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  • 1. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Steegmann, Juan-Luis
    Goldman, John M.
    Hehlmann, Ruediger
    European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 20132013In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, no 6, p. 872-884Article, review/survey (Refereed)
    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)

  • 2. Baccarani, Michele
    et al.
    Hoffmann, Verena Sophia
    Rosti, Gianantonio
    Castagnetti, Fausto
    Saussele, Susanne
    Guilhot, Joelle
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    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 Trials2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 3. Baccarani, Michele
    et al.
    Saglio, Giuseppe
    Goldman, John
    Hochhaus, Andreas
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Appelbaum, Frederick
    Apperley, Jane
    Cervantes, Francisco
    Cortes, Jorge
    Deininger, Michael
    Gratwohl, Alois
    Guilhot, Francois
    Horowitz, Mary
    Hughes, Timothy
    Kantarjian, Hagop
    Larson, Richard
    Niederwieser, Dietger
    Silver, Richard
    Hehlmann, Rudiger
    Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet2006In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 108, no 6, p. 1809-1820Article in journal (Refereed)
    Abstract [en]

    The introduction of imatinib mesylate (IM) has revolutionized the treatment of chronic myeloid leukemia (CML). Although experience is too limited to permit evidence-based evaluation of survival, the available data fully justify critical reassessment of CML management. The panel therefore reviewed treatment of CML since 1998. It confirmed the value of IM (400 mg/day) and of conventional allogeneic hematopoietic stem cell transplantation (alloHSCT). It recommended that the preferred initial treatment for most patients newly diagnosed in chronic phase should now be 400 mg IM daily. A dose increase of IM, alloHSCT, or investigational treatments were recommended in case of failure, and could be considered in case of suboptimal response. Failure was defined at 3 months (no hematologic response [HR]), 6 months (incomplete HR or no cytogenetic response [CgR]), 12 months (less than partial CgR [Philadelphia chromosome-positive (Ph(+)) > 35%]), 18 months (less than complete CgR), and in case of HR or CgR loss, or appearance of highly IM-resistant BCR-ABL mutations. Suboptimal response was defined at 3 months (incomplete HR), 6 months (less than partial CgR), 12 months (less than complete CgR), 18 months (less than major molecular response [MMolR]), and, in case of MMolR loss, other mutations or other chromosomal abnormalities. The importance of regular monitoring at experienced centers was highlighted.

  • 4. Brune, Mats
    et al.
    Castaigne, Sylvie
    Catalano, John
    Gehlsen, Kurt
    Ho, Anthony D.
    Hofmann, Wolf-Karsten
    Hogge, Donna E.
    Nilsson, Bo
    Or, Reuven
    Romero, Ana I.
    Rowe, Jacob M.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Spearing, Ruth
    Stadtmauer, Edward A.
    Szer, Jeff
    Wallhult, Elisabeth
    Hellstrand, Kristoffer
    Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial2006In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 108, no 1, p. 88-96Article in journal (Other academic)
    Abstract [en]

    The primary objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.5 mg); both compounds were administered by subcutaneous injection twice daily. Study arms were balanced for age, sex, previous treatment, leukemic karyotypes, time from CR to inclusion, and frequency of secondary leukemia. Three years after enrollment of the last patient, treatment with HDC/IL-2 was found to improve LFS over control in the study population (CR1 + CR > 1, n = 320; P < .01, log-rank test). For patients in CR1 (n = 261), treatment significantly improved LFS (P = .01) with 3-year LFS estimates of 40% (HDC/IL-2) compared with 26% (control). Side effects were typically mild to moderate. These results indicate that HDC/IL-2 treatment offers an efficacious and tolerable treatment for patients with AML in remission.

  • 5.
    Christiansson, Lisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mustjoki, Satu
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Loskog, Angelica S.I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mangsbo, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The use of multiplex platforms for absolute and relative protein quantification of clinical material2014In: EuPA Open Proteomics, ISSN 2212-9685, Vol. 3, p. 37-47Article in journal (Refereed)
    Abstract [en]

    When introducing multiplex platforms to measure protein content in precious clinical material there is an increased risk of cross reactivity, loss of sensitivity as well as accuracy. In this paper, four multiplex platforms and one singleplex platform were compared by running pre- and post-treatment plasma samples from CML patients. We found a variation of absolute protein concentrations between platforms. For some of the analytes and platforms, relative differences between pre- and post-treatment samples correlated. We conclude that absolute concentrations measured by different platforms should be compared with caution and comparing relative differences could be more accurate.

  • 6.
    Christiansson, Lisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Söderlund, Stina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hjorth-Hansen, Henrik
    Dept of Hematology St Olavs hospital, Dept of Cancer Research and Molecular Medicine, Norweigan University of Science and Technology, Trondheim, Norway.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Markevärn, Berit
    Avdelningen för Hematologi, Norrlands universitetssjukhus.
    Richter, Johan
    Avdelningen för hematologi och koagulation, Skånes universitetssjukhus .
    Stenke, Leif
    Avdelningen för hematologi, Karolinska universitetssjukhuset och Karolinska institutet .
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Mustjoki, Satu
    University of Helsinki.
    Loskog, Angelica S I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Imatinib or dasatinib treatment of chronic myeloid leukemia reduces circulating myeloid-derived suppressor cells but increases their CD40 expressionManuscript (preprint) (Other academic)
  • 7.
    Christiansson, Lisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Söderlund, Stina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Svensson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mustjoki, Satu
    University of Helsinki.
    Bengtsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Loskog, Angelica S I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Increased Level of Myeloid-Derived Suppressor Cells, Programmed Death Receptor Ligand 1/Programmed Death Receptor 1, and Soluble CD25 in Sokal High Risk Chronic Myeloid Leukemia2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 1, p. e55818-Article in journal (Refereed)
    Abstract [en]

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

  • 8. Druker, Brian J.
    et al.
    Guilhot, Francois
    O'Brien, Stephen G.
    Gathmann, Insa
    Kantarjian, Hagop
    Gattermann, Norbert
    Deininger, Michael W. N.
    Silver, Richard T.
    Goldman, John M.
    Stone, Richard M.
    Cervantes, Francisco
    Hochhaus, Andreas
    Powell, Bayard L.
    Gabrilove, Janice L.
    Rousselot, Philippe
    Reiffers, Josy
    Cornelissen, Jan J.
    Hughes, Timothy
    Agis, Hermine
    Fischer, Thomas
    Verhoef, Gregor
    Shepherd, John
    Saglio, Giuseppe
    Gratwohl, Alois
    Nielsen, Johan L.
    Radich, Jerald P.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Taylor, Kerry
    Baccarani, Michele
    So, Charlene
    Letvak, Laurie
    Larson, Richard A.
    Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia2006In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 355, no 23, p. 2408-2417Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy. METHODS: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events. RESULTS: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events. CONCLUSIONS: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].)

