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  • 101. Falk, Ingrid Jakobsen
    et al.
    Fyrberg, Anna
    Hermanson, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Nahi, Hareth
    Palmqvist, Lars
    Paul, Christer
    Paul, Esbjorn
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Stockelberg, Dick
    Wei, Yuan
    Green, Henrik
    Lotfi, Kourosh
    Correlation between cytidine deaminase single nucleotide polymorphisms and in vitro drug sensitivity, DNA methylation and outcome in normal karyotype acute myelogenous leukemia2013In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 73, no 8Article in journal (Other academic)
  • 102. Falk, Ingrid Jakobsen
    et al.
    Fyrberg, Anna
    Paul, Esbjorn
    Nahi, Hareth
    Hermanson, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Rosenquist, Richard Brandell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Palmqvist, Lars
    Stockelberg, Dick
    Wei, Yuan
    Green, Henrik
    Lotfi, Kourosh
    Decreased survival in normal karyotype AML with single-nucleotide polymorphisms in genes encoding the AraC metabolizing enzymes cytidine deaminase and 5 '-nucleotidase2013In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 88, no 12, p. 1001-1006Article in journal (Refereed)
    Abstract [en]

    De novo acute myeloid leukemia with normal karyotype (NK-AML) comprises a large group of patients with no common cytogenetic alterations and with a large variation in treatment response. Single-nucleotide polymorphisms (SNPs) in genes related to the metabolism of the nucleoside analogue AraC, the backbone in AML treatment, might affect drug sensitivity and treatment outcome. Therefore, SNPs may serve as prognostic biomarkers aiding clinicians in individualized treatment decisions, with the aim of improving patient outcomes. We analyzed polymorphisms in genes encoding cytidine deaminase (CDA 79A> C rs2072671 and 2451C> T rs532545), 50-nucleotidase (cN-II 7A> G rs10883841), and deoxycytidine kinase (DCK 30UTR 948T> C rs4643786) in 205 de novo NK-AML patients. In FLT3-internal tandem duplication (ITD)-positive patients, the CDA 79C/C and 2451T/T genotypes were associated with shorter overall survival compared to other genotypes (5 vs. 24 months, P< 0.001 and 5 vs. 23 months, P50.015, respectively), and this was most pronounced in FLT3-ITD-positive/NPM1-positive patients. We observed altered in vitro sensitivity to topoisomerase inhibitory drugs, but not to nucleoside analogues, and a decrease in global DNA methylation in cells carrying both CDA variant alleles. A shorter survival was also observed for the cN-II variant allele, but only in FLT3-ITD-negative patients (25 vs. 31 months, P50.075). Our results indicate that polymorphisms in genes related to nucleoside analog drug metabolism may serve as prognostic markers in de novo NK-AML. Am. J. Hematol. 88: 1001-1006, 2013.

  • 103. Falk, Ingrid Jakobsen
    et al.
    Fyrberg, Anna
    Paul, Esbjorn
    Nahi, Hareth
    Hermanson, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Rosenquist, Richard Brandell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Palmqvist, Lars
    Stockelberg, Dick
    Wei, Yuan
    Green, Henrik
    Lotfi, Kourosh
    Impact of ABCB1 single nucleotide polymorphisms 1236C>T and 2677G>T on overall survival in FLT3 wild-type de novo AML patients with normal karyotype2014In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 167, no 5, p. 671-680Article in journal (Refereed)
    Abstract [en]

    Drug resistance is a clinically relevant problem in the treatment of acute myeloid leukaemia (AML). We have previously reported a relationship between single nucleotide polymorphisms (SNPs) of ABCB1, encoding the multi-drug transporter P-glycoprotein, and overall survival (OS) in normal karyotype (NK)-AML. Here we extended this material, enabling subgroup analysis based on FLT3 and NPM1 status, to further elucidate the influence of ABCB1 SNPs. De novo NK-AML patients (n = 201) were analysed for 1199G>A, 1236C>T, 2677G>T/A and 3435C>T, and correlations to outcome were investigated. FLT3 wild-type 1236C/C patients have significantly shorter OS compared to patients carrying the variant allele; medians 20 vs. 49 months, respectively, P = 0.017. There was also an inferior outcome in FLT3 wild-type 2677G/G patients compared to patients carrying the variant allele, median OS 20 vs. 35 months, respectively, P = 0.039. This was confirmed in Cox regression analysis. Our results indicate that ABCB1 1236C>T and 2677G>T may be used as prognostic markers to distinguish relatively high risk patients in the intermediate risk FLT3 wild-type group, which may contribute to future individualizing of treatment strategies.

  • 104.
    Forsman, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Uzameckis, Dmitrijs
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Åleskog, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Bindra, Amarinder
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Pipkorn, Rüdiger
    Lejniece, Sandra
    Kozireva, Svetlana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Murovska, Modra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Single-tube nested quantitative PCR: a rational and sensitive technique for detection of retroviral DNA. Application to RERV-H/HRV-5 and confirmation of its rabbit origin2003In: Journal of Virological Methods, ISSN 0166-0934, E-ISSN 1879-0984, Vol. 111, no 1, p. 1-11Article in journal (Refereed)
    Abstract [en]

    It was reported earlier that a few patients suffering from non-Hodgkin's lymphoma had low amounts of DNA from the so-called fifth human exogenous retrovirus, HRV-5. A sensitive and rational method for large-scale screening for HRV-5 DNA was therefore developed. It is a single-tube nested quantitative PCR (stnQPCR), which uses two functionally isolated primer pairs and one probe target distinct from related endogenous retroviral sequences, yet encompassing known HRV-5 variation, allowing optimal use of sequence conservation. DNA from lymphoma, myeloma, and follicular dendritic cell lines was tested for HRV-5 positivity, as was DNA from whole blood of blood donors, non-Hodgkin's lymphoma and systemic lupus erythematosus patients, as well as DNA from lymph node biopsies of rheumatoid arthritis patients with lymphoma. One blood donor, one systemic lupus erythematosus patient, two previously known positive non-Hodgkin's lymphoma patients, and one rheumatoid arthritis lymphoma patient, came out positive. They had 24, 2, 148, 480 and 30 proviral copies per microg of DNA from PBMC or lymphoma tissue, respectively. During the completion of this work it was reported that HRV-5 is a rabbit endogenous retrovirus (RERV-H), and that HRV-5 positivity was due to presence of rabbit DNA. DNA from six RERV-H/HRV-5 positive samples was therefore retested. Three also contained rabbit mitochondrial DNA. A search for HRV-5 antibodies using synthetic peptides was negative in sera from three RERV-H/HRV-5 positive individuals, as well as in 144 other sera, according with a noninfectious origin of the RERV-H/HRV-5 DNA in human samples. A search for possible sources of rabbit DNA contamination was negative. Methods for prevention of PCR contamination were strictly adhered to. Three samples from RERV-H/HRV-5 positive individuals positive at the Uppsala laboratory were retested at one or two other laboratories, and all three were positive. Two other samples, which were positive in the Riga laboratory, were tested also in London and also found positive. One non-Hodgkin's lymphoma patient was RERV-H/HRV-5 positive in four consecutive samples, showing that positivity was a property of that patient. It is concluded that the stnQPCR developed to detect and quantify minute amounts of RERV-H/HRV-5 DNA is a principle which can be applied widely and HRV-5 is a RERV-H. Its presence in a few human blood samples could not be explained.

  • 105. Frandsen, Thomas Leth
    et al.
    Heyman, Mats
    Abrahamsson, Jonas
    Vettenranta, Kim
    Asberg, Ann
    Vaitkeviciene, Goda
    Pruunsild, Kaie
    Toft, Nina
    Birgens, Henrik
    Hallböök, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Quist-Paulsen, Petter
    Griskevicius, Laimonas
    Helt, Louise
    Hansen, Birgitte Vilsboll
    Schmiegelow, Kjeld
    Complying with the European Clinical Trials directive while surviving the administrative pressure: An alternative approach to toxicity registration in a cancer trial2014In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, no 2, p. 251-259Article in journal (Refereed)
    Abstract [en]

    The European Clinical Trials Directive of 2004 has increased the amount of paper work and reduced the number of initiated clinical trials. Particularly multinational trials have been delayed. To meet this challenge we developed a novel, simplified, fast and easy strategy for on-line toxicity registration for patients treated according to the Nordic/Baltic acute lymphoblastic leukaemia protocol, NOPHO ALL 2008, for children and young adults, including three randomisations. We used a risk-assessment based approach, avoiding reporting of expected adverse events and instead concentrating on 20 well-known serious, but rarer events with focus on changes in therapy introduced in the treatment protocol. This toxicity registration strategy was approved by the relevant regulatory authorities in all seven countries involved, as compliant within the EU directive of 2004. The centre compliance to registration was excellent with 98.9% of all patients being registered within 5 weeks from the requested quarterly registration. Currently, four toxicities (thrombosis, fungal infections, pancreatitis and allergic reactions) have been chosen for further detailed exploration due to the cumulative fraction of patients with positive registrations exceeding 5%. This toxicity registration offers real-time toxicity profiles of the total study cohort and provides early warnings of specific toxicities that require further investigation.

  • 106. Genovese, Giulio
    et al.
    Kaehler, Anna K.
    Handsaker, Robert E.
    Lindberg, Johan
    Rose, Samuel A.
    Bakhoum, Samuel F.
    Chambert, Kimberly
    Mick, Eran
    Neale, Benjamin M.
    Fromer, Menachem
    Purcell, Shaun M.
    Svantesson, Oscar
    Landen, Mikael
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lehmann, Sören
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Gabriel, Stacey B.
    Moran, Jennifer L.
    Lander, Eric S.
    Sullivan, Patrick F.
    Sklar, Pamela
    Groenberg, Henrik
    Hultman, Christina M.
    McCarroll, Steven A.
    Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 371, no 26, p. 2477-2487Article in journal (Refereed)
    Abstract [en]

    Background Cancers arise from multiple acquired mutations, which presumably occur over many years. Early stages in cancer development might be present years before cancers become clinically apparent. Methods We analyzed data from whole-exome sequencing of DNA in peripheral-blood cells from 12,380 persons, unselected for cancer or hematologic phenotypes. We identified somatic mutations on the basis of unusual allelic fractions. We used data from Swedish national patient registers to follow health outcomes for 2 to 7 years after DNA sampling. Results Clonal hematopoiesis with somatic mutations was observed in 10% of persons older than 65 years of age but in only 1% of those younger than 50 years of age. Detectable clonal expansions most frequently involved somatic mutations in three genes (DNMT3A, ASXL1, and TET2) that have previously been implicated in hematologic cancers. Clonal hematopoiesis was a strong risk factor for subsequent hematologic cancer (hazard ratio, 12.9; 95% confidence interval, 5.8 to 28.7). Approximately 42% of hematologic cancers in this cohort arose in persons who had clonality at the time of DNA sampling, more than 6 months before a first diagnosis of cancer. Analysis of bone marrow-biopsy specimens obtained from two patients at the time of diagnosis of acute myeloid leukemia revealed that their cancers arose from the earlier clones. Conclusions Clonal hematopoiesis with somatic mutations is readily detected by means of DNA sequencing, is increasingly common as people age, and is associated with increased risks of hematologic cancer and death. A subset of the genes that are mutated in patients with myeloid cancers is frequently mutated in apparently healthy persons; these mutations may represent characteristic early events in the development of hematologic cancers.

