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  • 1. Abelsson, J
    et al.
    Merup, M
    Birgegård, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    WeisBjerrum, O
    Brinch, L
    Brune, M
    Johansson, P
    Kauppila, M
    Lenhoff, S
    Liljeholm, M
    Malm, C
    Remes, K
    Vindelöv, L
    Andréasson, B
    The outcome of allo-HSCT for 92 patients with myelofibrosis in the Nordic countries2012Inngår i: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 47, nr 3, s. 380-386Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Between 1982 and 2009 a total of 92 patients with myelofibrosis (MF) in chronic phase underwent allo-SCT in nine Nordic transplant centers. Myeloablative conditioning (MAC) was given to 40 patients, and reduced intensity conditioning (RIC) was used in 52 patients. The mean age in the two groups at transplantation was 46±12 and 55±8 years, respectively (P<0.001). When adjustment for age differences was made, the survival of the patients treated with RIC was significantly better (P=0.003). Among the RIC patients, the survival was significantly (P=0.003) better for the patients with age <60 years (a 10-year survival close to 80%) than for the older patients. The type of stem cell donor did not significantly affect the survival. No significant difference was found in TRM at 100 days between the MAC- and the RIC-treated patients. The probability of survival at 5 years was 49% for the MAC-treated patients and 59% in the RIC group (P=0.125). Patients treated with RIC experienced significantly less aGVHD compared with patients treated with MAC (P<0.001). The OS at 5 years was 70, 59 and 41% for patients with Lille score 0, 1 and 2, respectively (P=0.038, when age adjustment was made). Twenty-one percent of the patients in the RIC group were given donor lymphocyte infusion because of incomplete donor chimerism, compared with none of the MAC-treated patients (P<0.002). Nine percent of the patients needed a second transplant because of graft failure, progressive disease or transformation to AML, with no significant difference between the groups. Our conclusions are (1) allo-SCT performed with RIC gives a better survival compared with MAC. (2) age over 60 years is strongly related to a worse outcome and (3) patients with higher Lille score had a shorter survival.

  • 2. Abelsson, Johanna
    et al.
    Andreasson, Bjorn
    Samuelsson, Jan
    Hultcrantz, Malin
    Ejerblad, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Johansson, Berit
    Emanuel, Robyn
    Mesa, Ruben
    Johansson, Peter
    Patients with polycythemia vera have worst impairment of quality of life among patients with newly diagnosed myeloproliferative neoplasms2013Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 54, nr 10, s. 2226-2230Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The quality of life (QoL) at the time of diagnosis of myeloproliferative neoplasm (MPN) has, to date, not been studied. One hundred and seventy-nine patients with MPN: 80 with essential thrombocythemia (ET), 73 with polycythemia vera (PV), 22 with primary myelofibrosis (PMF) and four with MPN undifferentiated, were included in this study. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQC30) and the MPN-Symptom Assessment Form (MPN-SAF) were used to evaluate QoL. Fatigue was the most reported symptom in these patients. Patients with PV reported significantly higher mean scores for inactivity, dizziness, cough, itching, depression and lower total QoL compared to patients with ET. Patients with PV had significantly more headache and itching compared to patients with PMF. When the newly diagnosed patients with MPN were compared with a cohort of patients with MPN with mean disease duration of 7.8 years, the differences were most striking for patients with PMF, with significantly more fatigue, abdominal discomfort, concentration problems, insomnia, fever, weight loss and lower overall QoL developed over time.

  • 3.
    Abu Sabaa, Amal
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Mörth, Charlott
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Berglund, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Hashemi, Jamileh
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Freyhult, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Kamali-Moghaddam, Masood
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg och funktionsgenomik.
    Robelius, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    T-cell Leukaemia/Lymphoma Protein 1A (TCL1A) In Diffuse Large B-cell lymphoma (DLBCL)Manuskript (preprint) (Annet vitenskapelig)
  • 4.
    Abu Sabaa, Amal
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Mörth, Charlott
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Molin, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Freyhult, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Kamali-Moghaddam, Masood
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg och funktionsgenomik.
    Robelius, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Plasma Protein Profiling using Multiplex Extension Assay in Diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP: A descriptive studyManuskript (preprint) (Annet vitenskapelig)
  • 5.
    Afram, G.
    et al.
    Karolinska Inst, Med, Stockholm, Sweden..
    Watz, E.
    ONK PAT, Ctr Apheresis, Stockholm, Sweden..
    Remberger, M.
    ONK PAT, Ctr Allogene Stem Cell Transplantat, Immunol, Stockholm, Sweden..
    Axdorph-Nygell, U.
    ONK PAT, Ctr Apheresis, Stockholm, Sweden..
    Sundin, M.
    Karolinska Inst, Pediat Haematol, Stockholm, Sweden..
    Hagglund, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Mattsson, J.
    Karolinska Inst, Ctr Stem Cell Transplantat, Stockholm, Sweden..
    Uhlin, M.
    Karolinska Inst, Ctr Stem Cell Transplantat, Stockholm, Sweden..
    Extracorporeal photopheresis as treatment for moderate-severe chronic graft-versus-host disease2016Inngår i: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 51, s. S138-S138Artikkel i tidsskrift (Annet vitenskapelig)
  • 6.
    Afram, Gabriel
    et al.
    Karolinska Univ Hosp Huddinge, Dept Hematol, Stockholm, Sweden.
    Perez Simon, Jose Antonio
    Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Dept Hematol,Inst Biomed Sevilla IBIS, Seville, Spain.
    Remberger, Mats
    Karolinska Univ Hosp Huddinge, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden.
    Caballero-Velazquez, Teresa
    Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Dept Hematol,Inst Biomed Sevilla IBIS, Seville, Spain.
    Martino, Rodrigo
    Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain.
    Luis Pinana, Jose
    Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain;Hosp Clin Univ, Dept Hematol, Valencia, Spain.
    Ringden, Olle
    Karolinska Univ Hosp Huddinge, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden.
    Esquirol, Albert
    Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain.
    Lopez-Corral, Lucia
    Hosp Univ Salamanca IBSAL, Dept Hematol, Salamanca, Spain.
    Garcia, Irene
    Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain.
    Lopez-Godino, Oriana
    Hosp Univ Salamanca IBSAL, Dept Hematol, Salamanca, Spain.
    Sierra, Jordi
    Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain.
    Caballero, Dolores
    Hosp Univ Salamanca IBSAL, Dept Hematol, Salamanca, Spain.
    Ljungman, Per
    Vazquez, Lourdes
    Hosp Univ Salamanca IBSAL, Dept Hematol, Salamanca, Spain.
    Hägglund, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Reduced intensity conditioning increases risk of severe cGVHD: identification of risk factors for cGVHD in a multicenter setting2018Inngår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 35, nr 6, artikkel-id 79Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Aim is to identify risk factors for the development of cGVHD in a multicenter setting. Patients transplanted between 2000 and 2006 were analyzed (n = 820). Donors were HLA-identical siblings (57%), matched unrelated donors (30%), and HLA-A, B or DR antigen mismatched (13%). Reduced intensity conditioning (RIC) was given to 65% of patients. Overall incidence of cGVHD was 46% for patients surviving more than 100 days after HSCT (n = 747). Older patient age [HR 1.15, p < 0.001], prior acute GVHD [1.30, p = 0.024], and RIC [1.36, p = 0.028] increased overall cGVHD. In addition, RIC [4.85, p < 0.001], prior aGVHD [2.14, p = 0.001] and female donor to male recipient [1.80, p = 0.008] increased the risk of severe cGVHD. ATG had a protective effect for both overall [0.41, p < 0.001] and severe cGVHD [0.20, p < 0.001]. Relapse-free survival (RFS) was impaired in patients with severe cGVHD. RIC, prior aGVHD, and female-to-male donation increase the risk of severe cGVHD. ATG reduces the risk of all grades of cGVHD without hampering RFS. GVHD prophylaxis may be tailored according to the risk profile of patients.

    Fulltekst (pdf)
    fulltext
  • 7.
    Afram, Gabriel
    et al.
    Karolinska Univ Lab, Hematol Ctr, Stockholm, Sweden;Karolinska Inst, Div Hematol, Dept Med, Stockholm, Sweden.
    Watz, Emma
    Karolinska Univ Lab, Dept Clin Immunol & Transfus Med, Stockholm, Sweden;Karolinska Inst, Div Transplantat Surg, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Remberger, Mats
    Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden;Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Nygell, Ulla Axdorph
    Karolinska Univ Lab, Hematol Ctr, Stockholm, Sweden;Karolinska Univ Lab, Dept Clin Immunol & Transfus Med, Stockholm, Sweden;Karolinska Inst, Div Transplantat Surg, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Sundin, Mikael
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Hematol Immunol SCT Sect, Stockholm, Sweden;Karolinska Inst, Div Pediat, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Hägglund, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Mattsson, Jonas
    Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden;Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Uhlin, Michael
    Karolinska Univ Lab, Dept Clin Immunol & Transfus Med, Stockholm, Sweden;Karolinska Inst, Div Transplantat Surg, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Higher response rates in patients with severe chronic skin graft-versus-host disease treated with extracorporeal photopheresis2019Inngår i: Central European Journal of Immunology, ISSN 1426-3912, E-ISSN 1644-4124, Vol. 44, nr 1, s. 84-91Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Different forms of graft-versus-host disease (GVHD) remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The prognosis for steroid-refractory chronic GVHD (cGVHD) remains poor. Our aim was to evaluate extracorporeal photopheresis (ECP) treatment in cGVHD patients with different organ involvement to detect subgroups of patients with the best response.

    Material and methods: Thirty-four patients who underwent HSCT and developed moderate (n = 7) or severe (n = 27) steroid-refractory or steroid-dependent cGVHD treated with ECP were included in the analysis. A matched cGVHD control patient group untreated with ECP was collected for comparison.

    Results: Compared to the control group and the stable/progressive disease (SD/PD) patients, individuals with complete/partial remission have higher overall survival and lower transplant-related mortality. Furthermore, patients with complete and partial remission (CR/PR) had significantly higher levels of albumin and platelets after ECP treatment compared to patients with stable or progressive cGVHD (SD/PD). Corticosteroid treatment and other immunosuppressive agents could successfully be tapered in the CR/PR group compared to the SD/PD patients. In this study patients with skin cGVHD are those with the highest rate of CR/PR after ECP treatment.

    Conclusions: Our results suggest that ECP treatment is safe and effective for patients with predominantly skin, oral and liver cGVHD.