  • 9.
    Goldberg, Stuart L.
    et al.
    Hackensack Univ, Med Ctr, John Theurer Canc Ctr, 92 Second St, Hackensack, NJ 07601 USA..
    Cortes, Jorge E.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA..
    Gambacorti-Passerini, Carlo
    Univ Milano Bicocca, San Gerardo Hosp, Monza, Italy..
    Hehlmann, Ruediger
    Heidelberg Univ, Mannheim, Germany..
    Khoury, H. Jean
    Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA..
    Michallet, Mauricette
    Ctr Hosp Lyon Sud, Pierre Benite, France..
    Paquette, Ron L.
    Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA..
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Uppsala Univ, Uppsala, Sweden..
    Zyczynski, Teresa
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Foreman, Aimee
    ICON Plc, San Francisco, CA USA..
    Abruzzese, Elisabetta
    S Eugenio Hosp, Rome, Italy..
    Andorsky, David
    Rocky Mt Canc Ctr, Boulder, CO USA..
    Beeker, Aart
    Spaarne Hosp, Hoofddorp, Netherlands..
    Cony-Makhoul, Pascale
    Ctr Hosp Annecy Genevois, Pringy, France..
    Hansen, Richard
    Inst Med, IDGGQ, Kaiserslautern, Germany..
    Lomaia, Elza
    Federal Almazov North West Med Res Ctr, St Petersburg, Russia..
    Olavarria, Eduardo
    Imperial Coll London, Hammersmith Hosp, London, England..
    Mauro, Michael J.
    Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA..
    First-line treatment selection and early monitoring patterns in chronic phase-chronic myeloid leukemia in routine clinical practice: SIMPLICITY2017In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 92, no 11, p. 1214-1223Article in journal (Refereed)
    Abstract [en]

    Achieving successful outcomes in chronic phase-chronic myeloid leukemia (CP-CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP-CML receiving first-line imatinib (n = 416), dasatinib (n = 418) or nilotinib (n = 408) in the US and 6 European countries in routine clinical practice. Twelve-month follow-up data of 1242 prospective patients (enrolled October 01 2010-September 02 2015) are reported. 81% of patients had baseline comorbidities. Treatment selection was based on perceived efficacy over patient comorbidity profile. There was a predominance of imatinib-treated patients enrolled earlier in the study, with subsequent shift toward dasatinib- and nilotinib-treated patients by 2013/2014. Monitoring for either CyR/MR improved over time and was documented for 36%, 82%, and 95% of patients by 3, 6, and 12 months, respectively; 5% had no documentation of CyR/MR monitoring during the first year of therapy. Documentation of MR/CyR testing was higher in Europe than the US (P < .001) and at academic versus community practices (P = .001). Age <65 years, patients being followed at sites within Europe, those followed at academic centers and patients no longer on first-line therapy were more likely to be monitored by 12 months. SIMPLICITY demonstrates that the NCCN and ELN recommendations on response monitoring have not been consistently translated into routine clinical practice. In the absence of appropriate monitoring practices, clinical response to TKI therapy cannot be established, any needed changes to treatment strategy will thus not be implemented, and long-term patient outcomes are likely to be impacted.

  • 10. Guilhot, Joelle
    et al.
    Baccarani, Michele
    Clark, Richard E.
    Cervantes, Francisco
    Guilhot, Francois
    Hochhaus, Andreas
    Kulikov, Sergei
    Mayer, Jiri
    Petzer, Andreas L.
    Rosti, Gianantonio
    Rousselot, Philippe
    Saglio, Giuseppe
    Saussele, Susanne
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Steegmann, Juan-Luis
    Zaritskey, Andrey
    Hehlmann, Ruediger
    Definitions, methodological and statistical issues for phase 3 clinical trials in chronic myeloid leukemia: a proposal by the European LeukemiaNet2012In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 119, no 25, p. 5963-5971Article in journal (Refereed)
    Abstract [en]

    The treatment policy of chronic myeloid leukemia (CML), particularly with tyrosine kinase inhibitors, has been influenced by several recent studies that were well designed and rapidly performed, but their interpretation is of some concern because different end points and methodologies were used. To understand and compare the results of the previous and future studies and to translate their conclusion into clinical practice, there is a need for common definitions and methods for analyses of CML studies. A panel of experts was appointed by the European LeukemiaNet with the aim of developing a set of definitions and recommendations to be used in design, analyses, and reporting of phase 3 clinical trials in this disease. This paper summarizes the consensus of the panel on events and major end points of interest in CML. It also focuses on specific issues concerning the intention-to-treat principle and longitudinal data analyses in the context of long-term follow-up. The panel proposes that future clinical trials follow these recommendations.

  • 11.
    Hagberg, Anette
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wickenberg-Bolin, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Göransson, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Isaksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Bengtsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Barbany, Gisela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gene expression analysis identifies a genetic signature potentially associated with response to alpha-IFN in chronic phase CML patients2007In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 31, no 7, p. 931-938Article in journal (Refereed)
    Abstract [en]

    Microarray-based gene expression analysis was performed on diagnostic chronic phase CML patient samples prior to interferon treatment. Fifteen patient samples corresponding to six cytogenetic responders and nine non-responders were included. Genes differentially expressed between responder and non-responder patients were listed and a subsequent leave-one-out cross validation (LOOV) procedure showed that the top 20 genes allowed the highest prediction accuracy. The relevant genes were quantified by real-time PCR that supported the microarray results. We conclude that it might be possible to use gene expression analysis to predict future response to interferon in CML diagnostic samples.

  • 12.
    Hansson, Mats G
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Feltelius, Nils
    Forsberg, Joanna Stjernschantz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Hasford, Joerg
    Medical registries represent vital patient interests and should not be dismantled by stricter regulation2012In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 36, no 6, p. 575-578Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Medical registries serve patients as beneficiaries of quality standards and new treatment opportunities. However, it has been argued that registries threaten patient privacy interests and should therefore be more strictly regulated.

    METHODS AND RESULTS:

    With the European Treatment and Outcome Study for Chronic Myeloid Leukemia as a concrete example we identify and describe how four of the major arguments put forward for stricter regulation fail.