  • 107. Geyer, H.
    et al.
    Emanuel, R.
    Dueck, A.
    Kiladjian, J. J.
    Xiao, Z.
    Slot, S.
    Zweegman, S.
    Sackman, F.
    Kerguelen Fuentes, A.
    Hernandez-Maraver, D.
    Dohner, K.
    Harrison, C.
    Radia, D.
    Muxi, P.
    Besses, C.
    Cervantes, F.
    Johansson, P.
    Andreasson, B.
    Rambaldi, A.
    Barbui, T.
    Vannucchi, A.
    Passamonti, F.
    Samuelsson, J.
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Bonatz, K.
    Reiter, A.
    Boyer, F.
    Etienne, G.
    Ianotto, J. C.
    Ranta, D.
    Roy, L.
    Cahn, J. Y.
    Maldonado, N.
    Barosi, G.
    Ferrari, M.
    Cannon, K.
    te Boekhorst, P. A.
    Klauke, K.
    Schouten, H.
    Pahl, H.
    Griesshammer, M.
    Stegelmann, F.
    Lehmann, T.
    Xu, Z.
    Zhang, Y.
    Sun, X.
    Xu, J.
    Zhang, P.
    Mesa, R.
    Gender Differences and MPN Symptom Burden: An Analysis by the MPN Quality of Life International Study Group (MPN-QOL ISG)2014In: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, p. 396-397Article in journal (Other academic)
  • 108.
    Geyer, H.
    et al.
    Mayo Clin, Phoenix, AZ USA..
    Kosiorek, H.
    Mayo Clin, Phoenix, AZ USA..
    Dueck, A.
    Mayo Clin, Phoenix, AZ USA..
    Slot, S.
    Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Zweegman, S.
    Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Kiladjian, J. J.
    Hosp St Louis, Paris, France..
    Boekhorst, P.
    Erasmus MC, Rotterdam, Netherlands..
    Schouten, H.
    Maastricht Univ, Med Ctr, Maastricht, Netherlands..
    Sackmann, F.
    Fundaleu, Buenos Aires, DF, Argentina..
    Fuentes, A.
    Univ Hosp La Paz, Madrid, Spain..
    Hernandez-Maraver, D.
    Univ Hosp La Paz, Madrid, Spain..
    Pahl, H.
    Univ Hosp Freiburg, Freiburg, Germany..
    Stegelmann, F.
    Univ Hosp Ulm, Ulm, Germany..
    Doehner, K.
    Univ Hosp Ulm, Ulm, Germany..
    Bonatz, K.
    Med Klin, Mannheim, Germany..
    Reiter, A.
    Med Klin, Mannheim, Germany..
    Boyer, F.
    CHU Angers, Angers, France..
    Etienne, G.
    CHU Angers, Angers, France..
    Ianotto, J. C.
    Univ Hosp, Brest, France..
    Ranta, D.
    Univ Hosp, Nancy, France..
    Roy, L.
    Ctr Hosp Univ, Poitiers, France..
    Cahn, J. Y.
    CHU Grenoble, Grenoble, France..
    Harrison, C.
    Guys & St Thomas NHS Fdn Trust, London, England..
    Radia, D.
    Guys & St Thomas NHS Fdn Trust, London, England..
    Muxi, P.
    Hosp Britanico, Montevideo, Uruguay..
    Maldonado, N.
    Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA..
    Besses, C.
    Hosp Mar, Barcelona, Spain..
    Cervantes, F.
    Univ Barcelona, Barcelona, Spain..
    Johansson, P.
    NU Hosp Org, Uddevalla, Sweden..
    Barosi, G.
    IRCCS Policlin S Matteo Fdn, Pavia, Italy..
    Passamonti, F.
    Fdn IRCCS Policlin San Matteo, Pavia, Italy..
    Andreasson, B.
    NU Hosp Org, Uddevalla, Sweden..
    Samuelsson, J.
    Stockholm South Hosp, Stockholm, Sweden..
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Sun, X.
    Chinese Acad Med Sci, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Xu, J.
    Chinese Acad Med Sci, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Zhang, P.
    Chinese Acad Med Sci, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Xu, Z.
    Chinese Acad Med Sci, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Barbui, T.
    Osped Riuniti Bergamo, Bergamo, Italy.;Osped Riuniti Bergamo, Bergamo, Italy..
    Senyak, Z.
    MPN Forum, Asheville, NC USA..
    Grieshammer, M.
    Johannes Wesling Klinikum, Minden, Germany..
    Rambaldi, A.
    Osped Riuniti Bergamo, Bergamo, Italy..
    Ferrari, M.
    Osped Riuniti Bergamo, Bergamo, Italy..
    Lehmann, T.
    Univ Basel Hosp, Basel, Switzerland..
    Scherber, R.
    Mayo Clin, Phoenix, AZ USA..
    Mesa, R.
    Mayo Clin, Phoenix, AZ USA..
    Development Of An Mf Patient Reported Outcome (Pro) Tool For Fda Qualification: Comprehensive Literature Search And Physician Cognitive Debriefing Results2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 564-564Article in journal (Other academic)
  • 109.
    Geyer, H.
    et al.
    Mayo Clin, Scottsdale, AZ USA..
    Kosiorek, H.
    Mayo Clin, Scottsdale, AZ USA..
    Scherber, R.
    Mayo Clin, Scottsdale, AZ USA..
    Dueck, A.
    Mayo Clin, Scottsdale, AZ USA..
    Jean-Jacques, K.
    Hosp St Louis, Paris, France..
    Xiao, Z.
    Chinese Acad Med Sci, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Zweegman, S.
    Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Sackman, F.
    Fundaleu, Buenos Aires, DF, Argentina..
    Hernandez-Maraver, D.
    Univ Hosp La Paz, Madrid, Spain..
    Dohner, K.
    Univ Hosp Ulm, Ulm, Germany..
    Harrison, C.
    Guys & St Tomas NHS Fdn Trust, London, England..
    Radia, D.
    Guys & St Tomas NHS Fdn Trust, London, England..
    Muxi, P.
    Hosp Britanico, Montevideo, Uruguay..
    Besses, C.
    Hosp Del Mar, Barcelona, Spain..
    Cervantes, F.
    Univ Barcelona, Barcelona, Spain..
    Johansson, P.
    NU Hosp Org, Uddevalla, Sweden..
    Andreasson, B.
    NU Hosp Org, Uddevalla, Sweden..
    Rambaldi, A.
    Azienda Ospedal, Bergamo, Italy..
    Barbui, T.
    Azienda Ospedal, Bergamo, Italy..
    Vannucchi, A.
    Osped Circolo Varese, Varese, Italy..
    Passamonti, F.
    Fdn IRCCS Policlin San Matteo, Pavia, Italy..
    Samuelsson, J.
    Stockholm South Hosp, Stockholm, Sweden..
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Bonatz, K.
    Med Klin, Mannheim, Germany..
    Reiter, A.
    Med Klin, Mannheim, Germany..
    Boyer, F.
    Ctr Hosp Univ, Angers, France..
    Etienne, G.
    Inst Bergonie, Bordeaux, France..
    Ianotto, J. -C
    Ranta, D.
    Univ Hosp, Nancy, France..
    Roy, L.
    Ctr Hosp Univ, Poitiers, France..
    Cahn, J. -Y
    Maldonado, N.
    Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA..
    Barosi, G.
    IRCCS Policlin S Matteo Fdn, Pavia, Italy..
    Ferrari, M.
    Osped Riuniti Bergamo, I-24100 Bergamo, Italy..
    Cannon, K.
    Mayo Clin, Scottsdale, AZ USA..
    te Boekhorst, P. A. W.
    Erasmus MC, Rotterdam, Netherlands..
    Klauke, K.
    Leiden Univ, Med Ctr, Leiden, Netherlands..
    Schouten, H.
    Maastricht Univ, Med Ctr, Maastricht, Netherlands..
    Pahl, H.
    Univ Hosp Freiburg, Freiburg, Germany..
    Griesshammer, M.
    Johannes Wesling Klinikum, Minden, Germany..
    Stegelmann, F.
    Univ Hosp Ulm, Ulm, Germany..
    Lehmann, T.
    Univ Basel Hosp, CH-4031 Basel, Switzerland..
    Xu, Z.
    Chinese Acad Med Sci, Inst Hematol, Tianjin, Peoples R China.;Blood Dis Hosp, Tianjin, Peoples R China..
    Zhang, Y.
    Chinese Acad Med Sci, Inst Hematol, Tianjin, Peoples R China.;Blood Dis Hosp, Tianjin, Peoples R China..
    Sun, X.
    Chinese Acad Med Sci, Inst Hematol, Tianjin, Peoples R China.;Blood Dis Hosp, Tianjin, Peoples R China..
    Xu, J.
    Chinese Acad Med Sci, Inst Hematol, Tianjin, Peoples R China.;Blood Dis Hosp, Tianjin, Peoples R China..
    Zhang, P.
    Chinese Acad Med Sci, Inst Hematol, Tianjin, Peoples R China.;Blood Dis Hosp, Tianjin, Peoples R China..
    Mesa, R.
    Mayo Clin, Scottsdale, AZ USA..
    PRIMARY MYELOFIBROSIS, POST-ET AND POST-PV MYELOFIBROSIS HAVE DISTINCT CLINICAL PROFILES AND SYMPTOMATIC BURDENS: AN ANALYSIS BY THE MPN QUALITY OF LIFE INTERNATIONAL STUDY GROUP (MPN-QOL ISG)2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, p. 261-262Article in journal (Other academic)
  • 110.
    Geyer, H.
    et al.
    Mayo Clin, Phoenix, AZ USA..
    Scherber, R.
    OHSU, Portland, OR USA..
    Kosiorek, H.
    Mayo Clin, Phoenix, AZ USA..
    Dueck, A.
    Mayo Clin, Phoenix, AZ USA..
    Kiladjian, J. J.
    Hosp St Louis, Paris, France..
    Slot, S.
    Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Zweegman, S.
    Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Boekhorst, P.
    Erasmus Med Cener, Rotterdam, Netherlands..
    Schouten, H.
    Maastricht Univ, Med Ctr, Maastricht, Netherlands..
    Sackmann, F.
    Fundaleu, Buenos Aires, DF, Argentina..
    Fuentes, A.
    Univ Hosp La Paz, Madrid, Spain..
    Hernandez-Maraver, D.
    Univ Hosp La Paz, Madrid, Spain..
    Pahl, H.
    Univ Hosp Freiburg, Freiburg, Germany..
    Stegelmann, F.
    Univ Hosp Ulm, Ulm, Germany..
    Doehner, K.
    Univ Hosp Ulm, Ulm, Germany..
    Bonatz, K.
    Med Klin, Mannheim, Germany..
    Reiter, A.
    Med Klin, Mannheim, Germany..
    Boyer, F.
    Ctr Hosp Univ, Angers, France..
    Etienne, G.
    Ctr Hosp Univ, Angers, France..
    Ianotto, J. C.
    Hosp Univ, Brest, France..
    Ranta, D.
    Hosp Univ, Nancy, France..
    Roy, L.
    Ctr Hosp Univ, Poitiers, France..
    Cahn, J. Y.
    Ctr Hosp Univ, Grenoble, France..
    Harrison, C.
    Guys & St Thomas NHS Fdn Trust, London, England..
    Radia, D.
    Guys & St Thomas NHS Fdn Trust, London, England..
    Muxi, P.
    Hosp Britanico, Montevideo, Uruguay..
    Maldonado, N.
    Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA..
    Besses, C.
    Hosp del Mar, Barcelona, Spain..
    Cervantes, F.
    Univ Barcelona, Barcelona, Spain..
    Johansson, P.
    NU Hosp Org, Uddevalla, Sweden..
    Barosi, G.
    IRCCS Policlin S Matteo Fdn, Pavia, Italy..
    Vannucchi, A.
    Osped Circolo Varese, Varese, Italy..
    Passamonti, F.
    Fdn IRCCS Policlin San Matteo, Pavia, Italy..
    Andreasson, B.
    NU Hosp Org, Uddavalla, Sweden..
    Samuelsson, J.
    Stockholm South Hosp, Stockholm, Sweden..
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Sun, X.
    Chinese Acad Med Sci, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Xu, J.
    Chinese Acad Med Sci, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Zhang, P.
    Chinese Acad Med Sci, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Xu, Z.
    Chinese Acad Med Sci, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Barbui, T.
    Osped Riuniti Bergamo, Bergamo, Italy.;Osped Riuniti Bergamo, Bergamo, Italy..
    Senyak, Z.
    MPN Forum, Asheville, NC USA..
    Grieshammer, M.
    Johannes Wesling Klinikum, Minden, Germany..
    Rambaldi, A.
    Osped Riuniti Bergamo, Bergamo, Italy..
    Ferrari, M.
    Osped Riuniti Bergamo, Bergamo, Italy..
    Lehmann, T.
    Univ Basel Hosp, Basel, Switzerland..
    Mesa, R.
    Mayo Clin, Phoenix, AZ USA..
    Impact Of Splenomegaly On Mpn Symptoms And Association With Clinical Features: An Analysis By The Mpn Quality Of Life International Study Group2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 555-555Article in journal (Other academic)
  • 111.
    Geyer, Holly L.
    et al.
    Mayo Clin, Div Hosp Internal Med, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA..
    Andreasson, Bjorn
    NU Hosp Org, Internal Med, Uddevalla, Sweden..
    Kosiorek, Heidi E.
    Mayo Clin, Sect Biostat, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA..
    Dueck, Amylou C.
    Mayo Clin, Sect Biostat, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA..
    Scherber, Robyn M.
    Oregon Hlth & Sci Univ, Dept Hematol & Oncol, Portland, OR 97201 USA..
    Martin, Kari A.
    Mayo Clin, Dept Psychiat, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA..
    Butler, Kristina A.
    Mayo Clin, Dept Gynecol, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA..
    Harrison, Claire N.
    Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England..
    Radia, Deepti H.
    Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England..
    Cervantes, Francisco
    Univ Barcelona, Dept Hematol, Hosp Clin, IDIBAPS, Barcelona, Spain..
    Kiladjian, Jean-Jacques
    Hosp St Louis, Clin Invest Ctr, Paris, France..
    Reiter, Andreas
    Univ Mannheim, Med Clin, D-68131 Mannheim, Germany..
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Passamonti, Francesco
    Univ Pavia, Dept Hematol, IRCCS Fdn San Matteo Polyclin, Via Palestro 3, I-27100 Pavia, Italy..
    Senyak, Zhenya
    MPN Forum, Asheville, NC USA..
    Vannucchi, Alessandro M.
    Circolo Hosp, Div Hematol, Varese, Italy..
    Paoli, Chiara
    Univ Florence, Dept Med, Florence, Italy..
    Xiao, Zhijian
    Chinese Acad Med Sci, Inst Hematol, MDS & MPN Ctr, Tianjin, Peoples R China.;Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Samuelsson, Jan
    Stockholm South Hosp, Dept Internal Med, Stockholm, Sweden..
    Mesa, Ruben A.
    Mayo Clin, Div Hematol Oncol, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA..
    The role of sexuality symptoms in myeloproliferative neoplasm symptom burden and quality of life: An analysis by the MPN QOL International Study Group2016In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 122, no 12, p. 1888-1896Article in journal (Refereed)
    Abstract [en]

