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  • 101.
    Mortzell, Monica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Berlin, G.
    Nilsson, T.
    Axelsson, C. G.
    Efvergren, M.
    Audzijoni, J.
    Griskevicius, A.
    Ptak, J.
    Blaha, M.
    Tomsova, H.
    Liumbruno, G. M.
    Centoni, P.
    Newman, E.
    Eloot, S.
    Dhondt, A.
    Tomaz, J.
    Witt, V.
    Rock, G.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Thrombotic microangiopathy2011Inngår i: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 45, nr 2, s. 119-123Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Thrombotic microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura (UP) and hemolytic uremic syndrome (HUS). There are many secondary causes of TMA, many of them could mimic TTP or HUS. This article presents a short overview on TMA. In conclusion TMA is the result of various etiology reasons and pathologic reactions with various clinical entities. It is important to focus on a thorough history including family history when deciding on a diagnosis. Analysis of ADAMTS 13 and ADAMTS 13-antibodies may help to decide continued therapy. (C) 2011 Elsevier Ltd. All rights reserved.

  • 102. Mulligan, Stephen P
    et al.
    Karlsson, Karin
    Strömberg, Mats
    Jønsson, Viggo
    Gill, Devinder
    Hammerström, Jens
    Hertzberg, Mark
    McLennan, Roger
    Uggla, Bertil
    Norman, John
    Wallvik, Jonas
    Sundström, Gunnel
    Johansson, Hemming
    Brandberg, Yvonne
    Liliemark, Jan
    Juliusson, Gunnar
    Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic leukemia2014Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 55, nr 12, s. 2769-2777Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We conducted a randomized phase III trial to compare the efficacy and safety of two purine analogs, cladribine and fludarabine, with high-dose chlorambucil, in patients with previously untreated chronic lymphocytic leukemia (CLL). Between 1997 and 2004, 223 patients with CLL were randomly assigned to cladribine, fludarabine or chlorambucil, for six cycles of therapy with frequent health-related quality of life assessments. There was no statistical difference for the primary endpoint of overall response with cladribine (70%), fludarabine (67%) and chlorambucil (59%), or complete remission (12%, 7% and 8%), respectively. However, the median progression-free survival (25, 10, 9 months) and median time to second treatment (40, 22, 21 months) were superior with cladribine. There was no significant difference in overall survival (96, 82 and 91 months), nor in toxicity or HRQoL assessments. Monotherapy with cladribine gives superior PFS and longer response duration than fludarabine and chlorambucil as first-line treatment of CLL.

  • 103. Mustjoki, Satu
    et al.
    Richter, Johan
    Barbany, Gisela
    Ehrencrona, Hans
    Dybedal, Ingunn
    Fioretos, Thoas
    Gedde-Dahl, Tobias
    Gjertsen, Bjorn
    Hovland, Randi
    Jalkanen, Sari E.
    Josefsen, Dag
    Koskenvesa, Perttu
    Lassen, Carin
    Latvala, Kirsi
    Majeed, Waleed
    Malm, Claes
    Markevärn, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Mosfegh, Ali
    Ohm, Lotta
    Olofsson, Tor
    Olsson-Stromberg, Ulla
    Rapakko, Katrin
    Remes, Karil
    Stentoft, Jesper
    Stenke, Leif
    Suominen, Merja
    Thunberg, Sara
    Bjerrum, Ole Weiss
    Simonsson, Bengt
    Porkka, Kimmo
    Hjorth-Hansen, Henrik
    Favorable therapeutic responses in newly diagnosed CML-CP patients induced by Dasatinib are reflected at the CD34+CD38+Progenitor cell but not at the CD34+CD38-Stem cell level: Results from randomized NordCML006 study2011Inngår i: 53rd ASH Annual Meeting and Exposition, December 10-13, 2011: Program: Oral and Poster AbstractsType: OralSession: 632. Chronic Myeloid Leukemia - Therapy: Prediction of Response Monday, December 12, 2011: 4:30 PM Ballroom 20BC (San Diego Convention Center), American Society of Hematology , 2011, Vol. 118, nr 21Konferansepaper (Fagfellevurdert)
  • 104.
    Mörtzell Henriksson, Monica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Newman, E
    Witt, V
    Derfler, K
    Leitner, G
    Eloot, S
    Dhondt, A
    Deeren, D
    Rock, G
    Ptak, J
    Blaha, M
    Lanska, M
    Gasova, Z
    Hrdlickova, R
    Ramlow, W
    Prophet, H
    Liumbruno, G
    Mori, E
    Griskevicius, A
    Audzijoniene, J
    Vrielink, H
    Rombout, S
    Aandahl, A
    Sikole, A
    Tomaz, J
    Lalic, K
    Mazic, S
    Strineholm, V
    Brink, B
    Berlin, G
    Dykes, J
    Toss, F
    Axelsson, C G
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nilsson, T
    Norda, R
    Knutson, F
    Ramsauer, Bernd
    Skövde.
    Wahlström, A
    Adverse events in apheresis: an update of the WAA registry data2016Inngår i: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 54, nr 1, s. 2-15Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Apheresis with different procedures and devices are used for a variety of indications that may have different adverse events (AEs). The aim of this study was to clarify the extent and possible reasons of various side effects based on data from a multinational registry. The WAA-apheresis registry data focus on adverse events in a total of 50846 procedures in 7142 patients (42% women). AEs were graded as mild, moderate (need for medication), severe (interruption due to the AE) or death (due to AE). More AEs occurred during the first procedures versus subsequent (8.4 and 5.5%, respectively). AEs were mild in 2.4% (due to access 54%, device 7%, hypotension 15%, tingling 8%), moderate in 3% (tingling 58%, urticaria 15%, hypotension 10%, nausea 3%), and severe in 0.4% of procedures (syncope/hypotension 32%, urticaria 17%, chills/fever 8%, arrhythmia/asystole 4.5%, nausea/vomiting 4%). Hypotension was most common if albumin was used as the replacement fluid, and urticaria when plasma was used. Arrhythmia occurred to similar extents when using plasma or albumin as replacement. In 64% of procedures with bronchospasm, plasma was part of the replacement fluid used. Severe AEs are rare. Although most reactions are mild and moderate, several side effects may be critical for the patient. We present side effects in relation to the procedures and suggest that safety is increased by regular vital sign measurements, cardiac monitoring and by having emergency equipment nearby.

  • 105.
    Mörtzell, Monica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Berlin, G.
    Nilsson, T.
    Axelsson, C. G.
    Efvergren, M.
    Audzijoni, J.
    Griskevicius, A.
    Ptak, J.
    Blaha, M.
    Tomsova, H.
    Liumbruno, G. M.
    Centoni, P.
    Newman, E.
    Eloot, S.
    Dhondt, A.
    Tomaz, J.
    Witt, V.
    Rock, G.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Analyses of data of patients with Thrombotic Microangiopathy in the WAA registry2011Inngår i: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 45, nr 2, s. 125-131Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Thrombotic Microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. The aim of this study was to investigate the outcome and prognostic variables of TMA-patients. Materials and methods: Data were consecutively retrieved from the WAA-apheresis registry (www.waa-registry.org) during 2003-2009. Included were all 120 patients (1237 procedures) who suffered from various forms of TMA, as registered by the ICD-10 code M31.1. Besides registry data, more extensive information was retrieved from the latest 64 patients. Adverse events of the TMA patients were compared to those of the other patients in the registry. Results: The mean age was 46 years (range 11-85 years, 57% women). In 72% therapeutic apheresis was due to an acute indication while a long-term indication was present in 28%. Plasma exchange was performed by centrifugation and filtration technique (95% and 4%, respectively), and immunoadsorption in 1% of the patients. Only fresh frozen plasma was used as replacement fluid in 69% of procedures. Adverse events were more frequent than in the general apheresis population (10% versus 5%, RR 1.9, CI 1.6-2.3). No death occurred due to apheresis treatment. Three percent of the procedures were interrupted. Bronchospasm and/or anaphylactic shock were present in two patients and one patient suffered from TRALI. At admission 26% were bedridden and needed to be fed. The risk of dying during the treatment period was significantly higher if the patient also suffered from a compromising disease, such as cancer. There was an inverse correlation between the ADAMTS13 level and the antibody titer (r = -0.47, p = 0.034). Conclusions: Patients with TMA have an increased risk for moderate and severe AE compared to the general apheresis population. Many patients were severely ill at admission. The prognosis is worse if the patient also has a severe chronic disease. Even slightly increased ADAMTS13-antibody titers seem to have a negative impact on the ADAMTS13 levels. (C) 2011 Elsevier Ltd. All rights reserved.