    CONCLUSION:

    We conclude that medical registries should be promoted both for research and quality control, and that the regulatory bureaucratic burden should be reduced.

  • 13. Hehlmann, R.
    et al.
    Cortes, J.
    Gambacorti-Passerini, C.
    Goldberg, S. L.
    Khoury, H. J.
    Mauro, M.
    Michallet, M.
    Mohamed, H.
    Powell, T.
    Paquette, R.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Subar, M.
    Zyczynski, T.
    TYROSINE KINASE INHIBITOR (TKI) SWITCHING: EXPERIENCE FROM SIMPLICITY, A PROSPECTIVE OBSERVATIONAL STUDY OF CHRONIC-PHASE CHRONIC MYELOID LEUKEMIA (CP-CML) PATIENTS IN CLINICAL PRACTICE2014In: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, no S1, p. 328-329Article in journal (Other academic)
  • 14. Hjorth-Hansen, Henrik
    et al.
    Stenke, Leif
    Söderlund, Stina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Dreimane, Arta
    Ehrencrona, Hans
    Gedde-Dahl, Tobias
    Gjertsen, Bjørn Tore
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Koskenvesa, Perttu
    Lotfi, Kourosh
    Majeed, Waleed
    Markevärn, Berit
    Ohm, Lotta
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Remes, Kari
    Suominen, Merja
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Porkka, Kimmo
    Mustjoki, Satu
    Richter, Johan
    Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006)2015In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 64, no 3, p. 243-250Article in journal (Refereed)
    Abstract [en]

    We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100 mg QD or imatinib 400 mg QD and report outcome as an intention-to-treat analysis with 36 months follow-up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR(3.0) was reached at 3 months in 36% vs. 8% (P = 0.02), at 12 months in 81% vs. 46% (P = 0.02) and at 18 months in 73% vs. 65% (n.s.) of the patients in the two groups. In contrast, MR(4.5) was consistently superior in the dasatinib group at all time points from 6 months onwards, reaching 61% vs. 21% (P < 0.05) at 36 months. Sixty-four vs. 71% of the patients in the dasatinib and imatinib arms, respectively, remained on assigned drug. Dasatinib dose was frequently reduced, but with maintained excellent effect. One imatinib patient progressed to blastic phase, but no CML-related deaths occurred. In conclusion, our data compare favourably with those of the dasatinib registration study, DASISION. The fast and deep molecular responses induced by dasatinib compared with imatinib may be exploited to increase the proportion of patients who can achieve a treatment-free remission after treatment discontinuation.

  • 15. Hoffmann, V.
    et al.
    Lindoerfer, D.
    Thaler, J.
    Labar, B.
    Melanthiou, F.
    Mayer, J.
    Everaus, H.
    Porkka, K.
    Guillhot, J.
    Schubert-Fritschle, G.
    Castagnetti, F.
    Lejniece, S.
    Griskevicius, L.
    Thielen, N.
    Hellmann, A.
    Turkina, A.
    Zaritskey, A.
    Bogdanovic, A. D.
    Indrak, K.
    Zupan, I. P.
    Casado, L. F.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Clark, R. E.
    Hehlmann, R.
    Hasford, J.
    Baccarani, M.
    The Eutos Population Based Registry - Incidences of CML Across Europe2014In: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, no S1, p. 72-72Article in journal (Other academic)
  • 16. Hoffmann, V S
    et al.
    Baccarani, M
    Hasford, J
    Castagnetti, F
    Di Raimondo, F
    Casado, L F
    Turkina, A
    Zackova, D
    Ossenkoppele, G
    Zaritskey, A
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Indrak, K
    Sninska, Z
    Sacha, T
    Clark, R
    Bogdanovic, A
    Hellmann, A
    Griskevicius, L
    Schubert-Fritschle, G
    Sertic, D
    Guilhot, J
    Lejniece, S
    Zupan, I
    Burgstaller, S
    Koskenvesa, P
    Everaus, H
    Costeas, P
    Lindoerfer, D
    Rosti, G
    Saussele, S
    Hochhaus, A
    Hehlmann, R
    Treatment and outcome of 2904 CML patients from the EUTOS population-based registry2017In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 3, p. 593-601Article in journal (Refereed)
    Abstract [en]

    The European Treatment and Outcome Study (EUTOS) population-based registry includes data of all adult patients newly diagnosed with Philadelphia chromosome-positive and/or BCR-ABL1+ chronic myeloid leukemia (CML) in 20 predefined countries and regions of Europe. Registration time ranged from 12 to 60 months between January 2008 and December 2013. Median age was 55 years and median observation time was 29 months. Eighty percent of patients were treated first line with imatinib, and 17% with a second-generation tyrosine kinase inhibitor, mostly according to European LeukemiaNet recommendations. After 12 months, complete cytogenetic remission (CCyR) and major molecular response (MMR) were achieved in 57% and 41% of patients, respectively. Patients with high EUTOS risk scores achieved CCyR and MMR significantly later than patients with low EUTOS risk. Probabilities of overall survival (OS) and progression-free survival for all patients at 12, 24 and 30 months was 97%, 94% and 92%, and 95%, 92% and 90%, respectively. The new EUTOS long-term survival score was validated: the OS of patients differed significantly between the three risk groups. The probability of dying in remission was 1% after 24 months. The current management of patients with tyrosine kinase inhibitors resulted in responses and outcomes in the range reported from clinical trials. These data from a large population-based, patient sample provide a solid benchmark for the evaluation of new treatment policies.Leukemia advance online publication, 23 September 2016; doi:10.1038/leu.2016.246.

  • 17. Hoffmann, V. S.
    et al.
    Baccarani, M.
    Hasford, J.
    Lindoerfer, D.
    Burgstaller, S.
    Sertic, D.
    Costeas, P.
    Mayer, J.
    Indrak, K.
    Everaus, H.
    Koskenvesa, P.
    Guilhot, J.
    Schubert-Fritschle, G.
    Castagnetti, F.
    Di Raimondo, F.
    Lejniece, S.
    Griskevicius, L.
    Thielen, N.
    Sacha, T.
    Hellmann, A.
    Turkina, A. G.
    Zaritskey, A.
    Bogdanovic, A.
    Sninska, Z.
    Zupan, I.
    Steegmann, J-L
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Clark, R. E.
    Covelli, A.
    Guidi, G.
    Hehlmann, R.
    The EUTOS population-based registry: incidence and clinical characteristics of 2904 CML patients in 20 European Countries2015In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 29, no 6, p. 1336-1343Article in journal (Refereed)
    Abstract [en]

    This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100 000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.