    Fulltekst (pdf)
    FULLTEXT01
  • 8.
    Ajeganova, Sofia
    et al.
    Karolinska Inst, Dept Med Huddinge, S-14186 Stockholm, Sweden..
    Tesfa, Daniel
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med Huddinge, S-14186 Stockholm, Sweden.;Roche AB, Med Affairs, S-10074 Stockholm, Sweden..
    Hägglund, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Fadeel, Bengt
    Karolinska Inst, Inst Environm Med, Unit Mol Toxicol, S-17177 Stockholm, Sweden..
    Vedin, Inger
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med Huddinge, S-14186 Stockholm, Sweden..
    Zignego, Anna Linda
    Univ Florence, Ctr Syst Manifestat Hepatitis Viruses, Dept Internal Med, I-50134 Florence, Italy..
    Palmblad, Jan
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med Huddinge, S-14186 Stockholm, Sweden..
    Effect of FCGR polymorphism on the occurrence of late-onset neutropenia and flare-free survival in rheumatic patients treated with rituximab2017Inngår i: Arthritis Research & Therapy , E-ISSN 1478-6362, Vol. 19, artikkel-id 44Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The causes and mechanisms of late-onset neutropenia (LON) following rituximab treatment in patients with rheumatic diseases are not known. In this study, we aimed to investigate the role of established Fc gamma receptor gene (FCGR) polymorphisms and B-cell-activating factor (BAFF) gene promoter polymorphisms for the development of LON and for the efficacy of rituximab in patients with rheumatic diseases. Methods: A single-center case-control retrospective study was nested in a cohort of 214 consecutive patients with rheumatic diseases treated with rituximab. Eleven patients presented with LON. Fifty non-LON control subjects were matched by diagnosis, age, sex, and treatments. Single-nucleotide polymorphisms of FCGR (FCGR2A 131H/R, FCGR2B 232I/T, FCGR3A 158V/F) and BAFF promoter polymorphism -871C/T were analyzed with polymerase chain reaction-based techniques, and serum immunoglobulin M (IgM) and BAFF levels were analyzed by enzyme-linked immunosorbent assay. Flare-free survival was related to LON occurrence and polymorphisms. Results: The FCGR3A V allele, but not other FCGR polymorphisms, correlated with the occurrence of LON; each V allele conferred a fourfold increased OR for LON (p = 0.017). FCGR3A 158V/V and presentation with LON were associated with a longer flare-free survival (p = 0.023 and p = 0.031, respectively). FCGR3A 158V/V was related to lower IgM levels (p = 0.016). Serum BAFF levels showed no relationship with LON and BAFF -871C/T promoter polymorphism. There was a tendency toward longer flare-free survival in patients with the BAFF -871T/T allotype compared with the C/T or C/C allotypes (p = 0.096). Conclusions: The results of the present study suggest that presentation with LON may be a result of the intrinsic efficacy of rituximab in patients with rheumatic diseases. LON could indicate a longer biological and therapeutic activity of rituximab modulated by a certain genotypic polymorphism: the high-affinity FCGR3A V allele. This genotype and the occurrence of LON are both related to longer flare-free survival, suggestive of common mechanisms for LON and duration of response to rituximab. The role of the BAFF -871C/T promoter polymorphism in LON occurrence is unclear.

    Fulltekst (pdf)
    fulltext
  • 9.
    Al-Amin, Rasel A.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Johansson, Lars
    Department of Medical Biochemistry and Biophysics, Chemical Biology Consortium Sweden (CBCS), Science for Life Laboratory, Karolinska Institutet.
    Abdurakhmanov, Eldar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Landegren, Nils
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Center for Molecular Medicine, Department of Medicine (Solna), Science for Life Laboratory, Karolinska Institutet.
    Löf, Liza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Arngården, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Blokzijl, Andries
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Svensson, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hammond, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lönn, Peter
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Haybaeck, Johannes
    Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck; Diagnostic and Research Institute of Pathology, Medical University of Graz.
    Kamali-Moghaddam, Masood
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jenmalm Jensen, Annika
    Department of Medical Biochemistry and Biophysics, Chemical Biology Consortium Sweden (CBCS), Science for Life Laboratory, Karolinska Institutet.
    Danielson, U. Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Artursson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lundbäck, Thomas
    Department of Medical Biochemistry and Biophysics, Chemical Biology Consortium Sweden (CBCS), Science for Life Laboratory, Karolinska Institutet.
    Landegren, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Monitoring drug–target interactions through target engagement-mediated amplification on arrays and in situ2022Inngår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 50, nr 22, s. e129-e129Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Drugs are designed to bind their target proteins in physiologically relevant tissues and organs to modulate biological functions and elicit desirable clinical outcomes. Information about target engagement at cellular and subcellular resolution is therefore critical for guiding compound optimization in drug discovery, and for probing resistance mechanisms to targeted therapies in clinical samples. We describe a target engagement-mediated amplification (TEMA) technology, where oligonucleotide-conjugated drugs are used to visualize and measure target engagement in situ, amplified via rolling-circle replication of circularized oligonucleotide probes. We illustrate the TEMA technique using dasatinib and gefitinib, two kinase inhibitors with distinct selectivity profiles. In vitro binding by the dasatinib probe to arrays of displayed proteins accurately reproduced known selectivity profiles, while their differential binding to fixed adherent cells agreed with expectations from expression profiles of the cells. We also introduce a proximity ligation variant of TEMA to selectively investigate binding to specific target proteins of interest. This form of the assay serves to improve resolution of binding to on- and off-target proteins. In conclusion, TEMA has the potential to aid in drug development and clinical routine by conferring valuable insights in drug–target interactions at spatial resolution in protein arrays, cells and in tissues.

    Fulltekst (pdf)
    fulltext
  • 10.
    Ali, Dina
    et al.
    Karolinska Univ Hosp, Haematol Ctr, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Haematol & Regenerat Med HERM, Stockholm, Sweden..
    Mohammad, Dara K.
    Karolinska Inst, Karolinska Hosp Huddinge, Clin Res Ctr, Dept Lab Med, Stockholm, Sweden..
    Mujahed, Huthayfa
    Karolinska Univ Hosp, Haematol Ctr, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Haematol & Regenerat Med HERM, Stockholm, Sweden..
    Jonson-Videsater, Kerstin
    Karolinska Univ Hosp, Dept Clin Immunol, Stockholm, Sweden..
    Nore, Beston
    Karolinska Inst, Karolinska Hosp Huddinge, Clin Res Ctr, Dept Lab Med, Stockholm, Sweden..
    Paul, Christer
    Karolinska Univ Hosp, Haematol Ctr, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Haematol & Regenerat Med HERM, Stockholm, Sweden..
    Lehmann, Sören
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi. Karolinska Univ Hosp, Haematol Ctr, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Haematol & Regenerat Med HERM, Stockholm, Sweden..
    Anti-leukaemic effects induced by APR-246 are dependent on induction of oxidative stress and the NFE2L2/HMOX1 axis that can be targeted by PI3K and mTOR inhibitors in acute myeloid leukaemia cells2016Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 174, nr 1, s. 117-126Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The small molecule APR-246 (PRIMA-1(MET)) is a novel drug that restores the activity of mutated and unfolded TP53 protein. However, the mechanisms of action and potential off-target effects are not fully understood. Gene expression profiling in TP53 mutant KMB3 acute myeloid leukaemia (AML) cells showed that genes which protected cells from oxidative stress to be the most up-regulated. APR-246 exposure also induced reactive oxygen species (ROS) formation and depleted glutathione in AML cells. The genes most up-regulated by APR-246, confirmed by quantitative real time polymerase chain reaction, were heme oxygenase-1 (HMOX1, also termed HO-1), SLC7A11 and RIT1. Up-regulation of HMOX1, a key regulator of cellular response to ROS, was independent of TP53 mutational status. NFE2L2 (also termed Nrf2), a master regulator of HMOX1 expression, showed transcriptional up-regulation and nuclear translocation by APR-246. Down-regulation of NFE2L2 by siRNA in AML cells significantly increased the antitumoural effects of APR-246. The PI3K inhibitor wortmannin and the mTOR inhibitor rapamycin inhibited APR-246-induced nuclear translocation of NFE2L2 and counteracted the protective cellular responses to APR-246, resulting in synergistic cell killing together with APR-246. In conclusion, ROS induction is important for antileukaemic activities of APR-246 and inhibiting the protective response of the Nrf-2/HMOX1 axis using PI3K inhibitors, enhances the antileukaemic effects.

  • 11.
    Ali, M. M.
    et al.
    Oslo Univ Hosp, Dept Haematol, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Gronvold, B.
    Oslo Univ Hosp, Dept Haematol, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Remberger, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi. Oslo Univ Hosp, Dept Haematol, Oslo, Norway.; Uppsala Univ Hosp, KFUE, Uppsala, Sweden..
    Abrahamsen, I. W.
    Oslo Univ Hosp, Dept Haematol, Oslo, Norway..
    Myhre, A. E.
    Oslo Univ Hosp, Dept Haematol, Oslo, Norway..
    Tjonnfjord, G. E.
    Oslo Univ Hosp, Dept Haematol, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Floisand, Y.
    Univ Oslo, Inst Clin Med, Ctr Canc Cell Reprogramming, Oslo, Norway.;Clatterbridge Canc Ctr NHS Fdn Trust, Liverpool, Merseyside, England..
    Gedde-Dahl, T.
    Oslo Univ Hosp, Dept Haematol, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Addition of Anti-thymocyte Globulin in Allogeneic Stem Cell Transplantation With Peripheral Stem Cells From Matched Unrelated Donors Improves Graft-Versus-Host Disease and Relapse Free Survival2021Inngår i: Clinical Lymphoma, Myeloma & Leukemia, ISSN 2152-2650, E-ISSN 2152-2669, Vol. 21, nr 9, s. 598-605Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In 2014 we introduced anti-thymocyte globulin (ATG) to the graft-versus-host disease (GvHD) prophylaxis regimen in allogeneic stem cell transplantation (Allo-HSCT) with peripheral stem cells (PBSC) from matched unrelated donors (MUD). We analysed the outcomes of 415 patients who went through MUD alto-HSCT and received PBSC with or without ATG. We report dramatic reduction of the incidence of chronic GvHD and our study illustrates the benefit of ATG in addition to standard GvHD prophylaxis. Anti-thymocyte globulin (ATG) is commonly used to prevent graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To evaluate the impact of ATG as part of the GvHD prophylaxis in our institution, we report the outcome of 415 patients with matched unrelated donors (MUD) transplanted for hemato-logical malignancies with or without ATG from 2005 to 2019 at Oslo University Hospital, Norway. The following groups were compared: (1) 154 patients transplanted with peripheral blood stem cells (PBSC) without ATG 2005-2014. (2) 137 patients transplanted with bone marrow stem cells (BMSC) 2005-2019. (3) 124 patients transplanted with PBSC and ATG (PBSC + ATG) 2014-2019. Three years survival was similar in the groups, 61% following allografting with PBSC, 54% with BMSC, and 59% with PBSC + ATG. Acute GvHD grade III-IV was 14%, 14%, and 7%; chronic GvHD was 81%, 32, and 26%; and extensive cGvHD 44%, 15%, and 6% in the corresponding groups. Both acute and chronic GvHD were significantly reduced in the PBSC + ATG-versus the PBSC group (p < 0.05 and p < 0.001 respectively).Transplant-related mortality (TRM) was 33%, 25%, and 17% (p = 0.18). Graft versus host disease and relapse free survival (GRFS) at 3 years was 43 %, 43%, and 64% in the groups. Adding ATG to the GvHD prophylaxis regimen of MUD allo-HSCT with PBSC resulted in a substantial reduction of both acute and chronic GvHD without compromising the disease control, reflected in a superior 3 years GRFS.