  • 106. Nagel, Gabriele
    et al.
    Stocks, Tanja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Spaeth, Daniela
    Hjartaker, Anette
    Lindkvist, Bjorn
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bjorge, Tone
    Manjer, Jonas
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Engeland, Anders
    Ulmer, Hanno
    Selmer, Randi
    Concin, Hans
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Schlenk, Richard F.
    Metabolic factors and blood cancers among 578,000 adults in the metabolic syndrome and cancer project (Me-Can)2012Inngår i: Annals of Hematology, ISSN 0939-5555, E-ISSN 1432-0584, Vol. 91, nr 10, s. 1519-1531Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We investigated associations between metabolic factors and blood cancer subtypes. Data on body mass index (BMI), blood pressure, blood glucose, total cholesterol, and triglycerides from seven prospective cohorts were pooled (n = 578,700; mean age = 44 years). Relative risks of blood cancers were calculated from Cox regression models. During mean follow-up of 12 years, 2,751 incident and 1,070 fatal cases of blood cancers occurred. Overall, higher BMI was associated with an increased blood cancer risk. In gender-specific subgroup analyses, BMI was positively associated with blood cancer risk (p = 0.002), lymphoid neoplasms (p = 0.01), and Hodgkin's lymphoma (p = 0.02) in women. Further associations with BMI were found for high-grade B-cell lymphoma (p = 0.02) and chronic lymphatic leukemia in men (p = 0.05) and women (p = 0.01). Higher cholesterol levels were inversely associated with myeloid neoplasms in women (p = 0.01), particularly acute myeloid leukemia (p = 0.003), and glucose was positively associated with chronic myeloid leukemia in women (p = 0.03). In men, glucose was positively associated with risk of high-grade B-cell lymphoma and multiple myeloma, while cholesterol was inversely associated with low-grade B-cell lymphoma. The metabolic syndrome score was related to 48 % increased risk of Hodgkin's lymphoma among women. BMI showed up as the most consistent risk factor, particularly in women. A clear pattern was not found for other metabolic factors.

  • 107. Nahi, Hareth
    et al.
    Hägglund, Hans
    Ahlgren, Thomas
    Bernell, Per
    Hardling, Mats
    Karlsson, Karin
    Lazarevic, Vladimir Lj
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Linderholm, Mats
    Smedmyr, Bengt
    Åström, Maria
    Hallböök, Helene
    An investigation into whether deletions in 9p reflect prognosis in adult precursor B-cell acute lymphoblastic leukemia: a multi-center study of 381 patients2008Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 93, nr 11, s. 1734-1738Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In acute lymphoblastic leukemia, besides age and white cell count at diagnosis, the cytogenetic abnormalities t(9;22)/BCR-ABL and t(4;11)/MLL-AF4 are important prognostic markers and are often included in the treatment stratification of patients with adult acute lymphoblastic leukemia. Deletions in 9p are seen in about 9% of cases of adult acute lymphoblastic leukemia, but their prognostic impact has been controversial. Cytogenetic data from 381 patients diagnosed with B-precursor acute lymphoblastic leukemia were reviewed. Chromosomal analysis was successful in 240 cases. Of these cases, 18 (8%) had abnormalities in 9p and they were compared with patients with normal karyotypes and patients with t(9;22)/BCR-ABL. Patients with abnormalities of chromosome 9 showed significantly shorter overall survival compared with patients with normal karyotypes. In fact, overall survival was similar to that in the poor prognosis t(9;22)/BCR-ABL-positive group. Our data suggest that chromosomal abnormalities involving 9p may have a significant negative impact on survival in adult B-precursor acute lymphoblastic leukemia.

  • 108. Nahi, Hareth
    et al.
    Liwing, Johan
    Aldrin, Anders
    Andreasson, Johan
    Blimark, Cecilie
    Carlson, Kristina
    Enestig, Jon
    Flogegard, Max
    Forsberg, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Gruber, Astrid
    Johansson, Peter
    Kviele, Helene
    Lauri, Birgitta
    Mellqvist, Ulf-Henrik
    Nasman, Per
    Swedin, Agneta
    Svensson, Magnus
    Uttervall, Katarina
    Aschan, Johan
    Is Multiple Myeloma a Chronic Disease?: A Population Based Study Comparing 1843 Patients to a Matched Swedish Population2012Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 120, nr 21Artikkel i tidsskrift (Annet vitenskapelig)
  • 109. Nielsen, Stine N.
    et al.
    Eriksson, Frank
    Rosthoej, Susanne
    Andersen, Mette K.
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Hasle, Henrik
    Hjalgrim, Lisa L.
    Aasberg, Ann
    Abrahamsson, Jonas
    Heyman, Mats
    Jónsson, Ólafur G.
    Pruunsild, Kaie
    Vaitkeviciené, Goda E.
    Vettenranta, Kim
    Schmiegelow, Kjeld
    Children with low-risk acute lymphoblastic leukemia are at highest risk of second cancers2017Inngår i: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 64, nr 10, artikkel-id e26518Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The improved survival rates for childhood acute lymphoblastic leukemia (ALL) may be jeopardized by the development of a second cancer, which has been associated with thiopurine therapy. Procedure: We retrospectively analyzed three sequential Nordic Society of Paediatric Haematology and Oncology's protocols characterized by increasing intensity of thiopurine-based maintenance therapy. We explored the risk of second cancer in relation to protocols, risk group, thiopurine methyltransferase (TPMT) activity, ALL high hyperdiploidy (HeH), and t(12;21)[ETV6/RUNX1]. Results: After median 9.5 years (interquartile range, 5.4-15.3 yrs) of follow-up, 40 of 3,591 patients had developed a second cancer, of whom 38 had non-high-risk B-cell precursor ALL. Patients with standard-risk ALL, who received the longest maintenance therapy, had the highest adjusted hazard of second cancer (hazard ratio [HR], intermediate vs. standard risk: 0.16, 95% CI: 0.06-0.43, P < 0.001; HR, high vs. standard risk: 0.09, 95% CI: 0.02-0.49, P = 0.006); no significant effects of protocol, age, or white blood cell count at diagnosis, ALL HeH, or t(12;21)[ETV6/RUNX1] were observed. A subset analysis on the patients with standard-risk ALL did not show an increased hazard of second cancer from either HeH or t(12;21) (adjusted HR 2.02, 95% CI: 0.69-5.96, P = 0.20). The effect of low TPMT low activity was explored in patients reaching maintenance therapy in clinical remission (n = 3,368); no association with second cancer was observed (adjusted HR 1.43, 95% CI: 0.54-3.76, P = 0.47). Conclusions: The rate of second cancer was generally highest in patients with low-risk ALL, but we could not identify a subset at higher risk than others.

  • 110.
    Nilsson, R. Jonas A.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Balaj, Leonora
    Hulleman, Esther
    van Rijn, Sjoerd
    Pegtel, D. Michiel
    Walraven, Maudy
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Gerritsen, Winald R.
    Verheul, Henk M.
    Vandertop, W. Peter
    Noske, David P.
    Skog, Johan
    Wurdinger, Thomas
    Blood platelets contain tumor-derived RNA biomarkers2011Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, nr 13, s. 3680-3683Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Diagnostic platforms providing biomarkers that are highly predictive for diagnosing, monitoring, and stratifying cancer patients are key instruments in the development of personalized medicine. We demonstrate that tumor cells transfer (mutant) RNA into blood platelets in vitro and in vivo, and show that blood platelets isolated from glioma and prostate cancer patients contain the cancer-associated RNA biomarkers EGFRvIII and PCA3, respectively. In addition, gene-expression profiling revealed a distinct RNA signature in platelets from glioma patients compared with normal control subjects. Because platelets are easily accessible and isolated, they may form an attractive platform for the companion diagnostics of cancer.

  • 111.
    Nilsson Sojka, Birgitta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Sojka, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    The blood donation experience: self-reported motives and obstacles for donating blood2008Inngår i: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 94, nr 1, s. 56-63Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and Objectives The aim of the study was to investigate motives for donating blood as well as difficulties and obstacles associated with blood donation as perceived by the donors themselves.

    Materials and Methods Six hundred consecutive blood donors (i.e. all blood donors with a history of at least one previous whole blood donation attending, during nine working days, the Blood Centre of Umea University Hospital) received a self-administered questionnaire that contained questions aimed at elucidating motives for donating blood (general motives for donating blood, specific motives for the first donation and motives for continuing to be an active blood donor). Questions concerning difficulties and obstacles that had to be overcome in order to continue being a blood donor were also included in the questionnaire.

    Results Altogether 531 whole blood donors filled in the questionnaire (88.5%; 322 men and 209 women). No statistically significant differences were found between male and female blood donors concerning general reasons and motives related to donating blood. The most frequently reported reasons for giving blood the first time were 'influence from a friend' (47.2% of donors) and 'request via media' (23.5% of donors). Among general reasons/motives with highest ranking of importance, the most commonly reported motive for donating blood were 'general altruism' (40.3%), 'social responsibility/obligation' (19.7%) and 'influence from friends' (17.9%). General altruism' and 'social responsibility/obligation' were also the most frequent reasons for continuing to donate blood (68.4 and 16.0%, respectively). The most commonly reported obstacle to becoming a regular blood donor was 'laziness' (19.1%) followed by 'fear of needles' (10.5%).

    Conclusions Altruism was the most common general motive for donating blood and also for continuing to be an active blood donor. Yet, for the first blood donation, direct 'influence from friends/relatives', 'media appeal' and other types of recruitment were more commonly reported as reasons or motives for donating blood than altruism. The findings support the notion that different strategies should be used/adopted to get people to donate blood the first time (e.g. recruitment through other blood donors using, for example, the 'bring a friend along' method) and to retain these subjects as active blood donors (e.g. by information and by strengthening their sense of being a blood donor or their self-efficacy etc.).

  • 112. Norda, R.
    et al.
    Schott, U.
    Berseus, O.
    Akerblom, O.
    Nilsson, B.
    Ekdahl, K. N.
    Stegmayr, Bernd G.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Knutson, F.
    Complement activation products in liquid stored plasma and C3a kinetics after transfusion of autologous plasma2012Inngår i: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 102, nr 2, s. 125-133Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and Objectives: Keeping a small stock of liquid plasma readily available for transfusion is common practise in Sweden. We report data on complement activation markers in plasma components during storage in the liquid state and the kinetics of C3a-desArg after transfusion of autologous plasma with high content of C3a-desArg.

