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  • 1. Abonia, J Pablo
    et al.
    Hallgren, Jenny
    Harvard Medical School, Boston, MA.
    Jones, Tatiana
    Shi, Tong
    Xu, Yuhui
    Koni, Pandelakis
    Flavell, Richard A
    Boyce, Joshua A
    Austen, K Frank
    Gurish, Michael F
    Alpha-4 integrins and VCAM-1, but not MAdCAM-1, are essential for recruitment of mast cell progenitors to the inflamed lung2006In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 108, no 5, p. 1588-1594Article in journal (Refereed)
    Abstract [en]

    Normal mouse lungs lack appreciable numbers of mast cells (MCs) or MC progenitors (MCp's), yet the appearance of mature MCs in the tracheobronchial epithelial surface is a characteristic of allergic, T-cell-dependent pulmonary inflammation. We hypothesized that pulmonary inflammation would recruit MCp's to inflamed lungs and that this recruitment would be regulated by distinct adhesion pathways. Ovalbumin-sensitized and challenged mice had a greater than 28-fold increase in the number of MCp's in the lungs. In mice lacking endothelial vascular cell adhesion molecule 1 (VCAM-1) and in wild-type mice administered blocking monoclonal antibody (mAb) to VCAM-1 but not to mucosal addressin CAM-1 (MadCAM-1), recruitment of MCp's to the inflamed lung was reduced by greater than 75%. Analysis of the integrin receptors for VCAM-1 showed that in beta7 integrin-deficient mice, recruitment was reduced 73% relative to wild-type controls, and in either BALB/c or C57BL/6 mice, mAb blocking of alpha4, beta1, or beta7 integrins inhibited the recruitment of MCp's to the inflamed lung. Thus, VCAM-1 interactions with both alpha4beta1 and alpha4beta7 integrins are essential for the recruitment and expansion of the MCp populations in the lung during antigen-induced pulmonary inflammation. Furthermore, the MCp is currently unique among inflammatory cells in its partial dependence on alpha4beta7 integrins for lung recruitment.

  • 2.
    Agarwal, Prasoon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Kalushkova, Antonia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Enroth, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Alzrigat, Mohammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Osterborg, Anders
    Nilsson, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Öberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Jernberg-Wiklund, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    An Epigenomic Map of Multiple Myeloma Reveals the Importance of Polycomb Gene Silencing for the Malignancy2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 3.
    Agathangelidis, Andreas
    et al.
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece..
    Chatzidimitriou, Anastasia
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Gemenetzi, Katerina
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece.;Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece..
    Giudicelli, Veronique
    Univ Montpellier, Ctr Natl Rech Sci CNRS, Inst Genet Humaine IGH, Unite Mixte Rech UMR, Montpellier, France..
    Karypidou, Maria
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece..
    Plevova, Karla
    Masaryk Univ, Fac Med, Dept Internal Med Hematol & Oncol, Univ Hosp Brno, Brno, Czech Republic.;Masaryk Univ, Ctr Mol Med, Cent European Inst Technol, Brno, Czech Republic..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Yan, Xiao-Jie
    Feinstein Inst Med Res, Northwell Hlth, Manhasset, NY USA..
    Jeromin, Sabine
    MLL Munich Leukemia Lab, Munich, Germany..
    Schneider, Christof
    Univ Hosp Med Ctr, Ulm, Germany..
    Pedersen, Lone Bredo
    Copenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Tschumper, Renee C.
    Mayo Clin, Dept Immunol, Rochester, MN USA..
    Sutton, Lesley-Ann
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Baliakas, Panagiotis
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Scarfo, Lydia
    Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Strateg Res Program CLL,Ist Ricovero & Cura Carat, Milan, Italy..
    van Gastel, Ellen J.
    Univ Med Ctr UMC, Dept Immunol, Lab Med Immunol, Erasmus MC, Rotterdam, Netherlands..
    Armand, Marine
    Sorbonne Univ, Ctr Rech Cordeliers, Dept Biol Hematol, Hop Pitie Salpetriere,AP HP,UMR S 1138, Paris, France..
    Tausch, Eugen
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Biderman, Bella
    Natl Res Ctr Hematol, Moscow, Russia..
    Baer, Constance
    MLL Munich Leukemia Lab, Munich, Germany..
    Bagnara, Davide
    Univ Genoa, Dept Expt Med, Genoa, Italy..
    Navarro, Alba
    Ctr Invest Biomed Red Oncol CIBERONC, Madrid, Spain.;Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain..
    de Septenville, Anne Langlois
    Sorbonne Univ, Ctr Rech Cordeliers, Dept Biol Hematol, Hop Pitie Salpetriere,AP HP,UMR S 1138, Paris, France..
    Guido, Valentina
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Haematol Dept, Mol Pathol Unit, Milan, Italy..
    Mitterbauer-Hohendanner, Gerlinde
    Med Univ Vienna, Dept Lab Med, Vienna, Austria..
    Dimovski, Aleksandar
    Ss Cyril & Methodius Univ Skopje, Fac Pharm, Skopje, North Macedonia..
    Brieghel, Christian
    Copenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Lawless, Sarah
    Belfast City Hosp, Clin Haematol, Belfast Hlth & Social Care Trust, Belfast, Antrim, North Ireland..
    Meggendorfer, Manja
    MLL Munich Leukemia Lab, Munich, Germany..
    Brazdilova, Kamila
    Masaryk Univ, Fac Med, Dept Internal Med Hematol & Oncol, Univ Hosp Brno, Brno, Czech Republic.;Masaryk Univ, Ctr Mol Med, Cent European Inst Technol, Brno, Czech Republic..
    Ritgen, Matthias
    Univ Hosp Schleswig Holstein, Med Dept 2, Campus Kiel, Kiel, Germany..
    Facco, Monica
    Univ Padua, Dept Med DIMED, Hematol & Clin Immunol Unit, Padua, Italy.;Veneto Inst Mol Med, Padua, Italy..
    Tresoldi, Cristina
    Ist Sci San Raffaele, Div Immunol Transplantat & Infect Dis, IRCCS, Milan, Italy..
    Visentin, Andrea
    Univ Padua, Dept Med DIMED, Hematol & Clin Immunol Unit, Padua, Italy.;Veneto Inst Mol Med, Padua, Italy..
    Patriarca, Andrea
    Univ Eastern Piedmont Osped Maggiore Carita, Dept Translat Med, Div Hematol, Novara, Italy..
    Catherwood, Mark
    Belfast City Hosp, Clin Haematol, Belfast Hlth & Social Care Trust, Belfast, Antrim, North Ireland..
    Bonello, Lisa
    Azienda Osped Univ AOU, City Hlth & Sci Turin, Gen Anatomopathol & Mol Oncogenet, Turin, Italy..
    Sudarikov, Andrey
    Natl Res Ctr Hematol, Moscow, Russia..
    Vanura, Katrina
    Med Univ Vienna, Dept Lab Med, Vienna, Austria..
    Roumelioti, Maria
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Francova, Hana Skuhrova
    Masaryk Univ, Fac Med, Dept Internal Med Hematol & Oncol, Univ Hosp Brno, Brno, Czech Republic..
    Moysiadis, Theodoros
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece..
    Veronese, Silvio
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Haematol Dept, Mol Pathol Unit, Milan, Italy..
    Giannopoulos, Krzysztof
    Med Univ Lublin, Expt Hematooncol Dept, Lublin, Poland..
    Mansouri, Larry
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Karan-Djurasevic, Teodora
    Univ Belgrade, Inst Mol Genet & Genet Engn, Belgrade, Serbia..
    Sandaltzopoulos, Raphael
    Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece..
    Bodor, Csaba
    Semmelweis Univ, Dept Pathol & Expt Canc Res 1, MTA SE Momentum Mol Oncohematol Res Grp, Budapest, Hungary..
    Fais, Franco
    Univ Genoa, Dept Expt Med, Genoa, Italy.;IRCCS Osped Policlin San Martino, UO Mol Pathol, Genoa, Italy..
    Kater, Arnon
    Univ Amsterdam, Amsterdam UMC, Amsterdam Infect & Immun Inst, Dept Hematol,Canc Ctr Amsterdam, Amsterdam, Netherlands..
    Panovska, Irina
    Ss Cyril & Methodius Univ Skopje, Fac Med, Dept Hematol, Skopje, North Macedonia..
    Rossi, Davide
    Inst Southern Switzerland, Div Hematol Oncol, Bellinzona, Switzerland..
    Alshemmari, Salem
    Kuwait Univ, Fac Med, Dept Med, Kuwait, Kuwait..
    Panagiotidis, Panagiotis
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Costeas, Paul
    Ctr Study Haematol Malignancies, Nicosia, Cyprus.;Karaiskakio Fdn, Nicosia, Cyprus..
    Espinet, Blanca
    Hosp Mar, Serv Patol & Serv Hematol, Lab Citogenet Mol, Lab Citol Hematol, Barcelona, Spain..
    Antic, Darko
    Clin Ctr Serbia, Clin Hematol, Belgrade, Serbia..
    Foroni, Letizia
    Hammersmith Hosp, London, England..
    Montillo, Marco
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Haematol Dept, Mol Pathol Unit, Milan, Italy..
    Trentin, Livio
    Univ Padua, Dept Med DIMED, Hematol & Clin Immunol Unit, Padua, Italy.;Veneto Inst Mol Med, Padua, Italy..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Hematol Dept, Hematocrit HCT Unit, Thessaloniki, Greece..
    Gaidano, Gianluca
    Univ Eastern Piedmont Osped Maggiore Carita, Dept Translat Med, Div Hematol, Novara, Italy..
    di Celle, Paola Francia
    Azienda Osped Univ AOU, City Hlth & Sci Turin, Gen Anatomopathol & Mol Oncogenet, Turin, Italy..
    Niemann, Carsten
    Copenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Campo, Elias
    Ctr Invest Biomed Red Oncol CIBERONC, Madrid, Spain.;Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain.;Univ Barcelona, Hosp Clin Barcelona, Barcelona, Spain..
    Anagnostopoulos, Achilles
    Hammersmith Hosp, London, England..
    Pott, Christiane
    Univ Hosp Schleswig Holstein, Med Dept 2, Campus Kiel, Kiel, Germany..
    Fischer, Kirsten
    Univ Hosp Cologne, Cologne, Germany..
    Hallek, Michael
    Univ Cologne, Dept & Internal Med, Cologne, Germany..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Stilgenbauer, Stephan
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Haferlach, Claudia
    MLL Munich Leukemia Lab, Munich, Germany..
    Jelinek, Diane
    Mayo Clin, Dept Immunol, Scottsdale, AZ USA..
    Chiorazzi, Nicholas
    Feinstein Inst Med Res, Northwell Hlth, Manhasset, NY USA..
    Pospisilova, Sarka
    Masaryk Univ, Fac Med, Dept Internal Med Hematol & Oncol, Univ Hosp Brno, Brno, Czech Republic.;Masaryk Univ, Ctr Mol Med, Cent European Inst Technol, Brno, Czech Republic..
    Lefranc, Marie-Paule
    Univ Montpellier, Ctr Natl Rech Sci CNRS, Inst Genet Humaine IGH, Unite Mixte Rech UMR, Montpellier, France..
    Kossida, Sofia
    Univ Montpellier, Ctr Natl Rech Sci CNRS, Inst Genet Humaine IGH, Unite Mixte Rech UMR, Montpellier, France..
    Langerak, Anton W.
    Univ Med Ctr UMC, Dept Immunol, Lab Med Immunol, Erasmus MC, Rotterdam, Netherlands..
    Belessi, Chrysoula
    Nikea Gen Hosp, Hematol Dept, Piraeus, Greece..
    Davi, Frederic
    Univ Med Ctr UMC, Dept Immunol, Lab Med Immunol, Erasmus MC, Rotterdam, Netherlands..
    Rosenquist, Richard
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Karolinska Univ Lab, Clin Genet, Stockholm, Sweden..
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Strateg Res Program CLL,Ist Ricovero & Cura Carat, Milan, Italy..
    Stamatopoulos, Kostas
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL2021In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 137, no 10, p. 1365-1376Article in journal (Refereed)
    Abstract [en]