  • 12. Ali, Muhammad
    et al.
    Giannakopoulou, Eirini
    Li, Yingqian
    Lehander, Madeleine
    Virding Culleton, Stina
    Yang, Weiwen
    Knetter, Cathrine
    Odabasi, Mete Can
    Bollineni, Ravi Chand
    Yang, Xinbo
    Foldvari, Zsofia
    Böschen, Maxi-Lu
    Taraldsrud, Eli
    Strønen, Erlend
    Toebes, Mireille
    Hillen, Amy
    Mazzi, Stefania
    de Ru, Arnoud H.
    Janssen, George M. C.
    Kolstad, Arne
    Tjønnfjord, Geir Erland
    Lie, Benedicte A.
    Griffioen, Marieke
    Lehmann, Sören
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Osnes, Liv Toril
    Buechner, Jochen
    Garcia, K. Christopher
    Schumacher, Ton N.
    van Veelen, Peter A.
    Leisegang, Matthias
    Jacobsen, Sten Eirik W.
    Woll, Petter
    Olweus, Johanna
    T cells targeted to TdT kill leukemic lymphoblasts while sparing normal lymphocytes2022Inngår i: Nature Biotechnology, ISSN 1087-0156, E-ISSN 1546-1696, Vol. 40, nr 4, s. 488-498Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Unlike chimeric antigen receptors, T-cell receptors (TCRs) can recognize intracellular targets presented on human leukocyte antigen (HLA) molecules. Here we demonstrate that T cells expressing TCRs specific for peptides from the intracellular lymphoid-specific enzyme terminal deoxynucleotidyl transferase (TdT), presented in the context of HLA-A*02:01, specifically eliminate primary acute lymphoblastic leukemia (ALL) cells of T- and B-cell origin in vitro and in three mouse models of disseminated B-ALL. By contrast, the treatment spares normal peripheral T- and B-cell repertoires and normal myeloid cells in vitro, and in vivo in humanized mice. TdT is an attractive cancer target as it is highly and homogeneously expressed in 80–94% of B- and T-ALLs, but only transiently expressed during normal lymphoid differentiation, limiting on-target toxicity of TdT-specific T cells. TCR-modified T cells targeting TdT may be a promising immunotherapy for B-ALL and T-ALL that preserves normal lymphocytes.

    Fulltekst (pdf)
    fulltext
  • 13.
    Alvarez-Larran, Alberto
    et al.
    Inst Invest Biomed August Pi & Sunyer IDIBAP, Hosp Clin, Hematol Dept, Barcelona, Spain..
    Sant'Antonio, Emanuela
    Univ Hosp Paolo Giaccone, Hematol Div, Palermo, Italy..
    Harrison, Claire
    Guys & StThomasNHS Fdn Trust, Dept Haematol, London, England..
    Kiladjian, Jean-Jacques
    Univ Paris, Ctr Invest Clin, Hop St Louis, AP HP,INSERM,CIC1427, Paris, France..
    Griesshammer, Martin
    Univ Bochum, Johannes Westing Med Ctr Minden UKRUB, Oncol Hemostaseol & Palliat Care, Bochum, Germany..
    Mesa, Ruben
    UT Hlth San Antonio MD Anderson, Mays Canc Ctr, San Antonio, TX USA..
    Ianotto, Jean Christophe
    CHRU Brest, Serv Hematol Clin, Inst Cancerol Hematol, Brest, France..
    Palandri, Francesca
    Univ Bologna, Ist Ematol Seragnor, IRCCS Azienda Osped, Bologna, Italy..
    Hernandez-Boluda, Juan Carlos
    Hosp Clin Valencia, Hematol Dept, Valencia, Spain..
    Birgegård, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Nangalia, Jyoti
    Wellcome Sanger Inst, Cambridge, England..
    Koschmieder, Steffen
    Rhein Westfal TH Aachen, Fac Med, Dept Hematol Oncol Hemostaseol & Stem Cell Transp, Aachen, Germany..
    Rumi, Elisa
    Univ Pavia, Dept Mol Med, Pavia, Italy..
    Barbui, Tiziano
    Res Fdn Papa Giovanni XXIII Hosp, I-24127 Bergamo, Italy..
    Unmet clinical needs in the management of CALR-mutated essential thrombocythaemia: a consensus-based proposal from the European LeukemiaNet2021Inngår i: The Lancet Haematology, E-ISSN 2352-3026, Vol. 8, nr 9, s. E658-E665Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Recommendations regarding management of essential thrombocythaemia rely on studies done before the discovery of the CALR mutation. On May 20, 2020, the European LeukemiaNet annual meeting was held with the goal to identify unmet clinical needs in myeloproliferative neoplasms. Because patients with a CALR mutation have specific clinical characteristics, treatment of CALR-mutated essential thrombocythaemia was considered an unmet clinical need by the European LeukemiaNet. The elaboration of a consensus document with recommendations according to current evidence was proposed as a solution for resolving uncertainties in the treatment of CALR-mutated essential thrombocythaemia. A steering committee comprising four European LeukemiaNet members was then formed and a panel of ten experts in the field was recruited. The experts proposed 51 potential unmet clinical needs in the management of CALR-mutated essential thrombocythaemia and were asked to score the relevance of each topic. Those topics that obtained the highest scores as relevant unmet clinical needs were identified, including antiplatelet therapy in patients at low risk, definition of extreme thrombocytosis and its management in patients at low risk, indications of cytoreduction and targets of therapy, first-line treatment of choice in young patients (<60 years), and management of pregnancy. After the steering committee revised the available evidence for each topic, a consensus on management and proposal for improving knowledge was achieved by use of an email-based, two round, Delphi approach. Consensus was achieved when 90% of the panellists agreed with a statement and included 14 recommendations and six solution proposals. Key recommendations included careful observation for asymptomatic patients with classical, low-risk, CALR-mutated essential thrombocythaemia without cardiovascular risk factors; caution in the use of antiplatelet therapy for symptomatic patients at low risk with platelet counts of 1000-1500 × 109 platelets per L, in such cases cytoreduction is an adequate option, especially if adquired Von Willebrand disease is present; cytoreduction is recommended for extreme thrombocytosis (platelet count >1500 × 109 platelets per L) with pegylated interferon alfa being the preferred option for younger patients; both hydroxycarbamide and anagrelide might be given to patients ineligible for pegylated interferon alfa; and treatment algorithms for patients with high-risk pregnancies should not be changed according to genotype. The European LeukemiaNet proposes to use these recommendations in the routine management of patients with CALR-mutated essential thrombocythaemia, and designing new clinical studies in this field might be useful. 

  • 14.
    Amin, Kawa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi. Dept. of Microbiology/Immunology, University of Sulaimani, Sulaimani, Iraq.
    Hurst, David S
    Roomans, Godfried M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Sveus, Lahja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Eosinophils and neutrophils in biopsies from the middle ear of atopic children with otitis media with effusion1999Inngår i: Inflammation Research, ISSN 1023-3830, E-ISSN 1420-908X, Vol. 48, nr 12, s. 626-631, artikkel-id 10669113Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE AND DESIGN:

    The majority of patients with otitis media with effusion (OME) and atopy have been shown to have elevated levels of eosinophil cationic protein (ECP) in their middle ear fluid. The mechanism underlying these elevated levels of ECP is not clear. The purpose of this study was to investigate the feasibility of a quantitative determination of eosinophils and neutrophils in the middle ear lining by specific immunocytochemical markers, in order to study the extent of the involvement of these cells in patients with OME.

    METHODS:

    Bilateral middle ear biopsies from five children with persistent OME and atopy confirmed by in vitro testing were evaluated for the presence of eosinophils and neutrophils with monoclonal antibodies against specific granule proteins. Five subjects who had no signs of effusion or infection but were undergoing routine tympanoplasty for dry perforations served as controls. The biopsies were embedded in a plastic resin to improve the structural preservation of the target cells and to increase the resolution in the light microscope. Dual markers were used to determine which marker was better for eosinophils and neutrophils, respectively. The following markers were used: eosinophil cationic protein (EG2), and eosinophil peroxidase (EPO) for eosinophils and myeloperoxidase (MPO) and human neutrophil lipocalin (HNL) for neutrophils.

    RESULTS:

    Antibodies against EPO gave a more localized and intense staining than antibodies against EG2. Antibodies against HNL appear more specific to neutrophils than antibodies against MPO that also recognize monocytes. The number of cells was determined both in the tissue and in the mucus covering the epithelium. Eosinophils and neutrophils were present in the subepithelial connective tissue and in the mucus blanket in the middle ear of patients with OME in significantly higher number than in the control group. In general, there were more inflammatory cells in the mucus than in the tissue itself, but the number of inflammatory cells in the mucus showed a significant positive correlation with the number of inflammatory cells in the tissue. There was a significant positive correlation between the number of neutrophils and the number of eosinophils in the tissue as well as in the mucus, irrespective of which marker was used.

    CONCLUSION:

    The results of this study show the feasibility of using specific antibodies to identify eosinophils and neutrophils in the middle ear. The initial data suggest that atopic children with OME have higher numbers of such cells as compared to non-OME controls.

  • 15.
    Anande, Govardhan
    et al.
    Univ New South Wales Sydney, Adult Canc Program, Lowy Canc Res Ctr, Sydney, NSW, Australia.;Univ New South Wales Sydney, Prince Wales Clin Sch, Sydney, NSW, Australia..
    Deshpande, Nandan P.
    Univ New South Wales Sydney, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia..
    Mareschal, Sylvain
    Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Batcha, Aarif M. N.
    Ludwig Maximilians Univ Munchen, Fac Med, Inst Med Data Proc Biometr & Epidemiol, Munich, Germany.;Ludwig Maximilians Univ Munchen, Data Integrat Future Med, Munich, Germany..
    Hampton, Henry R.
    Univ New South Wales Sydney, Adult Canc Program, Lowy Canc Res Ctr, Sydney, NSW, Australia.;Univ New South Wales Sydney, Prince Wales Clin Sch, Sydney, NSW, Australia..
    Herold, Tobias
    Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Med 3, Munich, Germany.;Helmholtz Zentrum Munchen, Res Unit Apoptosis Hematopoiet Stem Cells, German Res Ctr Environm Hlth, Munich, Germany..
    Lehmann, Sören
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi. Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Wilkins, Marc R.
    Univ New South Wales Sydney, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia..
    Wong, Jason W. H.
    Univ New South Wales Sydney, Adult Canc Program, Lowy Canc Res Ctr, Sydney, NSW, Australia.;Univ New South Wales Sydney, Prince Wales Clin Sch, Sydney, NSW, Australia.;Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, Hong Kong, Peoples R China..
    Unnikrishnan, Ashwin
    Univ New South Wales Sydney, Adult Canc Program, Lowy Canc Res Ctr, Sydney, NSW, Australia.;Univ New South Wales Sydney, Prince Wales Clin Sch, Sydney, NSW, Australia..
    Pimanda, John E.
    Univ New South Wales Sydney, Adult Canc Program, Lowy Canc Res Ctr, Sydney, NSW, Australia.;Univ New South Wales Sydney, Prince Wales Clin Sch, Sydney, NSW, Australia.;Univ New South Wales Sydney, Sch Med Sci, Dept Pathol, Sydney, NSW, Australia.;Prince Wales Hosp, Dept Haematol, Sydney, NSW, Australia..
    RNA Splicing Alterations Induce a Cellular Stress Response Associated with Poor Prognosis in Acute Myeloid Leukemia2020Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 26, nr 14, s. 3597-3607Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: RNA splicing is a fundamental biological process that generates protein diversity from a finite set of genes. Recurrent somatic mutations of splicing factor genes are common in some hematologic cancers but are relatively uncommon in acute myeloid leukemia (AML, < 20% of patients). We examined whether RNA splicing differences exist in AML, even in the absence of splicing factor mutations.