  • 18.
    Hoffmann, V. S.
    et al.
    Univ Munich, Inst Med Informat Sci Biometry & Epidemiol, Munich, Germany..
    Baccarani, M.
    Univ Bologna, Bologna, Italy..
    Hasford, J.
    Univ Munich, Inst Med Informat Sci Biometry & Epidemiol, Munich, Germany..
    Lindoerfer, D.
    Univ Munich, Munich, Germany..
    Burgstaller, S.
    Klinikum Wells Grieskirchen, Wells, Austria..
    Sertic, D.
    Univ Hosp Ctr, Zagreb, Croatia..
    Costeas, P.
    Karaiskakio Fdn, Nicosia, Cyprus..
    Mayer, J.
    Masaryk Univ Hosp, Brno, Czech Republic..
    Indrak, K.
    Palacky Univ, CR-77147 Olomouc, Czech Republic..
    Everaus, H.
    Tartu Univ Hosp, Tartu, Estonia..
    Koskenvesa, P.
    Biomedicum Helsinki, Helsinki, Finland..
    Guilhot, J.
    CHU Poitiers, Tartu, Estonia..
    Schubert-Fritschle, G.
    Univ Munich, Munich, Germany..
    Castagnetti, F.
    Univ Bologna, Bologna, Italy..
    di Raimondo, F.
    Univ Catania, Catania, Italy..
    Lejniece, S.
    Riga Eastern Clin Univ Hosp, Riga, Latvia..
    Griskevicius, L.
    Vilnius Univ Hosp, Vilnius, Lithuania..
    Thielen, N.
    Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.;Healthcare Minist Russian Federat, FSBI Hematol Res Ctr, Moscow, Russia..
    Sacha, T.
    Jagellonian Univ Hosp, Krakow, Poland..
    Hellmann, A.
    Med Univ Gdansk, Gdansk, Poland..
    Turkina, A.
    Zaritskey, A.
    St Petersburg State Med Univ, St Petersburg, Russia..
    Bogdanovic, A.
    Univ Belgrade, Belgrade, Serbia..
    Sninska, Z.
    Univ Hosp Bratislava, Bratislava, Slovakia..
    Zupan, I.
    Univ Clin Ctr Ljubljana, Ljubljana, Slovenia..
    Steegmann, J. -L
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Clark, R.
    Royal Liverpool Univ Hosp, Liverpool, Merseyside, England..
    Hehlmann, R.
    Heidelberg Univ, Mannheim, Germany..
    ANALYSIS OF TREATMENT AND OUTCOME DATA OF 2904 PATIENTS FROM THE EUTOS POPULATION-BASED REGISTRY2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, p. 181-181Article in journal (Other academic)
  • 19. Hoffmann, Verena
    et al.
    Baccarani, Michele
    Hasford, Joerg
    Guilhot, Joelle
    Saussele, Susanne
    Rosti, Gianantonio
    Guilhot, Francois
    Porkka, Kimmo
    Ossenkoppele, Gert
    Lindoerfer, Doris
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Pfirrmann, Markus
    Hehlmann, Ruediger
    The EUTOS CML score aims to support clinical decision-making2012In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 119, no 12, p. 2966-2967Article in journal (Refereed)
  • 20. Hoffmann, Verena S.
    et al.
    Lindoerfer, Doris
    Thaler, Josef
    Boris, Labar
    Melanthiou, Frederiki
    Mayer, Jiri
    Everaus, Hele
    Guilhot, Joelle
    Schubert-Fritschle, Gabriele
    Castagnetti, Fausto
    Lejniece, Sandra
    Griskevicius, Laimonas
    Thielen, Noortje
    Sacha, Tomasz
    Hellmann, Andrzej
    Turkina, Anna G.
    Zaritskey, Andrey
    Bogdanovic, Andrija
    Indrak, Karel
    Zupan, Irena
    Steegmann, Juan Luis
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Clark, Richard
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hehlmann, Ruediger
    Hasford, Joerg
    Baccarani, Michele
    Incidence of CML in Europe -- a Comparison of 19 European Countries with US SEER Data2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 21.
    Hoffmann, Verena Sophia
    et al.
    Univ Munich, Inst Med Informat Verarbeitung Biometrie & Epidem, Munich, Germany..
    Baccarani, Michele
    Univ Bologna, Inst Hematol, Bologna, Italy..
    Hasford, Joerg
    Univ Munich, Inst Med Informat Verarbeitung Biometrie & Epidem, Munich, Germany..
    Lindoerfer, Doris
    Univ Munich, Inst Med Informat Verarbeitung Biometrie & Epidem, Munich, Germany..
    Burgstaller, Sonja
    Klinikum Wels Grieskirchen, Wels, Austria..
    Sertic, Dubravka
    Univ Hosp Ctr Zagreb, Div Hematol, Dept Med, Zagreb, Croatia..
    Costeas, Paul
    Karaiskakio Fdn, Nicosia, Cyprus..
    Mayer, Jiri
    Masaryk Univ Hosp, Brno, Czech Republic..
    Indrak, Karel
    Palacky Univ, Univ Hosp, Dept Hematol Oncol, CR-77147 Olomouc, Czech Republic..
    Everaus, Hele
    Tartu Univ Hosptial, Hematol Oncol, Tartu, Estonia..
    Koskenvesa, Perttu
    Helsinki Univ Cent Hosp, Helsinki, Finland.;Biomedicum Helsinki, Hematol Res Unit, Helsinki, Finland..
    Guilhot, Joelle
    CHU Poitiers, INSERM, CIC 1402, Poitiers, France..
    Schubert-Fritschle, Gabriele
    Univ Munich, Munich Canc Registry, Munich, Germany..
    Castagnetti, Fausto
    Univ Bologna, Sch Med, Bologna, Italy..
    Di Raimondo, Francesco
    Univ Catania, Div Hematol, Azienda Policlin OVE, Catania, Italy..
    Lejniece, Sandra
    Riga Eastern Clin Univ Hosp, Natl Hematol Ctr, Riga, Latvia..
    Griskevicius, Laimonas
    Vilnius Univ Hosp Santariskiu Klinikos, Vilnius, Lithuania..
    Thielen, Noortje
    Vrije Univ Amsterdam, Med Ctr, Dept Hematol, Amsterdam, Netherlands..
    Sacha, Thomas
    Jagellonian Univ Hosp, Dept Hematol, Krakow, Poland..
    Hellmann, Andrzej
    Med Univ Gdansk, Dept Hematol & Transplantat, Gdansk, Poland..
    Turkina, Anna
    Natl Res Ctr Hematol, Moscow, Russia..
    Zaritskey, Audrey
    St Petersburg State Med Univ, St Petersburg, Russia..
    Bogdanovic, Andrija
    Univ Belgrade, Clin Ctr Serbia, Belgrade, Serbia..
    Sninska, Zuzana
    Univ Hosp Bratislava, Dept Hematol, Bratislava, Slovakia..
    Zupan, Lrena
    Univ Clin Ctr Ljubljana, Dept Hematol, Ljubljana, Slovenia..
    Casado, Felipe
    Hosp Virgen de la Salud, Serv Hematol, Toledo, OH, Spain..
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Clark, Richard E.
    Royal Liverpool Univ Hosp, Liverpool, Merseyside, England..
    Saussele, Susanne
    Heidelberg Univ, Med Fak Mannheim, Mannheim, Germany..
    Hochhaus, Andreas
    Univ Hosp Jena, Dept Hematol & Oncol, Jena, Germany..
    Hehlmann, Ruediger
    Heidelberg Univ, Med Klin 3, Mannheim, Germany..
    Treatment and Outcome Analysis of 2,904 Pateints from the EUTOS Population Based Registry2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 22.
    Höglund, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Sandin, Fredrik
    Hellstrom, Karin
    Bjoreman, Mats
    Bjorkholm, Magnus
    Brune, Mats
    Dreimane, Arta
    Ekblom, Marja
    Lehmann, Soren
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Ljungman, Per
    Malm, Claes
    Markevarn, Berit
    Myhr-Eriksson, Kristina
    Ohm, Lotta
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Sjalander, Anders
    Wadenvik, Hans
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Stenke, Leif
    Richter, Johan
    Tyrosine kinase inhibitor usage, treatment outcome, and prognostic scores in CML: report from the population-based Swedish CML registry2013In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, no 7, p. 1284-1292Article in journal (Refereed)
    Abstract [en]