    Chronic lymphocytic leukemia (CLL) is characterized by the existence of subsets of patients with (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins. Patients in certain major stereotyped subsets often display remarkably consistent clinicobiological profiles, suggesting that the study of BcR immunoglobulin stereotypy in CLL has important implications for understanding disease pathophysiology and refining clinical decision-making. Nevertheless, several issues remain open, especially pertaining to the actual frequency of BcR immunoglobulin stereotypy and major subsets, as well as the existence of higher-order connections between individual subsets. To address these issues, we investigated clonotypic IGHV-IGHD-IGHJ gene rearrangements in a series of 29 856 patients with CLL, by far the largest series worldwide. We report that the stereotyped fraction of CLL peaks at 41% of the entire cohort and that all 19 previously identified major subsets retained their relative size and ranking, while 10 new ones emerged; overall, major stereotyped subsets had a cumulative frequency of 13.5%. Higher-level relationships were evident between subsets, particularly for major stereotyped subsets with unmutated IGHV genes (U-CLL), for which close relations with other subsets, termed "satellites," were identified. Satellite subsets accounted for 3% of the entire cohort. These results confirm our previous notion that major subsets can be robustly identified and are consistent in relative size, hence representing distinct disease variants amenable to compartmentalized research with the potential of overcoming the pronounced heterogeneity of CLL. Furthermore, the existence of satellite subsets reveals a novel aspect of repertoire restriction with implications for refined molecular classification of CLL.

  • 4. Agathangelidis, Andreas
    et al.
    Darzentas, Nikos
    Hadzidimitriou, Anastasia
    Brochet, Xavier
    Murray, Fiona
    Yan, Xiao-Jie
    Davis, Zadie
    van Gastel-Mol, Ellen J.
    Tresoldi, Cristina
    Chu, Charles C.
    Cahill, Nicola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Giudicelli, Veronique
    Tichy, Boris
    Pedersen, Lone Bredo
    Foroni, Letizia
    Bonello, Lisa
    Janus, Agnieszka
    Smedby, Karin
    Anagnostopoulos, Achilles
    Merle-Beral, Helene
    Laoutaris, Nikolaos
    Juliusson, Gunnar
    di Celle, Paola Francia
    Pospisilova, Sarka
    Jurlander, Jesper
    Geisler, Christian
    Tsaftaris, Athanasios
    Lefranc, Marie-Paule
    Langerak, Anton W.
    Oscier, David Graham
    Chiorazzi, Nicholas
    Belessi, Chrysoula
    Davi, Frederic
    Rosenquist Brandell, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Ghia, Paolo
    Stamatopoulos, Kostas
    Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies2012In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 119, no 19, p. 4467-4475Article in journal (Refereed)
    Abstract [en]

    Mounting evidence indicates that grouping of chronic lymphocytic leukemia (CLL) into distinct subsets with stereotyped BCRs is functionally and prognostically relevant. However, several issues need revisiting, including the criteria for identification of BCR stereotypy and its actual frequency as well as the identification of "CLL-biased" features in BCR Ig stereotypes. To this end, we examined 7596 Ig VH (IGHV-IGHD-IGHJ) sequences from 7424 CLL patients, 3 times the size of the largest published series, with an updated version of our purpose-built clustering algorithm. We document that CLL may be subdivided into 2 distinct categories: one with stereotyped and the other with nonstereotyped BCRs, at an approximate ratio of 1: 2, and provide evidence suggesting a different ontogeny for these 2 categories. We also show that subset-defining sequence patterns in CLL differ from those underlying BCR stereotypy in other B-cell malignancies. Notably, 19 major subsets contained from 20 to 213 sequences each, collectively accounting for 943 sequences or one-eighth of the cohort. Hence, this compartmentalized examination of VH sequences may pave the way toward a molecular classification of CLL with implications for targeted therapeutic interventions, applicable to a significant number of patients assigned to the same subset.