    Experimental Design: We developed a bioinformatics pipeline to study alternative RNA splicing in RNA-sequencing data from large cohorts of patients with AML.

    Results: We have identified recurrent differential alternative splicing between patients with poor and good prognosis. These splicing events occurred even in patients without any discernible splicing factor mutations. Alternative splicing recurrently occurred in genes with specific molecular functions, primarily related to protein translation. Developing tools to predict the functional impact of alternative splicing on the translated protein, we discovered that approximately 45% of the splicing events directly affected highly conserved protein domains. Several splicing factors were themselves misspliced and the splicing of their target transcripts were altered. Studying differential gene expression in the same patients, we identified that alternative splicing of protein translation genes in ELNAdv patients resulted in the induction of an integrated stress response and upregulation of inflammation-related genes. Finally, using machine learning techniques, we identified a splicing signature of four genes which refine the accuracy of existing risk prognosis schemes and validated it in a completely independent cohort.

    Conclusions: Our discoveries therefore identify aberrant alternative splicing as a molecular feature of adverse AML with clinical relevance.

  • 16. Andersen, Christen L.
    et al.
    McMullin, Mary F.
    Ejerblad, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Zweegman, Sonja
    Harrison, Claire
    Fernandes, Savio
    Bareford, David
    Knapper, Steven
    Samuelsson, Jan
    Loefvenberg, Eva
    Linder, Olle
    Andreasson, Bjorn
    Ahlstrand, Erik
    Jensen, Morten K.
    Bjerrum, Ole W.
    Vestergaard, Hanne
    Larsen, Herdis
    Klausen, Tobias W.
    Mourits-Andersen, Torben
    Hasselbalch, Hans C.
    A phase II study of vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia2013Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 162, nr 4, s. 498-508Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 17. Andersen, Christen Lykkegaard
    et al.
    Bjorn, Mads Emil
    McMullin, Mary Frances
    Harrison, Claire
    Samuelsson, Jan
    Ejerblad, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Zweegman, Sonja
    Fernandes, Savio
    Bareford, David
    Knapper, Steven
    Lofvenberg, Eva
    Linder, Olle
    Andreasson, Bjorn
    Ahlstrand, Erik
    Jensen, Morten Krogh
    Bjerrum, Ole Weis
    Vestergaard, Hanne
    Larsen, Herdis
    Klausen, Tobias Wirenfeldt
    Mourits-Andersen, Torben
    Skov, Vibe
    Thomassen, Mads
    Kruse, Torben
    Gronbaek, Kirsten
    Hasselbalch, Hans Carl
    Circulating YKL-40 in patients with essential thrombocythemia and polycythemia vera treated with the novel histone deacetylase inhibitor vorinostat2014Inngår i: Leukemia Research, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 38, nr 7, s. 816-821Artikkel i tidsskrift (Fagfellevurdert)
    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. (C) 2014 Elsevier Ltd. All rights reserved.

  • 18.
    Angenendt, Linus
    et al.
    Univ Hosp Munster, Munster, Germany.
    Röllig, Christoph
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Montesinos, Pau
    Hosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain.
    Martinez-Cuadron, David
    Hosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain.
    Barragan, Eva
    Hosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain.
    Garcia, Raimundo
    Gen Hosp Castellon, Castellon de La Plana, Spain.
    Botella, Carmen
    Hosp Gen Alicante, Alicante, Spain.
    Martinez, Pilar
    Hosp 12 Octubre, Madrid, Spain.
    Ravandi, Farhad
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Kadia, Tapan
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Kantarjian, Hagop M.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Cortes, Jorge
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Juliusson, Gunnar
    Lund Univ, Lund, Sweden.
    Lazarevic, Vladimir
    Lund Univ, Lund, Sweden.
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Lehmann, Sören
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Recher, Christian
    CHU Toulouse, Toulouse, France.
    Pigneux, Arnaud
    CHU Bordeaux, Hop Haut Leveque, Bordeaux, France.
    Bertoli, Sarah
    CHU Toulouse, Toulouse, France.
    Dumas, Pierre-Yves
    CHU Bordeaux, Hop Haut Leveque, Bordeaux, France.
    Dombret, Herve
    Paris Diderot Univ, Paris, France.
    Preudhomme, Claude
    Inst Natl Sante & Rech Med Lille, Lille, France.
    Micol, Jean-Baptiste
    Paris Saclay Univ, Gustave Roussy, Villejuif, France.
    Terre, Christine
    Ctr Transfus Sanguine, Le Chesnay, France.
    Racil, Zdenek
    Masaryk Univ, Univ Hosp Brno, Brno, Czech Republic.
    Novak, Jan
    Charles Univ Prague, Univ Hosp Kralovske Vinohrady, Fac Med 3, Prague, Czech Republic.
    Zak, Pavel
    Charles Univ Prague, Univ Hosp Hradec Kralove, Hradec Kralove, Czech Republic.
    Wei, Andrew H.
    Monash Univ, Alfred Hosp, Melbourne, Vic, Australia.
    Tiong, Ing S.
    Monash Univ, Alfred Hosp, Melbourne, Vic, Australia.
    Wall, Meaghan
    St Vincents Hosp, Melbourne, Vic, Australia.
    Estey, Elihu
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
    Shaw, Carole
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
    Exeler, Rita
    Univ Munster, Munster, Germany.
    Wagenführ, Lisa
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Stölzel, Friedrich
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Thiede, Christian
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Stelljes, Matthias
    Univ Hosp Munster, Munster, Germany.
    Lenz, Georg
    Univ Hosp Munster, Munster, Germany.
    Mikesch, Jan-Henrik
    Univ Hosp Munster, Munster, Germany.
    Serve, Hubert
    Univ Hosp Frankfurt, Frankfurt, Germany.
    Ehninger, Gerhard
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Berdel, Wolfgang E.
    Univ Hosp Munster, Munster, Germany.
    Kramer, Michael
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Krug, Utz
    Klinikum Leverkusen, Leverkusen, Germany.
    Schliemann, Christoph
    Univ Hosp Munster, Munster, Germany.
    Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia: A Pooled Analysis of Individual Patient Data From Nine International Cohorts2019Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 37, nr 29, s. 2632-2642Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Nucleophosmin 1 (NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITDneg) or present with a low allelic ratio (FLT3-ITDlow). The 2017 European LeukemiaNet guidelines assume this is true regardless of accompanying cytogenetic abnormalities. We investigated the validity of this assumption.

    METHODS: We analyzed associations between karyotype and outcome in intensively treated patients with NPM1(mut)/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers.

    RESULTS: Among 2,426 patients with NPM1(mut)/FLT3-ITDneg/low AML, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. In patients with NPM1(mut)/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P < .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P < .001), and a higher 5-year cumulative incidence of relapse (43.6%, 44.2%, 51.9%, respectively; P = .0012). These associations remained in multivariable mixed-effects regression analyses adjusted for known clinicopathologic risk factors (P < .001 for all end points). In patients with adverse-risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome.

    CONCLUSION: Karyotype abnormalities are significantly associated with outcome in NPM1(mut)/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1(mut) share the same unfavorable prognosis as patients with NPM1 wild type and should be classified and treated accordingly. Thus, cytogenetic risk predominates over molecular risk in NPM1(mut)/FLT3-ITDneg/low AML.

  • 19.
    Antoni, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Estrada, Sergio
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Axelsson, Jan
    Carlson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Lindsjö, Lars
    Kero, Tanja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Granstam, Sven-Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Rosengren, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Vedin, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Wassberg, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    In Vivo Visualization of Amyloid Deposits in the Heart with 11C-PIB and PET2013Inngår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 54, nr 2, s. 213-220Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cardiac amyloidosis is a differential diagnosis in heart failure and is associated with high mortality. There is currently no noninvasive imaging test available for specific diagnosis. N-[methyl-11C]2-(4′-methylamino-phenyl)-6-hydroxybenzothiazole (11C-PIB) PET is used in the evaluation of brain amyloidosis. We evaluated the potential use of 11C-PIB PET in systemic amyloidosis affecting the heart.

    Methods:

    Patients (n = 10) diagnosed with systemic amyloidosis—including heart involvement of either monoclonal immunoglobulin light-chain (AL) or transthyretin (ATTR) type—and healthy volunteers (n = 5) were investigated with PET/CT using 11C-PIB to study cardiac amyloid deposits and with 11C-acetate to measure myocardial blood flow to study the impact of global and regional perfusion on PIB retention.

    Results:

    Myocardial 11C-PIB uptake was visually evident in all patients 15–25 min after injection and was not seen in any volunteer. A significant difference in 11C-PIB retention in the heart between patients and healthy controls was found. The data indicate that myocardial amyloid deposits in patients diagnosed with systemic amyloidosis could be visualized with 11C-PIB. No correlation between 11C-PIB retention index and myocardial blood flow as measured with 11C-acetate was found on the global level, whereas a positive correlation on the segmental level was seen in a single patient.

    Conclusion:

    11C-PIB and PET could be a method to study systemic amyloidosis of type AL and ATTR affecting the heart and should be investigated further both as a diagnostic tool and as a noninvasive method for treatment follow-up.

  • 20. Armuand, Gabriela M.
    et al.
    Rodriguez-Wallberg, Kenny A.
    Wettergren, Lena
    Ahlgren, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Lampic, Claudia
    Sex Differences in Fertility-Related Information Received by Young Adult Cancer Survivors2012Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, nr 17, s. 2147-2153Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose The aim was to investigate male and female cancer survivors' perception of fertility-related information and use of fertility preservation (FP) in connection with cancer treatment during reproductive age.

    Methods The study sample consisted of cancer survivors diagnosed from 2003 to 2007 identified in population-based registers in Sweden. Inclusion criteria included survivors who were age 18 to 45 years at diagnosis and had lymphoma, acute leukemia, testicular cancer, ovarian cancer, or female breast cancer treated with chemotherapy. Of 810 eligible participants, 484 survivors (60% response rate) completed a postal questionnaire.