    BACKGROUNDPatients with myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and myelofibrosis, are faced with oppressive symptom profiles that compromise daily functioning and quality of life. Among these symptoms, sexuality-related symptoms have emerged as particularly prominent and largely unaddressed. In the current study, the authors evaluated how sexuality symptoms from MPN relate to other patient characteristics, disease features, treatments, and symptoms. METHODSA total of 1971 patients with MPN (827 with essential thrombocythemia, 682 with polycythemia vera, 456 with myelofibrosis, and 6 classified as other) were prospectively evaluated and patient responses to the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ C30) were collected, along with information regarding individual disease characteristics and laboratory data. Sexuality scores were compared with an age-matched, healthy control population. RESULTSOverall, patients with MPN were found to have greater sexual dysfunction compared with the healthy population (MPN-SAF score of 3.6 vs 2.0; P<.001), with 64% of patients with MPN describing some degree of sexual dysfunction and 43% experiencing severe symptoms. The presence of sexual symptoms correlated closely with all domains of patient functionality (physical, social, cognitive, emotional, and role functioning) and were associated with a reduced quality of life. Sexual problems also were found to be associated with other MPN symptoms, particularly depression and nocturnal and microvascular-related symptoms. Sexual dysfunction was more severe in patients aged >65 years and in those with cytopenias and transfusion requirements, and those receiving certain therapies such as immunomodulators or steroids. ConclusionsThe results of the current study identify the topic of sexuality as a prominent issue for the MPN population, and this area would appear to benefit from additional investigation and management. Cancer 2016;122:1888-96. (c) 2016 American Cancer Society. Sexuality problems impact all domains of functionality, depression, microvascular symptoms, and overall quality of life among patients with myeloproliferative neoplasms. These problems correlate with patient age, the presence of cytopenias, transfusion requirements, and common therapies for myeloproliferative neoplasms. See also pages 1804-6.

  • 112.
    Geyer, Holly L.
    et al.
    Mayo Clin, Dept Internal Med, Scottsdale, AZ 85259 USA..
    Kosiorek, Heidi
    Mayo Clin, Sect Biostat, Scottsdale, AZ USA..
    Dueck, Amylou C.
    Mayo Clin, Sect Biostat, Scottsdale, AZ USA..
    Scherber, Robyn
    Oregon Hlth & Sci Univ, Portland, OR USA..
    Slot, Stefanie
    Vrije Univ Amsterdam Med Ctr, Dept Hematol, Amsterdam, Netherlands..
    Zweegman, Sonja
    Vrije Univ Amsterdam Med Ctr, Dept Hematol, Amsterdam, Netherlands..
    te Boekhorst, Peter A. W.
    Erasmus MC, Dept Hematol, Rotterdam, Netherlands..
    Senyak, Zhenya
    MPN Forum, Asheville, NC USA..
    Schouten, Harry C.
    MUMC, Dept Hematol, Maastricht, Netherlands..
    Sackmann, Federico
    Fundaleu, Buenos Aires, DF, Argentina..
    Kerguelen Fuentes, Ana
    Univ Hosp La Paz, Dept Haematol, Madrid, Spain..
    Hernandez-Maraver, Dolores
    Univ Hosp La Paz, Dept Haematol, Madrid, Spain..
    Pahl, Heike L.
    Univ Hosp Freiburg, Dept Mol Hematol, Freiburg, Germany..
    Griesshammer, Martin
    Johannes Wesling Klinikum, Minden, Germany..
    Stegelmann, Frank
    Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany..
    Doehner, Konstanze
    Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany..
    Lehmann, Thomas
    Univ Hosp, Dept Hematol, Basel, Switzerland..
    Bonatz, Karin
    Univ Med, Med Klin, Mannheim, Germany..
    Reiter, Andreas
    Univ Med, Med Klin, Mannheim, Germany..
    Boyer, Francoise
    Ctr Hosp Univ, Angers, France..
    Etienne, Gabriel
    Inst Bergonie, Bordeaux, France..
    Ianotto, Jean-Christophe
    Ctr Hosp Univ, Brest, France..
    Ranta, Dana
    Hosp Univ, Nancy, France..
    Roy, Lydia
    Ctr Hosp Univ, Poitiers, France..
    Cahn, Jean-Yves
    Ctr Hosp Univ, Grenoble, France..
    Harrison, Claire N.
    Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England..
    Radia, Deepti
    Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England..
    Muxi, Pablo
    Hosp Britan, Unidadde Hematol, Montevideo, Uruguay..
    Maldonado, Norman
    Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA..
    Besses, Carlos
    Hosp del Mar, Dept Hematol, Barcelona, Spain..
    Cervantes, Francisco
    Univ Barcelona, Hosp Clin, Dept Hematol, IDIBAPS, Barcelona, Spain..
    Johansson, Peter L.
    NU Hosp Org, Internal Med, Uddevalla, Sweden..
    Barbui, Tiziano
    Hosp Papa Giovanni XXIII, Res Fdn FROM, Bergamo, Italy..
    Barosi, Giovanni
    IRCCS Policlin S Matteo Fdn, Lab Clin Epidemiol, Pavia, Italy..
    Vannucchi, Alessandro M.
    Univ Florence, Ctr Res & Innovat Myeloproliferat Neoplasms, Florence, Italy..
    Paoli, Chiara
    Univ Florence, Ctr Res & Innovat Myeloproliferat Neoplasms, Florence, Italy..
    Passamonti, Francesco
    Univ Insubria, Dipartimento Med Clin & Sperimentale, Ematol, Varese, Italy..
    Andreasson, Bjorn
    NU Hosp Org, Internal Med, Uddevalla, Sweden..
    Ferrari, Maria L.
    Osped Riuniti Bergamo, Biol Sci, Bergamo, Italy..
    Rambaldi, Alessandro
    Hosp Papa Giovanni XXIII, Res Fdn FROM, Bergamo, Italy..
    Samuelsson, Jan
    Stockholm South Hosp, Dept Internal Med, Stockholm, Sweden..
    Cannon, Keith
    Mayo Clin, Dept Internal Med, Scottsdale, AZ 85259 USA..
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Xiao, Zhijian
    Chinese Acad Med Sci, Inst Hematol, MDS & MPN Ctr, Tianjin, Peoples R China.;Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Xu, Zefeng
    Chinese Acad Med Sci, Inst Hematol, MDS & MPN Ctr, Tianjin, Peoples R China.;Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Zhang, Yue
    Chinese Acad Med Sci, Inst Hematol, MDS & MPN Ctr, Tianjin, Peoples R China.;Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Sun, Xiujuan
    Chinese Acad Med Sci, Inst Hematol, MDS & MPN Ctr, Tianjin, Peoples R China.;Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Xu, Junqing
    Chinese Acad Med Sci, Inst Hematol, MDS & MPN Ctr, Tianjin, Peoples R China.;Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China..
    Kiladjian, Jean-Jacques
    Hosp St Louis, Clin Invest Ctr, Paris, France..
    Zhang, Peihong
    Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China.;Peking Union Med Coll, Tianjin, Peoples R China.;Chinese Acad Med Sci, Inst Hematol, Dept Pathol, Tianjin, Peoples R China..
    Gale, Robert Peter
    Imperial Coll, London, England..
    Mesa, Ruben A.
    Mayo Clin, Dept Hematol & Oncol, Scottsdale, AZ 85259 USA..
    Associations between gender, disease features and symptom burden in patients with myeloproliferative neoplasms: an analysis by the MPN QOL International Working Group2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, no 1, p. 85-93Article in journal (Refereed)
    Abstract [en]