  • 5.
    Albertsson-Lindblad, Alexandra
    et al.
    Skane Univ Hosp, Dept Oncol, SE-22185 Lund, Sweden..
    Kolstad, Arne
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway..
    Laurell, Anna
    Univ Uppsala Hosp, Dept Oncol, Uppsala, Sweden..
    Raty, Riikka
    Helsinki Univ Hosp, Dept Hematol, Helsinki, Finland..
    Gronbaek, Kirsten
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Sundberg, Jan
    Skane Univ Hosp, Dept Oncol, SE-22185 Lund, Sweden..
    Pedersen, Lone Bredo
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Ralfkiaer, Elisabeth
    Rigshosp, Dept Pathol, Copenhagen, Denmark..
    Karjalainen-Lindsberg, Marja-Liisa
    Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland..
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden; and..
    Ehinger, Mats
    Univ Lund Hosp, Dept Pathol Cytol, Lund, Sweden..
    Geisler, Christian
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Jerkeman, Mats
    Skane Univ Hosp, Dept Oncol, SE-22185 Lund, Sweden..
    Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma2016In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 128, no 14, p. 1814-1820Article in journal (Refereed)
    Abstract [en]

    For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter, open-label phase 1/2 trial, we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment for elderly patients with MCL. Patients >65 years with untreated MCL, stages II-IV were eligible for inclusion. Primary end points were maximally tolerable dose (MTD) of LEN and progression-free survival (PFS). Patients received 6 cycles every four weeks of L-B-R (L D1-14, B 90 mg/m(2) IV, days 1-2 and R 375 mg/m(2) IV, day 1) followed by single LEN (days 1-21, every four weeks, cycles 7-13). Fifty-one patients (median age 71 years) were enrolled from 2009 to 2013. In phase 1, the MTD of LEN was defined as 10 mg in cycles 2 through 6, and omitted in cycle 1. After 6 cycles, the complete remission rate (CRR) was 64%, and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3-year overall survival was 73%. Infection was the most common nonhematologic grade 3 to 5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in 3 patients: 2 Pneumocystis carinii pneumonia and 1 cytomegalovirus retinitis. Second primary malignancies (SPM) were observed in 8 patients (16%). LEN could safely be combined with R-B when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs, which may limit its use. This trial is registered at www.Clinicaltrials.gov as #NCT00963534.

  • 6. Aplenc, Richard
    et al.
    Zhang, Mei-Jie
    Sung, Lillian
    Zhu, Xiaochun
    Ho, Vincent T
    Cooke, Kenneth
    Dvorak, Christopher
    Hale, Gregory
    Isola, Luis M
    Lazarus, Hillard M
    McCarthy, Philip L
    Olsson, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Pulsipher, Michael
    Pasquini, Marcelo C
    Bunin, Nancy
    Effect of body mass in children with hematologic malignancies undergoing allogeneic bone marrow transplantation.2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 123, no 22, p. 3504-11Article in journal (Refereed)
    Abstract [en]

    The rising incidence of pediatric obesity may significantly affect bone marrow transplantation (BMT) outcomes. We analyzed outcomes in 3687 children worldwide who received cyclophosphamide-based BMT regimens for leukemias between 1990 and 2007. Recipients were classified according to age-adjusted body mass index (BMI) percentiles as underweight (UW), at risk of UW (RUW), normal, overweight (OW), or obese (OB). Median age and race were similar in all groups. Sixty-one percent of OB children were from the United States/Canada. Three-year relapse-free and overall survival ranged from 48% to 52% (P = .54) and 55% to 58% (P = .81) across BMI groups. Three-year leukemia relapses were 33%, 33%, 29%, 25%, and 21% in the UW, RUW, normal, OW, and OB groups, respectively (P < .001). Corresponding cumulative incidences for transplant-related mortality (TRM) were 18%, 19%, 21%, 22%, and 28% (P < .01). Multivariate analysis demonstrated a decreased risk of relapse compared with normal BMI (relative risk [RR] = 0.73; P < .01) and a trend toward higher TRM (RR = 1.28; P = .014). BMI in children is not significantly associated with different survival after BMT for hematologic malignancies. Obese children experience less relapse posttransplant compared with children with normal BMI; however, this benefit is offset by excess in TRM.