    Clinical management guidelines on malignant disorders are generally based on data from clinical trials with selected patient cohorts. In Sweden, more than 95% of all patients diagnosed with chronic myeloid leukemia (CML) are reported to the national CML registry, providing unique possibilities to compile population-based information. This report is based on registry data from 2002 to 2010, when a total of 779 patients (425 men, 354 women; median age, 60 years) were diagnosed with CML (93% chronic, 5% accelerated, and 2% blastic phase) corresponding to an annual incidence of 0.9/100 000. In 2002, approximately half of the patients received a tyrosine kinase inhibitor as initial therapy, a proportion that increased to 94% for younger (<70 years) and 79% for older (>80 years) patients during 2007-2009. With a median follow-up of 61 months, the relative survival at 5 years was close to 1.0 for patients younger than 60 years and 0.9 for those aged 60 to 80 years, but only 0.6 for those older than 80 years. At 12 months, 3% had progressed to accelerated or blastic phase. Sokal, but not European Treatment and Outcome Study, high-risk scores were significantly linked to inferior overall and relative survival. Patients living in university vs nonuniversity catchment areas more often received tyrosine kinase inhibitors up front but showed comparable survival.

  • 23.
    Höglund, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Sandin, Fredrik
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Epidemiology of chronic myeloid leukaemia: an update2015In: Annals of Hematology, ISSN 0939-5555, E-ISSN 1432-0584, Vol. 94, p. S241-S247Article, review/survey (Refereed)
    Abstract [en]

    National and regional population-based registries are, provided diagnostic accuracy and full coverage of the target population, indispensible tools for epidemiological research. Chronic myeloid leukaemia (CML) registries with more comprehensive reporting may also provide complementary data on treatment outcome to those obtained from clinical trials. Reports from several European CML registries consistently show a crude annual incidence of 0.7-1.0/100,000, a median age at diagnosis of 57-60 years and a male/female ratio of 1.2-1.7. The incidence of CML has been stable over time. Worldwide, variations in the reported incidence of CML may be due to methodological issues, but a true difference between different geographical areas and/or ethnical subgroups cannot be excluded. The prevalence of CML is not well known but has been estimated to be 10-12/100,000 inhabitants with a steady increase due to the dramatic improvement in survival of these patients. In recent population-based studies, CML patients have an overall survival that is comparable to that shown in large clinical trials, though relative survival in patients >70 years is still decreased. The importance of socio-economic factors and health-care setting for outcome and the possible increased risk of secondary cancer in CML are areas of ongoing research.

  • 24. Koskenvesa, Perttu
    et al.
    Kreutzman, Anna
    Rohon, Peter
    Pihlman, Markus
    Vakkila, Emmi
    Rasanen, Anu
    Vapaatalo, Mirja
    Remes, Kari
    Lundan, Tuija
    Hjorth-Hansen, Henrik
    Vakkila, Jukka
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Mustjoki, Satu
    Porkka, Kimmo
    Imatinib and pegylated IFN-alpha 2b discontinuation in first-line chronic myeloid leukemia patients following a major molecular response2014In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 92, no 5, p. 413-420Article in journal (Refereed)
    Abstract [en]

    Objectives Previous studies indicate that 40-50% of patients with chronic myeloid leukemia in prolonged complete molecular remission may discontinue imatinib therapy without imminent relapse. The combination of pegylated interferon-alpha (Peg-IFN-alpha 2b) and imatinib may increase the rate of successful discontinuation. Methods In this pilot study, we prospectively stopped imatinib from patients (n=12) who had achieved major molecular response (MMR) after >= 12months of treatment with either imatinib or imatinib+Peg-IFN-alpha 2b. Molecular monitoring was carried out monthly for BCR-ABL1. In addition, analyses of lymphocyte immunophenotype, function, and plasma cytokines were performed. Results In the monotherapy group, 5/6 patients lost MMR within 4months. One patient remains to date in MR4.0 61months after discontinuation. In the combination therapy group, 2/6 patients relapsed within 4months while still receiving Peg-IFN-alpha 2b. Four of six patients were able to discontinue both treatments, but three of these patients relapsed after 3months. One patient is still in sustained MR4.0 at 58months off all treatment. All relapsed patients re-responded to imatinib. The two successfully discontinued patients had either an increased number of NK-cells or functionally active T-cells. Conclusions A higher frequency of relapsed patients in our study in comparison with other studies may be due to the shorter duration of imatinib treatment prior to discontinuation. However, in selected patients with an active immune system, even a short duration of TKI therapy (<2yr) may allow for therapy discontinuation but this needs to be confirmed in larger prospective studies.

