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  • 1.
    Abedi, Mohammad R.
    et al.
    Örebro University Hospital. Department of Laboratory Medicine, Section for Transfusion Medicine.
    Doverud, Ann-Charlotte
    Department of Laboratory Medicine, Section for Transfusion Medicine, Örebro University Hospital.
    Preparation and Pathogen Inactivation of Double Dose Buffy Coat Platelet Products using the INTERCEPT Blood System2012In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 70, UNSP e4414Article in journal (Refereed)
    Abstract [en]

    Blood centers are faced with many challenges including maximizing production yield from the blood product donations they receive as well as ensuring the highest possible level of safety for transfusion patients, including protection from transfusion transmitted diseases. This must be accomplished in a fiscally responsible manner which minimizes operating expenses including consumables, equipment, waste, and personnel costs, among others.

    Several methods are available to produce platelet concentrates for transfusion. One of the most common is the buffy coat method in which a single therapeutic platelet unit (>= 2.0 x10(11) platelets per unit or per local regulations) is prepared by pooling the buffy coat layer from up to six whole blood donations. A procedure for producing "double dose" whole blood derived platelets has only recently been developed.

    Presented here is a novel method for preparing double dose whole blood derived platelet concentrates from pools of 7 buffy coats and subsequently treating the double dose units with the INTERCEPT Blood System for pathogen inactivation. INTERCEPT was developed to inactivate viruses, bacteria, parasites, and contaminating donor white cells which may be present in donated blood. Pairing INTERCEPT with the double dose buffy coat method by utilizing the INTERCEPT Processing Set with Dual Storage Containers (the "DS set"), allows blood centers to treat each of their double dose units in a single pathogen inactivation processing set, thereby maximizing patient safety while minimizing costs. The double dose buffy coat method requires fewer buffy coats and reduces the use of consumables by up to 50% (e.g. pooling sets, filter sets, platelet additive solution, and sterile connection wafers) compared to preparation and treatment of single dose buffy coat platelet units. Other cost savings include less waste, less equipment maintenance, lower power requirements, reduced personnel time, and lower collection cost compared to the apheresis technique.

  • 2.
    Acosta, Stefan
    et al.
    Vascular Center, Skåne University Hospital, Malmö, Sweden.
    Nilsson, Torbjörn
    Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
    Current status on plasma biomarkers for acute mesenteric ischemia2012In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 33, no 4, 355-361 p.Article in journal (Refereed)
    Abstract [en]

    Clinical diagnosis of acute mesenteric ischemia is difficult. The aim of this review is to provide current status on the search for an accurate plasma biomarker for acute mesenteric ischemia. A search using the medical subject heading terms marker and mesenteric ischemia or intestinal ischemia or superior mesenteric artery occlusion or mesenteric venous thrombosis in the Medline and Embase databases from 1980 to 2011. Studies without a control group or a control group consisted of healthy individuals (human studies), or studies on intestinal reperfusion were excluded. Twenty animal and twelve human studies were identified. In human studies, the studied series of patients had a control group that had a need of laparotomy (n = 2), suspected acute mesenteric ischemia (n = 7), acute abdomen (n = 2) or systemic inflammatory response syndrome (n = 1). D: -dimer has been found to be the most consistent highly sensitive early marker, but specificity was low. The follow-up study on α-glutathione S-transferase yielded inferior sensitivity and accuracy than the preliminary study, clearly questioning the value of this marker. Intestinal fatty acid binding globulin (I-FABP) and D: -lactate are both interesting markers, but the results were conflicting. Different cut-off levels have been used in the studies on I-FABP. The encouraging preliminary result of cobalt-albumin and urinary FABP as an accurate marker needs to be addressed in other study populations. The early clinical and laboratory diagnosis of intestinal ischemia remains a challenge. None of the proposed plasma-derived tests for acute mesenteric ischemia has as yet entered routine clinical practice. The proposed biomarkers need to be evaluated in a prospective clinical research project in patients with acute abdomen.

  • 3.
    Ahlstrand, Erik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Coagulase-negative staphylococci in hematological malignancy2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Bacterial infections are common in hematological malignancy. Coagulase-negative staphylococci (CoNS) are among the most prevalent causes of bacteremia in patients with hematological malignancies.

    In this thesis, different aspects of CoNS in hematological malignancy have been studied in four papers:

    In paper 1, CoNS blood culture isolates from patients with hematological malignancies treated at the University Hospital of Örebro from 1980 to 2009 were revaluated for the presence of reduced sensitivity to glycopeptides. A high incidence of heterogeneous-intermediate glycopeptide resistance was observed and there was a trend towards increasing incidence of this phenotype over time.

    In paper 2, the colonization pattern of CoNS among patients undergoing intensive chemotherapy for hematological malignancy was investigated. A successive homogenization and an accumulation of CoNS phenotypes mutually present in a majority of included patients were demonstrated.

    In paper 3, a PCR method to determine the clinical significance of positive blood cultures of the CoNS species Staphylococcus epidermidis was evaluated. The test failed to discriminate bloodstream infection from blood culture contamination.

    Finally, in paper 4, the long-term molecular epidemiology of S. epidermidis blood culture isolates from patients with hematological malignancies was studied with multilocus sequence typing. A predominance of sequence type 2 was demonstrated during the entire 30 year study period.

    In conclusion, the results are consistent with that CoNS have established as important pathogens by its capacity to colonize the human skin, its ability to reside and spread in the hospital environment and its rapid adaptation to stressors such as antimicrobials.

    List of papers
    1. Glycopeptide resistance in coagulase-negative staphylococci isolated in blood cultures from patients with hematological malignancies during three decades
    Open this publication in new window or tab >>Glycopeptide resistance in coagulase-negative staphylococci isolated in blood cultures from patients with hematological malignancies during three decades
    Show others...
    2011 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 30, no 11, 1349-1354 p.Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to determine if there was a long-term increase in glycopeptide minimum inhibitory concentration (MIC) values, MIC creep, among bloodstream isolates of Staphylococcus epidermidis and S. haemolyticus isolated from patients with hematological malignancies. We conducted a retrospective single-center study where all positive blood cultures of S. epidermidis (n = 387) and S. haemolyticus (n = 19) isolated from patients with hematological malignancies during three decades, 1980 to 2009, were re-evaluated for the presence of reduced susceptibility to vancomycin and teicoplanin. Three different methods for the detection of reduced susceptibility to glycopeptides were used; standard Etest, macromethod Etest, and glycopeptide resistance detection (GRD) Etest. The median MIC value for vancomycin was 2 mg/L. MIC values for vancomycin and teicoplanin did not show any statistically significant increase during the study period. The presence of heterogeneously glycopeptide-intermediate staphylococci (hGIS) was analyzed among 405 coagulase-negative staphylococci (CoNS) isolates. hGIS were found in 31-45% of the CoNS isolates by the macromethod Etest and in 53-67% by the GRD Etest during the three decades. In conclusion, we did not observe any long-term glycopeptide MIC creep determined by the standard Etest, although a high and increasing proportion of heterogeneous vancomycin resistance was observed.

    National Category
    Medical and Health Sciences
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-20840 (URN)10.1007/s10096-011-1228-8 (DOI)000295864800006 ()
    Available from: 2012-01-11 Created: 2012-01-11 Last updated: 2017-12-08Bibliographically approved
    2. Alteration of the colonization pattern of coagulase-negative staphylococci in patients undergoing treatment for hematological malignancy
    Open this publication in new window or tab >>Alteration of the colonization pattern of coagulase-negative staphylococci in patients undergoing treatment for hematological malignancy
    2012 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 31, no 7, 1679-1687 p.Article in journal (Refereed) Published
    Abstract [en]

    The aim was to prospectively describe the colonization pattern of coagulase-negative staphylococci (CoNS) and the relationship between colonizing and invasive CoNS isolates among patients undergoing treatment for hematological malignancy. Fourteen newly diagnosed patients were included with either multiple myeloma or acute leukemia. Patients were repeatedly sampled from nares, throat, axillae, and perineum, and the CoNS isolates obtained were phenotypically characterized together with blood isolates of CoNS using the PhenePlate system (PhP). During the treatment a gradual reduction in the heterogeneity of colonizing CoNS was observed as well as an inter-patient accumulation of phenotypically related and multi-drug-resistant CoNS. These clusters of CoNS persisted for 2–3 months after the end of therapy. Ten positive blood cultures of CoNS were obtained and in the majority of these cases CoNS of the same PhP type were found in superficial cultures collected prior to the blood culture sampling. In conclusion, the study shows that therapy for hematological malignancy is associated with a homogenization of colonizing CoNS isolates and that this acquired flora of CoNS is persistent several months after the end of therapy. Furthermore, the results suggest that the source of bloodstream infections of CoNS in hematological patients is colonizing CoNS of the skin and mucosa.

    Place, publisher, year, edition, pages
    New York, USA: Springer, 2012
    National Category
    Clinical Medicine Infectious Medicine
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-22579 (URN)10.1007/s10096-011-1493-6 (DOI)000304652800051 ()22124538 (PubMedID)2-s2.0-84865591558 (Scopus ID)
    Note

    Funding Agency:

    research committee of Örebro County Council, Sweden

    Available from: 2012-04-18 Created: 2012-04-18 Last updated: 2017-12-07Bibliographically approved
    3. Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies
    Open this publication in new window or tab >>Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies
    Show others...
    2014 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 6, 539-544 p.Article in journal (Refereed) Published
    Abstract [en]

    The aim was to investigate whether the detection and quantification of Staphylococcus epidermidis DNA in blood could distinguish S. epidermidis blood stream infections (BSIs) from blood culture contaminations in patients with hematological malignancies. The hld gene was chosen to identify S. epidermidis DNA and DNA in blood samples was detected by real-time PCR. Blood samples were obtained simultaneously with blood cultures positive for S. epidermidis (n = 30), during blood culture-negative episodes (n = 10) and episodes of bacteremia with other bacteria than S. epidermidis (n = 4) and from healthy blood donors (n = 10). In addition, DNA from S. epidermidis and a selection of other bacterial species were analyzed. Three different sets of criteria were used to classify episodes with positive blood cultures with S. epidermidis as BSIs or contaminations. All DNA preparations from S. epidermidis (n = 48) were hld-positive, but other bacterial species (n = 13) were negative. Sixteen (53%) of 30 blood samples from patients with blood cultures positive for S. epidermidis were hld-positive, but none of the controls. There was no clear association between a positive hld PCR and episodes interpreted as BSIs. In conclusion, hld PCR failed to distinguish S. epidermidis BSIs from blood culture contaminations in patients with hematological malignancies.

    Keyword
    coagulase-negative staphylococci; Staphylococcus epidermidis; hematological malignancy; blood culture contamination
    National Category
    Medical and Health Sciences
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-32422 (URN)10.1111/apm.12182 (DOI)24106819 (PubMedID)2-s2.0-84901231876 (Scopus ID)
    Available from: 2013-11-15 Created: 2013-11-15 Last updated: 2017-09-27Bibliographically approved
    4. Long-term molecular epidemiology of Staphylococcus epidermidis blood culture isolates from patients with haematological malignancies
    Open this publication in new window or tab >>Long-term molecular epidemiology of Staphylococcus epidermidis blood culture isolates from patients with haematological malignancies
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Staphylococcus epidermidis is an important cause of bloodstream infections in patients with haematological malignancies. Knowledge of the long-term epidemiology of these infections is limited. We surveyed all S. epidermidis blood culture isolates from patients treated for haematological malignancies at the University Hospital of Örebro, Sweden from 1980 to 2009. A total of 373 S. epidermidis isolates were identified and multilocus sequence typing and standard antibiotic susceptibility testing were employed to characterize these isolates. The majority of the isolates 361/373 (97%) belonged to clonal complex 2, and the 373 isolates were divided into 45 sequence types (STs); Simpson’s Diversity Index was 0.56. The most prevalent STs were ST2 (243/373, 65%) and ST215 (28/373, 8%). These two STs were isolated during the entire study period, and together caused temporal peaks in the incidence of positive blood cultures of S. epidermidis. Methicillin resistance was detected in 213/273 (78%) of all isolates. In the two predominating STs, ST2 and ST215, the proportion of methicillin resistance was 257/271 (95%); 234/271 (86%) displayed a multidrug-resistant phenotype. In conclusion, in this long-term study of patients with haematological malignancies, we demonstrate a predominance of methicillin-resistant ST2 among S. epidermidis blood culture isolates.