  • 7.
    Apollonio, Benedetta
    et al.
    Kings Coll London, Dept Haematooncol, London WC2R 2LS, England..
    Nicholas, Nicole S.
    Kings Coll London, Dept Haematooncol, London WC2R 2LS, England..
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Salisbury, Jon
    Kings Coll Hosp London, London, England..
    Patten, Piers E.
    Kings Coll Hosp London, Haematol, London, England..
    Kassam, Shireen
    Kings Coll Hosp London, London, England..
    Devereux, Stephen
    Kings Coll Hosp London, Haematol, London, England..
    Amini, Rose Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ramsay, Alan G.
    Kings Coll London, Dept Haematooncol, London WC2R 2LS, England..
    Diffuse Large B-Cell Lymphoma (DLBCL) Tumor Cells Reprogram Lymphatic Fibroblasts into Cancer-Associated Fibroblasts (CAFs) That Contribute to Tumor Microenvironment (TME)-Driven Immune Privilege2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 8.
    Armand, Marine
    et al.
    Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Boudjoghra, Myriam
    Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Xochelli, Aliki
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Canioni, Danielle
    Univ Paris 05, Hop Necker, AP HP, Dept Pathol, Paris, France..
    Tavernier, Magali Le Garff
    Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Colombo, Monica
    Azienda Osped Univ AOU San Martino IST, IRCCS, Direz Sci, Genoa, Italy..
    Rabiega, Pascaline
    Univ Paris 06, INSERM, UMR S1136, Inst Pierre Louis Epidemiol & Sante Publ, Paris, France..
    Molina, Thierry
    Univ Paris 05, Hop Necker, AP HP, Dept Pathol, Paris, France..
    Charlotte, Frederic
    Univ Paris 06, Paris, France.;Hop La Pitie Salpetriere, Dept Pathol, Paris, France..
    Michot, Jean-Marie
    Inst Gustave Roussy, Dept Hematol & Drug Developmen, Villejuif, France..
    Lesty, Claude
    Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Carrat, Fabrice
    Univ Paris 06, INSERM, UMR S1136, Inst Pierre Louis Epidemiol & Sante Publ, Paris, France..
    Ferrarini, Manlio
    Azienda Osped Univ AOU San Martino IST, IRCCS, Direz Sci, Genoa, Italy..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Besson, Caroline
    Hop Bicetre, Dept Internal Med & Clin Immunol Biol Immunol & H, Le Kremlin Bicetre, France.;Univ Paris Sud, F-94275 Le Kremlin Bicetre, France..
    Hermine, Olivier
    Hop Necker Enfants Malad, Dept Adult Hematol, Paris, France.;Paris Descartes Univ, Paris, France..
    Davi, Frederic
    Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Auto-Immune Origin of B Cells from HCV-Associated Lymphoma2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 9.
    Armand, Philippe
    et al.
    Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.;Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA..
    Zinzani, Pier Luigi
    Azienda Osped Univ Bologna, Ist Ricovero & Cura Carattere Sci, Ist Ematol Seragnoli, Bologna, Italy.;Univ Bologna, Dipartimento Sci Med & Chirurg, Bologna, Italy..
    Lee, Hun Ju
    Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX USA..
    Johnson, Nathalie A.
    Jewish Gen Hosp, Dept Med, Montreal, PQ, Canada..
    Brice, Pauline
    Hop St Louis, Hematooncol, Paris, France..
    Radford, John
    Christie NHS Fdn Trust, Dept Med Oncol, NIHR Clin Res Facil, Manchester, England.;Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester, England..
    Ribrag, Vincent
    Gustave Roussy, Early Drug Dev Dept DITEP, Villejuif, France..
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer Immunotherapy.
    Vassilakopoulos, Theodoros P.
    Natl & Kapodistrian Univ Athens, Laikon Gen Hosp, Dept Hematol & Bone Marrow Transplantat, Athens, Greece..
    Tomita, Akihiro
    Nagoya Univ, Grad Sch Med, Dept Hematol & Oncol, Nagoya, Japan..
    von Tresckow, Bastian
    Univ Cologne, Med Fac, Dept Internal Med 1, Cologne, Germany.;Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Dept Hematol & Stem Cell Transplantat, Essen, Germany.;Univ Cologne, Univ Hosp Cologne, Cologne, Germany..
    Shipp, Margaret A.
    Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA..
    Herrera, Alex F.
    City Hope Natl Med Ctr, Dept Hematol Hematopoiet Cell Transplantat, Duarte, CA USA..
    Lin, Jianxin
    Merck & Co Inc, Dept Med Oncol, Rahway, NJ USA..
    Kim, Eunhee
    Merck & Co Inc, Dept Med Oncol, Rahway, NJ USA..
    Chakraborty, Samhita
    Merck & Co Inc, Dept Med Oncol, Rahway, NJ USA..
    Marinello, Patricia
    Merck & Co Inc, Dept Med Oncol, Rahway, NJ USA..
    Moskowitz, Craig H.
    Univ Miami, Sylvester Comprehens Canc Ctr, Dept Med, Miami, FL USA..
    Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma2023In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 142, no 10, p. 878-886Article in journal (Refereed)
    Abstract [en]

    Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with acceptable safety in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). However, long-term response durability and outcome of patients who receive a second course after treatment discontinuation after complete response (CR) remain of clinical interest. We present KEYNOTE-087 data after >5 years of median follow-up. Patients with R/R cHL and progressive disease (PD) after autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV; cohort 1), salvage chemotherapy and BV without ASCT (cohort 2), or ASCT without subsequent BV (cohort 3), received pembrolizumab for <= 2 years. Patients in CR who discontinued treatment and subsequently experienced PD were eligible for second-course pembrolizumab. Primary end points were the objective response rate (ORR) using blinded central review and safety. The median follow-up was 63.7 months. ORR was 71.4% (95% confidence interval [CI], 64.8-77.4; CR, 27.6%; partial response, 43.8%). Median duration of response (DOR) was 16.6 months; median progression-free survival was 13.7 months. A quarter of responders, including half of complete responders, maintained a response for >= 4 years. Median overall survival was not achieved. Among 20 patients receiving second-course pembrolizumab, ORR for 19 evaluable patients was 73.7% (95% CI, 48.8-90.8); median DOR was 15.2 months. Any-grade treatment-related adverse events occurred in 72.9% of patients and grade 3 or 4 adverse events occurred in 12.9% of patients; no treatment-related deaths occurred. Single-agent pembrolizumab can induce durable responses, particularly in patients achieving CR. Second-course pembrolizumab frequently reinduced sustained responses after relapse from initial CR.

  • 10. Arne, Kolstad
    et al.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Jerkeman, Mats
    Gronbaek, Kirsten
    Elonen, Erkki
    Raty, Riikka
    Pedersen, Lone Bredo
    Loft, Annika
    Bogsrud, Trond Velde
    Nordstrom, Marie
    Hansen, Per Boye
    Fagerli, Unn-Merete
    Nilsson-Ehle, Herman
    Lauritzsen, Grete Fossum
    Lehmann, Anne Kristine
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Karjalainen-Lindsberg, Marja-Liisa
    Ralfkiaer, Elisabeth
    Ehinger, Mats
    Delabie, Jan
    Bentzen, Hans
    Schildt, Jukka
    Kostova-Aherdan, Kamelia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Frederiksen, Henrik
    Brown, Peter de Nully
    Geisler, Christian H.
    Nordic MCL3 Study: Zevalin Combined with High-Dose Chemotherapy Followed by Autologous Stem Cell Support As Late Intensification for Mantle Cell Lymphoma (MCL) Patients < 66 Years Not in CR After Induction Chemoimmunotherapy: No Benefit of Zevalin2012In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 120, no 21, p. 747-Article in journal (Refereed)
  • 11. Baccarani, Michele
    et al.
    Deininger, Michael W.
    Rosti, Gianantonio
    Hochhaus, Andreas
    Soverini, Simona
    Apperley, Jane F.
    Cervantes, Francisco
    Clark, Richard E.
    Cortes, Jorge E.
    Guilhot, Francois
    Hjorth-Hansen, Henrik
    Hughes, Timothy P.
    Kantarjian, Hagop M.
    Kim, Dong-Wook
    Larson, Richard A.
    Lipton, Jeffrey H.
    Mahon, Francois-Xavier
    Martinelli, Giovanni
    Mayer, Jiri
    Mueller, Martin C.
    Niederwieser, Dietger
    Pane, Fabrizio
    Radich, Jerald P.
    Rousselot, Philippe
    Saglio, Giuseppe
    Saussele, Susanne
    Schiffer, Charles
    Silver, Richard
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Steegmann, Juan-Luis
    Goldman, John M.
    Hehlmann, Ruediger
    European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 20132013In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, no 6, p. 872-884Article, review/survey (Refereed)
    Abstract [en]

