept Lab Med, Stockholm, Sweden.
    Norda, Rut
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Majeed, A.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, SE-17177 Stockholm, Sweden;Alfred Hlth, Dept Gastroenterol, Melbourne, Vic, Australia;Monash Univ, Cent Clin Sch, Melbourne, Vic, Australia.
    Searching for unknown transfusion-transmitted hepatitis viruses: a binational cohort study of 1.5 million transfused patients2018Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 284, nr 1, s. 92-103Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Both hepatitis B and C viruses were transmitted through blood transfusion before implementation of donor screening. The existence of additional, yet unknown transfusion transmittable agents causing liver disease could have important public health implications.

    Methods. Analyses were based on the Scandinavian Donations and Transfusions (SCANDAT2) database. Cox regression models were used to estimate the hazard ratio (HR) of developing chronic liver disease in recipients of blood from donors who later developed any chronic liver disease compared to recipients who received blood transfusion from healthy donors. We also studied whether the risk of liver disease was increased in patients who received units from high-risk' donors, defined as donors who had a higher than expected occurrence of liver disease amongst their previous recipients. All analyses were stratified before and after 1992 to account for the effect of screening for hepatitis C virus.

    Results. A total of 1 482 922 transfused patients were included in the analyses. Analyses showed evidence of transfusion transmission of liver diseases before, but not after the implementation of hepatitis C virus screening in 1992, with HRs for any liver disease of 1.38 [95% confidence interval (CI), 1.30-1.46] and 0.99 (95% CI, 0.91-1.07), before and after 1992, respectively. Similarly, blood components from 'high-risk' donors conferred increased risks before, but not after 1992.

    Conclusions. Our data provide no evidence for transfusion transmission of agents causing liver disease after the implementation of screening for hepatitis B and C, and suggest that if such transmission does occur, it is rare.

  • 145.
    Edgren, Gustaf
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden..
    Rostgaard, Klaus
    Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark..
    Vasan, Senthil K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden..
    Wikman, Agneta
    Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden..
    Norda, Rut
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Pedersen, Ole Birger
    Naestved Hosp, Dept Clin Immunol, Naestved, Denmark..
    Erikstrup, Christian
    Aarhus Univ Hosp, Dept Clin Immunol, DK-8000 Aarhus, Denmark..
    Nielsen, Kaspar Rene
    Aalborg Univ Hosp, Dept Clin Immunol, Aalborg, Denmark..
    Titlestad, Kjell
    Odense Univ Hosp, Dept Clin Immunol, DK-5000 Odense, Denmark..
    Ullum, Henrik
    Univ Copenhagen Hosp, Rigshosp, Dept Clin Immunol, Blood Bank, DK-2100 Copenhagen, Denmark..
    Melbye, Mads
    Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.;Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark.;Stanford Sch Med, Dept Med, Stanford, CA USA..
    Nyren, Olof
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden..
    Hjalgrim, Henrik
    Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark..
    The new Scandinavian Donations and Transfusions database (SCANDAT2): a blood safety resource with added versatility2015Inngår i: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 55, nr 7, s. 1600-1606Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BackgroundRisks of transfusion-transmitted disease are currently at a record low in the developed world. Still, available methods for blood surveillance might not be sufficient to detect transmission of diseases with unknown etiologies or with very long incubation periods. Study Design and MethodsWe have previously created the anonymized Scandinavian Donations and Transfusions (SCANDAT) database, containing data on blood donors, blood transfusions, and transfused patients, with complete follow-up of donors and patients for a range of health outcomes. Here we describe the re-creation of SCANDAT with updated, identifiable data. We collected computerized data on blood donations and transfusions from blood banks covering all of Sweden and Denmark. After data cleaning, two structurally identical databases were created and the entire database was linked with nationwide health outcomes registers to attain complete follow-up for up to 47 years regarding hospital care, cancer, and death. ResultsAfter removal of erroneous records, the database contained 25,523,334 donation records, 21,318,794 transfusion records, and 3,692,653 unique persons with valid identification, presently followed over 40 million person-years, with possibility for future extension. Data quality is generally high with 96% of all transfusions being traceable to their respective donation(s) and a very high (>97%) concordance with official statistics on annual number of blood donations and transfusions. ConclusionsIt is possible to create a binational, nationwide database with almost 50 years of follow-up of blood donors and transfused patients for a range of health outcomes. We aim to use this database for further studies of donor health, transfusion-associated risks, and transfusion-transmitted disease.