    Keyword
    Staphylococcus epidermidis, Bloodstream infection, Haematological malignancy, Multilocus sequence typing, Coagulase-negative staphylococci, Molecular epidemiology, Healthcare-associated infection
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:oru:diva-32423 (URN)
    Available from: 2013-11-15 Created: 2013-11-15 Last updated: 2017-10-17Bibliographically approved
  • 4.
    Andersen, Christen L.
    et al.
    Roskilde Hosp, Dept Haematol, DK-4000 Roskilde, Denmark.;Copenhagen Univ Hosp, Rigshosp, Dept Haematol, Copenhagen, Denmark..
    McMullin, Mary F.
    Queens Univ Belfast, Dept Haematol, Belfast, Antrim, North Ireland..
    Ejerblad, Elisabeth
    Univ Uppsala Hosp, Dept Haematol, Uppsala, Sweden..
    Zweegman, Sonja
    Vrije Univ Amsterdam Med Ctr, Dept Haematol, Amsterdam, Netherlands..
    Harrison, Claire
    Guys & St Thomas Hosp, Dept Haematol, London SE1 9RT, England.;NHS Fdn Trust, London, England..
    Fernandes, Savio
    Bareford, David
    Russells Hall Hosp, Dept Haematol, Dudley, England..
    Knapper, Steven
    Cardiff Univ, Dept Haematol, Cardiff CF10 3AX, S Glam, Wales..
    Samuelsson, Jan
    Stockholm South Hosp, Dept Internal Med, Stockholm, Sweden..
    Loefvenberg, Eva
    Karolinska Univ Hosp, Haematol Ctr, Stockholm, Sweden..
    Linder, Olle
    Andreasson, Bjorn
    NU Hosp Org, Uddevalla Hosp, Dept Haematol, Uddevalla, Sweden..
    Ahlstrand, Erik
    Örebro University Hospital.
    Jensen, Morten K.
    Herlev Hosp, Dept Haematol, DK-2730 Herlev, Denmark..
    Bjerrum, Ole W.
    Vestergaard, Hanne
    Odense Univ Hosp, Dept Haematol, DK-5000 Odense, Denmark..
    Larsen, Herdis
    Viborg Hosp, Dept Internal Med, Dept Haematol, Viborg, Denmark..
    Klausen, Tobias W.
    Mourits-Andersen, Torben
    Esbjerg Cent Hosp, Dept Haematol, Esbjerg, Denmark..
    Hasselbalch, Hans C.
    Roskilde Hosp, Dept Haematol, DK-4000 Roskilde, Denmark..
    A phase II study of vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia2013In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 162, no 4, 498-508 p.Article in journal (Refereed)
    Abstract [en]

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

  • 5.
    Andersen, Christen Lykkegaard
    et al.
    Roskilde Univ Hosp, Dept Hematol, DK-4000 Roskilde, Denmark..
    Bjorn, Mads Emil
    Roskilde Univ Hosp, Dept Hematol, DK-4000 Roskilde, Denmark..
    McMullin, Mary Frances
    Queen Univ Belfast, Dept Haematol, Belfast BT9 7AB, Antrim, North Ireland..
    Harrison, Claire
    NHS Fdn Trust, Dept Haematol, London SE1 9R, England..
    Samuelsson, Jan
    Stockholm South Hosp, Dept Internal Med, S-11883 Stockholm, Sweden..
    Ejerblad, Elisabeth
    Univ Uppsala Hosp, Dept Hematol, SE-75185 Uppsala, Sweden..
    Zweegman, Sonja
    Vrije Univ Amsterdam Med Ctr, Dept Hematol, NL-1081 HV Amsterdam, Netherlands..
    Fernandes, Savio
    Russells Hall Hosp, Dept Haematol, Dudley DY1 2HQ, England..
    Bareford, David
    Russells Hall Hosp, Dept Haematol, Dudley DY1 2HQ, England..
    Knapper, Steven
    Cardiff Univ, Dept Haematol, Cardiff CF14 4XN, S Glam, Wales..
    Lofvenberg, Eva
    Karolinska Univ Hosp, Hematol Ctr, SE-14186 Stockholm, Sweden..
    Linder, Olle
    Orebro Univ Hosp, Dept Med, Div Hematol, SE-70185 Orebro, Sweden..
    Andreasson, Bjorn
    NU Hosp Org, Uddevalla Hosp, Dept Hematol, SE-45180 Uddevalla, Sweden..
    Ahlstrand, Erik
    Örebro University Hospital. Dept Med, Div Hematol.
    Jensen, Morten Krogh
    Herlev Hosp, Dept Hematol, DK-2730 Herlev, Denmark..
    Bjerrum, Ole Weis
    Copenhagen Univ Hosp, Rigshosp, Dept Hematol, DK-2100 Copenhagen O, Denmark..
    Vestergaard, Hanne
    Odense Univ Hosp, Dept Hematol, DK-5000 Odense C, Denmark..
    Larsen, Herdis
    Viborg Hosp, Dept Hematol, Dept Internal Med, DK-8800 Viborg, Denmark..
    Klausen, Tobias Wirenfeldt
    Herlev Hosp, Dept Hematol, DK-2730 Herlev, Denmark..
    Mourits-Andersen, Torben
    Esbjerg Cent Hosp, Dept Hematol, DK-6700 Esbjerg, Denmark..
    Skov, Vibe
    Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark..
    Thomassen, Mads
    Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark..
    Kruse, Torben
    Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark..
    Gronbaek, Kirsten
    Copenhagen Univ Hosp, Rigshosp, Dept Hematol, DK-2100 Copenhagen O, Denmark..
    Hasselbalch, Hans Carl
    Roskilde Univ Hosp, Dept Hematol, DK-4000 Roskilde, Denmark..
    Circulating YKL-40 in patients with essential thrombocythemia and polycythemia vera treated with the novel histone deacetylase inhibitor vorinostat2014In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 38, no 7, 816-821 p.Article in journal (Refereed)
    Abstract [en]

    YKL-40 regulates vascular endothelial growth factors and induces tumor proliferation. We investigated YKL-40 before and after treatment with vorinostat in 31 polycythemia vera (PV) and 16 essential thrombocythemia (ET) patients. Baseline PV patient levels were 2 times higher than in healthy controls (P<0.0001) and 1.7 times higher than in ET (P = 0.02). A significant correlation between YKL-40 at baseline and neutrophils, CRP, LDH, JAK2V617F and platelets in PV patients was observed, as well as a significantly greater reduction of YKL-40 levels in PV patients responding to therapy. YKL-40 might be a novel marker of disease burden and progression in myeloproliferative neoplasms.

  • 6.
    Arinell, Karin
    et al.
    Orebro Univ Hosp, Dept Cardiol, S-70185 Orebro, Sweden..
    Fröbert, Ole
    Örebro University Hospital. Dept Cardiol.
    Blanc, Stephane
    Inst Pluridisciplinaire Hubert Curien, Dept Ecol Physiol & Ethol, Dept Ecol, Strasbourg, France..
    Larsson, Anders
    Uppsala Univ, Dept Clin Chem, Uppsala, Sweden..
    Christensen, Kjeld
    Örebro University Hospital. Dept Cardiol.
    Downregulation of platelet activation markers during long-term immobilization2013In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 24, no 5, 369-374 p.Article in journal (Refereed)
    Abstract [en]

    Immobilization and sedentary lifestyle are risk factors for venous thromboembolism and cardiovascular disease, yet little is known about platelet function during long-term physical inactivity. Our aim was to investigate platelet activation markers and their coupling to standardized immobilization: platelet-derived growth factor (PDGF-BB) and P-selectin. We studied 15 healthy females participating in the Women International Space simulation for Exploration study. Following a 20-day ambulatory control period, the subjects underwent 60 days of bed rest in head-down tilt position (-6 degrees) 24 hours a day, finalized by 20 days of recovery. The subjects were randomized into two groups during bed rest: a control group (n = 8) that remained physically inactive and an exercise group (n = 7) that participated in both supine resistance and aerobic exercise training. Blood samples for the analysis of platelet activation markers were collected at baseline (5 days before bed rest), after 44 days of bed rest and 8 days into the recovery period. Compared to baseline, the levels of P-selectin and PDGF-BB decreased after bed rest (by 55%, p = 0.01 and 73%, p < 0.03, respectively) and remained decreased in the recovery period (by 76%, p < 0.001 and 78%, p < 0.02, respectively, compared to baseline). Platelet count (baseline value for the exercise group 260 000/mu l +/- 34 000 and baseline value for the control group 210 000/mu l +/- 30 000) did not change during the bed rest study (two-way repeated measurements ANOVA, p = ns). There were no statistical differences between the physically inactive and the exercise group. During long-term immobilization, a known risk factor for thrombosis, the levels of P-selectin and PDGF-BB decreased. Our findings indicate downregulation of platelet activation during immobilization.

  • 7.
    Bergfelt, E.
    et al.
    Haematology, Dept of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Kozlowski, Piotr
    Örebro University, School of Health Sciences.
    Ahlberg, L.
    Dept of Haematology, University Hospital of Linköping, Linköping, Sweden.
    Bernell, P.
    Div of Haematology, Dept of Medicine, Karolinska Institutet, Karolinska University, Stockholm, Sweden.
    Hulegårdh, E.
    Dept of Haematology and Coagulation, Sahlgrenska University Hospital, Göteborg, Sweden.
    Karbach, H.
    Dept of Haematology, Cancer Centre, University Hospital of Umeå, Umeå, Sweden.
    Karlsson, K.
    Dept of Haematology, Skåne University Hospital, Lund, Sweden .
    Tomaszewska-Toporska, B.
    Dept of Haematology, Skåne University Hospital, Lund, Sweden .
    Åström, Maria
    Örebro University, School of Medical Sciences.
    Hallböök, H.
    Haematology, Dept of Medical Sciences, Uppsala University, Uppsala, Sweden.
    RELAPSE OF ACUTE LYMPHOBLASTIC LEUKAEMIA IN OLDER/ELDERLY PATIENTS: A SWEDISH POPULATION-BASED STUDY2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no Suppl. 1, 34-35 p.Article in journal (Other academic)
  • 8.
    Bergfelt, E.
    et al.
    Department of Medical Sciences, Haematology, Uppsala University, Uppsala, Sweden.
    Kozlowski, Piotr
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Åström, Maria
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ahlberg, L.
    Department of Haematology, University Hospital of Linköping, Linköping, Sweden.
    Bernell, P.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Haematol, Stockholm, Sweden.
    Hulegårdh, E.
    Department of Haematology and Coagulation, Sahlgrenska University Hospital, Göteborg, Sweden.
    Karbach, H.
    Umeå Univ Hosp, Ctr Canc, Dept Haematol, Umeå, Sweden.
    Karlsson, K.
    Department of Haematology, Skåne University Hospital, Lund, Sweden.
    Tomaszewska-Toporska, B.
    Department of Haematology, Skåne University Hospital, Lund, Sweden.
    Hallböök, H.
    Department of Medical Sciences, Haematology, Uppsala University, Uppsala, Sweden.
    Prognosis in older/elderly patients with acute lymphoblastic leukaemia diagnosed 2005-2012: results from a Swedish population-based study2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, no Suppl. 1, 202-202 p.Article in journal (Other academic)
  • 9.
    Boknäs, Niklas
    et al.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping.
    Faxälv, Lars
    Department of Clinical and Experimental Medicine, Linköping University, Linköping.
    Sanchez Cenellas, Daniel
    Department of Clinical and Experimental Medicine, Linköping University, Linköping.
    Wallstedt, Maria
    Department of Clinical and Experimental Medicine, Linköping University, Linköping.
    Ramström, Sofia
    Department of Clinical and Experimental Medicine, Linköping University, Linköping.
    Grenegård, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Lindahl, Tomas L.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping.
    Thrombin-induced platelet activation via PAR4: pivotal role for exosite II2014In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 112, no 3, 558-565 p.Article in journal (Refereed)
    Abstract [en]

    Thrombin-induced platelet activation via PAR1 and PAR4 is an important event in haemostasis. Although the underlying mechanisms responsible for ensuring efficient PAR1 activation by thrombin have been extensively studied, the potential involvement of recognitions sites outside the active site of the protease in thrombin-induced PAR4 activation is largely unknown. In this study, we developed a new assay to assess the importance of exosite I and II for PAR4 activation with alpha- and gamma-thrombin. Surprisingly, we found that exosite II is critical for activation of PAR4. We also show that this dependency on exosite II likely represents a new mechanism, as it is unaffected by blockage of the previously known interaction between thrombin and glycoprotein Ib alpha.