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

  • 12. Baccarani, Michele
    et al.
    Hoffmann, Verena Sophia
    Rosti, Gianantonio
    Castagnetti, Fausto
    Saussele, Susanne
    Guilhot, Joelle
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Steegmann, Juan Luis
    Mayer, Jiri
    Indrak, Karel
    Turkina, Anna G.
    Zaritskey, Andrey
    Labar, Boris
    Zupan, Irena
    Thielen, Noortje
    Clark, Richard E.
    Thaler, Josef
    Melanthiou, Frederiki
    Everaus, Hele
    Porkka, Kimmo
    Bogdanovic, Andrija
    Schubert-Fritschle, Gabriel
    Panagiotidis, Panagiotis
    Masszi, Tamas
    Lejniece, Sandra
    Griskevicius, Laimonas
    Hellmann, Andrzej
    Prejzner, Witold
    Sacha, Tomasz
    Almeida, Antonio
    Dyagil, Irina
    Colita, Adriana
    Mihaylov, Georgi G.
    Hehlmann, Rudiger
    Hasford, Joerg
    Lindoerfer, Doris
    Baseline Characteristics of CML Patients Accross Europe - Comparing Real-World Patients with Patient Collectives Included in Clinical Trials2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 13. Baccarani, Michele
    et al.
    Rosti, Gianantonio
    Castagnetti, Fausto
    Haznedaroglu, Ibrahim
    Porkka, Kimmo
    Abruzzese, Elisabetta
    Alimena, Giuliana
    Ehrencrona, Hans
    Hjorth-Hansen, Henrik
    Kairisto, Veli
    Levato, Luciano
    Martinelli, Giovanni
    Nagler, Arnon
    Lanng Nielsen, Johan
    Ozbek, Ugur
    Palandri, Francesca
    Palmieri, Fausto
    Pane, Fabrizio
    Rege-Cambrin, Giovanna
    Russo, Domenico
    Specchia, Giorgina
    Testoni, Nicoletta
    Weiss-Bjerrum, Ole
    Saglio, Giuseppe
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study2009In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 113, no 19, p. 4497-4504Article in journal (Refereed)
    Abstract [en]

    Imatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph(+)) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic use of a higher dose of IM could lead to better results, 216 patients with Ph(+) CML at high risk (HR) according to the Sokal index were randomly assigned to receive IM 800 mg or 400 mg daily, as front-line therapy, for at least 1 year. The CCgR rate at 1 year was 64% and 58% for the high-dose arm and for the standard-dose arm, respectively (P = .435). No differences were detectable in the CgR at 3 and 6 months, in the molecular response rate at any time, as well as in the rate of other events. Twenty-four (94%) of 25 patients who could tolerate the full 800-mg dose achieved a CCgR, and only 4 (23%) of 17 patients who could tolerate less than 350 mg achieved a CCgR. This study does not support the extensive use of high-dose IM (800 mg daily) front-line in all CML HR patients. This trial was registered at www.clinicaltrials.gov as #NCT00514488.

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

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

  • 15.
    Bahram, Fuad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Wu, Siqin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Öberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Luscher, Bernhard
    Larsson, Lars-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Posttranslational regulation of Myc function in response to phorbol ester/interferon-gamma-induced differentiation of v-Myc-transformed U-937 monoblasts1999In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 93, no 11, p. 3900-3912Article in journal (Refereed)
    Abstract [en]

    The transcription factors of the Myc/Max/Mad network are important regulators of cell growth, differentiation, and apoptosis and are frequently involved in tumor development. Constitutive expression of v-Myc blocks phorbol ester (TPA)-induced differentiation of human U-937 monoblasts. However, costimulation with interferon-gamma (IFN-gamma) and TPA restores terminal differentiation and G1 cell-cycle arrest despite continuous expression of v-Myc. The mechanism by which TPA + IFN-gamma counteract v-Myc activity has not been unravelled. Our results show that TPA + IFN-gamma treatment led to an inhibition of v-Myc- and c-Myc-dependent transcription, and a specific reduction of v-Myc:Max complexes and associated DNA-binding activity, whereas the steady state level of the v-Myc protein was only marginally affected. In contrast, TPA + IFN-gamma costimulation neither increased the expression of Mad1 or other mad/mnt family genes nor altered heterodimerization or DNA-binding activity of Mad1. The reduced amount of v-Myc:Max heterodimers in response to treatment was accompanied by partial dephosphorylation of v-Myc and c-Myc. Phosphatase treatment of Myc:Max complexes lead to their dissociation, thus mimicking the effect of TPA + IFN-gamma. In addition to modulation of the expression of Myc/Max/Mad network proteins, posttranslational negative regulation of Myc by external signals may, therefore, be an alternative biologically important level of control with potential therapeutic relevance for hematopoietic and other tumors with deregulated Myc expression.

  • 16.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Agathangelidis, Andreas
    Hadzidimitriou, Anastasia
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sutton, Lesley-Ann
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Minga, Eva
    Tsanousa, Athina
    Scarfo, Lydia
    Davis, Zadie
    Yan, Xiao-Jie
    Shanafelt, Tait
    Plevova, Karla
    Sandberg, Yorick
    Vojdeman, Fie Juhl
    Boudjogra, Myriam
    Tzenou, Tatiana
    Chatzouli, Maria
    Chu, Charles C.
    Veronese, Silvio
    Gardiner, Anne
    Mansouri, Larry
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Smedby, Karin E.
    Pedersen, Lone Bredo
    Moreno, Denis
    Van Lom, Kirsten
    Giudicelli, Veronique
    Francova, Hana Skuhrova
    Nguyen-Khac, Florence
    Panagiotidis, Panagiotis
    Juliusson, Gunnar
    Angelis, Lefteris
    Anagnostopoulos, Achilles
    Lefranc, Marie-Paule
    Facco, Monica
    Trentin, Livio
    Catherwood, Mark
    Montillo, Marco
    Geisler, Christian H.
    Langerak, Anton W.
    Pospisilova, Sarka
    Chiorazzi, Nicholas
    Oscier, David
    Jelinek, Diane F.
    Darzentas, Nikos
    Belessi, Chrysoula
    Davi, Frederic
    Ghia, Paolo
    Rosenquist, Richard Brandell
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Stamatopoulos, Kostas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 125, no 5, p. 856-859Article in journal (Refereed)
    Abstract [en]

    An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset # 2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset # 2. Within subset # 2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset # 2/IGHV3-21 was enriched for IGHV-unmutated cases (P =.002). Subset # 2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset # 2/IGHV3-21 (22 vs 60 months, P =.001). No such difference was observed between non-subset # 2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset # 2 emerges as uniformly aggressive, contrasting non-subset # 2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.