  • 25.
    Larfors, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Parental Age, Family Size, and Offspring's Risk of Childhood and Adult Acute Leukemia2012In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 21, no 7, p. 1185-1190Article in journal (Refereed)
    Abstract [en]

    Background: An association between childhood acute leukemia and advanced parental age was observed more than 50 years ago, and the association has been repeated in several, but not all, subsequent studies. In contrast to the many studies addressing childhood leukemia, few have included adult patients.

    Methods: In this register-based case control study, we examined the association between parental age and incidence of acute leukemia in 2,660 childhood cases and 4,412 adult cases of acute leukemia, compared with 28,288 age-matched controls selected from a population-based register. Relative risks were estimated with conditional logistic regression.

    Results: We found a small increased risk of childhood acute lymphoblastic leukemia with increasing paternal age (adjusted OR, 1.05 per 5-year increase in age). Risk estimates were similar for childhood acute myeloid leukemia (AML), whereas no association was found with adult leukemia. Meanwhile, we observed a decreased risk of adult AML with increasing number of siblings, both older and younger.

    Conclusions: The results support the idea of a prenatal etiology of leukemia but indicate that parental age effects are limited to childhood cases. Impact: This is the first large study on parental age and leukemia risk, which includes adult cases. The finding on family size and risk of adult AM L needs to be validated in future studies.

  • 26. Larson, Richard A.
    et al.
    Conti, Rena
    Padula, William V.
    Apperley, Jane F.
    Baccarani, Michele
    Eigendorff, Ekkehard
    Guilhot, Francois
    Guilhot, Joelle
    Mahon, Francois-Xavier
    Martinelli, Giovanni
    Mayer, Jiri
    Mueller, Martin C.
    Niederwieser, Dietger
    Saussele, Susanne
    Schiffer, Charles A.
    Silver, Richard T.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hehlmann, Rudiger
    What Is the Most Cost-Effective Strategy for Treating Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia (CML) after Imatinib Loses Patent Exclusivity?2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 27. Lindoerfer, D.
    et al.
    Hoffmann, V. S.
    Rosti, G.
    Castagnetti, F.
    Saussele, S.
    Guilhot, J.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Steegmann, J. L.
    Mayer, J.
    Indrak, K.
    Turkina, A. G.
    Zaritskey, A.
    Labar, B.
    Zupan, I. P.
    Thielen, N.
    Clark, R. E.
    Thaler, J.
    Melanthiou, F.
    Everaus, H.
    Porkka, K.
    Bogdanovic, A. D.
    Schubert-Fritschle, G.
    Panagiotidis, P.
    Masszi, T.
    Lejniece, S.
    Griskevicius, L.
    Hellmann, A.
    Prejzner, W.
    Sacha, T.
    Almeida, A.
    Dyagil, I.
    Colita, A.
    Mihaylov, G.
    Hehlmann, R.
    Hasford, J.
    Baccarani, M.
    The Eutos Population-Based Registry: Evaluation of Baseline Characteristics and First Treatment Choices Of 2983 Newly Diagnosed Chronic Myeloid Leukemia (Cml) Patients from 20 European Countries2014In: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, no S1, p. 238-239Article in journal (Other academic)
  • 28. Mauro, Michael
    et al.
    Gambacorti-Passerini, Carlo
    Goldberg, Stuart L.
    Cortes, Jorge E.
    Khoury, H. Jean
    Michallet, Mauricette
    Paquette, Ronald
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Turner, Michelle P.
    Mohamed, Hesham
    Subar, Milayna
    Zyczynski, Teresa
    Cytogenetic and Molecular Responses in Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) in a Prospective Observational Study (SIMPLICITY)2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 29. Mustjoki, S.
    et al.
    Richter, J.
    Barbany, G.
    Ehrencrona, H.
    Fioretos, T.
    Gedde-Dahl, T.
    Gjertsen, B. T.
    Hovland, R.
    Hernesniemi, S.
    Josefsen, D.
    Koskenvesa, P.
    Dybedal, I.
    Markevarn, B.
    Olofsson, T.
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Rapakko, K.
    Thunberg, S.
    Stenke, L.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Porkka, K.
    Hjorth-Hansen, H.
    Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients2013In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 27, no 7, p. 1520-1526Article in journal (Refereed)
    Abstract [en]

    Chronic myeloid leukemia (CML) stem cells appear resistant to tyrosine kinase inhibitors (TKIs) in vitro, but their impact and drug sensitivity in vivo has not been systematically assessed. We prospectively analyzed the proportion of Philadelphia chromosome-positive leukemic stem cells (LSCs, Ph+CD34+CD38=) and progenitor cells (LPCs, Ph+CD34+CD38+) from 46 newly diagnosed CML patients both at the diagnosis and during imatinib or dasatinib therapy (ClinicalTrials.gov NCT00852566). At diagnosis, the proportion of LSCs varied markedly (1-100%) between individual patients with a significantly lower median value as compared with LPCs (79% vs 96%, respectively, P = 0.0001). The LSC burden correlated with leukocyte count, spleen size, hemoglobin and blast percentage. A low initial LSC percentage was associated with less therapy-related hematological toxicity and superior cytogenetic and molecular responses. After initiation of TKI therapy, the LPCs and LSCs rapidly decreased in both therapy groups, but at 3 months time point the median LPC level was significantly lower in dasatinib group compared with imatinib patients (0.05% vs 0.68%, P = 0.032). These data detail for the first time the prognostic significance of the LSC burden at diagnosis and show that in contrast to in vitro data, TKI therapy rapidly eradicates the majority of LSCs in patients.