    The myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis, are distinguished by their debilitating symptom profiles, life-threatening complications and profound impact on quality of life. The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated. In this study we evaluated how gender relates to patients' characteristics, disease complications and overall symptom expression. A total of 2,006 patients (polycythemia vera=711, essential thrombocythemia=830, myelofibrosis=460, unknown=5) were prospectively evaluated, with patients completing the Myeloproliferative Neoplasm-Symptom Assessment Form and Brief Fatigue Inventory Patient Reported Outcome tools. Information on the individual patients' characteristics, disease complications and laboratory data was collected. Consistent with known literature, most female patients were more likely to have essential thrombocythemia (48.6% versus 33.0%; P<0.001) and most male patients were more likely to have polycythemia vera (41.8% versus 30.3%; P<0.001). The rate of thrombocytopenia was higher among males than females (13.9% versus 8.2%; P<0.001) and males also had greater red-blood cell transfusion requirements (7.3% versus 4.9%; P=0.02) with shorter mean disease duration (6.4 versus 7.2 years, P=0.03). Despite there being no statistical differences in risk scores, receipt of most therapies or prior complications (hemorrhage, thrombosis), females had more severe and more frequent symptoms for most individual symptoms, along with overall total symptom score (22.8 versus 20.3; P<0.001). Females had particularly high scores for abdominal-related symptoms (abdominal pain/discomfort) and microvascular symptoms (headache, fatigue, insomnia, concentration difficulties, dizziness; all P<0.01). Despite complaining of more severe symptom burden, females had similar quality of life scores to those of males. The results of this study suggest that gender contributes to the heterogeneity of myeloproliferative neoplasms by influencing phenotypic profiles and symptom expression.

  • 113. Geyer, Holly L.
    et al.
    Scherber, Robyn M.
    Dueck, Amylou C.
    Kiladjian, Jean-Jacques
    Xiao, Zhijian
    Slot, Stefanie
    Zweegman, Sonja
    Sackmann, Federico
    Kerguelen Fuentes, Ana
    Hernandez-Maraver, Dolores
    Doehner, Konstanze
    Harrison, Claire N.
    Radia, Deepti
    Muxi, Pablo
    Besses, Carlos
    Cervantes, Francisco
    Johansson, Peter L.
    Andreasson, Bjorn
    Rambaldi, Alessandro
    Barbui, Tiziano
    Vannucchi, Alessandro M.
    Passamonti, Francesco
    Samuelsson, Jan
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Mesa, Ruben A.
    Distinct clustering of symptomatic burden among myeloproliferative neoplasm patients: retrospective assessment in 1470 patients2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 123, no 24, p. 3803-3810Article in journal (Refereed)
    Abstract [en]

    Symptom burden in myeloproliferative neoplasms (MPNs) is heterogeneous even among patients within the same MPN diagnosis. Using cluster analysis from prospectively gathered symptom burden data in 1470 international patients with essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF), we assessed for the presence of clusters and relationship to disease features and prognosis. In MF (4 clusters identified), clusters significantly differed by Dynamic International Prognostic Scoring System (DIPSS) risk (P < .001), leukopenia (P = .009), thrombocytopenia (P < .001), and spleen size (P = .02). Although an association existed between clusters and DIPSS risk, high symptom burden was noted in some low and intermediate-1-risk MF patients. In PV (5 clusters identified), total symptom score increased across clusters (P < .001), but clusters did not significantly differ by PV risk or the risk assessment variable of age. Among ET patients (5 clusters identified), clusters differed by gender (P = .04), anemia (P = .01), and prior hemorrhage (P = .047). Total symptom score increased across clusters (P < .001), but clusters did not significantly differ by International Prognostic Score for ET risk including the risk assessment variables. Significant symptom heterogeneity exists within each MPN subtype, sometimes independent of disease features or prognosis.

  • 114. Geyer, Holly Lynn
    et al.
    Dueck, Amylou C.
    Emanuel, Robyn M.
    Kiladjian, Jean-Jacques
    Slot, Stefanie
    Zweegman, Sonja
    Boekhorst, Peter
    Commandeur, Suzan
    Schouten, Harry C.
    Sackmann, Federico
    Kerguelen Fuentes, Ana
    Hernandez-Maraver, Dolores
    Pahl, Heike
    Griesshammer, Martin
    Stegelmann, Frank
    Doehner, Konstanze
    Boyer, Francoise
    Etienne, Gabriel
    Lanotto, Jean-Christophe
    Ranta, Dana
    Roy, Lydia
    Cahn, Jean-Yves
    Harrison, Claire N.
    Radia, Deepti H.
    Muxi, Pablo J.
    Maldonado, Norman I.
    Besses, Carlos
    Cervantes, Francisco
    Johansson, Peter
    Barosi, Giovanni
    Vannucchi, Alessandro M.
    Passamonti, Francesco
    Andreasson, Bjorn
    Ferarri, Maria L.
    Rambaldi, Alessandro
    Samuelsson, Jan
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Xiao, Zhijian
    Zhang, Yue
    Sun, Xiujuan
    Xu, Junqing
    Gale, Robert Peter
    Tefferi, Ayalew
    Zhang, Peihong
    Lehmann, Thomas
    Reiter, Andreas
    Bonatz, Karin
    Mesa, Ruben A.
    The Myelofibrosis Symptom Burden (MF-SB): An International Phenotypic Cluster Analysis of 329 Patients2012In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 120, no 21, p. 1731-Article in journal (Refereed)
  • 115. Geyer, Holly Lynn
    et al.
    Scherber, Robyn M.
    Dueck, Amylou Constance
    Kiladjian, Jean-Jacques
    Xiao, Zhijian
    Slot, Stephanie
    Zweegman, Sonja
    Kerguelen Fuentes, Ana
    Hernandez-Maraver, Dolores
    Dohner, Konstanze
    Harrison, Claire N.
    Radia, Deepti H.
    Muxi, Pablo J.
    Sackman, Federico
    Besses, Carlos
    Cervantes, Francisco
    Johansson, Peter L.
    Andreasson, Bjorn
    Rambaldi, Alessandro
    Barbui, Tiziano
    Vannucchi, Alessandro M.
    Passamonti, Francesco
    Samuelsson, Jan
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Bonatz, Karin
    Reiter, Andreas
    Boyer, Francoise
    Etienne, Gabriel
    Ianotto, Jean-Christophe
    Ranta, Dana
    Roy, Lydia
    Cahn, Jean-Yves
    Maldonado, Norman I.
    Barosi, Giovanni
    Ferrari, Maria
    Cannon, Keith
    te Boekhorst, Peter
    Schouten, Harry C.
    Pahl, Heike L.
    Griesshammer, Martin
    Stegelmann, Frank
    Lehmann, Thomas
    Xu, Zefeng
    Zhang, Yue
    Sun, Xiujuan
    Xu, Junqing
    Zhang, Peihong
    Mesa, Ruben
    Symptom Severity and Clinical Variables of Polycythemia Vera Patients with Splenomegaly, Phlebotomy Requirements and/or Hydroxyurea Use: a Retrospective Evaluation of 1334 Patients2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 116. Geyer, Holly
    et al.
    Scherber, Robyn
    Kosiorek, Heidi
    Dueck, Amylou C
    Kiladjian, Jean-Jacques
    Xiao, Zhijian
    Slot, Stefanie
    Zweegman, Sonja
    Sackmann, Federico
    Fuentes, Ana Kerguelen
    Hernández-Maraver, Dolores
    Döhner, Konstanze
    Harrison, Claire N
    Radia, Deepti
    Muxi, Pablo
    Besses, Carlos
    Cervantes, Francisco
    Johansson, Peter L
    Andreasson, Bjorn
    Rambaldi, Alessandro
    Barbui, Tiziano
    Bonatz, Karin
    Reiter, Andreas
    Boyer, Francoise
    Etienne, Gabriel
    Ianotto, Jean-Christophe
    Ranta, Dana
    Roy, Lydia
    Cahn, Jean-Yves
    Maldonado, Norman
    Barosi, Giovanni
    Ferrari, Maria L
    Gale, Robert Peter
    Birgegard, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Xu, Zefeng
    Zhang, Yue
    Sun, Xiujuan
    Xu, Junqing
    Zhang, Peihong
    Te Boekhorst, Peter A W
    Commandeur, Suzan
    Schouten, Harry
    Pahl, Heike L
    Griesshammer, Martin
    Stegelmann, Frank
    Lehmann, Thomas
    Senyak, Zhenya
    Vannucchi, Alessandro M
    Passamonti, Francesco
    Samuelsson, Jan
    Mesa, Ruben A
    Symptomatic Profiles of Patients With Polycythemia Vera: Implications of Inadequately Controlled Disease2016In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, no 2, p. 151-+Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with disabling symptoms and a heightened risk of life-threatening complications. Recent studies have demonstrated the effectiveness of JAK inhibitor therapy in patients with PV patients who have a history of prior hydroxyurea (HU) use (including resistance or intolerance), phlebotomy requirements, and palpable splenomegaly. We aimed to determine how these features contribute alone and in aggregate to the PV symptom burden.