  • 10.
    Boknäs, Niklas
    et al.
    Linköping University, Linköping, Sweden .
    Faxälv, Lars
    Linköping University, Linköping, Sweden .
    Ström, Jakob O.
    Linköping University, Linköping, Sweden .
    Tengvall, Pentti
    University of Gothenburg, Gothenburg, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden .
    Ramström, Sofia
    Linköping University, Linköping, Sweden .
    Lindahl, Tomas L.
    Linköping University, Linköping, Sweden .
    Platelets do not generate activated factor XII: how inappropriate experimental models have led to misleading conclusions2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 10, 1692-1694 p.Article in journal (Refereed)
  • 11.
    Danielsson, Signe
    et al.
    Medicinska kliniken, Universitetssjukhuset Örebro, Örebro.
    Merup, Mats
    Hematologiskt centrum, Karolinska universitetssjukhuset, Huddinge.
    Olsson, Lovisa A.
    Laboratoriemedicinska länskliniken/klinisk kemi, Universitetssjukhuset, Örebro.
    Palmblad, Jan
    Hematologiskt centrum, Karolinska universitetssjukhuset, Huddinge; Institutionen för medicin, Karolinska institutet, Stockholm.
    Åström, Maria
    Medicinska kliniken, Universitetssjukhuset Örebro, Örebro.
    X-bunden trombocytopeni med talassemi i två svenska familjer: Överväg hereditära orsaker till trombocytopeni och benmärgsfibros2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 34-35, 1474-7 p.Article in journal (Other academic)
  • 12.
    Faxälv, Lars
    et al.
    Linköping University, Linköping, Sweden.
    Boknäs, Niklas
    Linköping University, Linköping, Sweden.
    Ström, Jakob O.
    Linköping University, Linköping, Sweden.
    Tengvall, Pentti
    Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden.
    Ramström, Sofia
    Linköping University, Linköping, Sweden.
    Lindahl, Tomas L.
    Linköping University, Linköping, Sweden.
    Putting polyphosphates to the test: evidence against platelet-induced activation of factor XII2013In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, no 23, 3818-3824 p.Article in journal (Refereed)
    Abstract [en]

    The recent claim that stimulated platelets activate the intrinsic pathway of coagulation by the release of polyphosphates has been considered a breakthrough in hemostasis research. In little more than 3 years, the original publication by Müller et al has been cited >100 times. However, none of the citing articles has sought to independently validate this potentially paradigm-shifting concept. To this end, we performed extensive experimentation in vitro and in vivo in an attempt to verify the claim that factor XII (FXII) is primarily activated by stimulated platelets. In contrast to the original assertion, platelet-derived polyphosphates were found to be weak activators of FXII, with a FXIIa-generating activity of <10% compared with equivalent concentrations of kaolin. Using different coagulation assays, it was shown that platelet contribution to whole blood coagulation was unrelated to the generation of activated FXII in vitro. Additionally, key results used to verify the hypothesis in the original study in vivo were found to be irreproducible. We conclude that platelet-derived polyphosphates are not physiologically relevant activators of FXII.

  • 13.
    Fergedal, May
    et al.
    Department of Pathology, Örebro Medical Center Hospital, Örebro, Sweden.
    Åström, Maria
    Department of Internal Medicine, Örebro Medical Center Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Department of Internal Medicine, Örebro Medical Center Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Department of Pathology, Örebro Medical Center Hospital, Örebro, Sweden.
    Differences in CD14 and alpha-naphthyl acetate esterase positivity and relation to prognosis in AML1998In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 22, no 1, 25-30 p.Article in journal (Refereed)
    Abstract [en]

    Alpha-naphthyl acetate esterase (ANAE) and CD14 expression, used for determination of monocytic cells, were compared and related to prognosis in 65 AML patients. Bone marrow aspiration material from AML patients has been used for the cytochemistry as well as flow cytometry. All non-erythroid cells have been included in the evaluation in both methods. 17/65 cases showed at least 15% difference between the proportion CD14 and ANAE positive cells. Cases with 20% or more CD14 positivity had poorer prognosis. For FAB classes M0-M3, presence of 10% or more CD14 was negative for overall survival (P = 0.01). ANAE did not show significant prognostic influence.

  • 14.
    Forsström, Katrin
    Örebro University, Department of Clinical Medicine.
    Analysis of mean corpuscular volume and mean corpuscular haemoglobin value of blood donors rejected for low haemoglobin at Christian Medical College and Hospital in Vellore, India.2006Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Abstract

    Iron deficiency anaemia is the most common anaemia in India and nutritional iron deficiency is the cause of 90 % of the anaemias. MCV and MCH values below reference ranges indicate iron deficiency anaemia.

    The aim of this study was to analyze the MCV and MCH values in blood donors rejected for low haemoglobin to find out if they are anaemic. Then, based on the results, discuss if there’s a possibility to lower the cut off value for haemoglobin in blood donations at Christian Medical College and Hospital in Vellore, India.

    The blood bank at CMCH uses the copper sulphate method only to determine if the haemoglobin value is below or over 125 g/l, which is the cut off value for donating blood in India. The normal ranges for haemoglobin are 110 - 150 g/l for women and 130 - 170 g/l for men at CMCH which means that the hospital looses several healthy blood donors unnecessarily.

    The results of this study show that if the haemoglobin cut off value is lowered to 115 g/l,

    66.4 % of the rejected donors will still have a normal MCV and MCH value. Among the women, there are 85.7 % who have MCV and MCH values within reference range which speaks for a lowering of the Hb cut off value for women to 115 g/l. For men however, there were only 30 % that were within the MCV and MCH reference range and therefore a lowering of the Hb cut off value is not justified.

  • 15.
    Holmström, M.
    et al.
    Coagulation Unit, Department of Medicine Solna, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.
    Nangarhari, A.
    Department of Infectious Diseases, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.
    Öhman, J.
    Karolinska Institutet at Karolinska Hospital, Stockholm, Sweden.
    Duberg, Ann-Sofie
    Örebro University, School of Medical Sciences. Department of Infectious Diseases.
    Majeed, A.
    Coagulation Unit, Department of Medicine Solna, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Infectious Diseases, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.
    Aleman, S.
    Department of Infectious Diseases, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.
    Long-term liver-related morbidity and mortality related to chronic hepatitis C virus infection in Swedish patients with inherited bleeding disorders2016In: Haemophilia, ISSN 1351-8216, E-ISSN 1365-2516, Vol. 22, no 6, e494-e501 p.Article in journal (Refereed)
    Abstract [en]

    Introduction: Hepatitis C virus (HCV) infection is common in patients with inherited bleeding disorders treated with clotting factor concentrates prior to the introduction of viral inactivation of these products. The long-term consequences of hepatitis C infection in Swedish patients are not fully understood.

    Aim: To examine the impact of HCV infection on liver-related morbidity and mortality in Swedish patients with inherited bleeding disorders.

    Methods: We retrospectively collected data on 183 patients with inherited bleeding disorders infected with HCV who attended the Coagulation Unit at Karolinska University Hospital, Sweden. Data regarding end-stage liver disease (ESLD), defined as presence of ascites, encephalopathy, variceal bleeding, hepatocellular carcinoma or liver-related death, were collected from the patient records and the national registers.

    Results: The median follow-up time was 35.9 years (IQR 29.0-41.2). A total of 41% had achieved sustained virological response (SVR) after treatment. In total, 14.2% developed ESLD at the median age of 52.6 years (IQR 46.5-64.7). Nineteen (35.8%) of all deaths were due to liver-related causes. Co-infection with human immunodeficiency virus (HIV), older age at time of infection and severe form of bleeding disorder was associated with higher risk of developing ESLD, while SVR was a strong protective factor.

    Conclusions: This study demonstrated that liver-related morbidity and mortality was significant in patients with bleeding disorders and HCV infection in Sweden. Patients with HCV-infection should be candidates for treatment with the new highly effective antiviral drugs, since SVR proved to be a strong protective factor.

  • 16.
    Hulegardh, Erik
    et al.
    Sahlgrens Univ Hosp, Dept Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Tumor Registry, Gothenburg, Sweden..
    Nilsson, Christer
    Karolinska Univ Hosp, Hematol Ctr, Huddinge Stockholm & Reg Tumor Registry, Stockholm, Sweden..
    Lazarevic, Vladimir
    Skane Univ Hosp, Dept Hematol, Lund, Sweden.;Skane Univ Hosp, Reg Tumor Registry, Lund, Sweden.;Lund Univ, Lund, Sweden.;Linkoping Univ Hosp, Swedish Acute Myeloid Leukemia Grp, S-58185 Linkoping, Sweden..
    Garelius, Hege
    Sahlgrens Univ Hosp, Dept Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Tumor Registry, Gothenburg, Sweden.;Linkoping Univ Hosp, Swedish Acute Myeloid Leukemia Grp, S-58185 Linkoping, Sweden..
    Antunovic, Petar
    Linkoping Univ Hosp, Swedish Acute Myeloid Leukemia Grp, S-58185 Linkoping, Sweden.;Linkoping Univ Hosp, Dept Hematol, S-58185 Linkoping, Sweden.;Linkoping Univ Hosp, Reg Tumor Registry, S-58185 Linkoping, Sweden..
    Rangert Derolf, Asa
    Linkoping Univ Hosp, Swedish Acute Myeloid Leukemia Grp, S-58185 Linkoping, Sweden.;Karolinska Univ Hosp, Ctr Hematol, Stockholm, Sweden.;Karolinska Univ Hosp, Reg Tumor Registry, Stockholm, Sweden..
    Mollgard, Lars
    Sahlgrens Univ Hosp, Dept Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Tumor Registry, Gothenburg, Sweden.;Linkoping Univ Hosp, Swedish Acute Myeloid Leukemia Grp, S-58185 Linkoping, Sweden..
    Uggla, Bertil
    Örebro University Hospital. Swedish Acute Myeloid Leukemia Group, Sweden; Department of Medicine.
    Wennstrom, Lovisa
    Sahlgrens Univ Hosp, Dept Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Tumor Registry, Gothenburg, Sweden.;Linkoping Univ Hosp, Swedish Acute Myeloid Leukemia Grp, S-58185 Linkoping, Sweden..
    Wahlin, Anders
    Linkoping Univ Hosp, Swedish Acute Myeloid Leukemia Grp, S-58185 Linkoping, Sweden.;Umea Univ, Dept Radiat Sci, Umea, Sweden.;Norrland Univ Hosp, Reg Tumor Registry, Umea, Sweden..
    Hoglund, Martin
    Linkoping Univ Hosp, Swedish Acute Myeloid Leukemia Grp, S-58185 Linkoping, Sweden.;Acad Hosp, Dept Hematol, Uppsala, Sweden.;Acad Hosp, Reg Tumor Registry, Uppsala, Sweden..
    Juliusson, Gunnar
    Skane Univ Hosp, Dept Hematol, Lund, Sweden.;Skane Univ Hosp, Reg Tumor Registry, Lund, Sweden.;Lund Univ, Lund, Sweden.;Linkoping Univ Hosp, Swedish Acute Myeloid Leukemia Grp, S-58185 Linkoping, Sweden..
    Stockelberg, Dick
    Sahlgrens Univ Hosp, Dept Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Tumor Registry, Gothenburg, Sweden.;Linkoping Univ Hosp, Swedish Acute Myeloid Leukemia Grp, S-58185 Linkoping, Sweden..
    Lehmann, Soren
    Karolinska Univ Hosp, Hematol Ctr, Huddinge Stockholm & Reg Tumor Registry, Stockholm, Sweden.;Linkoping Univ Hosp, Swedish Acute Myeloid Leukemia Grp, S-58185 Linkoping, Sweden..
    Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: A report from the Swedish Acute Leukemia Registry2015In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, no 3, 208-214 p.Article in journal (Refereed)
    Abstract [en]