    Results The majority of male participants reported having received information about treatment impact on fertility (80%) and FP (68%), and more than half of the men banked frozen sperm (54%). Among women, less than half (48%) reported that they received information about treatment impact on fertility, and 14% reported that they received information about FP. Only seven women (2%) underwent FP. Predictors for receiving information about treatment impact on fertility were a pretreatment desire to have children (odds ratio [OR], 3.5), male sex (OR, 3.2), and being <= 35 years of age at diagnosis (OR, 2.0). Predictors for receiving information about FP included male sex (OR, 14.4), age <= 35 at diagnosis (OR, 5.1), and having no children at diagnosis (OR, 2.5).

    Conclusion Our results show marked sex differences regarding the receipt of fertility-related information and use of FP. There is an urgent need to develop fertility-related information adapted to female patients with cancer to improve their opportunities to participate in informed decisions regarding their treatment and future reproductive ability.

  • 21. Baccarani, Michele
    et al.
    Deininger, Michael W.
    Rosti, Gianantonio
    Hochhaus, Andreas
    Soverini, Simona
    Apperley, Jane F.
    Cervantes, Francisco
    Clark, Richard E.
    Cortes, Jorge E.
    Guilhot, Francois
    Hjorth-Hansen, Henrik
    Hughes, Timothy P.
    Kantarjian, Hagop M.
    Kim, Dong-Wook
    Larson, Richard A.
    Lipton, Jeffrey H.
    Mahon, Francois-Xavier
    Martinelli, Giovanni
    Mayer, Jiri
    Mueller, Martin C.
    Niederwieser, Dietger
    Pane, Fabrizio
    Radich, Jerald P.
    Rousselot, Philippe
    Saglio, Giuseppe
    Saussele, Susanne
    Schiffer, Charles
    Silver, Richard
    Simonsson, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Steegmann, Juan-Luis
    Goldman, John M.
    Hehlmann, Ruediger
    European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 20132013Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, nr 6, s. 872-884Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors, mandate regular updating of concepts and management. A European LeukemiaNet expert panel reviewed prior and new studies to update recommendations made in 2009. We recommend as initial treatment imatinib, nilotinib, or dasatinib. Response is assessed with standardized real quantitative polymerase chain reaction and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels <= 10% at 3 months, <1% at 6 months, and <= 0.1% from 12 months onward define optimal response, whereas >10% at 6 months and >1% from 12 months onward define failure, mandating a change in treatment. Similarly, partial cytogenetic response (PCyR) at 3 months and complete cytogenetic response (CCyR) from 6 months onward define optimal response, whereas no CyR (Philadelphia chromosome-positive [Ph1]>95%) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward define failure. Between optimal and failure, there is an intermediate warning zone requiring more frequent monitoring. Similar definitions are provided for response to second-line therapy. Specific recommendations are made for patients in the accelerated and blastic phases, and for allogeneic stem cell transplantation. Optimal responders should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved. (Blood. 2013; 122(6):872-884)

  • 22. Baccarani, Michele
    et al.
    Hoffmann, Verena Sophia
    Rosti, Gianantonio
    Castagnetti, Fausto
    Saussele, Susanne
    Guilhot, Joelle
    Simonsson, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Steegmann, Juan Luis
    Mayer, Jiri
    Indrak, Karel
    Turkina, Anna G.
    Zaritskey, Andrey
    Labar, Boris
    Zupan, Irena
    Thielen, Noortje
    Clark, Richard E.
    Thaler, Josef
    Melanthiou, Frederiki
    Everaus, Hele
    Porkka, Kimmo
    Bogdanovic, Andrija
    Schubert-Fritschle, Gabriel
    Panagiotidis, Panagiotis
    Masszi, Tamas
    Lejniece, Sandra
    Griskevicius, Laimonas
    Hellmann, Andrzej
    Prejzner, Witold
    Sacha, Tomasz
    Almeida, Antonio
    Dyagil, Irina
    Colita, Adriana
    Mihaylov, Georgi G.
    Hehlmann, Rudiger
    Hasford, Joerg
    Lindoerfer, Doris
    Baseline Characteristics of CML Patients Accross Europe - Comparing Real-World Patients with Patient Collectives Included in Clinical Trials2014Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, nr 21Artikkel i tidsskrift (Annet vitenskapelig)
  • 23.
    Baliakas, Panagiotis
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Hadzidimitriou, A.
    Inst Appl Biosci, Thessaloniki, Greece..
    Minga, E.
    Inst Appl Biosci, Thessaloniki, Greece..
    Agathangelidis, A.
    Univ Vita Salute San Raffaele, Milan, Italy.;Ist Sci San Raffaele, Div Expt Oncol, Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, Milan, Italy..
    Sutton, L. A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Scarfo, L.
    Univ Vita Salute San Raffaele, Milan, Italy.;Ist Sci San Raffaele, Div Expt Oncol, Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, Milan, Italy..
    Davis, Z.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Yan, X. J.
    Northwell Hlth, Feinstein Inst Med Res, New York, NY USA..
    Plevova, K.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Sandberg, Y.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Vojdeman, F. Juhl
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Tzenou, T.
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Chu, C. C.
    Northwell Hlth, Feinstein Inst Med Res, New York, NY USA..
    Veroneze, S.
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Mansouri, Larry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Smedby, K. E.
    Dept Med, Solna, Sweden.;Karolinska Inst, Clin Epidemiol Unit, Stockholm, Sweden..
    Giudicelli, V.
    Univ Montpellier, IMGT, LIGM, IGH, Montpellier, France..
    Nguyen-Khac, F.
    Dept Hematol, Paris, France.;Univ Paris 06, Hop Pitie Salpetriere, Paris, France..
    Panagiotidis, P.
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Juliusson, G.
    Lund Univ, Lund, Sweden.;Lund Stem Cell Ctr, Hosp Dept Hematol, Lund, Sweden..
    Anagnostopoulos, A.
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Lefranc, M. P.
    Univ Montpellier, IMGT, LIGM, IGH, Montpellier, France..
    Trentin, L.
    Univ Padua, Dept Med, Hematol & Clin Immunol Branch, Sch Med, Padua, Italy.;Venetian Inst Mol Med, Padua, Italy..
    Catherwood, M.
    Belfast City Hosp, Dept Hematooncol, Belfast, Antrim, North Ireland..
    Montillo, M.
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Niemann, C. U.
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Langerak, A. W.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Pospisilova, S.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Stavroyianni, N.
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Chiorazzi, N.
    Northwell Hlth, Feinstein Inst Med Res, New York, NY USA..
    Oscier, D.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Jelinek, D. F.
    Mayo Clin, Dept Immunol, Rochester, MN USA..
    Shanafelt, T.
    Mayo Clin, Dept Med, Div Hematol, Rochester, MN USA..
    Darzentas, N.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Belessi, C.
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Davi, F.
    Dept Hematol, Paris, France.;Univ Paris 06, Hop Pitie Salpetriere, Paris, France..
    Ghia, P.
    Univ Vita Salute San Raffaele, Milan, Italy.;Ist Sci San Raffaele, Div Expt Oncol, Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, Milan, Italy..
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    No Improvement In Long-Term Overall Survival After The Introduction Of Chemo(Immuno)Therapy For Chronic Lymphocytic Leukemia Patients Belonging To Stereotyped Subset #22016Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, s. 231-231Artikkel i tidsskrift (Annet vitenskapelig)
  • 24.
    Baliakas, Panagiotis
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Hadzidimitriou, Anastasia
    Inst Appl Biosci, Thessaloniki, Greece..
    Minga, Eva
    Inst Appl Biosci, Thessaloniki, Greece..
    Agathangelidis, Andreas
    Inst Appl Biosci, Thessaloniki, Greece.;Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS San Raffaele Sci Inst, Div Expt Oncol, Strateg Res Program CLL, Milan, Italy..
    Sutton, Lesley Ann
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Scarfo, Lydia
    Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS San Raffaele Sci Inst, Div Expt Oncol, Strateg Res Program CLL, Milan, Italy..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Yan, Xiao-Jie
    Northwell Hlth, Feinstein Inst Med Res, New York, NY USA..
    Plevova, Karla
    CEITEC Cent European Inst Technol, Masarykbrno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Sandberg, Yorick
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Vojdeman, Fie J.
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Tzenou, Tatiana
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Chu, Charles C.
    Northwell Hlth, Feinstein Inst Med Res, New York, NY USA..
    Veronese, Silvio
    Osped Niguarda Ca Granda, Mol Pathol Unit, Niguarda Canc Ctr, Milan, Italy.;Osped Niguarda Ca Granda, Dept Haematol, Niguarda Canc Ctr, Milan, Italy..
    Mansouri, Larry
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Smedby, Karin E.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden..
    Giudicelli, Veronique
    Univ Montpellier, Lab ImmunoGenet Mol LIGM, IMGT, IGH,UPR CNRS 1142, Montpellier, France..
    Nguyen-Khac, Florence
    Hematol Dept, Paris, France.;Univ Paris 06, Hop Pitie Salpetriere, Paris, France..
    Panagiotidis, Panagiotis
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Juliusson, Gunnar
    Lund Univ & Hosp, Dept Hematol, Lund Stem Cell Ctr, Lund, Sweden..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Lefranc, Marie-Paule
    Univ Montpellier, Lab ImmunoGenet Mol LIGM, IMGT, IGH,UPR CNRS 1142, Montpellier, France..
    Trentin, Livio
    Padova Univ, Hematol & Clin Immunol Branch, Dept Med, Sch Med, Padua, Italy.;Venetian Inst Mol Med, Padua, Italy..
    Catherwood, Mark
    Belfast City Hosp, Dept Hematooncol, Belfast, Antrim, North Ireland..
    Montillo, Marco
    Osped Niguarda Ca Granda, Mol Pathol Unit, Niguarda Canc Ctr, Milan, Italy.;Osped Niguarda Ca Granda, Dept Haematol, Niguarda Canc Ctr, Milan, Italy..
    Niemann, Carsten U.
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Langerak, Anton W.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Pospisilova, Sarka
    CEITEC Cent European Inst Technol, Masarykbrno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Chiorazzi, Nicholas
    Northwell Hlth, Feinstein Inst Med Res, New York, NY USA..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Jelinek, Diane F.
    Mayo Clin, Dept Immunol, Rochester, MN USA..
    Shanafelt, Tait
    Mayo Clin, Dept Med, Div Hematol, Rochester, MN USA..
    Darzentas, Nikos
    CEITEC Cent European Inst Technol, Masarykbrno, Czech Republic..
    Belessi, Chrysoula
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Davi, Frederic
    Hematol Dept, Paris, France..
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS San Raffaele Sci Inst, Div Expt Oncol, Strateg Res Program CLL, Milan, Italy..
    Rosenquist, Richard
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy2018Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 103, nr 4, s. E158-E161Artikkel i tidsskrift (Fagfellevurdert)
  • 25.
    Baliakas, Panagiotis
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Rosenquist Brandell, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Prognostic indices in chronic lymphocytic leukaemia: where do we stand how do we proceed?2016Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, nr 4, s. 347-357Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The remarkable clinical heterogeneity in chronic lymphocytic leukaemia (CLL) has highlighted the need for prognostic and predictive algorithms that can be employed in clinical practice to assist patient management and therapy decisions. Over the last 20 years, this research field has been rewarding and many novel prognostic factors have been identified, especially at the molecular genetic level. Whilst detection of recurrent cytogenetic aberrations and determination of the immunoglobulin heavy variable gene somatic hypermutation status have an established role in outcome prediction, next-generation sequencing has recently revealed novel mutated genes with clinical relevance (e.g. NOTCH1, SF3B1 and BIRC3). Efforts have been made to combine variables into prognostic indices; however, none has been universally adopted. Although a unifying model for all groups of patients and in all situations is appealing, this may prove difficult to attain. Alternatively, focused efforts on patient subgroups in the same clinical context and at certain clinically relevant 'decision points', that is at diagnosis and at initiation of first-line or subsequent treatments, may provide a more accurate approach. In this review, we discuss the advantages and disadvantages as well as the clinical applicability of three recently proposed prognostic models, the MD Anderson nomogram, the integrated cytogenetic and mutational model and the CLL-international prognostic index. We also consider future directions taking into account novel aspects of the disease, such as the tumour microenvironment and the dynamics of (sub)clonal evolution. These aspects are particularly relevant in view of the increasing number of new targeted therapies that have recently emerged.