    PATIENTS AND METHODS: Through prospective evaluation of 1,334 patients with PV who had characterized symptom burden, we assessed patient demographics, laboratory data, and the presence of splenomegaly by disease feature (ie, known HU use, known phlebotomy requirements, splenomegaly).

    RESULTS: The presence of each feature in itself is associated with a moderately high symptom burden (MPN symptom assessment form [SAF] total symptom score [TSS] range, 27.7 to 29.2) that persists independent of PV risk category. In addition, symptoms incrementally increase in severity with the addition of other features. Patients with PV who had all three features (PV-HUPS) faced the highest total score (MPN-SAF TSS, 32.5) but had similar individual symptom scores to patients with known HU use (PV-HU), known phlebotomy (PV-P), and splenomegaly (PV-S).

    CONCLUSION: The results of this study suggest that patients with PV who have any one of the features in question (known HU use, known phlebotomy, or splenomegaly) have significant PV-associated symptoms. Furthermore, it demonstrates that many PV symptoms remain severe independent of the number of features present.

  • 117. Giebel, Sebastian
    et al.
    Thomas, Xavier
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Geissler, Klaus
    Boiron, Jean-Michel
    Huguet, Francoise
    Koller, Elisabeth
    Jaeger, Ulrich
    Smedmyr, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hellmann, Andrzej
    Holowiecki, Jerzy
    The prophylactic use of granulocyte-colony stimulating factor during remission induction is associated with increased leukaemia-free survival of adults with acute lymphoblastic leukaemia: A joint analysis of five randomised trials on behalf of the EWALL2012In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 48, no 3, p. 360-367Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Granulocyte-colony stimulating factor (G-CSF) is used to prevent febrile neutropenia and support intense chemotherapy. However, its impact on long-term outcome in oncological patients including adults with acute lymphoblastic leukaemia (ALL) has not been determined so far.

    METHODS:

    In the current study follow-up data from individual patients recruited in five multicentre, prospective, randomised trials were pooled to perform a joint analysis. Among 347 adults and adolescents with ALL, 185 were assigned to receive prophylactically G-CSF along with induction chemotherapy while 162 patients were treated without G-CSF support.

    RESULTS:

    With the median follow-up of 5.3years, there was a tendency towards increased 5year probability of the overall survival for the G-CSF arm compared to the controls (32%±4% versus 23%±4%, p=.07), which reached statistical significance in a subgroup of T-ALL (51%±8% versus 29%±9%, p=.01) and among patients aged 21-40years (44%±6% versus 27%±6%, p=.03). The probability of leukaemia-free survival was 38%±4% and 24%±4% (p=.01) while the median remission duration equalled 33 and 17months (p=.007), respectively. In a multivariate analysis the prophylactic use of G-CSF was independently associated with reduced risk of relapse (hazard ratio (HR)=.64, p=.007) and treatment failure (HR=.67, p=.02).

    CONCLUSIONS:

    The prophylactic use of G-CSF during induction of ALL is associated with improved long-term outcome and should be recommended especially in a setting of T-ALL and in 'young adults'. Our analysis provides the first direct evidence coming from prospective trials for the impact of primary G-CSF prophylaxis on disease-free survival of oncological patients.

  • 118. Gimsing, Peter
    et al.
    Carlson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Turesson, Ingemar
    Fayers, Peter
    Waage, Anders
    Vangsted, Annette
    Mylin, Anne
    Gluud, Christian
    Juliusson, Gunnar
    Gregersen, Henrik
    Hjorth-Hansen, Henrik
    Nesthus, Ingerid
    Dahl, Inger Marie S.
    Westin, Jan
    Nielsen, Johan Lanng
    Knudsen, Lene Meldgaard
    Ahlberg, Lucia
    Hjorth, Martin
    Abildgaard, Niels
    Andersen, Niels Frost
    Linder, Olle
    Wisloeff, Finn
    Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial2010In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 11, no 10, p. 973-982Article in journal (Refereed)
    Abstract [en]

    Background Compared with placebo, prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma. However, because of toxicity associated with long-term bisphosphonate treatment, establishing the lowest effective dose is important. This study compared the effect of two doses of pamidronate on health-related quality of life and skeletal morbidity in patients with newly diagnosed multiple myeloma. Methods This double-blind, randomised, phase 3 trial was undertaken at 37 clinics in Denmark, Norway, and Sweden. Patients with multiple myeloma who were starting antimyeloma treatment were randomly assigned in a 1:1 ratio to receive one of two doses of pamidronate (30 mg or 90 mg) given by intravenous infusion once a month for at least 3 years. Randomisation was done by use of a central, computerised minimisation system. Primary outcome was physical function after 12 months estimated by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire (scale 0-100). All patients who returned questionnaires at 12 months and were still on study treatment were included in the analysis of the primary endpoint. This study is registered with ClinicalTrials. gov, number NCT00376883. Findings From January, 2001, until August, 2005, 504 patients were randomly assigned to pamidronate 30 mg or 90 mg (252 in each group). 157 patients in the 90 mg group and 156 in the 30 mg group were included in the primary analysis. Mean physical function at 12 months was 66 points (95% CI 62.9-70.0) in the 90 mg group and 68 points (64.6-71.4) in the 30 mg group (95% CI of difference -6.6 to 3.3; p=0.52). Median time to first skeletal-related event in patients who had such an event was 9.2 months (8.1-10.7) in the 90 mg group and 10-2 months (7.3-14.0) in the 30 mg group (p=0.63). In a retrospective analysis, eight patients in the pamidronate 90 mg group developed osteonecrosis of the jaw compared with two patients in the 30 mg group. Interpretation Monthly infusion of pamidronate 30 mg should be the recommended dose for prevention of bone disease in patients with multiple myeloma.

  • 119.
    Giustacchini, Alice
    et al.
    Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England.;Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Biol Lab, Oxford, England..
    Thongjuea, Supat
    Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England.;Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Biol Lab, Oxford, England..
    Barkas, Nikolaos
    Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England.;Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Biol Lab, Oxford, England..
    Woll, Petter S.
    Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Biol Lab, Oxford, England..
    Povinelli, Benjamin J.
    Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England.;Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Biol Lab, Oxford, England..
    Booth, Christopher A. G.
    Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England.;Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Biol Lab, Oxford, England..
    Sopp, Paul
    Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England.;Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Biol Lab, Oxford, England..
    Norfo, Ruggiero
    Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England.;Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Biol Lab, Oxford, England..
    Rodriguez-Meira, Alba
    Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England.;Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Biol Lab, Oxford, England..
    Ashley, Neil
    Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England.;Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Biol Lab, Oxford, England..
    Jamieson, Lauren
    Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England.;Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Biol Lab, Oxford, England..
    Vyas, Paresh
    Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England..
    Anderson, Kristina
    Oslo Univ Hosp, Norwegian Radium Hosp, Dept Cellular Therapy, Oslo, Norway..
    Segerstolpe, Åsa
    Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.;Karolinska Inst, Integrated Cardio Metab Ctr, Huddinge, Sweden..
    Qian, Hong
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden..
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Mustjoki, Satu
    Univ Helsinki, Dept Clin Chem & Hematol, Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Helsinki, Finland..
    Sandberg, Rickard
    Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.;Ludwig Inst Canc Res, Stockholm, Sweden..
    Jacobsen, Sten Eirik W.
    Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England.;Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Biol Lab, Oxford, England.;Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.;Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Mead, Adam J.
    Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England.;Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Biol Lab, Oxford, England.;Churchill Hosp, NIHR Biomed Res Ctr, Oxford, England..
    Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia2017In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 23, no 6, p. 692-+Article in journal (Refereed)
    Abstract [en]

    Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis.

  • 120.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Melin, Beatrice
    Umeå Univ, Dept Radiat Sci, Umeå.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Beskow, Anna H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Björ, Ove
    Umeå Univ, Dept Radiat Sci, Umeå.
    Edqvist, Per-Henrik D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Helleday, Thomas
    Karolinska Inst, Div Translat Med & Chem Biol, Dept Med Biochem & Biophys, Sci Life Lab, Stockholm.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Henriksson, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hultdin, Magnus
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Jonsson, Håkan
    Umeå Univ, Dept Radiat Sci, Umeå.
    Larsson, Chatarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ljuslinder, Ingrid
    Umeå Univ, Dept Radiat Sci, Umeå.
    Mindus, Stephanie
    Akad Sjukhuset, Lung & Allergy Clin, Uppsala.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Riklund, Katrine
    Umeå Univ, Dept Radiat Sci, Umeå.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sandin, Fredrik
    Uppsala Univ Hosp, RCC Uppsala Örebro, Uppsala.
    Schwenk, Jochen M.
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, Solna.
    Stenling, Roger
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Stålberg, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Thellenberg Karlsson, Camilla
    Umeå Univ, Dept Radiat Sci, Umeå.
    Westermark, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Bergh, Anders
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Claesson-Welsh, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Palmqvist, Richard
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Sjöblom, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 187-194Article in journal (Refereed)
    Abstract [en]

    Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

    Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

    Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

    Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

  • 121.
    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.

  • 122.
    Granstam, Sven-Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Rosengren, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Vedin, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Carlson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Flachskampf, Frank A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Evaluation of patients with cardiac amyloidosis using echocardiography, ECG and right heart catheterization2013In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 20, no 1, p. 27-33Article in journal (Refereed)
    Abstract [en]

    Aims:

    To characterize patients with cardiac amyloidosis using echocardiography, electrocardiogram (ECG) and right heart catheterization (RHC).

    Methods and results:

    Fourteen patients with biopsy verified light chain or transthyretin cardiac amyloidosis were included. All patients had heart failure with markedly elevated NT-proBNP. Echocardiography demonstrated biventricular hypertrophy, left atrial enlargement and normal to slightly reduced left ventricular ejection fraction. Tissue Doppler septal e´ was low and median E/e´ was high. Within 6 months RHC was performed in eight of the patients. The restrictive filling pattern demonstrated by echocardiography corresponded well to median pulmonary wedge pressure (21 mmHg). Systolic pulmonary artery pressure (SPAP) was increased, whereas cardiac output and stroke volume were seen to be decreased with both methods. ECG demonstrated: low voltage (36%), abnormal R-progression (65%), ST-T abnormalities (71%) and high incidence of fibrillation (36%). In addition, a case report following the treatment of melphalan and dexamethasone is presented with improvement of hypertrophy, SPAP, left ventricular mass and e´.

    Conclusion:

    These findings should lead to a suspicion of cardiac amyloidosis and suggest further investigation.