    Patients with secondary acute myeloid leukemia (AML) often escape inclusion in clinical trials and thus, population-based studies are crucial for its accurate characterization. In this first large population-based study on secondary AML, we studied AML with an antecedent hematological disease (AHD-AML) or therapy-related AML (t-AML) in the population-based Swedish Acute Leukemia Registry. The study included 3,363 adult patients of which 2,474 (73.6%) had de novo AML, 630 (18.7%) AHD-AML, and 259 (7.7%) t-AML. Secondary AML differed significantly compared to de novo AML with respect to age, gender, and cytogenetic risk. Complete remission (CR) rates were significantly lower but early death rates similar in secondary AML. In a multivariable analysis, AHD-AML (HR 1.51; 95% CI 1.26-1.79) and t-AML (1.72; 1.38-2.15) were independent risk factors for poor survival. The negative impact of AHD-AML and t-AML on survival was highly age dependent with a considerable impact in younger patients, but without independent prognostic value in the elderly. Although patients with secondary leukemia did poorly with intensive treatment, early death rates and survival were significantly worse with palliative treatment. We conclude that secondary AML in a population-based setting has a striking impact on survival in younger AML patients, whereas it lacks prognostic value among the elderly patients. Am. J. Hematol. 90:208-214, 2015.

  • 17. Jones, I.
    et al.
    Böttiger, Anna K.
    Örebro University Hospital.
    Methaemoglobin does not interfere with the analysis of glucose in Terumo Venosafe Glycaemia tubes2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 2, 189-191 p.Article in journal (Refereed)
  • 18. Juliusson, Gunnar
    et al.
    Antunovic, Petar
    Derolf, Åsa
    Lehmann, Sören
    Möllgård, Lars
    Stockelberg, Dick
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences.
    Wahlin, Anders
    Höglund, Martin
    Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry2009In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 113, no 18, 4179-4187 p.Article in journal (Refereed)
    Abstract [en]

    Acute myeloid leukemia (AML) is most common in the elderly, and most elderly are thought to be unfit for intensive treatment because of the risk of fatal toxicity. The Swedish Acute Leukemia Registry covers 98% of all patients with AML (nonacute promyelocytic leukemia) diagnosed in 1997 to 2005 (n = 2767), with a median follow-up of 5 years, and reports eligibility for intensive therapy, performance status (PS), complete remission rates, and survival. Outcomes were strongly age and PS dependent. Early death rates were always lower with intensive therapy than with palliation only. Long-term survivors were found among elderly given intensive treatment despite poor initial PS. Total survival of elderly AML patients was better in the geographic regions where most of them were given standard intensive therapy. This analysis provides unique real world data from a large, complete, and unselected AML population, both treated and untreated, and gives background to treatment decisions for the elderly. Standard intensive treatment improves early death rates and long-term survival compared with palliation. Most AML patients up to 80 years of age should be considered fit for intensive therapy, and new therapies must be compared with standard induction.

  • 19.
    Juliusson, Gunnar J.
    et al.
    Department of Hematology and Oncology, Skåne University Hospital, Lund, Sweden; Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Abrahamsson, Jonas
    Department of Pediatrics, Institution for Clinical Sciences, Queen Silvia Children’s Hospital, Gothenburg, Sweden.
    Lazarevic, Vladimir Lj. J.
    Department of Hematology and Oncology, Skåne University Hospital, Lund, Sweden; Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Antunovic, Petar
    Department of Hematology, University Hospital Linköping, Linköping, Sweden.
    Derolf, Åsa Rangert
    Hematology Center, Karolinska University Hospital, Stockholm, Sweden.
    Garelius, Hege K. G.
    Department of Hematology, Sahlgrenska University Hospital Gothenburg, Gothenburg, Sweden.
    Lehmann, Sören
    Department of Hematology, Academic Hospital, Uppsala, Sweden.
    Myhr-Eriksson, Kristina
    Department of Hematology, Sunderby Hospital, Luleå, Sweden.
    Möllgård, Lars
    Department of Hematology, Sahlgrenska University Hospital Gothenburg, Gothenburg, Sweden.
    Uggla, Bertil
    Örebro University Hospital. Örebro University, School of Medical Sciences.
    Wahlin, Anders C. E.
    Department of Radiation Sciences, Umeå University, Umeå, Sweden.
    Wennström, Lovisa
    Department of Pediatrics, Institution for Clinical Sciences, Queen Silvia Children’s Hospital, Gothenburg, Sweden; Department of Hematology, Sahlgrenska University Hospital Gothenburg, Gothenburg, Sweden.
    Höglund, Martin
    Department of Hematology, Academic Hospital, Uppsala, Sweden.
    Swedish AML Group, Group author
    Swedish Childhood Leukemia Group, Group Author
    Prevalence and characteristics of survivors from acute myeloid leukemia in Sweden2017In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 3, 728-731 p.Article in journal (Refereed)
  • 20.
    Kozlowski, Piotr
    Örebro University, School of Health Sciences.
    Prognostic factors, treatment and outcome in adult acute lymphoblastic leukemia: Population-based studies in Sweden2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Acute lymphoblastic leukemia (ALL) has poor prognosis in older/elderly adults and in high-risk/relapsed disease. Recommended treatment of ALL was evaluated (study I-IV). Data was obtained from the Swedish Acute Leukemia registries and from patient records.

    I. We assessed ALL relapse treatment and outcome in 76 patients aged 15-65 years (y). Complete remission (CR) was achieved in 50/71 patients (70%). Of them, 29 underwent allogeneic hematopoietic stem cell transplantation (hSCT). Five year overall survival (OS) was 15%, but close to 50% in 19 patients <35y after hSCT.

    II. We studied outcome of treatment with the Hyper-CVAD protocol in 19 of 24 patients with T-ALL aged 18-72y. CR was reached in 89%, but 5y leukemia-free survival was only 29%, and 20% in 15 patients not transplanted in CR1. Six patients received hSCT in CR2. Finally, 5y OS in all 19 patients was 47%. The only negative prognostic factor found was age ≥35y.

    III. We evaluated minimal residual disease (MRD) monitoring in 35 patients with Philadelphia (Ph) negative B-ALL aged 46-79y and treated with the ABCDV protocol. The CR rate was 91%. MRD was measured by flow cytometry in 73% in CR1 (MRD1) and omitted in those >70y or with high-risk ALL. Five patients received hSCT (only one due to MRD). Five year OS in the whole cohort was 47%. Continuous CR but not OS was improved in patients with MRD1 <0.1 %.

    IV. We studied 155 patients with ALL (Ph+ in 35%) aged 55-85y and treated with remission induction/palliation (124/31). Both, intensive, and palliative treatment resulted in the CR rates of 70/83/16% and 3y OS of 26/32/3%. OS was negatively influenced by age and platelet count ≤35×109/L (but not Ph+). OS was not enhanced by introduction of an age-adapted protocol.

    We concluded that intensive treatment with subsequent allogeneic hSCT is the most reasonable option in younger patients with ALL recurrence (I). Hyper-CVAD has low relapse-preventing efficacy (II). MRD guided intensification is probably feasible in only a minority of older patients (III). Prognosis in elderly ALL is poor, but no longer impaired by Ph+ (IV).

    List of papers
    1. High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003-2007
    Open this publication in new window or tab >>High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003-2007
    Show others...
    2012 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 97, no 9, 1414-1421 p.Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: A minority of patients with adult acute lymphoblastic leukemia who relapse are rescued. The aim of this population-based study was to assess the results of reinduction treatment and allogeneic stem cell transplantation in patients in second complete remission.

    DESIGN AND METHODS: Between 2003-2007, 76 adults (<66 years) with relapsed acute lymphoblastic leukemia (Burkitt's leukemia excluded) were prospectively reported to The Swedish Adult Acute Leukemia Registry and later evaluated.

    RESULTS: Reinduction with: (i) mitoxantrone, etoposide, and cytarabine (MEA); (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor (FLAG-Asp); and (iii) cytarabine, betamethasone, cyclophosphamide, daunorubicin, and vincristine (ABCDV) resulted in complete remission in 6/9 (67%), 10/16 (63%) and 9/21 (43%) of the patients, respectively. Allogeneic stem cell transplantation was performed during second complete remission in 29 patients. Multivariate analysis regarding overall survival after relapse revealed that age over 35 years at diagnosis and relapse within 18 months were negative prognostic factors. Overall survival rates at 3 and 5 years were 22% (95% CI: 13-32) and 15% (95% CI: 7-24). Of 19 patients less than 35 years at diagnosis who underwent allogeneic stem cell transplantation in second remission, ten (53%) are still alive at a median of 5.5 years (range, 4.2-8.3) after relapse, whereas all patients over 35 years old at diagnosis have died.

    CONCLUSIONS: Allogeneic stem cell transplantation remains the treatment of choice for young adults with relapsed acute lymphoblastic leukemia. Both (i) mitoxantrone, etoposide, and cytarabine and (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor seem effective as reinduction treatments and should be further evaluated. New salvage strategies are needed, especially for patients over 35 years old at diagnosis.

    Place, publisher, year, edition, pages
    Ferrata Storti Foundation, 2012
    Keyword
    Acute lymphoblastic leukaemia, Adults, Minimal residual disease, Flow cytometry
    National Category
    Hematology Family Medicine
    Identifiers
    urn:nbn:se:oru:diva-48485 (URN)10.3324/haematol.2011.057851 (DOI)000308908300022 ()22511497 (PubMedID)2-s2.0-84865851061 (Scopus ID)
    Available from: 2016-02-23 Created: 2016-02-23 Last updated: 2017-11-30Bibliographically approved
    2. High relapse rate of T cell acute lymphoblastic leukemia in adults treated with Hyper-CVAD chemotherapy in Sweden
    Open this publication in new window or tab >>High relapse rate of T cell acute lymphoblastic leukemia in adults treated with Hyper-CVAD chemotherapy in Sweden
    Show others...
    2014 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 92, no 5, 377-381 p.Article in journal (Refereed) Published
    Abstract [en]

    Background: Hyper-CVAD is widely used to treat acute lymphoblastic leukemia (ALL) and aggressive lymphomas. This multicenter, population-based study assessed the efficacy of Hyper-CVAD as first-line therapy in patients with T-cell ALL (T-ALL).