  • 17.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hadzidimitriou, Anastasia
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Agathangelidis, Andreas
    Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, Ist Ricovero & Cura Carattere Sci, Div Expt Oncol, Dept Oncohematol, I-20132 Milan, Italy..
    Rossi, Davide
    Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Haematol, Novara, Italy..
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kminkova, Jana
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp, Brno, Czech Republic..
    Scarfo, Lydia
    Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, Ist Ricovero & Cura Carattere Sci, Div Expt Oncol, Dept Oncohematol, I-20132 Milan, Italy..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp, Brno, Czech Republic..
    Gaidano, Gianluca
    Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Haematol, Novara, Italy..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ghia, Paolo
    Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, Ist Ricovero & Cura Carattere Sci, Div Expt Oncol, Dept Oncohematol, I-20132 Milan, Italy..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Prognostic relevance of MYD88 mutations in CLL: the jury is still out2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 8, p. 1043-1044Article in journal (Refereed)
  • 18. Baliakas, Panagiotis
    et al.
    Hadzidimitriou, Anastasia
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Minga, Evangelia
    Agathangelidis, Andreas
    Tsanousa, Athina
    Scarfo, Lydia
    Davis, Zadie
    Yan, Joy
    Shanafelt, Tait D.
    Plevova, Karla
    Sandberg, Yorick
    Vojdeman, Fie Juhl
    Boudjoghra, Myriam
    Tzenou, Tatiana
    Chatzouli, Maria
    Chu, Charles C.
    Veronese, Silvio
    Gardiner, Anne Catherine
    Mansouri, Larry
    Smedby, Karin E.
    Pedersen, Lone
    Moreno, Denis
    van Lom, Kirsten
    Giudicelli, Veronique
    Francova, Hana
    Nguyen-Khac, Florence
    Panagiotidis, Panagiotis
    Juliusson, Gunnar
    Angelis, Lefteris
    Anagnostopoulos, Achilles
    Lefranc, Marie-Paule
    Facco, Monica
    Trentin, Livio
    Catherwood, Mark
    Montillo, Marco
    Geisler, Christian H.
    Langerak, Anton W.
    Pospisilova, Sarka
    Chiorazzi, Nicholas
    Oscier, David
    Jelinek, Diane F.
    Darzentas, Nikos
    Belessi, Chrysoula
    Davi, Frederic
    Rosenquist, Richard
    Ghia, Paolo
    Stamatopoulos, Kostas
    Clinical Impact of Stereotyped Antigen Receptors in Chronic Lymphocytic Leukemia2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 19.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Jeromin, Sabine
    Munich Leukemia Lab, Munich, Germany.
    Iskas, Michalis
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.
    Puiggros, Anna
    Hosp del Mar, Serv Patol, Lab Citogenet Mol, Barcelona, Spain;Inst Hosp del Mar Invest Med IMIM, Programa Recerca Canc, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain.
    Plevova, Karla
    Masaryk Univ, Cent European Inst Technol CEITEC, Brno, Czech Republic;Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic;Masaryk Univ, Fac Med, Brno, Czech Republic.
    Nguyen-Khac, Florence
    Hematol Dept, Paris, France;Sorbonne Univ, Hop Pitie Salpetriere, INSERM, U1138, Paris, France.
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England.
    Rigolin, Gian Matteo
    St Anna Univ Hosp, Hematol Sect, Ferrara, Italy.
    Visentin, Andrea
    Univ Padua, Dept Med, Hematol Div, Padua, Italy.
    Xochelli, Aliki
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece.
    Delgado, Julio
    Univ Barcelona, Hosp Clin, Dept Hematol, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain.
    Baran-Marszak, Fanny
    Hop Avicenne, Assistance Publ Hop Paris, Lab Hematol, Paris, France.
    Stalika, Evangelia
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece.
    Abrisqueta, Pau
    Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain.
    Durechova, Kristina
    Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic;Masaryk Univ, Fac Med, Brno, Czech Republic.
    Papaioannou, George
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.
    Eclache, Virginie
    Hop Avicenne, Assistance Publ Hop Paris, Lab Hematol, Paris, France.
    Dimou, Maria
    Univ Athens, Laikon Univ Hosp, Dept Propedeut Internal Med 1, Hematol Sect, Athens, Greece.
    Iliakis, Theodoros
    Univ Athens, Laikon Univ Hosp, Dept Propedeut Internal Med 1, Hematol Sect, Athens, Greece.
    Collado, Rosa
    Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain.
    Doubek, Michael
    Masaryk Univ, Cent European Inst Technol CEITEC, Brno, Czech Republic;Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic;Masaryk Univ, Fac Med, Brno, Czech Republic.
    Jose Calasanz, M.
    Univ Navarra, Dept Genet, Serv Genet Citogenet, Pamplona, Spain.
    Ruiz-Xiville, Neus
    Univ Autonoma Barcelona, Inst Recerca Leucemia Josep Carreras IJC, ICO Hosp Germans Trias & Pujol, Serv Lab Hematol, Badalona, Spain.
    Moreno, Carolina
    Hosp Univ Santa Creu & St Pau, Serv Hematol, Barcelona, Spain.
    Jarosova, Marie
    Masaryk Univ, Cent European Inst Technol CEITEC, Brno, Czech Republic;Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic;Masaryk Univ, Fac Med, Brno, Czech Republic.
    Leeksma, Alexander C.
    Univ Amsterdam, Acad Med Ctr Amsterdam, Dept Hematol & Lymphoma, Amsterdam, Netherlands;Univ Amsterdam, Acad Med Ctr Amsterdam, Myeloma Ctr Amsterdam, Amsterdam, Netherlands;Canc Ctr Amsterdam, Dept Expt Immunol, Amsterdam, Netherlands;Infect & Immun Inst Amsterdam, Amsterdam, Netherlands.
    Panayiotidis, Panayiotis
    Univ Athens, Laikon Univ Hosp, Dept Propedeut Internal Med 1, Hematol Sect, Athens, Greece.
    Podgornik, Helena
    Univ Med Ctr Ljubljana, Dept Hematol, Ljubljana, Slovenia.
    Cymbalista, Florence
    Hop Avicenne, Assistance Publ Hop Paris, Lab Hematol, Paris, France.
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.
    Trentin, Livio
    Univ Padua, Dept Med, Hematol Div, Padua, Italy.
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.
    Davi, Fred
    Hematol Dept, Paris, France;Sorbonne Univ, Hop Pitie Salpetriere, INSERM, U1138, Paris, France.
    Ghia, Paolo
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Kater, Arnon P.
    Univ Amsterdam, Acad Med Ctr Amsterdam, Dept Hematol & Lymphoma, Amsterdam, Netherlands;Univ Amsterdam, Acad Med Ctr Amsterdam, Myeloma Ctr Amsterdam, Amsterdam, Netherlands;Canc Ctr Amsterdam, Dept Expt Immunol, Amsterdam, Netherlands;Infect & Immun Inst Amsterdam, Amsterdam, Netherlands.
    Cuneo, Antonio
    St Anna Univ Hosp, Hematol Sect, Ferrara, Italy.
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol CEITEC, Brno, Czech Republic;Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic;Masaryk Univ, Fac Med, Brno, Czech Republic.
    Espinet, Blanca
    Hosp del Mar, Serv Patol, Lab Citogenet Mol, Barcelona, Spain;Inst Hosp del Mar Invest Med IMIM, Programa Recerca Canc, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain.
    Athanasiadou, Anastasia
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England.
    Haferlach, Claudia
    Munich Leukemia Lab, Munich, Germany.
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece.
    Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact2019In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 133, no 11, p. 1205-1216Article in journal (Refereed)
    Abstract [en]

    Recent evidence suggests that complex karyotype (CK) defined by the presence of >= 3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with >= 5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcomes, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and/or TP53 mutations [TP53abs]), and the expression of somatically hypermutated (M-CLL) or unmutated immunoglobulin heavy variable genes. Thus, they contrasted with CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and 112,119 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hyper-mutation status, we propose a novel hierarchical model in which patients with high-CK exhibit the worst prognosis, whereas those with mutated CLL lacking CK or TP53abs, as well as CK with 112,119, show the longest overall survival. Thus, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with >= 5 chromosomal aberrations emerges as prognostically adverse, independent of other biomarkers. Prospective clinical validation is warranted before ultimately incorporating high-CK in risk stratification of CLL.