  • 123. Greco, Raffaella
    et al.
    Bondanza, Attilio
    Oliveira, Maria Carolina
    Badoglio, Manuela
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Piehl, Fredrik
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Krasulova, Eva
    Simões, Belinda Pinto
    Carlson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Pohlreich, David
    Labopin, Myriam
    Saccardi, Riccardo
    Comi, Giancarlo
    Mancardi, Gian Luigi
    Bacigalupo, Andrea
    Ciceri, Fabio
    Farge, Dominique
    Autologous hematopoietic stem cell transplantation in neuromyelitis optica: A registry study of the EBMT Autoimmune Diseases Working Party2015In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, no 2, p. 189-197Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the central nervous system, hallmarked by pathogenic anti-aquaporin 4 antibodies. NMO prognosis is worse compared with multiple sclerosis.

    OBJECTIVE:

    The European Group for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) conducted a retrospective survey to analyze disease outcome following autologous stem cell transplantation (ASCT).

    METHODS:

    This retrospective multicenter study assessed the efficacy and safety of ASCT in 16 patients suffering from refractory NMO reported to the EBMT registry between 2001 and 2011.

    RESULTS:

    Fifteen patients were successfully mobilized with cyclophosphamide (Cy) and G-CSF, one with G-CSF alone. All patients received an unmanipulated autologous peripheral blood stem cell graft, after conditioning with BEAM plus anti-thymocyte globulin (ATG, n = 9 patients), thiotepa-Cy (n = 3) or Cy (200 mg/kg) plus ATG (n = 4). After a median follow-up of 47 months, three of 16 cases were progression and treatment free, while in the remaining 13 patients further treatments were administered for disability progression or relapse after ASCT. Altogether, relapse-free survival at three and five years was 31% and 10%, respectively, while progression-free survival remained 48% at three and five years.

    CONCLUSIONS:

    In these NMO patients, highly resistant to conventional treatment, ASCT allows for temporary control of the disease, despite a tendency to progress or relapse in the long term.

  • 124. Griesshammer, M.
    et al.
    Gugliotta, L.
    Harrison, C.
    Besses, C. R.
    Kiladjian, J-J
    Coll, R.
    Smith, J.
    Birgegard, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    The exels study: Real-world cytoreductive treatment patterns for essential thrombocythaemia in Europe (analysis of 3643 patients)2013In: Onkologie (Basel), ISSN 0378-584X, E-ISSN 1423-0240, Vol. 36, no Suppl. 7, p. 111-111Article in journal (Other academic)
  • 125.
    Griesshammer, M.
    et al.
    Johannes Wesling Klinikum, Minden, Germany..
    Stegelmann, F.
    Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany..
    Mohr, A.
    Matzdorff, A.
    Caritasklin St Theresia, Saarbrucken, Germany..
    Besses, C.
    Hosp del Mar, Dept Haematol, IMIM, Barcelona, Spain..
    Gugliotta, L.
    St Orsola Malpighi Hosp, Dept Haematol, Bologna, Italy..
    Harrison, C.
    Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England..
    Kiladjian, J. J.
    Hop St Louis, AP HP, Ctr Invest Clin, Paris, France..
    Hamdani, M.
    Shire Pharmaceut, Global Biometr, Wayne, NJ USA..
    Achenbach, H.
    Shire GmbH, Res & Dev, Zug, Switzerland..
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Treatment of essential thrombocythaemia in Europe: an observational study of 3649 high-risk patients in EXELS2015In: Oncology Research and Treatment, ISSN 2296-5270, Vol. 38, p. 216-216Article in journal (Other academic)
  • 126. Gugliotta, L.
    et al.
    Specchia, G.
    Gaidano, G.
    Scalzulli, P. R.
    Tieghi, A.
    Kiladjian, J-J
    Besses, C.
    Griesshammer, M.
    Harrison, C.
    Hamdani, M.
    Achenbach, H.
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Treatment Of Essential Thrombocythaemia In Europe: An Observational Study Of 3649 High-Risk Patients In Exels2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, p. 43-43Article in journal (Other academic)
  • 127.
    Gugliotta, L.
    et al.
    St Orsola Malpighi Hosp, Dept Haematol L & A Seragnoli, Bologna, Italy..
    Tortorella, G.
    Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, Italy..
    Besses, C.
    Hosp del Mar IMIM, Dept Haematol, Barcelona, Spain..
    Griesshammer, M.
    Johannes Wesling Med Ctr, Hematol & Oncol, Minden, Germany..
    Harrison, C.
    Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England..
    Kiladjian, J. J.
    Hop St Louis, APHP, Ctr Invest Clin, Paris, France..
    Wu, J.
    Shire Pharmaceut, Global Biometr, Lexington, MA USA..
    Achenbach, H.
    Shire GmbH, Res & Dev, Zug, Switzerland..
    Marelli, C.
    Shire GmbH, Res & Dev, Zug, Switzerland..
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Palpitations And Arrhythmia In 3649 High-Risk Patients With Essential Thrombocythemia: Results From The Prospective Long-Term Observational Exels Study2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 557-557Article in journal (Other academic)
  • 128. Gugliotta, Luigi
    et al.
    Besses, Carlos
    Griesshammer, Martin
    Harrison, Claire
    Kiladjian, Jean-Jacques
    Coll, Ruth
    Smith, Jonathan
    Abhyankar, Brihad
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Combination therapy of hydroxycarbamide with anagrelide in patients with essential thrombocythemia in the evaluation of Xagrid (R) efficacy and long-term safety study2014In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, no 4, p. 679-687Article in journal (Refereed)
    Abstract [en]

    Available information is limited regarding the use of cytoreductive combination therapy in high-risk patients with essential thrombocythemia. This analysis aims to evaluate the clinical relevance and patterns of cytoreductive combination treatment in European high-risk patients with essential thrombocythemia in the Evaluation of Xagrid (R) Efficacy and Long-term Safety study. Of 3643 patients, 347 (9.5%) received combination therapy. Data were recorded at each 6-month update. Of 347 patients who received combination therapy, 304 (87.6%) received hydroxycarbamide + anagrelide. Monotherapies received before this combination were hydroxycarbamide (n=167, 54.9%) and anagrelide (n=123, 40.5%). Median weekly doses of hydroxycarbamide and anagrelide were: 7000 and 10.5 mg when used as prior monotherapy; 3500 and 7.0 mg when used as add-on treatment. Overall, median platelet counts were 581x10(9)/L and 411x10(9)/L before and after starting hydroxycarbamide + anagrelide, respectively. In patients with paired data (n=153), the number of patients with platelet counts less than 400x10(9)/L increased from 33 (21.6%) to 74 (48.4%; P<0.0001), and with platelet counts less than 600x10(9)/L, from 82 (53.6%) to 132 (86.3%; P<0.0001). Hydroxycarbamide + anagrelide was discontinued in 158 patients: 76 (48.1%) stopped hydroxycarbamide, 59 (37.3%) stopped anagrelide, 19 (12.0%) stopped both and 4 (2.5%) had another therapy added. The most frequent reasons for discontinuation were intolerance/side-effects, lack of efficacy, and therapeutic strategy. Combination therapy, usually hydroxycarbamide + anagrelide, is used in approximately 10% of all high-risk patients with essential thrombocythemia and may be a useful approach in treating patients for whom monotherapy is unsatisfactory.

  • 129. Gugliotta, Luigi
    et al.
    Besses, Carlos
    Griesshammer, Martin
    Harrison, Claire N.
    Kiladjian, Jean-Jacques
    Coll, Ruth
    Smith, Jonathan
    Abhyankar, Brihad
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Combination of Cytoreductive Therapies in Patients with Essential Thrombocythemia: A Preliminary Report From the EXELS Study2012In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 120, no 21, p. 2842-Article in journal (Refereed)
  • 130. 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.

  • 131.
    Gunnarsson, N.
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Stenke, L.
    Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Sandin, F.
    Reg Canc Ctr, Uppsala, Sweden..
    Bjorkholm, M.
    Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Dreimane, A.
    Univ Hosp, Dept Hematol, Linkoping, Sweden..
    Lambe, M.
    Reg Canc Ctr, Uppsala, Sweden.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Markevarn, B.
    Univ Hosp, Dept Hematol, Umea, Sweden..
    Olsson-Stromberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Univ Hosp, Dept Med Sci, Uppsala, Sweden.;Univ Hosp, Div Hematol, Uppsala, Sweden..
    Wadenvik, H.
    Sahlgrens Univ Hosp, Dept Hematol, Gothenburg, Sweden..
    Richter, J.
    Skane Univ Hosp, Dept Hematol & Vasc Disorders, Lund, Sweden..
    Sjalander, A.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    No increased prevalence of malignancies among first-degree relatives of 800 patients with chronic myeloid leukemia: a population-based study in Sweden2017In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 8, p. 1825-1827Article in journal (Other academic)
  • 132.
    Gunnarsson, N.
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Stenke, L.
    Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Wallberg-Jonsson, S.
    Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Sandin, F.
    Reg Canc Ctr, Uppsala, Sweden..
    Björkholm, M.
    Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Dreimane, A.
    Linkoping Univ Hosp, Dept Hematol, Linkoping, Sweden..
    Lambe, M.
    Reg Canc Ctr, Uppsala, Sweden.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Markevarn, B.
    Univ Umea Hosp, Dept Hematol, Umea, Sweden..
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Wadenvik, H.
    Sahlgrens Univ Hosp, Dept Hematol, Gothenburg, Sweden..
    Richter, J.
    Skane Univ Hosp, Dept Hematol & Vasc Disorders, Lund, Sweden..
    Själander, A.
    Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Increased prevalence of prior malignancies and autoimmune diseases in patients diagnosed with chronic myeloid leukemia2016In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 30, no 7, p. 1562-1567Article in journal (Refereed)
    Abstract [en]

    We recently reported an increased incidence of second malignancies in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKI). To elucidate whether this increase may be linked, not to TKI but rather to a hereditary or acquired susceptibility to develop cancer, we estimated the prevalence of malignancies, autoimmune disease (AD) and chronic inflammatory disease (CID) in CML patients prior to their CML diagnosis. Nationwide population-based registers were used to identify patients diagnosed with CML in Sweden 2002-2012 and to estimate the prevalence of other malignancies, AD and CID prior to their CML diagnosis. For each patient with CML, five matched controls were selected from the general population. Conditional logistic regression was used to calculate odds ratios (OR). Nine hundred and eighty-four CML patients were assessed, representing more than 45 000 person-years of follow-up. Compared with matched controls, the prevalence of prior malignancies and AD was elevated in CML patients: OR 1.47 (95% confidence interval (CI) 1.20-1.82) and 1.55 (95% CI 1.21-1.98), respectively. No associations were detected between CML and previous CID. An increased prevalence of other malignancies and AD prior to the diagnosis of CML suggest that a hereditary or acquired predisposition to cancer and/or autoimmunity is involved in the pathogenesis of CML.