    Patients and methods: Between October 2002 and September 2006, 24 patients were diagnosed with T-ALL in Sweden; 19 were eligible for treatment with the protocol.

    Results: The median age was 32 yr (range 18-72 yr). Complete remission (CR) was obtained in 17 of 19 (89%) patients, and the treatment was relatively well tolerated. Allogeneic stem cell transplantation (SCT) was recommended in high-risk disease and was performed in four patients upfront. Two- and 5-yr leukemia-free survivals (LFS) in 17 patients with CR achievement were identical, at 29% (95% confidence interval [CI]: 8-51). Two- and 5-yr overall survival (OS) in whole cohort was 63% (95% CI: 42-85) and 47% (95% CI: 26-69), respectively. The 5-yr LFS for 15 patients who did not receive allogeneic SCT upfront were 20% (95% CI: 0-40), although 14 of 15 completed the protocol (eight cycles). Relapse occurred in 2 of 4 upfront-transplanted patients and in 12 of 15 patients treated with chemotherapy alone, six of whom received allogeneic SCT in CR2. Age ≥35 yr influenced OS negatively in univariate analysis (HR 5.1, 95% CI: 1.55-16.7).

    Conclusions: Hyper-CVAD treatment resulted in a high CR rate and appeared safe, but it showed poor efficacy at preventing relapse. Therefore, this treatment is no longer recommended for adults with T-ALL in Sweden.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2014
    Keyword
    antineoplastic combined chemotherapy protocols; treatment outcome; precursor T-cell lymphoblastic leukemia-lymphoma; stem cell transplantation
    National Category
    Hematology Family Medicine
    Identifiers
    urn:nbn:se:oru:diva-48486 (URN)10.1111/ejh.12269 (DOI)000334267500002 ()24443846 (PubMedID)2-s2.0-84898801134 (Scopus ID)
    Available from: 2016-02-23 Created: 2016-02-23 Last updated: 2017-11-30Bibliographically approved
    3. Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study
    Open this publication in new window or tab >>Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study
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    2015 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 32, no 4, 135Article in journal (Refereed) Published
    Abstract [en]

    The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46-79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status >= 2. MRD < 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.

    Keyword
    Acute lymphoblastic leukaemia, Adults, Minimal residual disease, Flow cytometry
    National Category
    Cancer and Oncology
    Research subject
    Oncology
    Identifiers
    urn:nbn:se:oru:diva-44342 (URN)10.1007/s12032-015-0582-2 (DOI)000351474100049 ()25796502 (PubMedID)
    Note

    Funding Agency:

    Lions Cancer Research Foundation, Uppsala

    Available from: 2015-04-20 Created: 2015-04-20 Last updated: 2017-12-04Bibliographically approved
    4. Age but not Philadelphia positivity impairs outcome in older/elderly patients with Acute Lymphoblastic Leukemia in the Swedish population
    Open this publication in new window or tab >>Age but not Philadelphia positivity impairs outcome in older/elderly patients with Acute Lymphoblastic Leukemia in the Swedish population
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Family Medicine
    Identifiers
    urn:nbn:se:oru:diva-48533 (URN)
    Available from: 2016-02-23 Created: 2016-02-23 Last updated: 2017-10-17Bibliographically approved
  • 21.
    Kozlowski, Piotr
    et al.
    Örebro University, School of Health Sciences.
    Lennmyr, Emma
    Dept of Medical Sciences, Uppsala University, Uppsala, sweden.
    Ahlberg, Lucia
    University Hospital of Linköping, Linköping, sweden.
    Bernell, Per
    Div of Hematology, Dept of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm.
    Hulegårdh, Erik
    Dept of Hematology and Coagulation, Sahlgrenska University Hospital, Göteborg, Sweden.
    Karbach, Holger
    Dept of Hematology, Cancer Center, University Hospital of Umeå, Umeå, Sweden.
    Karlsson, Karin
    Dept of Hematology and Oncology, Skåne University Hospital, Lund, Sweden.
    Tomaszewska-Toporska, Beata
    Dept of Hematology and Oncology, Skåne University Hospital, Lund, Sweden.
    Åström, Maria
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Hallböök, Heléne
    Dept of Medical Sciences, Uppsala University, Uppsala. Sweden.
    The Swedish Adult Acute Lymphoblastic Leukemia Group (SVALL), Group author
    Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden2017In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 99, no 2, 141-149 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Older/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials.

    METHODS: Using Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85 years, diagnosed with ALL 2005-2012.

    RESULTS: Of 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype. Philadelphia chromosome positivity (Ph+) occurred in 35%. Of the 155 B- and T- ALL patients, 80% were treated with intensive protocols, and 20% with a palliative approach. Higher age and WHO performance status ≥2 influenced the choice of palliation. Intensive, palliative, and both approaches, resulted in complete remission rate 83/16/70%, and 3 year overall survival (OS) 32/3/26%. The age-adapted protocol did not improve outcome. With intensive treatment, platelet count ≤35 × 10(9) /L, and age ≥75 years were adverse prognostic factors for OS, Ph+ was not. Male sex was an adverse prognostic factor in the 55-64 year group.

    CONCLUSIONS: We report a high frequency of Ph+ in older/elderly patients, with no evidence of poorer outcome compared to Ph negative disease. Overall prognosis for elderly patients with ALL remains dismal, despite the use of age-adapted treatment. This article is protected by copyright. All rights reserved.

  • 22.
    Kozlowski, Piotr
    et al.
    Örebro University Hospital. Department of Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Örebro University Hospital. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Befekadu, Rahel
    Örebro University, School of Medical Sciences. Department of Transfusion Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Hahn-Strömberg, Victoria
    Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
    The risk of renal disease is increased in lambda myeloma with bone marrow amyloid deposits2017In: Journal of Blood Medicine, ISSN 1179-2736, Vol. 8, 29-34 p.Article in journal (Refereed)
    Abstract [en]

    Background: Light chain amyloidosis (AL) is a rare deposition disease and is present in 10-15% of patients with myeloma (MM). In contrast to symptomatic AL in MM, presence of bone marrow (BM) amyloid deposits (AD) in MM is not connected to kidney damage. Renal AD but not BM-AD occur mostly in MM with lambda paraprotein (lambda MM).

    Methods: We investigated amyloid presence in BM clots taken at diagnosis in 84 patients with symptomatic MM and compared disease characteristics in MM with kappa paraprotein (kappa MM)/lambda MM with and without BM-AD.

    Results: Lambda MM with BM-AD was compared with kappa MM without BM-AD, kappa MM with BM-AD, and lambda MM without BM-AD: lambda MM with BM-AD patients had a significantly higher mean creatinine level (4.23 mg/dL vs 1.69, 1.14, and 1.28 mg/dL, respectively) and a higher proportion presented with severe kidney failure (6/11 [55%] vs 6/32 [19%], 1/22 [5%], and 3/19 [16%], respectively). Proteinuria was more common in lambda MM with BM-AD patients compared with kappa MM without BM-AD patients (8/11 [73%] vs 5/32 [16%], respectively).

    Conclusion: Kidney damage was more common in lambda MM with BM-AD indicating presence of renal AD.

  • 23.
    Kozlowski, Piotr
    et al.
    Örebro University Hospital. Hematology Section, Department of Medicine.
    Åström, Maria
    Örebro University Hospital. Hematology Section, Department of Medicine.
    Ahlberg, Lucia
    Department of Hematology, University Hospital of Linköping, Linköping.
    Bernell, Per
    Karolinska University Hospital, Stockholm.
    Hulegårdh, Erik
    Department of Hematology and Coagulation, Sahlgrenska University, Göteborg.
    Hägglund, Hans
    Karolinska University Hospital, Stockholm.
    Karlsson, Karin
    Department of Hematology, Skåne University Hospital, Lund.
    Markuszewska-Kuczymska, Alicja
    Department of Hematology, Cancer Center, University Hospital, Umeå.
    Tomaszewska-Toporska, Beata
    Department of Hematology, Skåne University Hospital, Lund.
    Smedmyr, Bengt
    Department of Hematology, Uppsala University, Uppsala.
    Amini, Rose-Marie
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Hallböök, Helene
    Department of Hematology, Uppsala University, Uppsala, Sweden.
    High relapse rate of T cell acute lymphoblastic leukemia in adults treated with Hyper-CVAD chemotherapy in Sweden2014In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 92, no 5, 377-381 p.Article in journal (Refereed)
    Abstract [en]

    Background: Hyper-CVAD is widely used to treat acute lymphoblastic leukemia (ALL) and aggressive lymphomas. This multicenter, population-based study assessed the efficacy of Hyper-CVAD as first-line therapy in patients with T-cell ALL (T-ALL).

    Patients and methods: Between October 2002 and September 2006, 24 patients were diagnosed with T-ALL in Sweden; 19 were eligible for treatment with the protocol.

    Results: The median age was 32 yr (range 18-72 yr). Complete remission (CR) was obtained in 17 of 19 (89%) patients, and the treatment was relatively well tolerated. Allogeneic stem cell transplantation (SCT) was recommended in high-risk disease and was performed in four patients upfront. Two- and 5-yr leukemia-free survivals (LFS) in 17 patients with CR achievement were identical, at 29% (95% confidence interval [CI]: 8-51). Two- and 5-yr overall survival (OS) in whole cohort was 63% (95% CI: 42-85) and 47% (95% CI: 26-69), respectively. The 5-yr LFS for 15 patients who did not receive allogeneic SCT upfront were 20% (95% CI: 0-40), although 14 of 15 completed the protocol (eight cycles). Relapse occurred in 2 of 4 upfront-transplanted patients and in 12 of 15 patients treated with chemotherapy alone, six of whom received allogeneic SCT in CR2. Age ≥35 yr influenced OS negatively in univariate analysis (HR 5.1, 95% CI: 1.55-16.7).

    Conclusions: Hyper-CVAD treatment resulted in a high CR rate and appeared safe, but it showed poor efficacy at preventing relapse. Therefore, this treatment is no longer recommended for adults with T-ALL in Sweden.

  • 24.
    Kozlowski, Piotr
    et al.
    1Hematology Section, Department of Medicine, Örebro University Hospital, Örebro.
    Åström, Maria
    Hematology Section, Department of Medicine, Örebro University Hospital, Örebro.
    Ahlberg, Lucia
    Department of Hematology, University Hospital of Linköping, Linköping.
    Bernell, Per
    Karolinska University Hospital, Stockholm.
    Hulegårdh, Erik
    Department of Hematology and Coagulation, Sahlgrenska.
    Hägglund, Hans
    Karolinska University Hospital, Stockholm.
    Karlsson, Karin
    Department of Hematology, Skåne University Hospital, Lund.
    Markuszewska-Kuczymska, Alicja
    Department of Hematology, Cancer Center, University Hospital, Umeå.
    Tomaszewska-Toporska, Beata
    Department of Hematology, Skåne University Hospital, Lund.
    Smedmyr, Bengt
    Department of Hematology, Uppsala University, Uppsala, Sweden.
    Hallböök, Helene
    Department of Hematology, Uppsala University, Uppsala, Sweden.
    High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003-20072012In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 97, no 9, 1414-1421 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A minority of patients with adult acute lymphoblastic leukemia who relapse are rescued. The aim of this population-based study was to assess the results of reinduction treatment and allogeneic stem cell transplantation in patients in second complete remission.