  • 30.
    Paquette, R.
    et al.
    Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA..
    Mauro, M.
    Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA..
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Abruzzese, E.
    S Eugenio Hosp, Rome, Italy..
    Andorksy, D.
    Rocky Mt Canc Ctr, Parker, CO USA..
    Hansen, R.
    Subar, M.
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Turner, M.
    ICON Plc, San Diego, CA USA..
    Zyczynski, T.
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Mohamed, H.
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Goldberg, S. L.
    Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA..
    CARDIOVASCULAR (CV)-RELATED HOSPITALIZATION IN PATIENTS WITH CHRONIC-PHASE CHRONIC MYELOID LEUKEMIA (CP-CML) IN SIMPLICITY, A PROSPECTIVE OBSERVATIONAL STUDY2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, p. 437-437Article in journal (Other academic)
  • 31.
    Pfirrmann, M.
    et al.
    Univ Munich, Inst Med Informationsverarbeitung Biometrie & Epi, Marchioninistr 15, D-81377 Munich, Germany..
    Baccarani, M.
    Univ Bologna, S Orsola Malpighi Hosp, Hematol & Oncol L&A Seragnoli, Bologna, Italy..
    Saussele, S.
    Heidelberg Univ, Med Fak Mannheim, Univ Med Mannheim, Med Klin 3, Mannheim, Germany..
    Guilhot, J.
    CHU Poitiers, INSERM, CIC 1402, Clin Invest Ctr, Poitiers, France..
    Cervantes, F.
    Univ Barcelona, IDIBAPS, Hosp Clin, Hematol Dept, Barcelona, Spain..
    Ossenkoppele, G.
    Vrije Univ Amsterdam, Med Ctr, Dept Hematol, Amsterdam, Netherlands..
    Hoffmann, V. S.
    Univ Munich, Inst Med Informationsverarbeitung Biometrie & Epi, Marchioninistr 15, D-81377 Munich, Germany..
    Castagnetti, F.
    Univ Bologna, S Orsola Malpighi Hosp, Hematol & Oncol L&A Seragnoli, Bologna, Italy..
    Hasford, J.
    Univ Munich, Inst Med Informationsverarbeitung Biometrie & Epi, Marchioninistr 15, D-81377 Munich, Germany..
    Hehlmann, R.
    Heidelberg Univ, Med Fak Mannheim, Univ Med Mannheim, Med Klin 3, Mannheim, Germany..
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia2016In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 30, no 1, p. 48-56Article in journal (Refereed)
    Abstract [en]

    In patients with chronic myeloid leukemia (CML), first-line imatinib treatment leads to 8-year overall survival (OS) probabilities above 80%. Many patients die of reasons unrelated to CML. This work tackled the reassessment of prognosis under particular consideration of the probabilities of dying of CML. Analyses were based on 2290 patients with chronic phase CML treated with imatinib in six clinical trials. 'Death due to CML' was defined by death after disease progression. At 8 years, OS was 89%. Of 208 deceased patients, 44% died of CML. Higher age, more peripheral blasts, bigger spleen and low platelet counts were significantly associated with increased probabilities of dying of CML and determined a new long-term survival score with three prognostic groups. Compared with the low-risk group, the patients of the intermediate-and the high-risk group had significantly higher probabilities of dying of CML. The score was successfully validated in an independent sample of 1120 patients. In both samples, the new score differentiated probabilities of dying of CML better than the Sokal, Euro and the European Treatment and Outcome Study (EUTOS) score. The new score identified 61% low-risk patients with excellent long-term outcome and 12% high-risk patients. The new score supports the prospective assessment of long-term antileukemic efficacy and risk-adapted treatment.

  • 32. Pfirrmann, M.
    et al.
    Saussele, S.
    Baccarani, M.
    Guilhot, J.
    Cervantes, F.
    Ossenkoppele, G.
    Lindoerfer, D.
    Hoffmann, V. S.
    Castagnetti, F.
    Hehlmann, R.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Overall survival and prognosis in patients with chronic myeloid leukaemia allocated to first-line imatinib treatment - new results from the EUTOS "In-Study" registry2013In: Onkologie (Basel), ISSN 0378-584X, E-ISSN 1423-0240, Vol. 36, no Suppl. 7, p. 100-100Article in journal (Other academic)
  • 33. Pfirrmann, M.
    et al.
    Saussele, S.
    Baccarani, M.
    Guilhot, J.
    Cervantes, F.
    Ossenkoppele, G.
    Lindoerfer, D.
    Hoffmann, Vs
    Castagnetti, F.
    Hehlmann, R.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Overall Survival and Prognosis in 2190 Patients with First-Line Imatinib Treatment Considering Death Due to Chronic Myeloid Leukaemia as the Only Event2014In: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, no S1, p. 531-532Article in journal (Other academic)
  • 34.
    Pfirrmann, Markus
    et al.
    Univ Munich, Inst Med Informat Verarbeitung Biometrie & Epidem, Munich, Germany..
    Hasford, Joerg
    Univ Munich, Inst Med Informat Verarbeitung Biometrie & Epidem, Munich, Germany..
    Saussele, Susanne
    Heidelberg Univ, Med Fak Mannheim, Mannheim, Germany..
    Turkina, Anna
    Natl Res Ctr Hematol, Moscow, Russia..
    Prejzner, Witold
    Med Univ Gdansk, Dept Hematol, Gdansk, Poland..
    Luis Steegmann, Juan
    Hosp Univ Princesa, Dept Hematol, Madrid, Spain..
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Zaritskey, Andrey
    St Petersburg State Med Univ, St Petersburg, Russia..
    Colita, Adriana
    Federat Ctr Hematol & Bone Marrow Transplantat, Fundeni Clin Inst, Bucharest, Romania..
    Zackova, Daniela
    Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic.;Masaryk Univ, Brno, Czech Republic..
    Janssen, Jeroen
    Vrije Univ Amsterdam, Med Ctr, Dept Hematol, Amsterdam, Netherlands..
    Cervantes, Francisco
    Univ Barcelona, Hosp Clin, IDIBAPS, Barcelona, Spain..
    Indrak, Karel
    Univ Palackianae, Dept Hematooncol, Olomouc, Czech Republic..
    Guilhot, Joelle
    CHU Poitiers, INSERM CIC 1402, Clin Invest Ctr, Poitiers, France..
    Hehlmann, Ruediger
    Heidelberg Univ, Med Fak Mannheim, Mannheim, Germany..
    Baccarani, Michele
    Univ Bologna, S Orsola Malpighi Hosp, Clin Dept Hematol & Oncol L&A Seragnoli, Bologna, Italy..
    The EUTOS Survival Score Is Preferable over the Sokal Score for Prognosis of Long-Term Survival of Patients with Chronic Myeloid Leukemia2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 35. Pfirrmann, Markus
    et al.
    Saussele, Susanne
    Baccarani, Michele
    Guilhot, Joelle
    Cervantes, Francisco
    Ossenkoppele, Gert J.
    Lindoerfer, Doris
    Hoffmann, Verena S.
    Castagnetti, Fausto
    Hehlmann, Ruediger
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Survival and Prognosis in Patients with First-Line Imatinib Treatment Under Particular Consideration of Death Due to Chronic Myeloid Leukemia2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 36. Saussele, S.
    et al.
    Adam, K.
    Hochhaus, A.
    Béné, M. C.
    Büchner, T.
    Burnett, A.
    Finazzi, G.
    Fonatsch, C.
    Gluckman, E.
    Gökbuget, N.
    Grimwade, D. J.
    Haferlach, T.
    Hallek, M.
    Hasford, J.
    Hoelzer, D.
    Ljungman, P.
    Niederwieser, D.
    Serve, H.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    de Witte, T. J.
    Hehlmann, R.
    Klinische Forschung im „European LeukemiaNet”2006In: Deutsche Medizinische Wochenschrift, ISSN 0012-0472, E-ISSN 1439-4413, Vol. 131, no 43, p. 2423-2426Article in journal (Refereed)
    Abstract [en]