  • 20.
    Ballesteros, Joan
    et al.
    Vivia Biotech, Madrid, Spain..
    Scarfo, Lydia
    Ist Sci San Raffaele, Unit Lymphoid Malignancies, Dept Oncohematol, I-20132 Milan, Italy..
    Mattsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Xochelli, Aliki
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Ranghetti, Pamela
    Univ Vita Salute San Raffaele, Milan, Italy.;Osped San Raffaele, Madrid, Spain..
    Primo, Daniel
    Vivia Biotech, Madrid, Spain..
    Robles, Alicia
    Vivia Biotech, Madrid, Spain..
    Gorrochategui, Julian
    Vivia Biotech, Madrid, Spain..
    Martinez-Lopez, Joaquin
    Hosp Univ 12 Octubre, Madrid, Spain..
    De la Serna, Javier
    Hosp Univ 12 Octubre, Madrid, Spain..
    Gonzalez, Marcos
    Hosp Clin Univ Salamanca, Salamanca, Spain..
    Munugalavadla, Veerendra
    Gilead Sci, Foster City, CA USA..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Stamatopoulos, Kostas
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Queva, Christophe
    Gilead Sci, Foster City, CA USA..
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS Ist Sci San Raffaele, Milan, Italy..
    An Innovative High-Throughput Ex Vivo Drug Assay Incorporating the Native Microenvironment Reveals a Novel Mechanism of Action of Idelalisib in CLL2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 21. Barosi, Giovanni
    et al.
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Finazzi, Guido
    Griesshammer, Martin
    Harrison, Claire
    Hasselbalch, Hans Carl
    Kiladjian, Jean-Jacques
    Lengfelder, Eva
    McMullin, Mary Frances
    Passamonti, Francesco
    Reilly, John T.
    Vannucchi, Alessandro M.
    Barbui, Tiziano
    Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference2009In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 113, no 20, p. 4829-4833Article in journal (Refereed)
    Abstract [en]

    European experts were convened to develop a definition of response to treatment in polycythemia vera (PV) and essential thrombocythemia (ET). Clinicohematologic (CH), molecular, and histologic response categories were selected. In ET, CH complete response (CR) was: platelet count less than or equal to 400 x 10(9)/L, no disease-related symptoms, normal spleen size, and white blood cell count less than or equal to 10 x 10(9)/L. Platelet count less than or equal to 600 x 10(9)/L or a decrease greater than 50% was partial response (PR). In PV, CH-CR was: hematocrit less than 45% without phlebotomy, platelet count less than or equal to 400 x 10(9)/L, white blood cell count less than or equal to 10 x 10(9)/L, and no disease-related symptoms. A hematocrit less than 45% without phlebotomy or response in 3 or more of the other criteria was defined as PR. In both ET and in PV, molecular CR was a reduction of any molecular abnormality to undetectable levels. Molecular PR was defined as a reduction more than or equal to 50% in patients with less than 50% mutant allele burden, or a reduction more than or equal to 25% in patients with more than 50% mutant allele burden. Bone marrow histologic response in ET was judged on megakaryocyte hyperplasia while on cellularity and reticulin fibrosis in PV. The combined use of these response definitions should help standardize the design and reporting of clinical studies.

  • 22. Barragan, A
    et al.
    Fernandez, V
    Chen, Q
    von Euler, A
    Wahlgren, M
    Spillmann, Dorothe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    The duffy-binding-like domain 1 of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a heparan sulfate ligand that requires 12 mers for binding2000In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 95, no 11, p. 3594-3599Article in journal (Refereed)
    Abstract [en]

    The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), present on the surfaces of parasitized red blood cells (pRBC), mediates rosetting, a virulent phenotype. Here, we show that pRBC specifically bind heparan sulfate (HS) and heparin onto their surfaces and that the rosetting ligand PfEMP1 specifically adheres to heparin-Sepharose when extracted from the surfaces of radioiodinated infected RBC. An analysis of the binding properties of the different regions of PfEMP1 provides evidence that the Duffy-binding-like domain-1 (DBL-1) is the predominant ligand involved in HS and heparin binding. Soluble DBL-1 requires a minimal heparin fragment size of a 12-mer ( approximately 4 kd) for binding and is critically dependent on N-sulfation. A 12-mer is also the minimal heparin fragment that disrupts naturally formed rosettes. DBL-1 binds specifically to erythrocytes and also to HS from endothelial cells and human aorta but not to chondroitin sulfate A, suggesting that different PfEMP1s mediate adhesion to distinct glycosaminoglycans in individual malaria parasites. Present data suggest that HS on endothelial cells may also be involved in the sequestration of pRBC. Elucidation of these binding mechanisms opens up new possibilities for therapeutic strategies targeting adhesive interactions of pRBC.

  • 23. Barrington, Sally F
    et al.
    Kirkwood, Amy A
    Franceschetto, Antonella
    Fulham, Michael J
    Roberts, Thomas H
    Almquist, Helén
    Brun, Eva
    Hjorthaug, Karin
    Viney, Zaid N
    Pike, Lucy C
    Federico, Massimo
    Luminari, Stefano
    Radford, John
    Trotman, Judith
    Fosså, Alexander
    Berkahn, Leanne
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    D'Amore, Francesco
    Sinclair, Donald A
    Smith, Paul
    O'Doherty, Michael J
    Stevens, Lindsey
    Johnson, Peter W
    PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.2016In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 127, no 12, p. 1531-1538Article in journal (Refereed)
    Abstract [en]

    International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.

  • 24.
    Berglund, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Thunberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    SNP rs6457327 is a predictor for overall survival in follicular lymphoma as well as survival after transformation2011In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, no 16, p. 4489-4489Article in journal (Refereed)
  • 25.
    Birgegård, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Besses, Carlos
    Griesshammer, Martin
    Gugliotta, Luigi
    Harrison, Claire N.
    Hamdani, Mohamed
    Achenbach, Heinrich
    Kiladjian, Jean-Jacques
    Treatment of Essential Thrombocythemia in Europe: An Observational Study of 3649 High-Risk Patients in Exels2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 26. Bjorklund, Andreas T.
    et al.
    Carlsten, Mattias
    Schaffer, Marie
    Liu, Lisa
    Cooley, Sarah A.
    Miller, Jeffrey S.
    Watz, Emma
    Palma, Marzia
    Hansson, Lotta
    Wahlin, Bjorn E.
    Mollgard, Lars
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Blomberg, Pontus
    Ljungman, Per T.
    Hellstrom-Lindberg, Eva
    Ljunggren, Hans-Gustaf
    Malmberg, Karl-Johan
    Early and Transient Microchimerism Associated with Complete Remission after Adoptively Transferred Haploidentical NK Cells Against High Risk Myelodysplastic Syndrome and Refractory Acute Myeloid Leukemia2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 27.
    Björkholm, Magnus
    et al.
    Karolinska Univ Hosp, Dept Med, Div Hematol, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Bower, Hannah
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Dickman, Paul W.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Lambert, Paul C.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Andersson, Therese M-L
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Temporal Trends in Chronic Myeloid Leukemia Outcome Using the Loss in Expectation of Life: A Swedish Population-Based Study2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 28.
    Björkman, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Oh, MyungShin
    Spotts, Gerald
    Schroth, Phillip
    Fritsch, Sandor
    Ewenstein, Bruce M.
    Casey, Kathleen
    Fischer, Kathelijn
    Blanchette, Victor S.
    Collins, Peter W.
    Population pharmacokinetics of recombinant factor VIII: the relationships of pharmacokinetics to age and body weight2012In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 119, no 2, p. 612-618Article in journal (Refereed)
    Abstract [en]

    Comparison of the pharmacokinetics (PK) of a coagulation factor between groups of patients can be biased by differences in study protocols, in particular between blood sampling schedules. This could affect clinical dose tailoring, especially in children. The aim of this study was to describe the relationships of the PK of factor VIII (FVIII) with age and body weight by a population PK model. The potential to reduce blood sampling was also explored. A model was built for FVIII PK from 236 infusions of recombinant FVIII in 152 patients (1-65 years of age) with severe hemophilia A. The PK of FVIII over the entire age range was well described by a 2-compartment model and a previously reported problem, resulting from differences in blood sampling, to compare findings from children and adults was practically abolished. The decline in FVIII clearance and increase in half-life with age could be described as continuous functions. Retrospective reduction of blood sampling from 11 to 5 samples made no important difference to the estimates of PK parameters. The obtained findings can be used as a basis for PK-based dose tailoring of FVIII in clinical practice, in all age groups, with minimal blood sampling.