    DESIGN AND METHODS: Between 2003-2007, 76 adults (<66 years) with relapsed acute lymphoblastic leukemia (Burkitt's leukemia excluded) were prospectively reported to The Swedish Adult Acute Leukemia Registry and later evaluated.

    RESULTS: Reinduction with: (i) mitoxantrone, etoposide, and cytarabine (MEA); (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor (FLAG-Asp); and (iii) cytarabine, betamethasone, cyclophosphamide, daunorubicin, and vincristine (ABCDV) resulted in complete remission in 6/9 (67%), 10/16 (63%) and 9/21 (43%) of the patients, respectively. Allogeneic stem cell transplantation was performed during second complete remission in 29 patients. Multivariate analysis regarding overall survival after relapse revealed that age over 35 years at diagnosis and relapse within 18 months were negative prognostic factors. Overall survival rates at 3 and 5 years were 22% (95% CI: 13-32) and 15% (95% CI: 7-24). Of 19 patients less than 35 years at diagnosis who underwent allogeneic stem cell transplantation in second remission, ten (53%) are still alive at a median of 5.5 years (range, 4.2-8.3) after relapse, whereas all patients over 35 years old at diagnosis have died.

    CONCLUSIONS: Allogeneic stem cell transplantation remains the treatment of choice for young adults with relapsed acute lymphoblastic leukemia. Both (i) mitoxantrone, etoposide, and cytarabine and (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor seem effective as reinduction treatments and should be further evaluated. New salvage strategies are needed, especially for patients over 35 years old at diagnosis.

  • 25.
    Lazarevic, Vladimir
    et al.
    Department of Hematology and Coagulation, Skåne University Hospital, Lund; Stem Cell Center, Lund University, Lund.
    Hörstedt, Ann-Sofi
    Regional Cancer Center in South Sweden, Skåne University Hospital, Lund.
    Johansson, Bertil
    Department of Clinical Genetics, University and Regional Laboratories Region Skåne, Lund; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund.
    Antunovic, Petar
    Department of Hematology, Linköping University Hospital, Linköping.
    Billström, Rolf
    Department of Medicine, Central Hospital Skövde, Skövde.
    Derolf, Asa
    Department of Medicine, Division of Hematology, Karolinska University Hospital, Stockholm and Huddinge.
    Lehmann, Sören
    Department of Medicine, Division of Hematology, Karolinska University Hospital, Stockholm and Huddinge.
    Möllgård, Lars
    Department of Medicine, Sahlgrenska University Hospital, Göteborg.
    Peterson, Stefan
    Regional Cancer Center in South Sweden, Skåne University Hospital, Lund.
    Stockelberg, Dick
    Department of Medicine, Sahlgrenska University Hospital, Göteborg.
    Uggla, Bertil
    Department of Medicine, Örebro University Hospital, Örebro.
    Vennström, Lovisa
    Department of Medicine, Sahlgrenska University Hospital, Göteborg.
    Wahlin, Anders
    Department of Radiation Sciences, Umeå University, Umeå.
    Höglund, Martin
    Department of Hematology, Academic Hospital, Uppsala.
    Juliusson, Gunnar
    Department of Hematology and Coagulation, Skåne University Hospital, Lund; Stem Cell Center, Lund University, Lund.
    Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia2015In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, no 5, 419-423 p.Article in journal (Refereed)
    Abstract [en]

    Unsuccessful cytogenetics (UC) in patients with acute myeloid leukaemia (AML) treated on different SWOG trials was recently reported to be associated with increased age and dismal outcome. To ascertain whether this holds true also in unselected patients with AML, we retrieved all cytogenetic reports in cases from the population-based Swedish AML Registry. Between 1997 and 2006, 1737 patients below 80 yr of age without myelosarcoma or acute promyelocytic leukaemia received intensive treatment. The frequencies of UC and unperformed cytogenetics (UPC) were 2.1% and 20%, respectively. The early death rates differed between the cytogenetic subgroups (P = 0.006) with the highest rates in patients with UC (14%) and UPC (12%) followed by high-risk (HR) AML, intermediate risk (IR) and standard risk (SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The complete remission rate was lower in UC and UPC and HR compared with the other risk groups (P < 0.001). The overall five-year survival rates were 25% for UC and 22% for UPC, whereas the corresponding frequencies for SR, IR and HR AML patients without UC and UPC were 64%, 31% and 15%, respectively. In conclusion, lack of cytogenetic data translates into a poor prognosis.

  • 26.
    Lazarevic, Vladimir Lj
    et al.
    Skåne University Hospital, Lund, Sweden; Stem Cell Center, Lund University, Lund, Sweden.
    Rosso, Aldana
    Skåne University Hospital, Lund, Sweden; Lund University, Lund, Sweden.
    Juliusson, Gunnar
    Skåne University Hospital, Lund, Sweden; Stem Cell Center, Lund University, Lund, Sweden.
    Antunovic, Petar
    Linköping University Hospital, Linköping, Sweden.
    Derolf, Åsa Rangert
    Karolinska University Hospital, Stockholm, Sweden.
    Deneberg, Stefan
    Karolinska University Hospital, Stockholm, Sweden.
    Möllgård, Lars
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Wennström, Lovisa
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Wahlin, Anders
    Umeå University, Umeå, Sweden.
    Höglund, Martin
    Academic Hospital, Uppsala, Sweden.
    Lehmann, Sören
    Academic Hospital, Uppsala, Sweden.
    Johansson, Bertil
    University and Regional Laboratories, Region Skåne, Lund, Sweden; Lund University, Lund, Sweden.
    Incidence and prognostic significance of isolated trisomies in adult acute myeloid leukemia: A population-based study from the Swedish AML registry2017In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 98, no 5, 493-500 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES AND METHODS: To ascertain the incidence/clinical implications of isolated autosomal trisomies in adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry.

    RESULTS: Of the 3179 cytogenetically informative AMLs diagnosed January 1997-May 2015, 246 (7.7%) had isolated trisomies. The frequency increased by age (2.4% at age 18-60 years vs. 23% at >60 years; P<.0001); the median age was 69 years. The five most common were +8 (4.0%), +13 (0.9%), +11 (0.8%), +21 (0.7%), and +4 (0.5%). Age and gender, types of AML and treatment, and complete remission and early death rates did not differ between the single trisomy and the intermediate risk (IR) groups or among cases with isolated gains of chromosomes 4, 8, 11, 13, or 21. The overall survival (OS) was similar in the single trisomy (median 1.6 years) and IR groups (1.7 years; P=.251). The OS differed among the most frequent isolated trisomies; the median OS was 2.5 years for +4, 1.9 years for +21, 1.5 years for +8, 1.1 years for +11, and 0.8 years for +13 (P=.013).

    CONCLUSION: AML with single trisomies, with the exception of +13, should be grouped as IR.

  • 27.
    Lazarevic, Vladimir
    et al.
    Skane Univ Hosp, Dept Hematol & Vasc Dis, SE-22185 Lund, Sweden.;Lund Univ, Stem Cell Ctr, Lund, Sweden..
    Rosso, Aldana
    Skane Univ Hosp, Epidemiol & Registry Ctr South Sweden, SE-22185 Lund, Sweden..
    Juliusson, Gunnar
    Skane Univ Hosp, Dept Hematol & Vasc Dis, SE-22185 Lund, Sweden.;Lund Univ, Stem Cell Ctr, Lund, Sweden..
    Antunovic, Petar
    Linkoping Univ Hosp, Dept Hematol, S-58185 Linkoping, Sweden..
    Rangert-Derolf, Asa
    Karolinska Univ Hosp, Div Hematol Stockholm & Huddinge, Dept Med, Karolinska, Sweden..
    Lehmann, Soren
    Karolinska Univ Hosp, Div Hematol Stockholm & Huddinge, Dept Med, Karolinska, Sweden..
    Mollgard, Lars
    Sahlgrens Univ Hosp, Dept Med, S-41345 Gothenburg, Sweden..
    Uggla, Bertil
    Örebro University Hospital.
    Wennstrom, Lovisa
    Sahlgrens Univ Hosp, Dept Med, S-41345 Gothenburg, Sweden..
    Wahlin, Anders
    Umea Univ, Dept Radiat Sci, Umea, Sweden..
    Hoglund, Martin
    Acad Hosp, Dept Hematol, Uppsala, Sweden..
    Johansson, Bertil
    Univ & Reg Labs Reg Skane, Dept Clin Genet, Lund, Sweden.;Lund Univ, Div Clin Genet, Dept Lab Med, Lund, Sweden..
    Prognostic significance of high hyperdiploid and triploid/tetraploid adult acute myeloid leukemia2015In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, no 9, 800-805 p.Article in journal (Refereed)
    Abstract [en]

    To ascertain the clinical implications of high hyperdiploid (HH; 49-65 chromosomes) and triploid/tetraploid (TT; >65 chromosomes) adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry. Of the 3,654 cytogenetically informative cases diagnosed between January 1997 and May 2014, 68 (1.9%) were HH (n=50)/TT (n=18). Patients with HH/TT were older than those with intermediate risk (IR) AML (median 71 years vs. 67 years; P=0.042) and less often had de novo AML (63% vs. 79%; P=0.004); no such differences were observed between HH/TT and complex karyotype (CK) AML. The overall survival (OS) was similar between patients with HH/TT and CK AML (median 0.9 years vs. 0.6 years; P=0.082), whereas OS was significantly longer (median 1.6 years; P=0.028) for IR AML. The OS was shorter for cases with HH than with TT (median 0.6 years vs. 1.4 years; P=0.032) and for HH/TT AMLs with adverse abnormalities (median 0.8 years vs. 1.1 years; P=0.044). In conclusion, HH/TT AML is associated with a poor outcome, but chromosome numbers >65 and absence of adverse aberrations seem to translate into a more favorable prognosis. Thus, HH/TT AMLs are clinically heterogeneous and should not automatically be grouped as high risk.Am. J. Hematol. 90:800-805, 2015. (c) 2015 Wiley Periodicals, Inc.