    Material and Methods: Plasma components were prepared by apheresis or from whole blood. C3 fragments (C3a-desArg, C3d, g, iC3), and soluble terminal complement complex (sC5b-9) were investigated. C3a-desArg kinetics was investigated in regular apheresis donors.

    Results: Apheresis plasma prepared by membrane centrifugation had significantly higher level of C3a-desArg, C3d, g and sC5b-9 from day 0 and low iC3, than plasma prepared by other methods. By storage day 7, C3a-desArg -levels were above the reference value in 88% of all components. After re-infusion of autologous plasma with high C3a-desArg content, there were rapid a1 and a2-distribution followed by a slower b-elimination phase.

    Conclusion: Plasma components prepared by different methods and stored in the liquid phase differ significantly in the amount and timing of complement activation. C3a-desArg present in plasma is rapidly eliminated after transfusion. Autologous plasma could be used to study complement kinetics in different clinical situations.

  • 113.
    Norrback, Karl-Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Enblad, Gunilla
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Sundström, Christer
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Telomerase activity in Hodgkin's disease1998Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 92, nr 2, s. 567-573Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Telomere maintenance executed by the action of telomerase seems to be a prerequisite for immortalization. Telomerase is found in most cell lines and malignant tumors. A telomerase-independent mechanism for telomere maintenance in Hodgkin's disease has been proposed in the absence of detectable telomerase activity. In this study, telomerase activity was detected in 31 of 77 Hodgkin's disease samples and a strong correlation between eosinophilia and absence of detectable telomerase activity was found. Purified eosinophils and specifically eosinophil-derived neurotoxin and eosinophilic cationic protein, both ribonucleases, were found to degrade telomerase. Purified neutrophils also exhibited weak telomerase degradative activity. Reanalysis of previously telomerase-negative Hodgkin's disease samples with eosinophilia using ribonuclease inhibitors resulted in the detection of telomerase activity. Ribonuclease-containing cells in vivo thus have a considerable impact on the detectability of telomerase. In Hodgkin's disease samples without eosinophilia, 24 of 27 exhibited telomerase activity at decreased levels compared with non-Hodgkin's lymphomas and at increased levels compared with reactive nodes indicative of a telomerase positive tumor component in Hodgkin's disease. Telomerase positivity of the Hodgkin's and Reed-Sternberg cells in vivo was also supported by high levels of telomerase expression in Hodgkin's disease cell lines. Based on our data, Hodgkin's lymphomas are potential targets for antitelomerase therapy.

  • 114.
    Norrback, Karl-Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Dahlenborg, Katarina
    Osterman, Pia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Carlsson, Roland
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Telomerase regulation and telomere dynamics in germinal centers2001Inngår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 67, nr 5-6, s. 309-317Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Telomere length maintenance, usually executed by telomerase, is a prerequisite for an extended or infinite division potential. Nevertheless most telomerase positive normal cells exhibit telomere shortening. This study details the telomerase expression and telomere dynamics in purified tonsil B cell subsets during the germinal center (GC) reaction. Significant telomere lengthening was observed as naive B cells matured to centroblasts and when centroblasts matured further to centrocytes, resulting in an increase in telomere length of about 4 kbp determined by Southern blotting. Immunopurified cell populations were also studied by fluorescence in situ hybridization and flow cytometry (flow-FISH) confirming that the GC B cells exhibited lengthened telomeres. These data were further verified in unpurified tonsil cells by combining flow-FISH and immunophenotyping using selected surface markers. Centroblasts expressed high levels of telomerase activity, which was increased in centrocytes, whereas resting naive, activated naive and memory B cells were telomerase activity negative. Expression levels of the catalytic subunit (hTERT) RNA paralleled the telomerase activity levels. The unique telomere elongation in GC B cells permits extensive proliferation during the GC reaction and provides the memory cells with a substantial increase in division potential. Understanding the telomere biology of GC cells is important in defining requirements for telomere elongation in vivo, with implications for the normal immune system as well as for lymphomas, and could provide insights into how the division potential of cells can be manipulated in vitro.

  • 115. Olsson, Linda
    et al.
    Zettermark, Sofia
    Biloglav, Andrea
    Castor, Anders
    Behrendtz, Mikael
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Paulsson, Kajsa
    Johansson, Bertil
    The genetic landscape of paediatric de novo acute myeloid leukaemia as defined by single nucleotide polymorphism array and exon sequencing of 100 candidate genes2016Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 174, nr 2, s. 292-301Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cytogenetic analyses of a consecutive series of 67 paediatric (median age 8 years; range 0-17) de novo acute myeloid leukaemia (AML) patients revealed aberrations in 55 (82%) cases. The most common subgroups were KMT2A rearrangement (29%), normal karyotype (15%), RUNX1-RUNX1T1 (10%), deletions of 5q, 7q and/or 17p (9%), myeloid leukaemia associated with Down syndrome (7%), PML-RARA (7%) and CBFBMYH11 (5%). Single nucleotide polymorphism array (SNP-A) analysis and exon sequencing of 100 genes, performed in 52 and 40 cases, respectively (39 overlapping), revealed >= 1 aberration in 89%; when adding cytogenetic data, this frequency increased to 98%. Uniparental isodisomies (UPIDs) were detected in 13% and copy number aberrations (CNAs) in 63% (median 2/case); three UPIDs and 22 CNAs were recurrent. Twenty-two genes were targeted by focal CNAs, including AEBP2 and PHF6 deletions and genes involved in AML-associated gene fusions. Deep sequencing identified mutations in 65% of cases (median 1/case). In total, 60 mutations were found in 30 genes, primarily those encoding signalling proteins (47%), transcription factors (25%), or epigenetic modifiers (13%). Twelve genes (BCOR, CEBPA, FLT3, GATA1, KIT, KRAS, NOTCH1, NPM1, NRAS, PTPN11, SMC3 and TP53) were recurrently mutated. We conclude that SNP-A and deep sequencing analyses complement the cytogenetic diagnosis of paediatric AML.

  • 116. Oskarsson, Trausti
    et al.
    Söderhall, Stefan
    Arvidson, Johan
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Montgomery, Scott
    Lausen, Birgitte
    Carlsen, Niels
    Hellebostad, Marit
    Glomstein, Anders
    Lahteenmäki, Päivi
    Pihkala, Ulla
    Jonsson, Olafur Gisli
    Heyman, Mats
    Relapsed acute lymphoblastic leukemia in the nordic countries - prognostic factors, treatment and outcome2012Inngår i: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 59, nr 6, s. 1007-1008Artikkel i tidsskrift (Annet vitenskapelig)
  • 117. Oskarsson, Trausti
    et al.
    Söderhäll, Stefan
    Arvidson, Johan
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Frandsen, Thomas L.
    Hellebostad, Marit
    Lähteenmäki, Päivi
    Jónsson, Ólafur G.
    Myrberg, Ida Hed
    Heyman, Mats
    Treatment-related mortality in relapsed childhood acute lymphoblastic leukemia2018Inngår i: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 65, nr 4, artikkel-id e26909Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment-related toxicity impacts survival.

    Procedure: In this retrospective population-based study, we described the causes of death and estimated the risk for treatment-related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL-92 and ALL-2000 trials.

    Results: Among the 483 patients who received relapse treatment with curative intent, we identified 52 patients (10.8%) who died of treatment-related causes. Twelve of these died before achieving second remission and 40 died in second remission. Infections were the cause of death in 38 patients (73.1%), predominantly bacterial infections during the chemotherapy phases of the relapse treatment. Viral infections were more common following hematopoietic stem cell transplantation (HSCT) in second remission. Independent risk factors for treatment-related mortality were as follows: high-risk stratification at relapse (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.3-3.9; P < 0.01), unfavorable cytogenetic aberrations (HR 3.4; 95% CI 1.3-9.2; P = 0.01), and HSCT (HR 4.64; 95% CI 2.17-9.92; P < 0.001). In contrast to previous findings, we did not observe any statistically significant sex or age differences. Interestingly, none of the 17 patients with Down syndrome died of treatment-related causes.

    Conclusions: Fatal treatment complications contribute significantly to the poor overall survival after relapse. Implementation of novel therapies with reduced toxicity and aggressive supportive care management are important to improve survival in relapsed childhood ALL.