  • 133.
    Gunnarsson, Niklas
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Gavle, Sweden..
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Stenke, Leif
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Jonsson, Solveig Wallberg
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Sandin, Fredrik
    Reg Canc Ctr, Uppsala, Sweden..
    Bjorkholm, Magnus
    Karolinska Univ Hosp, Div Hematol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Dreimane, Arta
    Linkoping Univ Hosp, Dept Hematol, S-58185 Linkoping, Sweden..
    Lambe, Mats
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Markevarn, Berit
    Umea Univ Hosp, Dept Hematol, S-90185 Umea, Sweden..
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Wadenvik, Hans
    Sahlgrens Univ Hosp, Dept Hematol, Gothenburg, Sweden..
    Richter, Johan
    Skane Univ Hosp, Dept Hematol & Vasc Disorders, Lund, Sweden..
    Sjalander, Anders
    Umea Univ, Dept Publ Hlth & Clin Med, Sundsvall, Sweden..
    Increased Prevalence of Prior Malignancies and Autoimmune Diseases in Patients Diagnosed with Chronic Myeloid Leukemia2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 134. Gunnarsson, Niklas
    et al.
    Leif, Stenke
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Sandin, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bjorkholm, Magnus
    Dreimane, Arta
    Lambe, Mats
    Markevarn, Berit
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Richter, Johan
    Wadenvik, Hans
    Wallvik, Jonas
    Sjalander, Anders
    Second Malignancies Following Treatment of Chronic Myeloid Leukemia in the Tyrosine Kinase Inhibitor Era2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 135.
    Gunnarsson, Niklas
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Sandin, Fredrik
    Reg Canc Ctr, Uppsala, Sweden..
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Univ Hosp, Dept Med Sci, Uppsala, Sweden.;Univ Hosp, Div Hematol, Uppsala, Sweden..
    Stenke, Leif
    Karolinska Inst, Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Björkholm, Magnus
    Karolinska Inst, Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Lambe, Mats
    Reg Canc Ctr, Uppsala, Sweden.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Univ Hosp, Dept Med Sci, Uppsala, Sweden.;Univ Hosp, Div Hematol, Uppsala, Sweden..
    Richter, Johan
    Skane Univ Hosp, Dept Hematol & Vasc Disorders, Lund, Sweden..
    Själander, Anders
    Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Population-based assessment of chronic myeloid leukemia in Sweden: striking increase in survival and prevalence2016In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 97, no 4, p. 387-392Article in journal (Refereed)
    Abstract [en]

    The clinical outcome for patients with chronic myeloid leukemia (CML) has improved dramatically following the introduction of tyrosine kinase inhibitors. An improved survival, combined with a constant incidence, is expected to increase the prevalence of CML. However, data on the prevalence of CML remain scarce. We examined the overall and relative (age and gender matched) survival and assessed the past, present, and projected future prevalence of CML in Sweden. Data on all patients diagnosed with CML between 1970 and 2012 were retrieved from the Swedish Cancer Register and the Swedish Cause of Death Register. The 5-year overall survival increased from 0.18 to 0.82, during the observed time period. Between 2006 and 2012, the 5-year relative survival was close to normal for 40-year-old, but considerably lower for 80-year-old CML patients. The observed prevalence tripled from 1985 to 2012, from 3.9 to 11.9 per 100 000 inhabitants. Assuming no further improvements in relative survival, the prevalence is projected to further increase by 2060 to 22.0 per 100 000 inhabitants (2587 persons in Sweden). The projected dramatic increase in CML prevalence has major medical and health economic implications and needs to be considered in planning how to organize future care of CML patients.

  • 136. Gunnarsson, Niklas
    et al.
    Stenke, Leif
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Sandin, Fredrik
    Bjorkholm, Magnus
    Dreimane, Arta
    Lambe, Mats
    Markevarn, Berit
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Richter, Johan
    Wadenvik, Hans
    Wallvik, Jonas
    Sjalander, Anders
    Second malignancies following treatment of chronic myeloid leukaemia in the tyrosine kinase inhibitor era2015In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 169, no 5, p. 683-688Article in journal (Refereed)
    Abstract [en]

    Given that tyrosine kinase inhibitors (TKIs) have dramatically improved the survival of patients with chronic myeloid leukaemia (CML), we were interested in examining the possible risk of long-term adverse events, such as the emergence of other neoplasms. Therefore, we studied the development of second malignancies in 868 patients diagnosed with CML between 2002 and 2011 using the Swedish CML register, cross-linked to the Swedish Cancer register. With a median follow-up of 37 (range 0-99)years, 65 (75%) patients developed 75 second malignancies (non-haematological), 52 of which were of the invasive type. Compared to expected rates in the background population, the risk of second malignancies was higher in the CML cohort, with a standardized incidence ratio (SIR) of 152 (95% CI 113-199). The SIR before and after the second year following diagnosis of CML was 158 and 147, respectively. Among specific cancer types, gastrointestinal and nose and throat cancer were significantly increased. Founded on a population-based material, our results indicate that CML patients treated in the TKI era are at an increased risk of developing a second malignancy, with indications that this risk may more likely be linked to CML itself rather than to the TKI treatment.

  • 137.
    Gunningberg, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Carli, Cheryl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Reduced pressure for fewer pressure ulcers: can real-time feedback of interface pressure optimise repositioning in bed?2016In: International Wound Journal, ISSN 1742-4801, E-ISSN 1742-481X, Vol. 13, no 5, p. 774-779Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to (i) describe registered nurses' and assistant nurses' repositioning skills with regard to their existing attitudes to and theoretical knowledge of pressure ulcer (PU) prevention, and (ii) evaluate if the continuous bedside pressure mapping (CBPM) system provides staff with a pedagogic tool to optimise repositioning. A quantitative study was performed using a descriptive, comparative design. Registered nurses (n = 19) and assistant nurses (n = 33) worked in pairs, and were instructed to place two volunteers (aged over 70 years) in the best pressure-reducing position (lateral and supine), first without viewing the CBPM monitor and then again after feedback. In total, 240 positionings were conducted. The results show that for the same person with the same available pressure-reducing equipment, the peak pressure varied considerably between nursing pairs. Reducing pressure in the lateral position appeared to be the most challenging. Peak pressures were significantly reduced, based on visual feedback from the CBPM monitor. The number of preventive interventions also increased, as well as patients' comfort. For the nurses as a group, the knowledge score was 59·7% and the attitude score was 88·8%. Real-time visual feedback of pressure points appears to provide another dimension to complement decision making with respect to PU prevention.

  • 138. Gustaf, Edgren
    et al.
    Bjorkholm, Magnus
    Bernell, Per
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Dickman, Paul W.
    Survival from Acute Lymphoblastic Leukemia (ALL) in Adult Patients in the United States and Sweden: Evidence of Recent Improvement2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 139. Gülen, T
    et al.
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Dahlén, B
    Nilsson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Mastocytosis: the puzzling clinical spectrum and challenging diagnostic aspects of an enigmatic disease2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, no 3, p. 211-228Article, review/survey (Refereed)
    Abstract [en]

    Mastocytosis is a complex disorder characterized by the accumulation of abnormal mast cells (MC) in the skin, bone marrow and/or other visceral organs. The clinical manifestations result from MC-derived mediators and, less frequently, from destructive infiltration of MCs. Patients suffer from a variety of symptoms including pruritus, flushing and life-threatening anaphylaxis. Whilst mastocytosis is likely to be suspected in a patient with typical skin lesions [i.e. urticaria pigmentosa (UP)], the absence of cutaneous signs does not rule out the diagnosis of this disease. Mastocytosis should be suspected in cases of recurrent, unexplained or severe insect-induced anaphylaxis or symptoms of MC degranulation without true allergy. In rare cases, unexplained osteoporosis or unexplained haematological abnormalities can be underlying feature of mastocytosis, particularly when these conditions are associated with elevated baseline serum tryptase levels. The diagnosis is based on the World Health Organization criteria, in which the tryptase level, histopathological and immunophenotypic evaluation of MCs and molecular analysis are crucial. A somatic KIT mutation, the most common of which is D816V, is usually detectable in MCs and their progenitors. Once a diagnosis of systemic mastocytosis (SM) is made, it is mandatory to assess the burden of the disease, its activity, subtype and prognosis, and the appropriate therapy. Mastocytosis comprises seven different categories that range from indolent forms, such as cutaneous and indolent SM, to progressive forms, such as aggressive SM and MC leukaemia. Although prognosis is good in patients with indolent forms of the disease, patients with advanced categories have a poor prognosis.

  • 140. Gülen, T
    et al.
    Möller Westerberg, C
    Lyberg, K
    Ekoff, M
    Kolmert, J
    Bood, J
    Öhd, J
    James, A
    Dahlén, S-E
    Nilsson, G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Department of Medicine, Clinical Immunology and Allergy Research Unit, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden; Mastocytosis Centre Karolinska, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden; Centre for Allergy research (CfA), Karolinska Institutet, Stockholm, Sweden .
    Dahlén, B
    Assessment of in vivo mast cell reactivity in patients with systemic mastocytosis.2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 7, p. 909-917Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with systemic mastocytosis (SM) have clinical signs of mast cell (MC) activation and increased levels of MC mediators. It is unclear whether the increased mediator levels are caused by increased numbers of tissue MCs, or whether these cells in affected individuals have a hyperactive phenotype.

    OBJECTIVE: To determine reactivity of the skin and the airways to directly acting mediators and indirectly acting mast cell secretagogues in subjects with SM.

    METHODS: were measured, as well as ex vivo basophil histamine release.

    RESULTS: Mast cell mediators in the blood and urine were significantly higher in patients with SM than in HC and A controls. Responsiveness to local activation of skin MCs (by morphine) and airway MCs (by mannitol) was similar in SM and HC groups. Likewise, end-organ responsiveness in the skin to histamine, and in the airways to methacholine, was similar in all three subject groups. There was no evidence of increased basophil reactivity in SM patients.

    CONCLUSIONS AND CLINICAL RELEVANCE: Mast cells in the skin and airways of subjects with SM do not exhibit hyper-reactivity towards the MC-activating stimuli morphine and mannitol, respectively. Therefore, the highly elevated baseline levels of MC mediators in SM are most likely due to increased MC numbers, rather than altered MC responsiveness. The underlying mechanisms could involve leakage of MC mediators, or dysfunctions in mediator synthesis, storage and release. One clinical implication of our study is that there is no contraindication to perform skin tests using morphine in subjects with mastocytosis.

  • 141.
    Hagglund, H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Strömberg, U.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Axelsson, H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Svenningsson, A.
    Isaksson, C.
    Wahlin, A.
    Andersen, O.
    Johansson, J.
    Press, R.
    Autologous haematopoietic stem cell transplantation: a viable treatment option for chronic inflammatory demyelinating polyneuropathy2013In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 48, no Suppl. 2, p. S336-S336Article in journal (Other academic)
  • 142.
    Haglund, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Åleskog, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Wickström, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Lindhagen, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    In vitro evaluation of clinical activity and toxicity of anticancer drugs using tumor cells from patients and cells representing normal tissues2012In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 69, no 3, p. 697-707Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to evaluate a phenotypic cell panel with tumor cells from various patients and normal cells for preclinical profiles of antitumor efficacy and toxicity of anticancer drugs.