  • 146.
    Ednersson, Susanne Bram
    et al.
    Sahlgrens Univ Hosp, Dept Pathol, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
    Stenson, Martin
    Kungalvs Hosp, Sect Haematol, Dept Med, Kungalv, Sweden;Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
    Stern, Mimmie
    South Alvsborg Hosp, Dept Med, Sect Haematol, Boras, Sweden;Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Fagman, Henrik
    Sahlgrens Univ Hosp, Dept Pathol, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
    Nilsson-Ehle, Herman
    Sahlgrens Univ Hosp, Sect Haematol & Coagulat, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
    Hasselblom, Sverker
    Dept Res Dev & Educ, Halmstad, Region Halland, Sweden.
    Andersson, Per-Ola
    South Alvsborg Hosp, Dept Med, Sect Haematol, Boras, Sweden;Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
    Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma patients2018Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 181, nr 6, s. 770-781Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Diffuse large B cell lymphoma (DLBCL) patients with early relapse or refractory disease have a very poor outcome. Immunochemotherapy resistance will probably, also in the era of targeted drugs, remain the major cause of treatment failure. We used proteomic mass spectrometry to analyse the global protein expression of micro-dissected formalin-fixed paraffin-embedded tumour tissues from 97 DLBCL patients: 44 with primary refractory disease or relapse within 1year from diagnosis (REF/REL), and 53 who were progression-free more than 5years after diagnosis (CURED). We identified 2127 proteins: 442 were found in all patients and 102 were differentially expressed. Sixty-five proteins were overexpressed in REF/REL patients, of which 46 were ribosomal proteins (RPs) compared with 2 of the 37 overexpressed proteins in CURED patients (P=7<bold></bold>6x10(-10)). Twenty of 37 overexpressed proteins in CURED patients were associated with actin regulation, compared with 1 of 65 in REF/REL patients (P=1<bold></bold>4x10(-9)). Immunohistochemical staining showed higher expression of RPS5 and RPL17 in REF/REL patients while MARCKS-like protein, belonging to the actin network, was more highly expressed in CURED patients. Even though functional studies aimed at individual proteins and protein interactions to evaluate potential clinical effect are needed, our findings suggest new mechanisms behind immunochemotherapy resistance in DLBCL.