  • 118. Palmblad, Jan
    et al.
    Björkholm, Magnus
    Kutti, Jack
    Lärfars, Gerd
    Löfvenberg, Eva
    Markevärn, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Merup, Mats
    Mauritzson, Nils
    Westin, Jan
    Samuelsson, Jan
    Birgegård, Gunnar
    TPO, but not soluble-IL-6 receptor, levels increase after anagrelide treatment of thrombocythemia in chronic myeloproliferative disorders2008Inngår i: International Journal of Medical Sciences, ISSN 1449-1907, E-ISSN 1449-1907, Vol. 5, nr 2, s. 87-91Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Anagrelide is often used in the treatment of thrombocythemia in myeloproliferative disease (MPD), but information concerning effects of treatment on cytokines involved in regulation of blood platelet levels is limited. Here, we investigated serum levels of thrombopoietin (TPO) and soluble IL-6 receptor (sIL-6R) in relation to response to treatment with and plasma concentrations of anagrelide. Samples from 45 patients with thrombocythemia due to MPD (ET=31, PV=14), being treated with anagrelide for 6 months, were analyzed for TPO, sIL-6R and anagrelide levels. The mean baseline platelet count was 983x10(9)/L. A reduction of platelets to <600 in asymptomatic or <400 x 10(9)/L in symptomatic patients was defined as a complete remission (CR), a reduction with >50% of baseline as partial remission, and <50% reduction as failure. At 6 months, 35 patients were in CR, 1 had a partial remission and 9 were treatment failures. For all patients, there was an increase in TPO of 44% from baseline; this change was more pronounced for patients with partial remission and failure. sIL-6R levels did not change significantly. There was no correlation between levels of anagrelide and cytokine levels at 6 months, and changes of cytokine levels did not relate to changes of platelet counts. Thus, a pronounced increase of TPO levels after 6 months of anagrelide treatment indicated that this treatment affected a major regulatory mechanism for megakaryocyte and platelet formation in MPD.

  • 119. Petersson, Annika
    et al.
    Ekblom, Kim
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi. Department of Research and Development, Region Kronoberg, Växjö.
    Evaluation of a routine hematology analyzer for quality control of leukoreduced plasma2019Inngår i: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 9, nr 10, s. 3214-3218Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Quality control of residual white blood cells (WBCs) and red blood cells (RBCs) in leukoreduced plasma is mandatory. Although technological advances have been made, analysis of quality controls using routine hematology analyzers has not generally been introduced. The aim of this study was to evaluate if the routine hematology analyzer Sysmex XN‐10, (Sysmex Nordic ApS) could be used for quality control of residual WBCs and RBCs in leukoreduced plasma.

    STUDY DESIGN AND METHODS: Linearity, accuracy, and precision were established for two Sysmex XN‐10 analyzers using spiked donor plasma. ADAM rWBC (NanoEnTek) and manual counting in the Bürker chamber (NanoEnTek) were reference methods for WBCs and RBCs, respectively. Twenty‐five consecutive leukoreduced donor plasma samples were also tested.

    RESULTS: For WBCs, the linearity criteria were met for the ADAM rWBC, but not for the Sysmex XN‐10 instruments. Precision on both Sysmex XN‐10 instruments was accurate only at 6 cells/μL, and accuracy was consistently acceptable only at 5 to 6 cells/μL. The precision and accuracy of the ADAM rWBC were acceptable at 2 to 6 cells/μL.

    For RBCs, both Sysmex XN‐10 instruments and manual counting in the Bürker chamber were linear and fulfilled the precision criteria. Accuracy was acceptable for both Sysmex instruments at 6 to 12 × 109 WBCs/L but fluctuated within the study's measuring range for the Bürker chamber.

    No false‐positive results were seen in the 25 consecutive donor plasma samples tested.

    CONCLUSION: For quality control purposes of leukoreduced plasma, the Sysmex XN‐10 analyzer is suitable for the enumeration of residual RBCs but not of residual WBCs.

  • 120. Petersson, Annika
    et al.
    Ekblom, Kim
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Methods for counting residual leukocytes in leukocyte-depleted plasma-a comparison between a routine hematology instrument, the Nageotte chamber, flow cytometry, and a fluorescent microscopy analyzer2017Inngår i: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 57, nr 5, s. 1192-1198Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Counting very low levels of leukocytes is technically challenging but mandatory for quality control of leukocyte-depleted plasma. Established assays, such as flow cytometry and counting in the Nageotte chamber, are laborious and expensive. The aim of this study was to test two alternative assays, the cerebrospinal fluid program in the routine hematology analyzer ADVIA 2120 and a fluorescence microscopy analyzer, the ADAM-rWBC. STUDY DESIGN AND METHODS: Linearity, accuracy, and precision were established for the ADVIA 2120, the ADAM-rWBC analyzer and the Nageotte chamber with flow cytometry as the reference method. Two hundred consecutive leukocyte-depleted donor plasma samples were also tested. RESULTS: The ADAM-rWBC analyzer and the Nageotte chamber fulfilled all quality requirements. Flow cytometry fulfilled the requirements for linearity and precision. The ADVIA 2120 analyzer did not fully reach the quality criteria, and flow cytometry did not reach quality criteria on accuracy. No false-positive results on donor plasma samples were recorded. CONCLUSION: The ADAM-rWBC is suitable for the purpose of quality control of residual leukocytes in leukocyte-depleted plasma. For the ADVIA 2120, further improvements and studies are needed to reach the quality requirements stated in this study.

  • 121. Qadri, Syed M.
    et al.
    Bissinger, Rosi
    Solh, Ziad
    Oldenborg, Per-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Eryptosis in health and disease: A paradigm shift towards understanding the (patho)physiological implications of programmed cell death of erythrocytes2017Inngår i: Blood reviews, ISSN 0268-960X, E-ISSN 1532-1681, Vol. 31, nr 6, s. 349-361Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    During the course of their natural ageing and upon injury, anucleate erythrocytes can undergo an unconventional apoptosis-like cell death, termed eryptosis. Eryptotic erythrocytes display a plethora of morphological alterations including volume reduction, membrane blebbing and breakdown of the membrane phospholipid asymmetry resulting in phosphatidylserine externalization which, in turn, mediates their phagocytic recognition and clearance from the circulation. Overall, the eryptosis machinery is tightly orchestrated by a wide array of endogenous mediators, ion channels, membrane receptors, and a host of intracellular signaling proteins. Enhanced eryptosis shortens the lifespan of circulating erythrocytes and confers a procoagulant phenotype; this phenomenon has been tangibly implicated in the pathogenesis of anemia, deranged microcirculation, and increased prothrombotic risk associated with a multitude of clinical conditions. Herein, we reviewed the molecular mechanisms dictating eryptosis and erythrophagocytosis and critically analyzed the current evidence leading to the pathophysiological ramifications of eryptotic cell death in the context of human disease.

  • 122.
    Ramsauer, Bernd
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Engels, Gerwin
    Arsov, Stefan
    Hadimeri, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sikole, Aleksandar
    Graaff, Reindert
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Comparing changes in plasma and skin autofluorescence in low-flux versus high-flux hemodialysis2015Inngår i: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 38, nr 9, s. 488-493Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Tissue advanced glycation end products (AGE) are increased in hemodialysis (HD) patients, especially those with cardiovascular complications. Skin autofluorescence (skin-AF) can noninvasively estimate the accumulation of AGE in tissue. The aim was to clarify whether HD using a high-flux (HF) dialyzer favors plasma-or skin-AF removal compared to low-flux (LF) dialysis. Material and methods: 28 patients were treated with either an HF-HD or LF-HD but otherwise unchanged conditions in a cross-over design. A glucose containing dialysate was used. Skin-AF was measured noninvasively with an AGE reader before and after HD. Fluorescence (370 nm/465 nm) of plasma (p-AF) was determined as total and nonprotein-bound fractions. Correction for hemoconcentrations were made using the change in serum albumin. Paired and nonpaired statistical analyses were used. Results: Skin-AF was unchanged after LF- and HF-dialysis. Total, free, and protein-bound p-AF was reduced after a single LF-HD by 21%, 28%, and 17%, respectively (P<.001). After HF HD total and free p-AF was reduced by 5% and 15%, respectively (P<.001), while protein bound values were unchanged. The LF-HD resulted in a more pronounced reduction of p-AF than did HF HD (P<.001). Serum albumin correlated inversely with p-AF in HF-HD. Conclusions: In the dialysis settings used there was no significant change in skin AF after dialysis, with LF or with HF dialysis. Although only limited reduction in plasma fluorescence was observed, this was more pronounced when performing LF dialysis. These data are not in overwhelming support of the use of HF dialysis in the setting used in this study.

  • 123. Refsum, Erle
    et al.
    Håkansson, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Mortberg, Anette
    Wikman, Agneta
    Westgren, Magnus
    Intracranial hemorrhages in neonates born from 32 weeks of gestation - low frequency of associated fetal and neonatal alloimmune thrombocytopenia: a register-based study2018Inngår i: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 58, nr 1, s. 223-231Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition, with an estimated incidence of one in 1000 to 2000 live births. Predominantly, FNAIT is due to maternal alloantibodies that target paternally derived human platelet antigen (HPA) 1a. The most feared complication is an intracranial hemorrhage (ICH). The aim of this study was to determine the frequency of associated maternal platelet (PLT) alloimmunization in a population of neonates born from 32 weeks of gestation and diagnosed with an ICH.

    STUDY DESIGN AND METHODS: The Swedish Neonatal Quality (SNQ) register was used to identify neonates diagnosed with an ICH born between 2003 and 2012. Mothers were invited to donate peripheral blood, to investigate their HPA-1a antigen status, and test for anti-HPA and anti-HLA Class I alloantibodies. Clinical data for the neonates were retrieved from the SNQ register and available clinical records.

    RESULTS: Of 286 registered neonates, 278 mothers were contacted. Of 105 analyzed maternal samples, two (1.9%) were HPA-1a antigen negative. Antibody analyses revealed in total three (2.9%) mothers with anti-HPA: one mother (0.94%) with anti-HPA-1a and two mothers (1.9%) with anti-HPA-5b, of whom one had concurrent anti-HPA-15a. Twenty-four percent tested positive for anti-HLA Class I antibodies. A total of 8.5% of neonates (5/59) with PLT counts available in clinical records were severely thrombocytopenic, with PLT counts of less than 50 × 109/L.