  • 28.
    Lehmann, Sören
    et al.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Unit of Hematology, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
    Deneberg, Stefan
    Unit of Hematology, Department of Medicine, Karolinska Institute Huddinge, Stockholm, Sweden.
    Antunovic, Petar
    Department of Hematology, Linköping University Hospital, Linköping, Sweden.
    Rangert-Derolf, Åsa
    Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.
    Garelius, Hege K. G.
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Lazarevic, Vladimir Lj J.
    Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.
    Myhr-Eriksson, Kristina
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Möllgård, Lars
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences. Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Wåhlin, Anders C. E.
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Wennström, Lovisa
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Höglund, Martin
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Juliusson, Gunnar J.
    Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.
    Early death rates remain high in high-risk APL: update from the Swedish Acute Leukemia Registry 1997-20132017In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 6, 1457-1459 p.Article in journal (Refereed)
  • 29.
    Malm, Kerstin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine.
    Kragsbjerg, E.
    Univ Orebro, Fac Med & Hlth, Dept Lab Med, SE-70182 Orebro, Sweden..
    Andersson, Sören
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine.
    Performance of Liaison XL automated immunoassay platform for blood-borne infection screening on hepatitis B, hepatitis C, HIV 1/2, HTLV 1/2 and Treponema pallidum serological markers2015In: Transfusion Medicine, ISSN 0958-7578, E-ISSN 1365-3148, Vol. 25, no 2, 101-105 p.Article in journal (Refereed)
    Abstract [en]

    ObjectivesAim of the study was to evaluate performance of a new fully automated platform, DiaSorin-LIAISON (R) XL (DiaSorin S.p.A, Vercelli, Italy), in blood donor screening, specifically for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (anti-HBc), hepatitis C antibodies (anti-HCV), HIV p24 antigen, HIV antibodies, human T-lymphotropic virus types 1 and 2 (HTLV-1/2) and Treponema pallidum antibodies. BackgroundIn screening for such viral and bacteriological blood-borne infections, sensitivity and specificity are of utmost importance. MethodsSensitivity was evaluated using selected panels of samples previously analysed on the Abbott Architect immunoanalyser (Abbott Laboratories, Abbott Park, IL, USA)-the gold standard for this evaluation. These samples were confirmed positive for HBsAg, anti-HBc, anti-HCV, HIV Ag/Ab, anti-HTLV-1/2 and antibodies to T. pallidum, respectively. Specificity analysis was assessed by analysing blood donor samples previously run on the Architect platform and found non-reactive for each marker. A total of 1100 donor samples (both new and regular donors) were tested. Previously, non-specific reactive samples were also run for every tested marker, as well as samples with autoimmune antibodies and antibodies to other infections. ResultsThree hundred seventy-eight samples positive for the tested markers (HBsAgn=51, anti-HBcn=52, anti-HCVn=75, anti-Treponema n=55, anti-HIV-1 n=79, anti-HIV-2 n=25, anti-HIV 1/2 n=3, anti-HTLV-1 n=28 anti-HTLV-2 n=10) were tested and found positive, suggesting a high sensitivity. A number of 342-1100 negative blood donors (depending on marker) have been tested, with very good specificity for the markers tested, ranging between 995 and 100%, respectively. ConclusionsThe LIAISON (R) XL platform demonstrated very high sensitivity for the markers tested and the specificity necessary to fulfil the stringent requirements for blood donor screening.

  • 30.
    Mulligan, Stephen P
    et al.
    Department of Haematology, Royal North Shore Hospital, St LeonardsSydney, NSW, Australia .
    Karlsson, Karin
    Department of Hematology, University Hospital, Linköping, Sweden; Department of Hematology, Skåne University Hospital, Lund, Sweden .
    Strömberg, Mats
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden .
    Jønsson, Viggo
    Department of Hematology, National Hospital, Copenhagen, Denmark .
    Gill, Devinder
    Department of Haematology, Princess Alexandra Hospital, Brisbane, Australia.
    Hammerström, Jens
    Department of Hematology, St Olav University Hospital, Trondheim, Norway .
    Hertzberg, Mark
    Department of Haematology, Westmead Hospital, Sydney, Australia .
    McLennan, Roger
    Department of Haematology, Ballarat Base Hospital, Ballarat, Australia .
    Uggla, Bertil
    Örebro University Hospital. Department of Medicine.
    Norman, John
    Department of Haematology, Royal Adelaide Hospital, Adelaide, Australia .
    Wallvik, Jonas
    Department of Medicine, Sundsvall, Sweden .
    Sundström, Gunnel
    Department of Hematology, Norrlands University Hospital, Umeå, Sweden .
    Johansson, Hemming
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden .
    Brandberg, Yvonne
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden .
    Liliemark, Jan
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden; Swedish Council on Health Technology Assessment, Stockholm, Sweden .
    Juliusson, Gunnar
    Department of Hematology, University Hospital, Linköping, Sweden; Department of Hematology, Skåne University Hospital, Lund, Sweden .
    Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic leukemia2014In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 55, no 12, 2769-2777 p.Article in journal (Refereed)
    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.

  • 31.
    Nylander, M
    et al.
    Cardiovascular Inflammation Research Centre, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry, Sweden; Deparment of Medical and Health Science, Division of Pharmacology, Linköping University, Sweden; Department of Clinical and Experimental Medicine, Division of Clinical Chemistry, University Hospital, Linköping, Sweden.
    Lindahl, T L
    Cardiovascular Inflammation Research Centre, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry, Sweden.
    Bengtsson, Torbjörn
    Deparment of Medical and Health Science, Division of Pharmacology, Linköping University, Sweden.
    Grenegård, M
    Deparment of Medical and Health Science, Division of Pharmacology, Linköping University, Sweden.
    The periodontal pathogen Porphyromonas gingivalis sensitises human blood platelets to epinephrine2008In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 19, no 5, 352-358 p.Article in journal (Refereed)
    Abstract [en]

    Recent studies indicate connections between periodontitis and atherothrombosis, and the periodontal pathogen Porphyromonas gingivalis has been found within atherosclerotic lesions. P. gingivalis-derived proteases, designated gingipains activate human platelets, probably through a "thrombin-like" activity on protease-activated receptors (PARs). However, the potential interplay between P. gingivalis and other physiological platelet activators has not been investigated. The aim of this study was to elucidate consequences and mechanisms in the interaction between P. gingivalis and the stress hormone epinephrine. By measuring changes in light transmission through platelet suspensions, we found that P. gingivalis provoked aggregation, whereas epinephrine alone never had any effect. Intriguingly, pre-treatment of platelets with a low, sub-threshold number of P. gingivalis (i.e. a density that did not directly provoke platelet aggregation) resulted in a marked aggregation response when epinephrine was added. This synergistic action was not inhibited by the cyclooxygenas inhibitor aspirin. Furthermore, fura-2-measurements revealed that epinephrine caused an intracellular Ca(2+) mobilization in P. gingivalis pre-treated platelets, whereas epinephrine alone had no effect. Inhibition of the arg-specific gingipains, but not the lys-specific gingipains, abolished the aggregation and the Ca(2+) response provoked by epinephrine. Similar results were achieved by separate blockage of platelet alpha(2)-adrenergic receptors and PARs. In conclusion, the present study shows that a sub-threshold number of P. gingivalis sensitizes platelets to epinephrine. We suggest that P. gingivalis-derived arg-specific gingipains activates a small number of PARs on the surface of the platelets. This leads to an unexpected Ca(2+) mobilization and a marked aggregation response when epinephrine subsequently binds to the alpha(2)-adrenergic receptor. The present results are consistent with a direct connection between periodontitis and stress, and describe a novel mechanism that may contribute to pathological platelet activation.

  • 32.
    Oskarsson, Trausti
    et al.
    Department of Pediatric Oncology, Astrid Lindgren Children’s Hospital, Stockholm, Sweden; Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Söderhäll, Stefan
    Department of Pediatric Oncology, Astrid Lindgren Children’s Hospital, Stockholm, Sweden; Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Arvidson, Johan
    Department of Pediatric Oncology, Uppsala University Hospital, Sweden.
    Forestier, Erik
    Department of Pediatrics, Umeå University Hospital, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology and Biostatistics; Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, UK.
    Bottai, Matteo
    Unit of Biostatistics, IMM, Karolinska Institutet, Stockholm, Sweden.
    Lausen, Birgitte
    Department of Pediatric Oncology, Rigshospitalet University Hospital, Copenhagen, Denmark.
    Carlsen, Niels
    Department of Pediatrics, Odense University Hospital, Denmark.
    Hellebostad, Marit
    Department of Pediatrics, Ullevål Hospital, Oslo, Norway.
    Lähteenmäki, Päivi
    Department of Pediatrics, Turku University Hospital, Turku, Finland.
    Saarinen-Pihkala, Ulla M
    Children’s Hospital, University of Helsinki and Helsinki University Central Hospital, Finland.
    Jónsson, Ólafur G
    Children’s Hospital, Landspitali University Hospital, Reykjavik, Iceland.
    Heyman, Mats
    Department of Pediatric Oncology, Astrid Lindgren Children’s Hospital, Stockholm, Sweden; Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment and outcome2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no 1, 68-76 p.Article in journal (Refereed)
    Abstract [en]

    Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the upfront therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following ALL relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications; and identify additional prognostic factors for overall survival. In total 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were included. There were no statistically significant differences in outcome between the upfront protocols or between the relapse-protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing 2002-2011 was 57.5 +/- 3.4% but 44.7 +/- 3.2% (p<0.001) if relapse occurred 1992-2001. Factors independently predicting mortality after relapse included short duration of first remission, bone marrow involvement, age ≥10 years, unfavorable cytogenetics and Down syndrome. T-cell immunophenotype was not an independent prognostic factor unless in combination with hyperleukocytosis at diagnosis. The outcome for early combined pre-B relapses was unexpectedly poor (5-year overall survival 38.0 +/- 10.6%) which supports the notion that these patients need further risk adjustment. Although survival outcomes have improved over time, development of novel approaches is urgent to increase survival in relapsed childhood acute lymphoblastic leukemia.

  • 33.
    Osterborg, Anders
    et al.
    Karolinska Univ Hosp, Dept Haematol, Stockholm, Sweden..
    Wierda, William G.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.;Canc Therapy Res Ctr, San Antonio, TX USA..
    Mayer, Jiri
    Fac Hosp Brno, Dept Internal Med Haematooncol, Brno, Czech Republic..
    Hess, Georg
    Johannes Gutenberg Univ Mainz, D-55122 Mainz, Germany..
    Hillmen, Peter
    Leeds Teaching Hosp, Leeds, W Yorkshire, England..
    Schetelig, Johannes
    Univ Klinickum Carl Gustav Carus, Dresden, Germany..
    Schuh, Anna
    Churchill Hosp, Oxford OX3 7LJ, England..
    Smolej, Lukas
    Univ Hosp, Fac Med Hradec Kralove, Hradec Kralove, Czech Republic.;Charles Univ Prague, Hradec Kralove, Czech Republic..
    Beck, Christian
    Moenchengladbach, Haematol Onkolog Inst, Rheydt, Germany..
    Dreyfus, Brigitte
    Hop Jean Bernanrd, Poitiers, France..
    Hellman, Andrzej
    Akad Med Gdansku, Gdansk, Poland..
    Kozlowski, Piotr
    Örebro University Hospital.
    Pfreundschuh, Michael
    Univ Saarlandes Kliniken, Homburg, Germany..
    Rizzi, Rita
    Azienda Ospendaliero Univ Policlin Consorziale, Bari, Italy..
    Spacek, Martin
    Fak Nemocnice, Prague 10, Czech Republic..
    Phillips, Jennifer L.
    GlaxoSmithKline, Collegeville, PA USA..
    Gupta, Ira V.
    Williams, Vanessa
    Glaxo SmithKline, Res Triangle Pk, NC USA..
    Jewell, Roxanne C.
    Glaxo SmithKline, Res Triangle Pk, NC USA..
    Nebot, Noelia
    Glaxo SmithKline, Res Triangle Pk, NC USA..
    Lisby, Steen
    Genmab AS, Copenhagen, Denmark..
    Dyer, Martin J. S.
    Univ Leicester, Ernest & Helen Scott Haematol Res Inst, Leicester, Leics, England..
    Ofatumumab retreatment and maintenance in fludarabine-refractory chronic lymphocytic leukaemia patients2015In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 170, no 1, 40-49 p.Article in journal (Refereed)
    Abstract [en]

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

  • 34.
    Peng, Xiang
    et al.
    Department of Nephrology, Qingyuan City Hospital of Jinan University, Guangdong, China; Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Ramström, Sofia
    Department of Experimental and Clinical Medicine, Linköping University, Linköping, Sweden.
    Kurz, Tino
    Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Grenegård, Magnus
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; .
    Segelmark, Mårten
    Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    The neutrophil serine protease PR3 induces shape change of platelets via the Rho/Rho kinase and Ca2+ signaling pathways2014In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 134, no 2, 418-425 p.Article in journal (Refereed)
    Abstract [en]

    Introduction: Proteinase 3 (PR3) is released from neutrophil azurophilic granules and exerts complex effects on the inflammatory process. PR3 catalyzes the degradation of a number of macromolecules, but the consequences on blood cells are less well defined. In the present study, the effect of PR3 on human platelets was thoroughly investigated.