  • 147.
    Edén, Desireé
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Mokhtari, Dariush
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Tissue factor/factor VIIA signaling promotes cytokine-induced beta cell death and impairs glucose stimulated insulin secretion from human pancreatic islets2015Inngår i: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, nr S2, s. 465-465, artikkel-id PO563-MONArtikkel i tidsskrift (Annet vitenskapelig)
  • 148.
    Ekberg, Sara
    et al.
    Karolinska Inst, Div Clin Epidemiol, Dept Medicin Solna, Stockholm, Sweden.
    Jerkeman, Mats
    Lund Univ, Inst Clin Sci, Dept Pathol & Oncol, Lund, Sweden.
    Andersson, Per-Ola
    Gothenburg Univ, Boras & Sahlgrenska Acad, South Alvsborg Hosp, Dept Hematol, Gothenburg, Sweden.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Wahlin, Bjoern E.
    Karolinska Inst, Div Hematol, Deparment Med Huddinge, Stockholm, Sweden.
    Hasselblom, Sverker
    Deparment Res Dev & Educ, Halmstad, Sweden.
    Andersson, Therese M.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Eloranta, Sandra
    Karolinska Inst, Div Clin Epidemiol, Dept Medicin Solna, Stockholm, Sweden.
    Smedby, Karin E.
    Karolinska Univ Hosp, Ctr Hematol, Solna, Sweden;Karolinska Inst, Div Clin Epidemiol, Dept Medicin Solna, Stockholm, Sweden.
    Long-term survival and loss in expectancy of life in a population-based cohort of 7114 patients with diffuse large B-cell lymphoma2018Inngår i: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 93, nr 8, s. 1020-1028Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Survival has improved among patients with diffuse large B-cell lymphoma (DLBCL) with the addition of anti-CD20 antibody therapy. We aimed to quantify trends and remaining loss in expectation of life (LEL) due to DLBCL at a national population-based level. Patients diagnosed with DLBCL 2000-2013 (N=7114) were identified through the Swedish Lymphoma Registry and classified according to the age-adjusted International Prognostic Index (aaIPI). The novel measure LEL is the difference between remaining life years among patients and the general population and was predicted using flexible parametric models from diagnosis and among 2-year survivors, by age and sex. Median age at DLBCL-diagnosis was 70 (18-105) years and 54.8% presented with stage III-IV disease. On average, LEL due to DLBCL decreased from 8.0 (95% CI: 7.7-8.3) to 4.6 (95% CI: 4.5-4.6) years over the study period. By risk group, LEL was most reduced among patients with aaIPI >= 2 aged 50-60 years. However, these patients were still estimated to lose >8 years in 2013 (eg, LELmales50years 8.6 years (95% CI: 5.0-12.3)). Among 2-year survivors, LEL was reduced from 6.1 years (95% CI: 5.6-6.5) (aaIPI >= 2) and 3.8 years (95% CI: 3.6-4.1) (aaIPI<2) to 1.1 (95% CI: 1.1-1.2) and 1.0 year (95% CI: 0.8-1.1), respectively. The reduction was observed across all ages. Results for females were similar. By using LEL we illustrate the improvement of DLBCL survival over time. Despite adequate immunochemotherapy, substantial LEL among patients with IPI >= 2 points to remaining unmet medical needs. We speculate that observed reduced losses among 2-year survivors indicate a reduction of late relapses.

  • 149.
    Ekstrand, C.
    et al.
    Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Solna, Sweden..
    Linder, M.
    Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Solna, Sweden..
    Cherif, Honar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Kieler, H.
    Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Solna, Sweden..
    Bahmanyar, S.
    Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Solna, Sweden..
    Increased susceptibility to infections before the diagnosis of immune thrombocytopenia2016Inngår i: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 14, nr 4, s. 807-814Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Infections after diagnosis of primary chronic immune thrombocytopenia (cITP) have mostly been connected to the immunomodulation treatment. Infections may trigger autoimmune diseases and may be a complication of an already impaired immune system. Objectives To investigate the association of cITP with infection before diagnosis. We also estimated the incidence of cITP based on the new definition by the International ITP Working Group. Methods We identified 1087 adults with primary cITP between 2006 and 2012 using the Swedish Patient Register. Data on infections not already associated with secondary ITP were also retrieved from the register. The standardized incidence ratios (SIRs), using the rates from the general population, and 95% confidence intervals (CIs) were estimated as a measure of relative risk. We used data from the Prescribed Drug Register to estimate SIR for anti-infective treatment. Results The incidence of cITP was 2.30 per 100 000 person-years (95% CI, 2.15-2.45). cITP was associated with an increased risk of serious infections requiring inpatient or outpatient care within 5 years before cITP diagnosis (SIR = 8.74; 95% CI, 7.47-10.18). Higher magnitude SIRs were observed for candidiasis, viral infection at an unspecified site and acute upper respiratory infections. For anti-infective drugs the SIR was 1.37 (1.25-1.50) and the highest SIRs were observed for amoxicillin, macrolides, nitrofurantoin and antivirals. Conclusion Patients with cITP have increased risks of infection and anti-infective treatments before their cITP diagnosis, with a more marked risk for candidiasis and viral infections. The findings indicate that infection is not only related to the immunomodulation treatment but also to the disease itself.

  • 150.
    Ekstrand, Charlotta
    et al.
    Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Linder, Marie
    Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Cherif, Honar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Kieler, Helle
    Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Bahmanyar, Shahram
    Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Increased Anti-infective Treatments Preceding a Diagnosis of Primary Immune Thrombocytopenia2015Inngår i: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 24, s. 411-412Artikkel i tidsskrift (Annet vitenskapelig)
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