    CONCLUSIONS: This retrospective cohort revealed a wide range of factors associated with ICH in neonates born from 32 weeks of gestation and suggests PLT alloimmunization to be a less common contributor than anticipated.

  • 124. Reimer, Jana
    et al.
    Knoess, Sabine
    Labuhn, Maurice
    Charpentier, Emmanuelle M.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Max Planck Institute for Infection Biology, Berlin, Germany.
    Goehring, Gudrun
    Schlegelberger, Brigitte
    Klusmann, Jan-Henning
    Heckl, Dirk
    CRISPR-Cas9-induced t(11;19)/MLL-ENL translocations initiate leukemia in human hematopoietic progenitor cells in vivo2017Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, nr 9, s. 1558-1566Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chromosomal translocations that generate oncogenic fusion proteins are causative for most pediatric leukemias and frequently affect the MLL/ KMT2A gene. In vivo modeling of bona fide chromosomal translocations in human hematopoietic stem and progenitor cells is challenging but essential to determine their actual leukemogenic potential. We therefore developed an advanced lentiviral CRISPR-Cas9 vector that efficiently transduced human CD34(+) hematopoietic stem and progenitor cells and induced the t(11; 19)/MLL-ENL translocation. Leveraging this system, we could demonstrate that hematopoietic stem and progenitor cells harboring the translocation showed only a transient clonal growth advantage in vitro. In contrast, t(11; 19)/MLL-ENL-harboring CD34(+) hematopoietic stem and progenitor cells not only showed longterm engraftment in primary immunodeficient recipients, but t(11; 19)/ MLL-ENL also served as a first hit to initiate a monocytic leukemia-like disease. Interestingly, secondary recipients developed acute lymphoblastic leukemia with incomplete penetrance. These findings indicate that environmental cues not only contribute to the disease phenotype, but also to t(11; 19)/ MLL-ENL-mediated oncogenic transformation itself. Thus, by investigating the true chromosomal t(11; 19) rearrangement in its natural genomic context, our study emphasizes the importance of environmental cues for the pathogenesis of pediatric leukemias, opening an avenue for novel treatment options.

  • 125.
    Roos, Göran
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Rosenquist, Richard
    Stilgenbauer, Stephan
    Or both? Response.2008Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 111, nr 12, s. 5756-5757Artikkel i tidsskrift (Annet vitenskapelig)
  • 126.
    Sandén, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renlund, Henrik
    Svensson, Peter J.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Bleeding complications in venous thrombosis patients on well-managed warfarin2016Inngår i: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 41, nr 2, s. 351-358Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Anticoagulation treatment is effective in preventing both death and recurrence in patients with venous thromboembolism (VTE), but at the same time confers a substantial risk of bleeding complications. The aim of this study was to examine the rate of and predictors for bleeding complications in VTE patients on warfarin with high treatment quality. In total 13,859 patients on warfarin for VTE between January 1st 2006 and December 31th 2011 were retrieved from the national quality register Auricula. The cohort was matched with the Swedish National Patient Register for complications and background characteristics, the Cause of Death Register for date and cause of death and the Swedish Prescribed Drug Register for retrieved medication. The rate of major bleeding was 2.36 per 100 treatment years, increasing with age from 1.25 to 4.33 for those under 60 or over 80 years of age, respectively. Factors found to independently increase the risk of bleeding complications were increasing age HR 1.02, cardiac failure HR 1.39, Chronic pulmonary disease HR 1.41, alcohol abuse HR 3.33, anaemia HR 1.75, hypertension HR 1.29 and a history of major bleeding HR 1.69. Warfarin as treatment for VTE is safe with a low rate of bleeding complications at least for the younger patient. In an era of NOAK, warfarin has a comparable safety profile among VTE patients and is still a valid treatment option.

  • 127.
    Sandén, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renlund, Henrik
    Svensson, Peter J
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Warfarin treatment complications do not correlate to cTTR when above 70%2015Inngår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, nr 6, s. 1185-1189Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The mean time in target range for each centre, cTTR, has previously been shown to correlate to the rate of complications in poorly managed warfarin treatment. However less is known about the correlation when warfarin treatment is well managed.

    OBJECTIVES: The aim of this study was to examine the correlation between cTTR and the rate of complications in a real life setting with cTTR above 70%, with focus on patients with warfarin due to atrial fibrillation or secondary prevention of a VTE.

    PATIENTS/METHODS: In total 66,605 patients with 89,293 treatment periods, corresponding to 179,624treatmentyears, with warfarin treatment due to VTE or AF between January 1st 2006 and December 31th 2011, was retrieved from the national quality register AuriculA. The cohort was matched with the National Patient Register in Sweden for complications and background characteristics.

    RESULTS: We found 172 centres and 68,797 treatment periods for AF and 166 centres and 20,496 treatment periods for VTE. Over 90% of the patients had a target range between INR 2-3. We found no correlation between increasing cTTR and reduction in the rate of complications for the AF patients. However, for VTE patients we saw a correlation between increasing cTTR and a reduced complication rate.

    CONCLUSIONS: Our results show that at very high cTTR levels, above 70%, further improvements in cTTR do not correlate to less treatment complications at least for patients with AF.

  • 128.
    Sandén, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Svensson, Peter J
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Venous thromboembolism and cancer risk2017Inngår i: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 43, nr 1, s. 68-73Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cancer increases the risk of venous thromboembolism (VTE) and about 20 % of all VTE are associated with cancer. VTE can also be used as a marker for occult cancer. The objective was to examine the correlation between VTE and cancer regarding predictors for a subsequent cancer diagnosis. Patients treated for VTE between January 1st 2006 and December 31th 2011 were extracted from the Swedish national quality register AuriculA and crossmatched with the Swedish National Patient Register. In total 7854 patients corresponding to 14284 treatments years were examined. Primary VTE was found in 6451 patients, with 3936 first and 2515 recurrent VTE. There were 1403 patients with secondary VTE. After a first or recurrent primary VTE the incidence of cancer diagnose was high being 9.4-10.0 % the first year compared to 2.7-2.5 % during the second year. Cancer in the digestive organs was the most common type of cancer among those with first primary VTE with 19.2 % of diagnoses. In multivariable analysis age was found to increase the risk of cancer diagnosis after both first and recurrent primary VTE HR 1.02 (CI 1.02-1.03) and HR 1.02 (CI 1.01-1.03). For a first primary VTE anemia HR 2.13 (CI 1.48-3.08) and male sex HR 1.38 (CI 1.09-1.76) increased the risk while hypertension HR 0.74 (0.57-0.96), dementia HR 0.30 (CI 0.10-0.95) and history of major bleeding HR 0.52 (CI 0.28-0.97) reduced the risk of a subsequent cancer diagnosis. There is a substantial proportion of patients being diagnosed with cancer the first year after a primary VTE, anaemia and male sex confers an increased risk.

  • 129. Simonsson, Bengt
    et al.
    Gedde-Dahl, Tobias
    Markevärn, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Remes, Kari
    Stentoft, Jesper
    Almqvist, Anders
    Björeman, Mats
    Flogegard, Max
    Koskenvesa, Perttu
    Lindblom, Anders
    Malm, Claes
    Mustjoki, Satu
    Myhr-Eriksson, Kristina
    Ohm, Lotta
    Räsänen, Anu
    Sinisalo, Marjatta
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Strömberg, Ulla
    Bjerrum, Ole Weiss
    Ehrencrona, Hans
    Gruber, Franz
    Kairisto, Veli
    Olsson, Karin
    Sandin, Fredrik
    Nagler, Arnon
    Nielsen, Johan Lanng
    Hjorth-Hansen, Henrik
    Porkka, Kimmo
    Combination of pegylated IFN-alpha 2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia2011Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, nr 12, s. 3228-3235Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Biologic and clinical observations suggest that combining imatinib with IFN-alpha may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission either to receive a combination of pegylated IFN-alpha 2b (Peg-IFN-alpha 2b) 50 mu g weekly and imatinib 400 mg daily (n = 56) or to receive imatinib 400 mg daily monotherapy (n = 56). The primary endpoint was the major molecular response (MMR) rate at 12 months after randomization. In both arms, 4 patients (7%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-alpha 2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-alpha 2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-alpha 2b treatment (< 12-week MMR rate 67%, > 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-alpha 2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg-IFN-alpha 2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.