    Because of their mortality, morbidity and incidence in all age groups, leukemias represent a challenge and a cost factor for society. In research, they serve as models for a variety of diseases and have a pivotal function in basic research and for patient care.

    The European LeukemiaNet (ELN) is a EU funded Network of excellence. Its major goal is the construction of an exemplary cooperative leukemia network for the improvement of medical care and of health related research in acute and chronic leukemias. This is achieved by improved mechanisms of cooperation among 78 national leukemia study groups and their 83 interdisciplinary partner groups that deal with the leukemias in research and in patient care in 22 countries. The network integrates about 1000 researchers in 125 participating institutions.

    In practice, cooperation between clinical and research groups is mediated by various instruments that improve communication, flow of information and interdisciplinary cooperation, and also increase information transfer from top research institutions to clinical translation. The improved cooperation and the accelerated information transfer from the „bench to the bedside” results in a better patient care that ultimately results in improved survival of patients and in superior competitiveness of involved research workers and clinicians.

    The major goals are:

    • Establishing common information and communication structures,

    • Creation of European networks for each leukemia

    • Establishing European platforms for each inter-disciplinary speciality

    • Performing clinical trials on an European level

    • Establishing European leukemia registries

    • Developing common definitions and standards

    • Developing guidelines and meta-analyses

    • Spread of excellence

    To reach these goals the network is organized in 17 Workpackages (WPs) each of which is subdivided into several components and deliverables. The WPs represent central services, set up European networks for each major leukemia or related syndrome and interdisciplinary European platforms for diagnostic specialities, and support treatment research, registries, meta-analyses and guidelines.

    After the second year of networking, the main structures concerning management, communication and information of the ELN have been established and consolidated. Web-based information is available on the central website (www.leukemia-net.org). Communication is accomplished through annual symposia, regular network and WP-meetings (nearly 60 in 2005), website, and the biannual newsletters.

    A central randomization service and registries are available for distinct leukemia entities, and a prototype of the electronic data capture facility service has been implemented. Several studies were initiated and are ongoing on a European level. Nearly all WPs have prepared or are preparing guidelines or consensus papers, e. g. guidelines on CML therapy, definitions for transplantation associated microangiopathy (TAM), therapy of infections in leukemias, harmonization of molecular monitoring in CML and a consensus on microarray-technology based diagnostics in leukemias.

    The main goals of the second funding period have been achieved, and thus the ELN is well prepared for further progress in its goals to improve diagnosis and treatment of the leukemias.

  • 37.
    Simonsson, B
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Kloke, O
    Stahel, R A
    ESMO Minimum Clinical Recommendations for the diagnosis, treatment and follow-up of chronic myelogenous leukemia (CML).2005In: Ann Oncol, ISSN 0923-7534, Vol. 16 Suppl 1, p. i52-3Article in journal (Refereed)
  • 38.
    Simonsson, Bengt
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Oberg, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Bjoreman, Mats
    Bjorkholm, Magnus
    Carneskog, Jan
    Karlsson, Karin
    Gahrton, Gosta
    Grimfors, Gunnar
    Hast, Robert
    Karle, Hans
    Linder, Olle
    Ljungman, Per
    Nielsen, Johan L
    Nilsson, Jonas
    Lofvenberg, Eva
    Department of Oncology, Radiology and Clinical Immunology.
    Malm, Claes
    Olsson, Karin
    Olsson-Stromberg, Ulla
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Paul, Christer
    Stenke, Leif
    Stentoft, Jesper
    Turesson, Ingemar
    Udén, Ann-Marie
    Wahlin, Anders
    Vilén, Lars
    Weis-Bjerrum, Ole
    Intensive treatment and stem cell transplantation in chronic myelogenous leukemia: long-term follow-up.2005In: Acta Haematol, ISSN 0001-5792, Vol. 113, no 3, p. 155-62Article in journal (Refereed)
  • 39.
    Söderlund, Stina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Christiansson, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Persson, Inger
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Hjorth-Hansen, H.
    Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Trondheim, Norway..
    Richter, J.
    Skane Univ Hosp, Dept Hematol Oncol & Radiat Phys, Lund, Sweden..
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Mustjoki, S.
    Univ Helsinki, Dept Hematol, Hematol Res Unit, Helsinki, Finland..
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Loskog, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Plasma Proteomics In Chronic Myeloid Leukemia Patients Before And After Initiation Of Tyrosine Kinase Inhibitor Therapy Reveals Induced Th1 Immunity And Loss Of Angiogenic Stimuli2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 730-730Article in journal (Other academic)
  • 40.
    Zyczynski, T.
    et al.
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Khoury, J.
    Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA..
    Goldberg, S.
    John Theurer Canc Ctr, Hackensack, NJ USA..
    Mauro, M.
    Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA..
    Michallet, M.
    Ctr Hosp Lyon Sud, Pierre Benite, France..
    Paquette, R.
    UCLA Med Ctr, Los Angeles, CA USA..
    Foreman, A.
    ICON Clin Res, San Francisco, CA USA..
    Subar, M.
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Turner, M.
    ICON Clin Res, San Francisco, CA USA..
    Daumont, Manley M.
    Bristol Myers Squibb Co, Paris, France..
    Hehlmann, R.
    Heidelberg Univ, Mannheim, Germany..
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Imatinib Discontinuation And Tki Switching Patterns In The Retrospective And Prospective Cohorts In Simplicity, A Study Of Chronic-Phase Chronic Myeloid Leukemia (Cp-Cml) Patients (Pts) In Routine Clinical Practice2016In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 19, no 7, p. A894-A895Article in journal (Refereed)
1 - 40 of 40
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