  • 26.
    Baliakas, Panagiotis
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Moreno, Carol
    Hosp Santa Creu & Sant Pau, Barcelona, Spain.
    Cuellar, Carolina
    St Pau Hosp, Barcelona, Spain.
    Scarfo, Lydia
    Osped San Raffaele, Segrate, Italy.
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Milan, Italy; IRCCS Ist Sci San Raffaele, Milan, Italy.
    Brandell, Richard Rosenquist
    Karolinska Inst, Stockholm, Sweden.
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Vicente, Eva Puy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Is FCR the treatment of choice for IGHV mutated CLL without poor FISH cytogenetics?2017Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 58, nr Supplement: 1, s. 170-171Artikkel i tidsskrift (Annet vitenskapelig)
  • 27.
    Barbuil, Tiziano
    et al.
    Osped Giovanni 23, Div Hematol, Bergamo, Italy.
    Tefferi, Ayalew
    Mayo Clin, Dept Med, Div Hematol, Rochester, MN USA.
    Vannucchi, Alessandro M.
    Univ Florence, AOU Careggi, Ctr Res & Innovat Myeloproliferat Neoplasms, CRIMM, Florence, Italy.
    Passamonti, Francesco
    Univ Insubria, Osped Circolo, Dept Med & Surg, Div Hematol,ASST Sette Laghi, Varese, Italy.
    Silvers, Richard T.
    Weill Cornell Med, Div Hematol Oncol, New York, NY USA.
    Hoffman, Ronald
    Mt Sinai Sch Med, Dept Med, Tisch Canc Inst, New York, NY USA.
    Verstovsek, Srdan
    Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
    Mesa, Ruben
    UT Hlth San Antonio Canc Ctr, San Antonio, TX USA.
    Kiladjian, Jean-Jacques
    Univ Paris 07, Hop St Louis, AP HP, INSERM,Ctr Invest Clin CIC 1427, Paris, France.
    Hehlmann, Rudiger
    Heidelberg Univ, Univ Hosp Mannheim, Dept Hematol & Oncol, Mannheim, Germany.
    Reiter, Andreas
    Heidelberg Univ, Univ Hosp Mannheim, Dept Hematol & Oncol, Mannheim, Germany.
    Cervantes, Francisco
    Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain.
    Harrison, Claire
    Guys & St Thomas NHS Fdn Trust, Dept Hematol, London, England.
    Mc Mullin, Mary Frances
    Queens Univ, Ctr Med Educ, Belfast, Antrim, North Ireland.
    Hasselbalch, Hans Carl
    Zealand Univ Hosp, Dept Hematol, Roskilde, Denmark.
    Koschmieder, Steffen
    Rhein Westfal TH Aachen, Fac Med, Dept Hematol Oncol Hemostaseol & Stem Cell Transp, Aachen, Germany.
    Marchetti, Monia
    Hosp Cardinal Massaia, Oncol SOC, Hematol Day Serv, Asti, Italy.
    Bacigalupo, Andrea
    Univ Cattolica Sacro Cuore, Fdn Policlin Univ Gemelli, Ist Ematol, Rome, Italy.
    Finazzil, Guido
    Osped Giovanni 23, Div Hematol, Bergamo, Italy.
    Kroeger, Nicolaus
    Univ Hosp Hamburg Eppendorf, Dept Stem Cell Transplantat, Hamburg, Germany.
    Griesshammer, Martin
    Univ Hannover, Acad Hosp, Johannes Wesling Med Ctr Minden, Dept Hematol & Oncol, Minden, Germany.
    Birgegård, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Barosi, Giovanni
    IRCCS Policlin S Matteo Fdn, Ctr Study Myelofibrosis, Pavia, Italy.
    Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet2018Inngår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 32, nr 5, s. 1057-1069Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    This document updates the recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) published in 2011 by the European LeukemiaNet (ELN) consortium. Recommendations were produced by multiple-step formalized procedures of group discussion. A critical appraisal of evidence by using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was performed in the areas where at least one randomized clinical trial was published. Seven randomized controlled trials provided the evidence base; earlier phase trials also informed recommendation development. Key differences from the 2011 diagnostic recommendations included: lower threshold values for hemoglobin and hematocrit and bone marrow examination for diagnosis of polycythemia vera (PV), according to the revised WHO criteria; the search for complementary clonal markers, such as ASXL1, EZH2, IDH1/IDH2, and SRSF2 for the diagnosis of myelofibrosis (MF) in patients who test negative for JAK2V617, CALR or MPL driver mutations. Regarding key differences of therapy recommendations, both recombinant interferon alpha and the JAK1/JAK2 inhibitor ruxolitinib are recommended as second-line therapies for PV patients who are intolerant or have inadequate response to hydroxyurea. Ruxolitinib is recommended as first-line approach for MF-associated splenomegaly in patients with intermediate-2 or high-risk disease; in case of intermediate-1 disease, ruxolitinib is recommended in highly symptomatic splenomegaly. Allogeneic stem cell transplantation is recommended for transplant-eligible MF patients with high or intermediate-2 risk score. Allogeneic stem cell transplantation is also recommended for transplant-eligible MF patients with intermediate-1 risk score who present with either refractory, transfusion-dependent anemia, blasts in peripheral blood > 2%, adverse cytogenetics, or high-risk mutations. In these situations, the transplant procedure should be performed in a controlled setting.

  • 28. Barosi, G
    et al.
    Tefferi, A
    Besses, C
    Birgegård, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Cervantes, F
    Finazzi, G
    Gisslinger, H
    Griesshammer, M
    Harrison, C
    Hehlmann, R
    Hermouet, S
    Kiladjian, J-J
    Kröger, N
    Mesa, R
    Mc Mullin, M F
    Pardanani, A
    Passamonti, F
    Samuelsson, J
    Vannucchi, A M
    Reiter, A
    Silver, R T
    Verstovsek, S
    Tognoni, G
    Barbui, T
    Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)2015Inngår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 29, nr 1, s. 20-26Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.

  • 29.
    Bergfelt, E.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Kozlowski, P.
    Univ Orebro, Fac Med & Hlth, Dept Med Sci, Haematol, Orebro, Sweden..
    Ahlberg, L.
    Univ Hosp Linkoping, Dept Haematol, Linkoping, Sweden..
    Bernell, P.
    Karolinska Univ, Karolinska Inst, Dept Med, Div Haematol, Stockholm, Sweden..
    Hulegardh, E.
    Sahlgrens Univ Hosp, Dept Haematol & Coagulat, Gothenburg, Sweden..
    Karbach, H.
    Karlsson, K.
    Univ Hosp Umea, Ctr Canc, Dept Haematol, Umea, Sweden.;Skane Univ Hosp, Dept Haematol, Lund, Sweden..
    Tomaszewska-Toporska, B.
    Skane Univ Hosp, Dept Haematol, Lund, Sweden..
    Astrom, M.
    Univ Orebro, Fac Med & Hlth, Dept Med Sci, Haematol, Orebro, Sweden..
    Hallböök, Helene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Relapse Of Acute Lymphoblastic Leukaemia In Older/Elderly Patients - A Swedish Population-Based Study2016Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, s. 34-35Artikkel i tidsskrift (Annet vitenskapelig)
  • 30.
    Bergfelt, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Kozlowski, P.
    Ahlberg, L.
    Hulegardh, E.
    Hägglund, H.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Karlsson, K.
    Markuszewska-Kuczymska, A.
    Tomaszewska-Toporska, B.
    Smedmyr, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Astrom, M.
    Amini, Rose Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Hallböök, Helene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Minimal Residual Disease in Adults with Philadelphia Negative B-Cell Precursor Acute Lymphoblastic Leukemia a Swedish Population-Based Study2014Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, nr S1, s. 279-280Artikkel i tidsskrift (Annet vitenskapelig)
  • 31.
    Bergfelt, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Kozlowski, P.
    Univ Orebro, Fac Med & Hlth, Dept Med, Haematol Sect, SE-70182 Orebro, Sweden..
    Astrom, M.
    Univ Orebro, Fac Med & Hlth, Dept Med, Haematol Sect, SE-70182 Orebro, Sweden..
    Ahlberg, L.
    Linkoping Univ Hosp, Dept Haematol, S-58185 Linkoping, Sweden..
    Bernell, P.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Haematol, Stockholm, Sweden..
    Hulegardh, E.
    Sahlgrens Univ Hosp, Dept Haematol & Coagulat, Gothenburg, Sweden..
    Karbach, H.
    Umea Univ Hosp, Ctr Canc, Dept Haematol, S-90185 Umea, Sweden..
    Karlsson, K.
    Skane Univ Hosp, Dept Haematol, Lund, Sweden..
    Tomaszewska-Toporska, B.
    Skane Univ Hosp, Dept Haematol, Lund, Sweden..
    Hallböök, Helene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    PROGNOSIS IN OLDER/ELDERLY PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKAEMIA DIAGNOSED 2005-2012: RESULTS FROM A SWEDISH POPULATION-BASED STUDY2015Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, s. 202-202Artikkel i tidsskrift (Annet vitenskapelig)
  • 32.
    Bergfelt, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Kozlowski, Piotr
    Ahlberg, Lucia
    Hulegardh, Erik
    Hagglund, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Karlsson, Karin
    Markuszewska-Kuczymska, Alicja
    Tomaszewska-Toporska, Beata
    Smedmyr, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Astrom, Maria
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Hallböök, Hélene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    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 study2015Inngår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 32, nr 4, artikkel-id 135Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 33.
    Bergfelt Lennmyr, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Registry-Based Studies in Adult Acute Lymphoblastic Leukemia in Sweden: Survival and Quality of Life2020Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Acute lymphoblastic leukemia (ALL), a common child malignancy, also constitutes a minor fraction of adult cancer with approximately 50 new cases per year in Sweden. While the five-year overall survival (OS) in pediatric ALL is more than 90%, the prognosis in adults is dismal. Using the Swedish ALL quality registry, this thesis investigates treatment and outcome of adult ALL according to national guidelines. In addition, the introduction of patient-reported outcome in the ALL and Acute Myeloid Leukemia registries is evaluated. 