  • 130. Simonsson, Bengt
    et al.
    Öberg, Gunnar
    Björeman, Mats
    Björkholm, Magnus
    Carneskog, Jan
    Karlsson, Karin
    Gahrton, Gösta
    Grimfors, Gunnar
    Hast, Robert
    Karle, Hans
    Linder, Olle
    Ljungman, Per
    Nielsen, Johan L
    Nilsson, Jonas
    Löfvenberg, Eva
    Malm, Claes
    Olsson, Karin
    Olsson-Strömberg, Ulla
    Paul, Christer
    Stenke, Leif
    Stentoft, Jesper
    Turesson, Ingemar
    Udén, Ann-Marie
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Vilén, Lars
    Weis-Bjerrum, Ole
    Intensive treatment and stem cell transplantation in chronic myelogenous leukemia: long-term follow-up2005Inngår i: Acta Haematologica, ISSN 0001-5792, E-ISSN 1421-9662, Vol. 113, nr 3, s. 155-162Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the present study we combined interferon (IFN) and hydroxyurea (HU) treatment, intensive chemotherapy and autologous stem cell transplantation (SCT) in newly diagnosed chronic myelogenous leukemia patients aged below 56 years, not eligible for allogeneic SCT. Patients who had an HLA-identical sibling donor and no contraindication went for an allogeneic SCT (related donor, RD). After diagnosis, patients not allotransplanted received HU and IFN to keep WBC and platelet counts low. After 6 months patients with Ph-positive cells still present in the bone marrow received 1–3 courses of intensive chemotherapy. Those who became Ph-negative after IFN + HU or after 1–3 chemotherapy courses underwent autologous SCT. Some patients with poor cytogenetic response were allotransplanted with an unrelated donor (URD). IFN + HU reduced the percentage of Ph-positive metaphases in 56% of patients, and 1 patient became Ph-negative. After one or two intensive cytotherapies 86 and 88% had a Ph reduction, and 34 and 40% became Ph-negative, respectively. In patients receiving a third intensive chemotherapy 92% achieved a Ph reduction and 8% became Ph-negative. The median survival after auto-SCT (n = 46) was 7.5 years. The chance of remaining Ph-negative for up to 10 years after autologous SCT was around 20%. The overall survival for allo-SCT RD (n = 91) and URD (n = 28) was almost the same, i.e. ≈60% at 10 years. The median survival for all 251 patients registered was 8 years (historical controls 3.5 years). The role of the treatment schedule presented in the imatinib era is discussed.

  • 131.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Low-molecular-weight heparin prophylaxis does not affect mortality in acutely ill medical patients at low risk for venous thromboembolism2012Inngår i: Evidence-Based Medicine, ISSN 1356-5524, E-ISSN 1473-6810, Vol. 17, nr 6, artikkel-id e12Artikkel i tidsskrift (Fagfellevurdert)
  • 132.
    Själander, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Sjögren, Vilhelm
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Renlund, Henrik
    Norrving, Bo
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Dabigatran, rivaroxaban and apixaban vs. high TTR warfarin in atrial fibrillationManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Objective: New oral anticoagulants are non-inferior compared with warfarin regarding stroke prevention in atrial fibrillation, with similar or decreased risk of bleeding. However, it is unclear whether high TTR warfarin is as effective and safe as NOACs. Our objective was to investigate efficacy and safety of apixaban, dabigatran or rivaroxaban compared with warfarin in clinical practice.

    Methods: Nationwide retrospective cohort study based on Swedish quality registries. Atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin between 2013-01-01 and 2015-12-31 were included. Main outcomes measures were all-cause stroke and systemic embolism, all-cause stroke, ischemic stroke, hemorrhagic stroke; major bleeding, intracranial bleeding, gastrointestinal bleeding, other bleeding (fatal or requiring hospital care); all-cause mortality; myocardial infarction.

    Results: The study included 64382 patients corresponding to 81176 treatment years. Of these, 37174 patients were instituted on warfarin, 6574 on dabigatran, 8323 on rivaroxaban and 12311 on apixaban. In warfarin treated patients, the time in therapeutic range was 71.4 %. After propensity score matching, there was no significant difference in risk of stroke or systemic embolism between NOAC and warfarin treated patients. Hazard ratios for major bleeding events were 0.63(95%CI 0.52-0.75) for apixaban, 0.74(0.62-0.87) for dabigatran and 1.06(0.92-1.23) for rivaroxaban, compared with warfarin.

    Conclusions: This study showed no difference between apixaban, dabigatran, or rivaroxaban compared to high TTR warfarin treatment regarding stroke prevention. However, fewer bleeding events were seen for apixaban and dabigatran, but not for rivaroxaban. Further studies are needed on the comparability of individual NOACs with respect to bleeding risks. 

  • 133.
    Sjögren, Vilhelm
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Grzymala-Lubanski, Bartosz
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renlund, Henrik
    Friberg, Leif
    Lip, Gregory Y. H.
    Svensson, Peter J.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Safety and efficacy of well managed warfarin: a report from the Swedish quality register Auricula2015Inngår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 113, nr 6, s. 1370-1377Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The safety and efficacy of warfarin in a large, unselected cohort of warfarin-treated patients with high quality of care is comparable to that reported for non-vitamin K antagonists. Warfarin is commonly used for stroke prevention in atrial fibrillation, as well as for treatment and prevention of venous thromboembolism. While reducing risk of thrombotic/embolic incidents, warfarin increases the risk of bleeding. The aim of this study was to elucidate risks of bleeding and thromboembolism for patients on warfarin treatment in a large, unselected cohort with rigorously controlled treatment. This was a retrospective, registry-based study, covering all patients treated with warfarin in the Swedish national anticoagulation register Auricula, which records both primary and specialised care. The study included 77,423 unselected patients with 100,952 treatment periods of warfarin, constituting 217,804 treatment years. Study period was January 1, 2006 to December 31, 2011. Atrial fibrillation was the most common indication (68%). The mean time in therapeutic range of the international normalised ratio (INR) 2.0-3.0 was 76.5%. The annual incidence of I severe bleeding was 2.24% and of thromboembolism 2.65%. The incidence of intracranial bleeding was 0.37% per treatment year in the whole population, and 0.38% among patients with atrial fibrillation. In conclusion, warfarin treatment where patients spend a high proportion of time in the therapeutic range is safe and effective, and will continue to be a valid treatment option in the era of newer oral anticoagulants.

  • 134.
    Sjögren, Vilhelm
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Grzymala-Lubanski, Bartosz
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Renlund, Henrik
    Svensson, Peter
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Safety and Efficacy of Bridging With Low-Molecular-Weight Heparin During Temporary Interruptions of Warfarin: A Register-Based Cohort Study2017Inngår i: Clinical and applied thrombosis/hemostasis, ISSN 1076-0296, E-ISSN 1938-2723, Vol. 23, nr 8, s. 961-966Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Low-molecular-weight heparin (LMWH) is often recommended as a bridging therapy during temporary interruptions in warfarin treatment, despite lack of evidence. The aim of this study was to see whether we could find benefit from LMWH bridging. We studied all planned interruptions of warfarin within the Swedish anticoagulation register Auricula during 2006 to 2011. Low-molecular-weight heparin bridging was compared to nonbridging (control) after propensity score matching. Complications were identified in national clinical registers for 30 days following warfarin cessation, and defined as all-cause mortality, bleeding (intracranial, gastrointestinal, or other), or thrombosis (ischemic stroke or systemic embolism, venous thromboembolism, or myocardial infarction) that was fatal or required hospital care. Of the 14 556 identified warfarin interruptions, 12 659 with a known medical background had a mean age of 69 years, 61% were males, mean CHADS2 (1 point for each of congestive heart failure, hypertension, age >/=75 years, diabetes, and 2 points for stroke or transient ischemic attack) score was 1.7, and CHA2DS2-VASc score was 3.4. The total number of LMWH bridgings was 7021. Major indications for anticoagulation were mechanical heart valve prostheses 4331, atrial fibrillation 1097, and venous thromboembolism 1331. Bridging patients had a higher rate of thrombotic events overall. Total risk of any complication did not differ significantly between bridging (1.5%) and nonbridging (1.2%). Regardless of indication for warfarin treatment, we found no benefit from bridging. The type of procedure prompting bridging was not known, and the likely reason for the observed higher risk of thrombosis with LMWH bridging is that low-risk procedures more often meant no bridging. Results from randomized trials are needed, especially for patients with mechanical heart valves.

  • 135.
    Skagerlind, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    How to reduce the exposure to anticoagulants when performing haemodialysis in patients with a bleeding risk: a study of methods used in clinical practise2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    When a patient suffers from kidney failure and also has an enhanced risk of bleeding, the standard haemodialysis (HD) treatment becomes a problem. When human blood comes in contact with artificial material, as in the tubing system and in the dialyser (the extra corporeal circuit, ECC), the coagulation system is activated. If there is no increased risk of bleeding a bolus dose of anticoagulation is given intravenous to the patient before HD to avoid clotting. The most common anticoagulants used during HD are unfractionated heparin (UFH) and low molecule weight heparins (LMWH). Without anticoagulants there will be a total coagulation (clotting) of the blood in the ECC, an interrupted treatment and a blood loss of up to 300 ml for the patient. With an ongoing bleeding or an increased risk of bleeding in a patient that also needs HD, there are various alternatives that can be used to avoid or lower the need of anticoagulation. However, there is no golden standard, neither in Sweden or worldwide.

    The overall aim of this Thesis was to evaluate the safety and the efficacy of various models of anticoagulation that may be used in patients with a bleeding risk.

    The first study examined a low-dose anticoagulation model that was locally developed in Umeå, Sweden in the 1980s. The primary aim was to clarify to what extent this priming model was safe and efficient during intermittent HD for patients with a bleeding risk. Consecutive acute HD treatment protocols (248 procedures in 68 patients) were included. There were 178 patients with an increased bleeding risk who had their ECC (tubes, chambers and dialyser) flushed through (priming) with Heparin-Albumin-priming (HA-priming). There were 70 patients with no increased bleeding risk who received standard intermittent HD (priming with saline); these patients also received a bolus dose of anticoagulation intravenous before dialysis.