    METHODS: The antitumor activity of fourteen anticancer drugs was tested in over one hundred tumor samples from patients with solid or hematological malignancies. Drug activity against four normal cell types was used for the assessment of normal tissue toxicity. In vitro activity of the drugs was compared with indications approved by the Food and Drug Administration and established adverse event profiles.

    RESULTS: In general, in vitro drug activity in tumor cells from patients reflected known clinical activity of the drugs investigated. For example, the clinical activity of imatinib in chronic myeloid leukemia was clearly detected in the tumor panel. Further, and in accordance with clinical use, cisplatin and bortezomib showed high activity in ovarian cancer and myeloma samples, respectively. The normal cell models roughly reflected known clinical toxicity profiles and were able to detect differences in therapeutic index, e.g., between targeted drugs and classical cytotoxic agents. For example, the high tolerability of imatinib and the well-known renal toxicity of cisplatin were demonstrated.

    CONCLUSIONS: In preclinical drug development, primary tumor cells from patients can be used for the prediction of cancer diagnosis-specific activity and may aid in the selection of diagnoses for clinical trials. By using tumor and toxicity panels together, information about therapeutic index may be derived, which may be useful when choosing among drug candidates with similar tumor effects.

  • 143.
    Hallböök, Helene
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hägglund, Hans
    Stockelberg, Dick
    Nilsson, Per-Gunnar
    Karlsson, Karin
    Björkholm, Magnus
    Linderholm, Mats
    Wahlin, Anders
    Linder, Olle
    Smedmyr, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Autologous and allogeneic stem cell transplantation in adult ALL: The Swedish Adult ALL Group experience2005In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 35, no 12, p. 1141-1148Article in journal (Refereed)
    Abstract [en]

    Adult patients with acute lymphoblastic leukaemia (ALL) have been treated according to national protocols in Sweden since 1986. Stem cell transplantation (SCT) has been recommended in first remission for patients with risk factors for relapse, and for standard risk patients only after relapse. In this retrospective study, the results of autologous and allogeneic SCT in these populations were evaluated. In total, 187 patients with a median age of 34 years (17-66 years) underwent SCT. The 5-year disease-free survival (DFS), for all patients, was 26% (Confidence intervals (CI) 20-32%). The 5-year DFS was higher for patients transplanted in first remission 32% (CI 24-40%) compared to 14% (CI 5-23%; P<0.0001) in patients transplanted beyond first remission. No significant differences in DFS (P=0.06) were determined between autologous, related donor and unrelated donor SCT in the whole cohort. A lower relapse rate was counterbalanced by higher treatment-related mortality in patients undergoing allogeneic SCT. In Philadelphia-positive ALL, allogeneic SCT was superior to autologous SCT, with a 5-year DFS of 30% (CI 12-47%) vs 0% (P=0.04). Limited chronic graft-versus-host-disease (GVHD) was associated with an improved DFS of 53% (CI 38-69%) compared to no chronic GVHD of 22% (CI 10-36%; P=0.0008), indicating a clinically important graft-versus-leukaemia effect.

  • 144.
    Hallböök, Helene
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lidström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Ciprofloxacin prophylaxis delays initiation of broad-spectrum antibiotic therapy and reduces the overall use of antimicrobial agents during induction therapy for acute leukaemia: A single-centre study2016In: INFECTIOUS DISEASES, ISSN 2374-4235, Vol. 48, no 6, p. 443-448Article in journal (Refereed)
    Abstract [en]

    Background Due to an outbreak of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, the routine use of fluoroquinolone prophylaxis was questioned. As a result, this study was conducted with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of broad-spectrum antibioctics and anti-mycotics. Methods A cohort of 139 consecutive patients with acute leukaemia treated with remission-inducing induction chemotherapy between 2004-2012 at the Department of Haematology in Uppsala University Hospital was analysed. Results Fifty-three patients (38%) received broad-spectrum antibiotics at the initiation of chemotherapy and were not eligible for prophylaxis. Of the remaining patients, the initiation of broad-spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The median duration of systemic antibiotic treatment was 6 days shorter in patients receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the cumulative (total) median days on systemic antibiotic treatment was shortened by 8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02), carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p < 0.01) were used significantly less often when ciprofloxacin prophylaxis was given. Conclusions Ciprofloxacin prophylaxis delayed empiric therapy by 3 days and reduced overall antibiotic use in this study. These benefits must be evaluated vs the risks of development of resistant bacterial strains, making fluoroquinolone prophylaxis an open question for debate.

  • 145.
    Halova, Ivana
    et al.
    Czech Acad Sci, Inst Mol Genet, Dept Signal Transduct, Prague, Czech Republic.
    Rönnberg, Elin
    Karolinska Univ Hosp, Karolinska Inst & Clin Immunol & Transfus Med, Dept Med, Immunol & Allergy Unit, Stockholm, Sweden.
    Draberova, Lubica
    Czech Acad Sci, Inst Mol Genet, Dept Signal Transduct, Prague, Czech Republic.
    Vliagoftis, Harissios
    Karolinska Univ Hosp, Karolinska Inst & Clin Immunol & Transfus Med, Dept Med, Immunol & Allergy Unit, Stockholm, Sweden; Univ Alberta, Alberta Resp Ctr, Edmonton, AB, Canada; Univ Alberta, Dept Med, Edmonton, AB, Canada.
    Nilsson, Gunnar P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet and Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Draber, Petr
    Czech Acad Sci, Inst Mol Genet, Dept Signal Transduct, Prague, Czech Republic.
    Changing the threshold-Signals and mechanisms of mast cell priming2018In: Immunological Reviews, ISSN 0105-2896, E-ISSN 1600-065X, Vol. 282, no 1, p. 73-86Article in journal (Refereed)
    Abstract [en]

    Mast cells play a key role in allergy and other inflammatory diseases involving engagement of multivalent antigen with IgE bound to high-affinity IgE receptors (FcεRIs). Aggregation of FcεRIs on mast cells initiates a cascade of signaling events that eventually lead to degranulation, secretion of leukotrienes and prostaglandins, and cytokine and chemokine production contributing to the inflammatory response. Exposure to pro-inflammatory cytokines, chemokines, bacterial and viral products, as well as some other biological products and drugs, induces mast cell transition from the basal state into a primed one, which leads to enhanced response to IgE-antigen complexes. Mast cell priming changes the threshold for antigen-mediated activation by various mechanisms, depending on the priming agent used, which alone usually do not induce mast cell degranulation. In this review, we describe the priming processes induced in mast cells by various cytokines (stem cell factor, interleukins-4, -6 and -33), chemokines, other agents acting through G protein-coupled receptors (adenosine, prostaglandin E2, sphingosine-1-phosphate, and β-2-adrenergic receptor agonists), toll-like receptors, and various drugs affecting the cytoskeleton. We will review the current knowledge about the molecular mechanisms behind priming of mast cells leading to degranulation and cytokine production and discuss the biological effects of mast cell priming induced by several cytokines.

  • 146.
    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.

  • 147. Harrison, C.
    et al.
    Besses, C.
    Kiladjian, J. J.
    Griesshammer, M.
    Gugliotta, L.
    Coll, R.
    Smith, J.
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Cytoreductive treatment patterns for essential thrombocythaemia in Europe: analysis of 3643 patients in the EXELS study2013In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 161, no SI, p. 17-17Article in journal (Other academic)
  • 148. Harrison, C.
    et al.
    Tiplady, C.
    Fernandes, S.
    Knechtli, C.
    Sadullah, S.
    Besses, C.
    Greisshammer, M.
    Gugliotta, L.
    Kiladjian, J. J.
    Hamdani, M.
    Achenbach, H.
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Treatment of essential thrombocythaemia in Europe: an observational study of 3649 high-risk patients in EXELS2015In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 169, no S1, p. 7-7Article in journal (Other academic)
  • 149. Hartmann, Karin
    et al.
    Escribano, Luis
    Grattan, Clive
    Brockow, Knut
    Carter, Melody C
    Alvarez-Twose, Ivan
    Matito, Almudena
    Broesby-Olsen, Sigurd
    Siebenhaar, Frank
    Lange, Magdalena
    Niedoszytko, Marek
    Castells, Mariana
    Oude Elberink, Joanna N G
    Bonadonna, Patrizia
    Zanotti, Roberta
    Hornick, Jason L
    Torrelo, Antonio
    Grabbe, Jürgen
    Rabenhorst, Anja
    Nedoszytko, Boguslaw
    Butterfield, Joseph H
    Gotlib, Jason
    Reiter, Andreas
    Radia, Deepti
    Hermine, Olivier
    Sotlar, Karl
    George, Tracy I
    Kristensen, Thomas K
    Kluin-Nelemans, Hanneke C
    Yavuz, Selim
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Sperr, Wolfgang R
    Schwartz, Lawrence B
    Triggiani, Massimo
    Maurer, Marcus
    Nilsson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Horny, Hans-Peter
    Arock, Michel
    Orfao, Alberto
    Metcalfe, Dean D
    Akin, Cem
    Valent, Peter
    Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology.2015In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825Article in journal (Refereed)
    Abstract [en]

    Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma.

  • 150. Hedenus, Michael
    et al.
    Karlsson, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Ludwig, Heinz
    Rzychon, Beate
    Felder, Marcel
    Roubert, Bernard
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Intravenous iron alone resolves anemia in patients with functional iron deficiency and lymphoid malignancies undergoing chemotherapy2014In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 31, no 12, p. 302-Article in journal (Refereed)
    Abstract [en]

    This randomized trial evaluated ferric carboxymaltose without erythropoiesis-stimulating agents (ESA) for correction of anemia in cancer patients with functional iron deficiency. Patients on treatment for indolent lymphoid malignancies, who had anemia [hemoglobin (Hb) 8.5-10.5 g/dL] and functional iron deficiency [transferrin saturation (TSAT) <= 20 %, ferritin >30 ng/mL (women) or >40 ng/mL (men)], were randomized to ferric carboxymaltose (1,000 mg iron) or control. Primary end point was the mean change in Hb from baseline to weeks 4, 6 and 8 without transfusions or ESA. Difficulties with patient recruitment led to premature termination of the study. Seventeen patients (8 ferric carboxymaltose and 9 control) were included in the analysis. In the ferric carboxymaltose arm, mean Hb increase was significantly higher versus control at week 8 (p = 0.021). All ferric carboxymaltose- treated patients achieved an Hb increase >1 g/dL (control 6/9; p = 0.087), and mean TSAT was >20 % from week 2 onwards. No treatment-related adverse events were reported. In conclusion, ferric carboxymaltose without ESA effectively increased Hb and iron status in this small patient population.

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