    In Paper I, measurement of minimal residual disease by flow cytometry was found to be feasible but not consistently applied in the 35 patients with Philadelphia (Ph)-negative B-ALL investigated. In Paper II, treatment, toxicity and outcome of 155 patients, 55-85 years (y) with ALL diagnosis between 2005 and 2012 were studied in detail by patient charts review. An age-adopted protocol recommended from 2009 did not result in better outcome. In Paper III, disease recurrence in the same cohort as Paper II was studied. The median overall survival (OS) after ALL relapse was 3.6 months. In Paper IV, the whole ALL registry was studied and OS was estimated in 930 adult patients diagnosed in the periods 1997-2006 and 2007-2015. Five year OS improved in patients 18-45y from 50% to 65%, in patients 46-65y from 25% to 46%, and in patients >65y from 7% to 11%. This demonstrates that young patients have the best prognosis, in part due to the introduction of a dose-intense “pediatric-like” chemotherapy protocol. Compared to women, middle-aged men were found to have a worse outcome.

    Historically, Philadelphia-positive (Ph-pos) ALL has a poor prognosis compared to Ph-negative ALL. In this material, the frequency of Ph-pos ALL was 34% of examined B-ALL. Analysis of the whole registry revealed that in 2007-2015, i.e. after the introduction of the tyrosine kinase inhibitor imatinib, Ph-pos ALL was no longer associated with inferior OS. In Paper V, ALL and Acute Myeloid Leukemia patients, six months after diagnosis, completed a web or paper questionnaire regarding quality of life, symptoms and experience with care. The response rate was 64%. Depression symptoms were frequent (18%), especially in young women who reported worrying about fertility.

    In summary, although OS in adult ALL has improved, more effective and less toxic therapies in upfront treatment are highly warranted. Collection of patient-reported outcome in a national quality registry is feasible and can add important aspects of cancer care that are not usually addressed.

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  • 34.
    Berggren, Daniel Moreno
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Folkvaljon, Y.
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Engvall, M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Sundberg, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Lehman, Sören
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Lambe, M.
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Antunovic, P.
    Linkoping Univ Hosp, Dept Hematol, Linkoping, Sweden..
    Garelius, H.
    Sahlgrens Univ Hosp, Dept Med, Sect Haematol & Coagulat, Gothenburg, Sweden..
    Hellström-Lindberg, E.
    Karolinska Univ Hosp, Ctr Hematol & Regenerat Med, Stockholm, Sweden..
    Jadersten, M.
    Karolinska Univ Hosp, Ctr Hematol & Regenerat Med, Stockholm, Sweden..
    Lorenz, F.
    Umea Univ, Dept Med Biosci, Umea, Sweden..
    Nilsson, L.
    Skane Univ Hosp, Dept Med, Lund, Sweden..
    Ejerblad, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Validation Of Prognostic Scoring Systems For Myelodysplastic Syndromes In The Swedish Mds-Register2016Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, s. 243-243Artikkel i tidsskrift (Annet vitenskapelig)
  • 35.
    Berggren, Daniel Moreno
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Folkvaljon, Yasin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Engvall, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Sundberg, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Lambe, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Antunovic, Petar
    Linkoping Univ Hosp, Dept Haematol, Linkoping, Sweden.
    Garelius, Hege
    Sahlgrens Univ Hosp, Sect Haematol & Coagulat, Dept Med, Gothenburg, Sweden.
    Lorenz, Fryderyk
    Umea Univ, Dept Med Biosci, Umea, Sweden.
    Nilsson, Lars
    Skane Univ Hosp, Dept Haematol Oncol & Radiat Phys, Lund, Sweden.
    Rasmussen, Bengt
    Orebro Univ Hosp, Sch Med Sci, Orebro, Sweden.
    Lehmann, Sören
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Hellstrom-Lindberg, Eva
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Huddinge, Ctr Haematol & Regenerat Med, Stockholm, Sweden.
    Jadersten, Martin
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Huddinge, Ctr Haematol & Regenerat Med, Stockholm, Sweden.
    Ejerblad, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population-based setting: a report from the Swedish MDS register2018Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 181, nr 5, s. 614-627Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 36.
    Berglund, Eva Caroline
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Barbany, Gisela
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Clin Genet, Solna, Sweden..
    Orsmark-Pietras, Christina
    Div Lab Med, Off Med Serv, Dept Clin Genet & Pathol, Lund, Sweden.;Lund Univ, Dept Lab Med, Div Clin Genet, Lund, Sweden.;Lund Univ, Sci Life Lab, Clin Genom Lund, Lund, Sweden..
    Fogelstrand, Linda
    Sahlgrens Univ Hosp, Dept Clin Chem, Gothenburg, Sweden.;Univ Gothenburg, Inst Biomed, Dept Lab Med, Sci Life Lab,Clin Genom Gothenburg, Gothenburg, Sweden..
    Abrahamsson, Jonas
    Queen Silv Childrens Hosp, Clin Sci, Gothenburg, Sweden..
    Golovleva, Irina
    Univ Umeå, Dept Med Biosci, Umeå, Sweden..
    Hallböök, Helene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Lazarevic, Vladimir
    Skane Univ Hosp, Dept Hematol Oncol & Radiat Phys, Lund, Sweden..
    Levin, Lars-Ake
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Nordlund, Jessica
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Noren-Nystrom, Ulrika
    Umeå Univ, Dept Clin Sci Pediat, Umeå, Sweden..
    Palle, Josefine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Thangavelu, Tharshini
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Palmqvist, Lars
    Sahlgrens Univ Hosp, Dept Clin Chem, Gothenburg, Sweden.;Univ Gothenburg, Inst Biomed, Dept Lab Med, Sci Life Lab,Clin Genom Gothenburg, Gothenburg, Sweden..
    Wirta, Valtteri
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Sci Life Lab, Clin Genom Stockholm, Solna, Sweden..
    Cavelier, Lucia
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Fioretos, Thoas
    Div Lab Med, Off Med Serv, Dept Clin Genet & Pathol, Lund, Sweden.;Lund Univ, Dept Lab Med, Div Clin Genet, Lund, Sweden.;Lund Univ, Sci Life Lab, Clin Genom Lund, Lund, Sweden..
    Rosenquist, Richard
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Clin Genet, Solna, Sweden..
    A Study Protocol for Validation and Implementation of Whole-Genome and -Transcriptome Sequencing as a Comprehensive Precision Diagnostic Test in Acute Leukemias2022Inngår i: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 9, artikkel-id 842507Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background:& nbsp;Whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS), with the ability to provide comprehensive genomic information, have become the focal point of research interest as novel techniques that can support precision diagnostics in routine clinical care of patients with various cancer types, including hematological malignancies. This national multi-center study, led by Genomic Medicine Sweden, aims to evaluate whether combined application of WGS and WTS (WGTS) is technically feasible and can be implemented as an efficient diagnostic tool in patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In addition to clinical impact assessment, a health-economic evaluation of such strategy will be performed.& nbsp.

    Methods and Analysis:& nbsp;The study comprises four phases (i.e., retrospective, prospective, real-time validation, and follow-up) including approximately 700 adult and pediatric Swedish AML and ALL patients. Results of WGS for tumor (90x) and normal/germline (30x) samples as well as WTS for tumors only will be compared to current standard of care diagnostics. Primary study endpoints are diagnostic efficiency and improved diagnostic yield. Secondary endpoints are technical and clinical feasibility for routine implementation, clinical utility, and health-economic impact.& nbsp.

    Discussion:& nbsp;Data from this national multi-center study will be used to evaluate clinical performance of the integrated WGTS diagnostic workflow compared with standard of care. The study will also elucidate clinical and health-economic impacts of a combined WGTS strategy when implemented in routine clinical care.

    Fulltekst (pdf)
    FULLTEXT01
  • 37.
    Besses, C.
    et al.
    Hosp del Mar IMIM, Serv Hematol, Barcelona, Spain..
    Bello-Lopez, J. L.
    Univ Santiago, Hosp Clin, E-15706 Santiago, Spain..
    De la Serna, J.
    Hosp Univ 12 Octubre, Madrid, Spain..
    Hernandez-Boluda, J. C.
    Hosp Clin Univ, Valencia, Spain..
    Loscertales, J.
    Hosp Univ La Princesa, Madrid, Spain..
    Griesshammer, M.
    Johannes Wesling Med Ctr, Serv Hematol & Oncol, Minden, Germany..
    Gugliotta, L.
    St Orsola Malpighi Hosp, Serv Hematol, Bologna, Italy..
    Harrison, C.
    Guys & St Thomas NHS Fdn Trust, Serv Hematol, London, England..
    Kiladjian, J. J.
    Hop St Louis, APHP, Ctr Invest Clin, Paris, France..
    Hamdani, M.
    Shire Pharmaceut, Global Biometr, Wayne, NJ USA..
    Achenbach, H.
    Shire AG, Res & Dev, Eysins, Switzerland..
    Birgegård, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Treatment Of Essential Thrombocythemia In Europe: Observational Study Of 3649 Patients Of High Risk (Exels)2015Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, s. 29-29Artikkel i tidsskrift (Annet vitenskapelig)
  • 38. Besses, Carlos
    et al.
    Kiladjian, Jean-Jacques
    Griesshammer, Martin
    Gugliotta, Luigi
    Harrison, Claire
    Coll, Ruth
    Smith, Jonathan
    Abhyankar, Brihad
    Birgegård, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Cytoreductive treatment patterns for essential thrombocythemia in Europe. Analysis of 3643 patients in the EXELS study2013Inngår i: Leukemia Research, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 37, nr 2, s. 162-168Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    EXELS is an ongoing phase IV non-interventional study; 3643 high-risk patients with essential thrombocythemia (ET) were recruited across 13 European countries. We report patient characteristics and cytoreductive treatment patterns of ET across Europe. Hydroxycarbamide (HC; 64.3%) and anagrelide (22.0%) were the two main cytoreductive treatments prescribed. The proportions of patients taking either HC or anagrelide varied across countries, as did the number of patients receiving anti-aggregatory therapy in addition to cytoreductive treatment. This real-world evidence demonstrates that, generally, treatment patterns of ET across Europe adhere to expert recommendations, with some notable variations between countries.