    The low-dose method entailed priming of the ECC with HA-priming with the intention to coat the surfaces with the solution and protect from blood to attach to it. Comparisons were made to dialysis in patients with no increased bleeding risk, who had received standard anticoagulation (SHD) with UFH or LMWH. The priming solutions were always discarded before HD was initiated. None or limited doses of UFH were added during the HD. There was no difference in extent of prematurely interrupted HA-primed dialysis compared to SHD (2.2 vs. 4.3%, p = 0.62). No secondary bleeding due to anticoagulation was reported in the protocols.

    Study 2 was performed to further clarify data in an extended group of acute intermittent HD using either HA-priming (885 treatments in 221 patients at risk of bleeding) or SHD (523 treatments in 100 patients with no bleeding risk who had received standard anticoagulation). In this extended study there was no difference in the extent of prematurely interrupted HA-dialysis (0.8%) compared to SHD (1%, p = 0.8). The results also showed less clotting for dialysers with a membrane area ≤ 1.7 m2. No secondary bleeding due to anticoagulation was reported in the protocols.

    Study 3 was an experimental in vitro study. The aim was to compare the anticoagulation effect of priming the ECC with different concentrations of albumin and/or heparin in saline. Priming with saline only was also evaluated. The priming fluids were always discarded after priming. Fresh whole blood from healthy human donors was used to perform in vitro dialyses in a recirculation system. The donated blood was equally divided into two bags, whereas one bag represented the control group and the other the intervention group. Priming with saline only and priming with albumin in saline resulted in rapid clotting of the blood in the ECC. These experiments indicated that HA-priming or priming with heparin in saline enabled fulfilment of all the in vitro dialyses.

    Study 4 was a clinical randomized cross-over study. The aim was to minimize the use of anticoagulant during HD in patients with a bleeding risk. Four different low-dose anticoagulation models were compared to SHD. Stable chronic HD patients participated in the study. The patients were their own controls. Aside from SHD, the four models of low-dose anticoagulation used were Heparin priming (H), HA-priming (HA), HA-priming in combination with a citrate containing dialysate (HAC), and a dialyser manufactured with a heparin-grafted membrane (Evodial®). The H-model was least suitable with 33 % interrupted treatments and the most extra doses of UFH needed. The HAC and Evodial® models were most preferable, both with an activated partial thromboplastin time (APTT) within references and with the least amounts of UFH needed. Evodial® had a lower urea reduction rate compared to the other models. HAC was the only model with no interrupted treatment. One patient suffered from a severe hypersensitivity reaction using Evodial®. No other side-effects were reported during the study.

    In conclusion an acute kidney injury is a life-threating situation that also includes patients with an increased bleeding risk and in need of HD for survival. If intermittent HD is the selected option, a priming of the ECC with a HA-solution in combination with a citrate containing dialysis fluid (HAC) is a safe and sufficient option for anticoagulation. Another option could be the heparin-grafted dialyser (Evodial®), although with a lower clearance coefficient and with a caution for a risk for hypersensitivity reaction or anaphylaxis.

  • 136.
    Skagerlind, Malin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad. Department of Nephrology, Centre of Medicine, University Hospital of Umeå, Umeå, Sweden.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    An evaluation of four modes of low-dose anticoagulation during intermittent haemodialysis2018Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 74, nr 3, s. 267-274Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Intensive care participants that need dialysis frequently suffer from increased risk of bleeding. Standard intermittent haemodialysis (SHD) includes anticoagulation to avoid clotting of the dialysis system. The aim of this study was to clarify which of four different low-dose anticoagulant modes was preferable in reducing the exposure to i.v. unfractionated heparin (heparin) and maintaining patency of the dialysis circuit. Twenty-three patients on SHD were included to perform haemodialysis with four modes of low-dose anticoagulation. For comparative analyses, patients served as their own control. Haemodialysis with a single bolus of tinzaparin at the start was compared to haemodialysis initiated without i.v. heparin but priming with (1) heparin in saline (H), (2) heparin and albumin in saline (HA), (3) heparin and albumin in combination with a citrate-containing dialysate (HAC), (4) saline and usinga heparin-coated filters (EvodialA (R)). The priming fluid was discarded before dialysis started. Blood samples were collected at 0, 30 and 180 min during haemodialysis. Smaller bolus doses of heparin (500 Units/dose) were allowed during the modes to avoid interruption by clotting. The mean activated partial thromboplastin (APTT) time as well as the doses of anticoagulation administered was highest with SHD and least with HAC and EvodialA (R). Mode H versus SHD had the highest rate of prematurely interrupted dialyses (33%, p = 0.008). The urea reduction rate was less with EvodialA (R) vs. SHD (p < 0.01). One hypersensitivity reaction occurred with EvodialA (R). Changes in blood cell concentrations and triglycerides differed between the modes. If intermittent haemodialysis is necessary in patients at risk of bleeding, anticoagulation using HAC and EvodialA (R) appeared most preferable with least administration of heparin, lowest APTT increase and lowest risk for prematurely clotted dialyzers in contrast to the least plausible H mode.

  • 137.
    Sojka, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Nilsson Sojka, Birgitta
    Adverse effects in blood donors after wholeblood donation: you find what you look for!2004Inngår i: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 44, nr 1, s. 135-136Artikkel i tidsskrift (Annet vitenskapelig)
  • 138.
    Späth, Florentin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wibom, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Krop, Esmeralda J. M.
    Johansson, Ann-Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergdahl, Ingvar A.
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Vermeulen, Roel
    Melin, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Biomarker Dynamics in B-cell Lymphoma: A Longitudinal Prospective Study of Plasma Samples Up to 25 Years before Diagnosis2017Inngår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 77, nr 6, s. 1408-1415Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The B-cell activation markers CXCL13, sCD23, (S)CD27, and sCD30 are associated with future lymphoma risk. However, a lack of information about the individual dynamics of markerdisease association hampers interpretation. In this study, we identified 170 individuals who had donated two prediagnostic blood samples before B-cell lymphoma diagnosis, along with 170 matched cancer-free controls from the Northern Sweden Health and Disease Study. Lymphoma risk associations were investigated by subtype and marker levels measured at baseline, at the time of the repeated sample, and with the rate of change in the marker level. Notably, we observed strong associations between CXCL13, sCD23, sCD27, and sCD30 and lymphoma risk in blood samples collected 15 to 25 years before diagnosis. B-cell activation marker levels increased among future lympho-ma cases over time, while remaining stable among controls. Associations between slope and risk were strongest for indolent lymphoma subtypes. We noted a marked association of sCD23 with chronic lymphocytic leukemia (ORSlope - 28, Ptrend(-)7.279 x 10 (-10)). Among aggressive lymphomas, the association between diffuse large B-cell lymphoma risk and slope was restricted to CXCL13. B-cell activation seemed to play a role in B-cell lymphoma development at early stages across different subtypes. Furthermore, B-cell activation presented differential trajectories in future lymphoma patients, mainly driven by indolent subtypes. Our results suggest a utility of these markers in predicting the presence of early occult disease and/or the screening and monitoring of indolent lymphoma in individual patients. 

  • 139. Staffas, Anna
    et al.
    Kanduri, Meena
    Hovland, Randi
    Rosenquist, Richard
    Ommen, Hans Beier
    Abrahamsson, Jonas
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Jahnukainen, Kirsi
    Jonsson, Olafur G.
    Zeller, Bernward
    Palle, Josefine
    Lonnerholm, Gudmar
    Hasle, Henrik
    Ehrencrona, Hans
    Palmqvist, Lars
    High ERG gene expression is an unfavorable prognostic marker in pediatric acute myeloid leukemia Response2012Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 119, nr 4, s. 1087-1088Artikkel i tidsskrift (Fagfellevurdert)
  • 140. Staffas, Anna
    et al.
    Kanduri, Meena
    Hovland, Randi
    Rosenquist, Richard
    Ommen, Hans Beier
    Abrahamsson, Jonas
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Jahnukainen, Kirsi
    Jonsson, Olafur G.
    Zeller, Bernward
    Palle, Josefine
    Lonnerholm, Gudmar
    Hasle, Henrik
    Palmqvist, Lars
    Ehrencrona, Hans
    Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia2011Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, nr 22, s. 5905-5913Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mutation status of FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1 have been identified as possible prognostic markers in acute myeloid leukemia (AML). We have performed a thorough prognostic evaluation of these genetic markers in patients with pediatric AML enrolled in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) 1993 or NOPHO 2004 protocols. Mutation status and expression levels were analyzed in 185 and 149 patients, respectively. Presence of FLT3-internal tandem duplication (ITD) was associated with significantly inferior event-free survival (EFS), whereas presence of an NPM1 mutation in the absence of FLT3-ITD correlated with significantly improved EFS. Furthermore, high levels of ERG and BAALC transcripts were associated with inferior EFS. No significant correlation with survival was seen for mutations in CEBPA and WT1 or with gene expression levels of MN1, FLT3, and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALC expression were identified as independent prognostic markers of inferior EFS. We conclude that analysis of the mutational status of FLT3 and NPM1 at diagnosis is important for prognostic stratification of patients with pediatric AML and that determination of the BAALC gene expression level can add valuable information. (Blood. 2011;118(22):5905-5913)

  • 141.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Apheresis in patients with severe sepsis and multi organ dysfunction syndrome2008Inngår i: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 38, nr 3, s. 203-208Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Apheresis is used as therapeutic approach to improve outcome of patients with severe sepsis, septic shock and multi organ dysfunction syndrome. The concept is to reduce the extent of toxins and cytokines as well as other activators of the various cascade systems. In addition the replacement of plasma, in some of the protocols, helps to substitute with substances that are consumed/complex bound by the inflammatory reactions during the severe clinical condition. This article reviews literature in the field of adsorption technologies as well as plasma exchange techniques.