    Methods: The experiments were performed on washed platelets freshly isolated from blood donated by healthy human volunteers. Platelets shape change and aggregation was measured on a Chrono-Log aggregometer. The phosphorylated form of MYPT1 was visualized by immunostaining. Platelet activation was further evaluated by flow cytometry.

    Results: PR3 induced platelet shape change but not aggregation. Flow cytometry analysis showed that PR3 induced no P-selectin expression or binding of fibrinogen to the platelets, and it did not change the activation in response to PAR1- or PAR4-activating peptides or to thrombin. Furthermore, Fura-2 measurement and immuno-blotting analysis, respectively, revealed that PR3 stimulated small intracellular Ca2+ mobilization and Thr696-specific phosphorylation of the myosin phosphatase target subunit 1 (MYPT1). Separate treatment of platelets with the Rho/Rho kinase inhibitor Y-27632 and the intracellular Ca2+ chelator BAPTA/AM reduced the shape change induced by PR3 whereas concurrent treatment completely inhibited it.

    Conclusion: The data shows that the neutrophil protease PR3 is a direct modulator of human platelets and causes shape change through activation of the Rho/Rho kinase and Ca2+ signaling pathways. This finding highlights an additional mechanism in the complex interplay between neutrophils and platelets.

  • 35.
    Sodergren, Anna L.
    et al.
    Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Holm, Ann-Charlotte B. Svensson
    Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Ramström, Sofia
    Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Lindström, Eva G.
    Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoöping University, Linköping, Sweden.
    Grenegård, Magnus
    Örebro University, School of Medical Sciences. Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoöping University, Linköping, Sweden; Department of Clinical Medicine.
    Öllinger, Karin
    Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by endothelial-derived substances2016In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 27, no 1, 86-92 p.Article in journal (Refereed)
    Abstract [en]

    Exocytosis of lysosomal contents from platelets has been speculated to participate in clearance of thrombi and vessel wall remodelling. The mechanisms that regulate lysosomal exocytosis in platelets are, however, still unclear. The aim of this study was to identify the pathways underlying platelet lysosomal secretion and elucidate how this process is controlled by platelet inhibitors. We found that high concentrations of thrombin induced partial lysosomal exocytosis as assessed by analysis of the activity of released N-acetyl--glucosaminidase (NAG) and by identifying the fraction of platelets exposing the lysosomal-associated membrane protein (LAMP)-1 on the cell surface by flow cytometry. Stimulation of thrombin receptors PAR1 or PAR4 with specific peptides was equally effective in inducing LAMP-1 surface expression. Notably, lysosomal exocytosis in response to thrombin was significantly reduced if the secondary activation by ADP was inhibited by the P2Y(12) antagonist cangrelor, while inhibition of thromboxane A(2) formation by treatment with acetylsalicylic acid was of minor importance in this regard. Moreover, the NO-releasing drug S-nitroso-N-acetyl penicillamine (SNAP) or the cyclic AMP-elevating eicosanoid prostaglandin I-2 (PGI(2)) significantly suppressed lysosomal exocytosis. We conclude that platelet inhibitors that mimic functional endothelium such as PGI(2) or NO efficiently counteract lysosomal exocytosis. Furthermore, we suggest that secondary release of ADP and concomitant signaling via PAR1/4- and P2Y(12) receptors is important for efficient platelet lysosomal exocytosis by thrombin.

  • 36.
    Vaht, Krista
    et al.
    Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden; Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Göransson, Magnus
    Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden; Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Carlson, Kristina
    Department of Hematology, Uppsala University Hospital, Umeå, Sweden.
    Isaksson, Cecilia
    Department of Hematology, Cancer Centre, University Hospital, Umeå, Sweden.
    Lenhoff, Stig
    Department of Hematology, Skåne University Hospital, Lund University, Malmö, Sweden.
    Sandstedt, Anna
    Department of Hematology, Linköping University Hospital, Linköping, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences. Section of Hematology Department of Medicine.
    Winiarski, Jacek
    Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Ljungman, Per
    Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Brune, Mats
    Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden; Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Andersson, Per-Ola
    South Älvsborg Hospital, Borås, Sweden; Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Incidence and outcome of acquired aplastic anemia: real-world data from patients diagnosed in Sweden from 2000-20112017In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, no 10, 1683-1690 p.Article in journal (Refereed)
    Abstract [en]

    A plastic anemia is a rare life-threatening disease. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, the outcome has improved considerably, and the 5-year survival is reported to be 70-80% in selected patient cohorts. Yet, contemporary population-based data on incidence and survival are lacking. We performed a national retrospective study to determine the incidence, treatment, and survival of patients with aplastic anemia diagnosed in Sweden from 2000-2011. Patients were included via the National Patient Registry, and diagnosed according to the Camitta criteria. In total, 257 confirmed cases were identified, with an overall incidence of 2.35 (95% CI: 2.06-2.64) cases per million inhabitants per year. Median age was 60 years (range: 2-92), and median follow up was 76 (0-193) months. Primary treatments included immunosuppressive therapy (63%), allogenic stem cell transplantation (10%), or single-agent cyclosporine/no specific therapy (27%). The 5-year survival was 90.7% in patients aged 0-18 years, 90.5% in patients aged 19-39 years, 70.7% in patients aged 40-59 years, and 38.1% in patients aged ≥60 years. Multivariate analysis showed that age (both 40-59 and ≥60 age groups), very severe aplastic anemia and single-agent cyclosporine/no specific therapy were independent risk factors for inferior survival. In conclusion, younger aplastic anemia patients experience a very good long-term survival, while that of patients ≥60 years in particular remains poor. Apparently, the challenge today is to improve the management of older aplastic anemia patients, and prospective studies to address this medical need are warranted.

  • 37.
    Vigren, P.
    et al.
    Linköping University Hospital, Linköping, Sweden.
    Ström, Jakob O.
    Linköping University, Linköping, Sweden.
    Petrini, P.
    Karolinska University Hospital, Stockholm, Sweden.
    Callander, M.
    Linköping University, Linköping, Sweden.
    Theodorsson, A.
    Linköping University Hospital, Linköping, Sweden.
    Treatment of spontaneous intracerebral haemorrhage in Glanzmann's thrombasthenia2012In: Haemophilia, ISSN 1351-8216, E-ISSN 1365-2516, Vol. 18, no 5, e381-e383 p.Article in journal (Refereed)
  • 38.
    Walker, Alex J.
    et al.
    Univ Nottingham, City Hosp Nottingham, Div Epidemiol & Publ Hlth, Nottingham NG5 1PB, England ; NIHR Biomed Res Unit, Nottingham Digest Dis Ctr, Nottingham, England.
    Grainge, Matthew J.
    Univ Nottingham, City Hosp Nottingham, Div Epidemiol & Publ Hlth, Nottingham NG5 1PB, England ; NIHR Biomed Res Unit, Nottingham Digest Dis Ctr, Nottingham, England.
    Card, Tim R.
    Univ Nottingham, City Hosp Nottingham, Div Epidemiol & Publ Hlth, Nottingham NG5 1PB, England ; NIHR Biomed Res Unit, Nottingham Digest Dis Ctr, Nottingham, England.
    West, Joe
    Univ Nottingham, City Hosp Nottingham, Div Epidemiol & Publ Hlth, Nottingham NG5 1PB, England ; NIHR Biomed Res Unit, Nottingham Digest Dis Ctr, Nottingham, England.
    Ranta, Susanna
    Karolinska Inst, Childhood Canc Res Unit, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet Sockholm Sweden, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden.
    Venous thromboembolism in children with cancer: A population-based cohort study2014In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 133, no 3, 340-344 p.Article in journal (Refereed)
    Abstract [en]

    Introduction: Cancer is a known risk factor for venous thromboembolism (VTE) in adults, but population-based data in children are scarce.

    Materials and methods: We conducted a cohort study utilising linkage of the Clinical Practice Research Database (primary care), Hospital Episodes Statistics (secondary care), UK Cancer Registry data and Office for National Statistics cause of death data. From these databases, we selected 498 children with cancer diagnosed between 1997 and 2006 and 20,810 controls without cancer. We calculated VTE incidence rates in children with cancer vs. controls, and hazard ratios (HRs) using Cox regression.

    Results: We identified four VTE events in children with cancer compared with four events in the larger control population corresponding to absolute risks of 1.52 and 0.06 per 1000 person-years respectively. The four children with VTE and cancer were diagnosed with hematological, bone or non-specified cancer. Childhood cancer was hence associated with a highly increased risk of VTE (HR adjusted for age and sex: 28.3; 95% CI = 7.0-114.5).

    Conclusions: Children with cancer are at increased relative risk of VTE compared to those without cancer. Physicians could consider thromboprophylaxis in children with cancer to reduce their excess risk of VTE however the absolute risk is extremely small and the benefit gained therefore would need to be balanced against the risk invoked of implementing such a strategy.

    Novelty & Impact Statements: While there is a reasonable level of knowledge about the risk of VTE in adult populations, it is not well known whether this risk is reflected in paediatric patients. We found a substantial increase in risk of VTE in children with cancer compared to a child population without cancer. While this finding is important, the absolute risk of VTE is still low and must be balanced with the risks of anticoagulation. (C) 2014 The Authors. Published by Elsevier Ltd. All rights reserved.

  • 39.
    Åström, Maria
    Dpt of medicine and laboratory medicine, Örebro University Hospital.
    Clinical cases: Presentation, diagnosis, treatment and follow-up: Case 2 - Chuvash polycythemia2015In: Congenital Erythrocytosis and Hereditary Thrombocytosis: Clinical presentation, diagnosis, treatment and follow-up. A practical guide with clinical cases. / [ed] Sylvie Hermouet, Portugal: European cooperation in science and technology , 2015Chapter in book (Other academic)
  • 40.
    Åström, Maria
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hahn-Strömberg, Victoria
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Zetterberg, Eva
    Departments of Medicine and Hematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden .
    Vedin, Inger
    Departments of Medicine and Hematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden .
    Merup, Mats
    Departments of Medicine and Hematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden .
    Palmblad, Jan
    Departments of Medicine and Hematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden .
    X-linked thrombocytopenia with thalassemia displays bone marrow reticulin fibrosis and enhanced angiogenesis: comparisons with primary myelofibrosis2015In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, no 3, E44-E48 p.Article in journal (Refereed)
    Abstract [en]

    X-linked thrombocytopenia with thalassemia (XLTT) is caused by the mutation 216R > Q in exon 4 of the GATA1 gene. Male hemizygous patients display macrothrombocytopenia, splenomegaly, and a β-thalassemia trait. We describe two XLTT families where three males were initially misdiagnosed as having primary myelofibrosis (PMF) and all five investigated males showed mild-moderate bone marrow (BM) reticulin fibrosis. Comparative investigations were performed on blood samples and BM biopsies from males with XLTT, PMF patients and healthy controls. Like PMF, XLTT presented with high BM microvessel density, low GATA1 protein levels in megakaryocytes, and elevated blood CD34+ cell counts. But unlike PMF, the BM microvessel pericyte coverage was low in XLTT, and no collagen fibrosis was found. Further, as evaluated by immunohistochemistry, expressions of the growth factors VEGF, AGGF1, and CTGF were low in XLTT megakaryocytes and microvessels but high in PMF. Thus, although the reticulin fibrosis in XLTT might simulate PMF, opposing stromal and megakaryocyte features may facilitate differential diagnosis. Additional comparisons between these disorders may increase the understanding of mechanisms behind BM fibrosis in relation to pathological megakaryopoiesis.

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