  • 39.
    Bhoi, Sujata
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Baliakas, Panagiotis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Cortese, Diego
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Sevov, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Smedby, Karin E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Juliusson, Gunnar
    Sutton, Lesley-Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Mansouri, Larry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    UGT2B17 expression: a novel prognostic marker within IGHV-mutated chronic lymphocytic leukemia?2016Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, nr 2, s. E63-E65Artikkel i tidsskrift (Fagfellevurdert)
  • 40.
    Bhoi, Sujata
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ljungström, Viktor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Baliakas, Panagiotis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Smedby, Karin E.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med Solna, Stockholm, Sweden..
    Juliusson, Gunnar
    Lund Univ, Dept Lab Med, Stem Cell Ctr, Hematol & Transplantat, Lund, Sweden..
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mansouri, Larry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Prognostic impact of epigenetic classification in chronic lymphocytic leukemia: The case of subset #22016Inngår i: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 11, nr 6, s. 449-455Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Based on the methylation status of 5 single CpG sites, a novel epigenetic classification of chronic lymphocytic leukemia (CLL) was recently proposed, classifying CLL patients into 3 clinico-biological subgroups with different outcome, termed memory like CLL (m-CLL), naive like CLL (n-CLL), and a third intermediate CLL subgroup (i-CLL). While m-CLL and n-CLL patients at large corresponded to patients carrying mutated and unmutated IGHV genes, respectively, limited information exists regarding the less defined i-CLL group. Using pyrosequencing, we investigated the prognostic impact of the proposed 5 CpG signature in a well-characterized CLL cohort (135 cases), including IGHV-mutated and unmutated patients as well as clinically aggressive stereotyped subset #2 patients. Overall, we confirmed the signature's association with established prognostic markers. Moreover, in the presence of the IGHV mutational status, the epigenetic signature remained independently associated with both time-to-first-treatment and overall survival in multivariate analyses. As a prime finding, we observed that subset #2 patients were predominantly classified as i-CLL, probably reflecting their borderline IGHV mutational status (97-99% germline identity), though having a similarly poor prognosis as n-CLL patients. In summary, we validated the epigenetic classifier as an independent factor in CLL prognostication and provide further evidence that subset #2 is a member of the i-CLL group, hence supporting the existence of a third, intermediate epigenetic subgroup.

  • 41.
    Birgegard, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Does anything work for anaemia in myelofibrosis?2014Inngår i: Baillière's Best Practice & Research: Clinical Haematology, ISSN 1521-6926, E-ISSN 1532-1924, Vol. 27, nr 2, s. 175-185Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Anaemia is a common finding at diagnosis in myelofibrosis, and becomes a symptomatic problem in most patients with time. There are several treatment options for specific anaemia treatment, none of which has been tested in large, randomized, controlled trials. However, as myelofibrosis is not a disease with spontaneous remissions, even non-randomized trials carry weight In this survey, the existing evidence will be analysed, both for the commonly used treatments like erythropoiesis-stimulating agents, androgens and thalidomide and for the new drugs in the area, and conclusions will be drawn concerning standard clinical anaemia treatment in myelofibrosis, which according to evidence from studies has a 40-50% chance of response in patients with not too advanced disease. (C) 2014 Elsevier Ltd. All rights reserved.

  • 42.
    Birgegård, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    15. Anemi och järn2012Inngår i: Blodets sjukdomar: lärobok i hematologi / [ed] Gösta Gahrton & Gunnar Juliusson, Lund: Studentlitteratur, 2012, 1. uppl, s. 195-213Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 43.
    Birgegård, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Advances and challenges in the management of essential thrombocythemia2015Inngår i: Therapeutic advances in hematology, ISSN 2040-6215, Vol. 6, nr 3, s. 142-156Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The new World Health Organization (WHO) diagnostic criteria for essential thrombocythemia (ET) issued in 2008 made an important distinction between true ET and early myelofibrosis (MF), which has helped to identify a more homogenous population for the diagnosis with longer survival and much less transformation to overt MF. The recent finding of a new mutation (CALR), which is mutually exclusive with JAK2 and MPL mutations, adds to the characterization of ET patients, since there are important phenotypic differences between the mutation types. CALR patients are younger, have lower white blood cell counts (WBC) and a lower thrombosis incidence. A growing field of interest is the state of hypercoagulation due to dysfunction of hemostatic systems, cell-cell interaction and hereditary prothrombotic traits. Activation of platelets, WBC and endothelial cells has been found, making the whole intravascular milieu prothrombotic. Several risk score models, based on retrospective studies, have been developed lately, distinguishing patient groups with graded risk for complications and death. Even if these may be helpful in evaluating patients, they have not been validated in prospective studies and there are not enough data to support their use as a basis for treatment algorithms. The traditional risk factors age, previous thrombosis and platelets >1500 × 10(9)/l are still recommended for the distinction between high risk and low risk ET and the decision to give cytoreductive therapy. However, cardiovascular (CV) risk factors add to thrombosis risk and should be considered both for specific treatment in any risk group and for upgrading low risk patients with high CV risk to an intermediary group where active therapy with aspirin and cytoreduction may be considered. First-line cytoreductive therapy differs with age; in younger patients interferon (IFN) or anagrelide are preferable, in older patients hydroxycarbamide (HC). Second-line therapy for younger patients is HC, for older patients IFN or anagrelide (ANA). JAK2 inhibitors may be suitable in rare cases with symptoms not responding to other therapy.

  • 44.
    Birgegård, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Järnbristanemi och sekundär anemi2011Inngår i: Internmedicin / [ed] Ulf Dahlström, Stergios Kechagias & Leif Stenke, Stockholm: Liber, 2011, 5. uppl, s. 365-371Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 45.
    Birgegård, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Pharmacological management of essential thrombocythemia2013Inngår i: Expert Opinion on Pharmacotherapy, ISSN 1465-6566, E-ISSN 1744-7666, Vol. 14, nr 10, s. 1295-1306Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Introduction: Two factors have deeply influenced the area of essential thrombocythemia (ET). A gain-of-function mutation in the pseudokinase region of the JAK2 gene, which partly explains the pathophysiology of myeloproliferative neoplasms (MPNs), was discovered in 2005 and is present in 50 - 60% of ET patients. Furthermore, the 2008 WHO MPN classification outlined criteria for the separation of ET and early or prefibrotic primary myelofibrosis (PMF). However, these and other new findings have not yet changed the pharmacotherapy of ET, which is based on risk stratification for thrombohemorrhagic risk and aims to reduce thrombosis and bleeding. Areas covered: Studies on the basis for and the validation of the WHO classification as well as studies on possible new risk factors are covered. The most important drugs for ET treatment and consensus recommendations for management of ET are also presented. Expert opinion: The new WHO classification should be used for both ET studies and clinical practice, since true ET has a different prognosis than early PMF. The management of patients should be based on risk stratification. Age >60 years or previous throbosis (high risk) and platelet counts >1500 x 10(9)/l warrant cytoreductive treatment, and high risk patients and selected low risk patients should be given anti-aggregation therapy.

  • 46.
    Birgegård, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    The Use of Anagrelide in Myeloproliferative Neoplasms, with Focus on Essential Thrombocythemia2016Inngår i: Current Hematologic Malignancy Reports, ISSN 1558-8211, E-ISSN 1558-822X, Vol. 11, nr 5, s. 348-355Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Anagrelide (ANA) is a drug with specific platelet-lowering activity, used primarily in ET, registered as a second-line drug in essential thrombocythemia (ET) in Europe and in some countries as first-line therapy, in USA licensed by FDA for thrombocythemia in myeloproliferative neoplasms (MPN). The platelet-lowering efficacy is similar to that of hydroxycarbamide (HC), around 70 % complete response and 90 % partial response. Side effects are common, especially headache and tachycardia, but usually subside or disappear within a few weeks. Around 20 % of patients stop ANA therapy due to side effects or insufficient response. Studies of treatment patterns in Europe show that ANA is preferentially given to younger patients, probably because of the concern for a possible leukemogenic effect of the common first-line drug, HC. Only two randomized studies have compared the efficacy of ANA and HC in preventing thrombosis and haemorrhage, the larger of them showing a slightly better efficacy of HC, the other showing non-inferiority of ANA to HC. A recent observational 5-year study of 3600 patients shows a low and basically similar efficacy of ANA and other cytoreductive therapies in ET. ANA does not appear to inhibit fibrosis development, and probably due to its anticoagulation properties, the combination of ASA and ANA produces an increased rate of haemorrhage. Combination of ANA with HC or interferon (IFN) is feasible and effective in patients with insufficient platelet response to mono-therapy.

    Fulltekst (pdf)
    fulltext
  • 47.
    Birgegård, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Övriga myeloproliferativa Sjukdomar2011Inngår i: Internmedicin / [ed] Ulf Dahlström, Stergios Kechagias & Leif Stenke, Stockholm: Liber, 2011, 5. uppl, s. 410-418Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 48.
    Birgegård, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Besses, C.
    Hosp del Mar, IMIM, Dept Haematol, Barcelona, Spain..
    Griesshammer, M.
    Johannes Wesling Med Ctr, Hematol & Oncol, Minden, Germany..
    Gugliotta, L.
    St Orsola Malpighi Hosp, Dept Haematol, L & A Seragnoli, Bologna, Italy..
    Harrison, C.
    Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England..
    Hamdani, M.
    Shire Pharmaceut, Global Biometr, Wayne, NJ USA..
    Achenbach, H.
    Shire GmbH, Res & Dev, Zug, Switzerland..
    Kiladjian, J. -J
    RISK FACTORS FOR THROMBOHEMORRHAGIC AND TRANSFORMATION EVENTS IN 3649 HIGH-RISK PATIENTS WITH ESSENTIAL THROMBOCYTHEMIA: RESULTS FROM THE PROSPECTIVE LONG-TERM OBSERVATIONAL EXELS STUDY2015Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, s. 160-161Artikkel i tidsskrift (Annet vitenskapelig)
  • 49.
    Birgegård, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Besses, C.
    Hosp del Mar, IMIM, Dept Haematol, Barcelona, Spain..
    Griesshammer, M.
    Johannes Wesling Med Ctr, Hematol & Oncol, Minden, Germany..
    Gugliotta, L.
    St Orsola Malpighi Hosp, Dept Haematol, L&A Seragnoli, Bologna, Italy..
    Harrison, C.
    Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England..
    Hamdani, M.
    Shire Pharmaceut, Global Biometr, Wayne, PA USA..
    Achenbach, H.
    Shire AG, Res & Dev, Eysins, Switzerland..
    Kiladjian, J-J
    Hop St Louis, APHP, Ctr Invest Clin, Paris, France..
    Treatment of high risk ET: data from the EXELS study2016Inngår i: Leukemia Research, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 44, s. S7-S8Artikkel i tidsskrift (Annet vitenskapelig)
  • 50.
    Birgegård, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Besses, Carlos
    Griesshammer, Martin
    Gugliotta, Luigi
    Harrison, Claire N.
    Hamdani, Mohamed
    Achenbach, Heinrich
    Kiladjian, Jean-Jacques
    Treatment of Essential Thrombocythemia in Europe: An Observational Study of 3649 High-Risk Patients in Exels2014Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, nr 21Artikkel i tidsskrift (Annet vitenskapelig)
1234567 1 - 50 of 599
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