  • 142.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Registry Committee, World Apheresis Association, Sweden.
    Apheresis registries advancement: Plans for comparison of aggregate data and clarification of ethical considerations2017Inngår i: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 56, nr 5, s. 642-642Artikkel i tidsskrift (Annet vitenskapelig)
  • 143.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    ESFH letter2008Inngår i: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 38, nr 2, s. 91-91Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 144.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Uremic Toxins and Lipases in Haemodialysis: A Process of Repeated Metabolic Starvation2014Inngår i: Toxins, ISSN 2072-6651, E-ISSN 2072-6651, Vol. 6, nr 5, s. 1505-1511Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Severe kidney disease results in retention of uremic toxins that inhibit key enzymes for lipid breakdown such as lipoprotein lipase (LPL) and hepatic lipase (HL). For patients in haemodialysis (HD) and peritoneal dialysis (PD) the LPL activity is only about half of that of age and gender matched controls. Angiopoietin, like protein 3 and 4, accumulate in the uremic patients. These factors, therefore, can be considered as uremic toxins. In animal experiments it has been shown that these factors inhibit the LPL activity. To avoid clotting of the dialysis circuit during HD, anticoagulation such as heparin or low molecular weight heparin are added to the patient. Such administration will cause a prompt release of the LPL and HL from its binding sites at the endothelial surface. The liver rapidly degrades the release plasma compound of LPL and HL. This results in a lack of enzyme to degrade triglycerides during the later part of the HD and for another 3-4 h. PD patients have a similar baseline level of lipases but are not exposed to the negative effect of anticoagulation.

  • 145.
    Stegmayr, Bernd G
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ptak, J
    Nilsson, T
    Berlin, G
    Mirea, V
    Axelsson, CG
    Griskevicius, A
    Centoni, P
    Liumbruno, G
    Audzijoniene, J
    Mokvist, K
    Lassen, Ewa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Knutson, F
    Norda, R
    Mörtzell, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Prophet, H
    Ramlow, W
    Blaha, M
    Witt, V
    Efvergren, M
    Tomaz, J
    Newman, E
    Eloot, S
    Dhondt, A
    Lalic, K
    Sikole, A
    Derfler, K
    Hrdlickova, R
    Tomsova, H
    Gasova, Z
    Bhuiyan-Ludvikova, Z
    Ramsauer, Bernd
    Skövde, Sweden.
    Vrielink, H
    Panorama of adverse events during cytapheresis2013Inngår i: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 48, nr 2, s. 155-156Artikkel i tidsskrift (Annet vitenskapelig)
  • 146.
    Stegmayr, Bernd
    et al.
    Division of Nephrology, Department of Internal Medicine, University Hospital of Northern Sweden.
    Klingstedt, Jonas
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för interaktiva medier och lärande (IML).
    Grahn, Bengt Erik
    Vinnervik, Peter
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för interaktiva medier och lärande (IML).
    The new WAA apheresis registry2006Inngår i: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 34, nr 3, s. 259-262Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The WAA (World Apheresis Association) registry for apheresis has been developed to enable registration through internet by centers all around the world. It is of no charge for the registering centers. The new version is available at the site www.iml.umu.se/medicin.

    Until now more than 5700 treatments have been registered from centers in 6 countries. It allows registration of acute or chronic therapeutic apheresis and also collection of stem cells, cellapheresis, photopheresis and various adsorption technologies.

    Registration includes diagnoses, access, anticoagulation, replacement fluids, mode of treatment, volumes processed, techniques used and adverse events that develop. Analyses of data enables improvement of quality of apheresis. The new registry enables you to change data that were wrongly entered as well as add data that was missed when you firstly entered the file. We cordially invite all of you to join the registration procedure.

  • 147. Stenson, Martin
    et al.
    Pedersen, Anders
    Hasselblom, Sverker
    Nilsson-Ehle, Herman
    Karlsson, Bengt Göran
    Pinto, Rui
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi. Bioinformatics for Life Sciences (BILS), Gothenburg, Sweden.
    Andersson, Per-Ola
    Serum nuclear magnetic resonance-based metabolomics and outcome in diffuse large B-cell lymphoma patients - a pilot study2016Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 57, nr 8, s. 1814-1822Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The prognosis for diffuse large B-cell lymphoma (DLBCL) patients with early relapse or refractory disease is dismal. To determine if clinical outcome correlated to diverse serum metabolomic profiles, we used H-1 nuclear magnetic resonance (NMR) spectroscopy and compared two groups of DLBCL patients treated with immunochemotherapy: i) refractory/early relapse (REF/REL; n=27) and ii) long-term progression-free (CURED; n=60). A supervised multivariate analysis showed a separation between the groups. Among discriminating metabolites higher in the REF/REL group were the amino acids lysine and arginine, the degradation product cadaverine and a compound in oxidative stress (2-hydroxybutyrate). In contrast, the amino acids aspartate, valine and ornithine, and a metabolite in the glutathione cycle, pyroglutamate, were higher in CURED patients. Together, our data indicate that NMR-based serum metabolomics can identify a signature for DLBCL patients with high-risk of failing immunochemotherapy, prompting for larger validating studies which could lead to more individualized treatment of this disease.

  • 148.
    Sulniute, Rima
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Shen, Yue
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Guo, Yong-Zhi
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Fallah, Mahsa
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ahlskog, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ny, Lina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Rakhimova, Olena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Brodén, Jessica
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Boija, Hege
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Moghaddam, Aliyeh
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Li, Jinan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Wilczynska, Malgorzata
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ny, Tor
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Plasminogen is a critical regulator of cutaneous wound healing2016Inngår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 115, nr 5, s. 1001-1009Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Wound healing is a complicated biological process that consist of partially overlapping inflammatory, proliferation and tissue remodelling phases. A successful wound healing depends on a proper activation and subsequent termination of the inflammatory phase. The failure to terminate the inflammation halts the completion of wound healing and is a known reason for formation of chronic wounds. Previous studies have shown that wound closure is delayed in plasminogen deficient mice, and a role for plasminogen in dissection of extracellular matrix was suggested. However, our finding that plasminogen is transported to the wound by inflammatory cells early during the healing process, where it potentiates inflammation, indicates that plasminogen may also have other roles in the wound healing process. Here we report that plasminogen-deficient mice have extensive fibrin and neutrophil depositions in the wounded area long after re-epithelialisation, indicating inefficient debridement and chronic inflammation. Delayed formation of granulation tissue suggests that fibroblast function is impaired in the absence of plasminogen. Therefore, in addition to its role in the activation of inflammation, plasminogen is also crucial for subsequent steps, including resolution of inflammation and activation of the proliferation phase. Importantly, supplementation of plasminogen-deficient mice with human plasminogen leads to a restored healing process that is comparable to that in wild-type mice. Besides of being an activator of the inflammatory phase during wound healing, plasminogen is also required for the subsequent termination of inflammation. Based on these results, we propose that plasminogen may be an important future therapeutic agent for wound treatment.

  • 149. Swartling, L. P.
    et al.
    Allard, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Torlen, J.
    Ljungman, P.
    Mattsson, J.
    Sparrelid, E.
    Prolonged Outbreak of Adenovirus A31 Among Allogeneic Stem Cell Transplant Recipients2015Inngår i: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 50 1, s. S77-S77Artikkel i tidsskrift (Annet vitenskapelig)
  • 150. Söderlund, Stina
    et al.
    Dahlén, Torsten
    Sandin, Fredrik
    Olsson-Strömberg, Ulla
    Creignou, Maria
    Dreimane, Arta
    Lübking, Anna
    Markevärn, Berit
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wadenvik, Hans
    Stenke, Leif
    Richter, Johan
    Höglund, Martin
    Advanced phase chronic myeloid leukaemia (CML) in the tyrosine kinase inhibitor era: a report from the Swedish CML register2017Inngår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 98, nr 1, s. 57-66Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: The primary goal in management of chronic phase (CP) chronic myeloid leukaemia (CML) is to prevent disease progression to accelerated phase (AP) or blast crisis (BC). We have evaluated progression rates in a decentralised healthcare setting and characterised patients progressing to AP/BC on TKI treatment.

    METHODS: Using data from the Swedish CML register, we identified CP-CML patients diagnosed 2007-2011 who progressed to AP/BC within 2 yrs from diagnosis (n = 18) as well as patients diagnosed in advanced phase during 2007-2012 (n = 36) from a total of 544 newly diagnosed CML cases. We evaluated baseline characteristics, progression rates, outcome and adherence to guidelines for monitoring and treatment.

    RESULTS: The cumulative progression rate at 2 yrs was 4.3%. All 18 progression cases had been treated with imatinib, and six progressed within 6 months. High-risk EUTOS score was associated to a higher risk of progression. Insufficient cytogenetic and/or molecular monitoring was found in 33%. Median survival after transformation during TKI treatment was 1.4 yrs. In those presenting with BC and AP, median survival was 1.6 yrs and not reached, respectively.

    CONCLUSION: In this population-based setting, progression rates appear comparable to that reported from clinical trials, with similar dismal patient outcome. Improved adherence to CML guidelines may minimise the risk of disease progression.

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