  • 29. Bomben, Riccardo
    et al.
    Dal Bo, Michele
    Capello, Daniela
    Benedetti, Dania
    Marconi, Daniela
    Zucchetto, Antonella
    Forconi, Francesco
    Maffei, Rossana
    Ghia, Emanuela M.
    Laurenti, Luca
    Bulian, Pietro
    Del Principe, Maria Ilaria
    Palermo, Giuseppe
    Thorselius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Degan, Massimo
    Campanini, Renato
    Guarini, Anna
    Del Poeta, Giovanni
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Efremov, Dimitar G.
    Marasca, Roberto
    Foa, Robin
    Gaidano, Gianluca
    Gattei, Valter
    Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study2007In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 109, no 7, p. 2989-2998Article in journal (Refereed)
    Abstract [en]

    IGHV3-21-using chronic lymphocytic leukemia (CLL) is a distinct entity with restricted immunoglobulin gene features and poor prognosis and is more frequently encountered in Northern than Southern Europe. To further investigate this subset and its geographic distribution in the context of a country (Italy) with both continental and Mediterranean areas, 37 IGHV3-21 CLLs were collected out of 1076 cases enrolled by different institutions from Northern or Central Southern Italy. Of the 37 cases, 18 were identified as homologous (hom)HCDR3-IGHV3-21 CLLs and were found almost exclusively (16 of 18) in Northern Italy; in contrast, 19 nonhomHCDR3-IGHV3-21 cases were evenly distributed throughout Italy. Clinically, poor survivals were documented for IGHV3-21 CLLs as well as for subgroups of mutated and homHCDR3-IGHV3-21 CLLs. Negative prognosticators CD38, ZAP-70, CD49d, and CD79b were expressed at higher levels in homHCDR3 than nonhomHCDR3-IGHV3-21 cases. Differential gene expression profiling (GEP) of 13 IGHV3-21 versus 52 non-IGHV3-21 CLLs identified, among 122 best-correlated genes, TGFB2 and VIPR1 as down- and up-regulated in IGHV3-21 CLL cases, respectively. Moreover, GEP of 7 homHCDR3 versus 6 nonhomHCDR3-IGHV3-21 CLLs yielded 20 differentially expressed genes, with WNT-16 being that expressed at the highest levels in homHCDR3-IGHV3-21 CLLs. Altogether, IGHV3-21 CLLs, including those with homHCDR3, had a peculiar global phenotype in part explaining their worse clinical outcome.

  • 30.
    Bona, Kira
    et al.
    Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Oncol, Div Populat Sci, Boston, MA 02115 USA..
    Brazauskas, Ruta
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res CIBMTR, Inst Hlth & Equ, Milwaukee, WI 53226 USA.;Med Coll Wisconsin, Inst Hlth & Equ, Div Biostat, Milwaukee, WI 53226 USA..
    He, Naya
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res CIBMTR, Inst Hlth & Equ, Milwaukee, WI 53226 USA..
    Lehmann, Leslie
    Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Oncol, Boston Childrens Hosp, Boston, MA 02115 USA..
    Abdel-Azim, Hisham
    Univ Southern Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA 90007 USA..
    Ahmed, Ibrahim A.
    Childrens Mercy Hosp & Clin, Dept Hematol Oncol & Bone Marrow Transplantat, Kansas City, MO USA..
    Al-Homsi, A. Samer
    New York Univ Langone Hlth, New York, NY USA..
    Aljurf, Mahmoud
    King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riyadh, Saudi Arabia..
    Arnold, Staci D.
    Emory Univ, Childrens Healthcare Atlanta, Aflac Canc & Blood Disorder Ctr, Atlanta, GA 30322 USA..
    Badawy, Sherif M.
    Ann & Robert H Lurie Childrens Hosp Chicago, Div Hematol Oncol & Stem Cell Transplant, Chicago, IL 60611 USA.;Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA..
    Battiwalla, Minoo
    Sarah Cannon Blood Canc Network, Nashville, TN USA..
    Beattie, Sara
    Tom Baker Canc Clin, Dept Psychosocial Oncol & Rehabil, Calgary, AB, Canada.;Univ Calgary, Dept Oncol, Calgary, AB, Canada..
    Bhatt, Neel S.
    Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA..
    Dalal, Jignesh
    Cleveland Case Western Reserve Sch Med, Rainbow Babies & Childrens Hosp, Cleveland, OH USA..
    Dandoy, Christopher E.
    Univ Cincinnati, Sch Med, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA..
    Angel Diaz, Miguel
    Hosp Infantil Univ Nino Jesus, Dept Hematol Oncol, Madrid, Spain..
    Frangoul, Haydar A.
    TriStar Centennial, Childrens Hosp, Nashville, TN USA.;Sarah Cannon Res Inst, Nashville, TN USA..
    Freytes, Cesar O.
    Texas Transplant Inst, San Antonio, TX USA..
    Ganguly, Siddhartha
    Univ Kansas Hlth Syst, Div Hematol Malignancy & Cellular Therapeut, Kansas City, KS USA..
    George, Biju
    Christian Med Coll & Hosp, Dept Haematol, Vellore, Tamil Nadu, India..
    Gomez-Almaguer, David
    Univ Autonoma Nuevo, Hosp Univ Dr Jose E Gonzalez, Monterrey, Mexico..
    Hahn, Theresa
    Roswell Park Comprehens Canc Ctr, Dept Med, Buffalo, NY USA..
    Kamble, Rammurti T.
    Baylor Coll Med, Ctr Cell & Gene Therapy, Div Hematol & Oncol, Houston, TX USA..
    Knight, Jennifer M.
    Med Coll Wisconsin, Dept Psychiat, Milwaukee, WI 53226 USA..
    LeMaistre, C. Fred
    Sarah Cannon Blood Canc Network, Nashville, TN USA..
    Law, Jason
    Tufts Med Ctr, Div Pediat Hematol Oncol, Floating Hosp Children, Boston, MA 02111 USA..
    Lazarus, Hillard M.
    Case Western Reserve Univ, Univ Hosp Cleveland Med Ctr, Cleveland, OH 44106 USA..
    Majhail, Navneet S.
    Cleveland Clin, Blood & Marrow Transplant Program, Taussig Canc Inst, Cleveland, OH 44106 USA..
    Olsson, Richard F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research Sörmland. Karolinska Inst, Dept Lab Med, Stockholm, Sweden..
    Preussler, Jaime
    Natl Marrow Donor Program Be Match, CIBMTR, Minneapolis, MN USA..
    Savani, Bipin N.
    Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA..
    Schears, Raquel
    Univ Cent Florida, Dept Emergency Med, Orlando, FL 32816 USA..
    Seo, Sachiko
    Dokkyo Med Univ, Dept Hematol & Oncol, Mibu, Tochigi, Japan..
    Sharma, Akshay
    St Jude Childrens Res Hosp, Dept Bone Marrow Transplantat & Cellular Therapy, 332 N Lauderdale St, Memphis, TN 38105 USA..
    Srivastava, Alok
    Christian Med Coll & Hosp, Ctr Stem Cell Res, Vellore, Tamil Nadu, India..
    Steinberg, Amir
    Mt Sinai Hosp, Div Hematol & Oncol, New York, NY 10029 USA..
    Szwajcer, David
    Univ Manitoba, CancerCare Manitoba, Winnipeg, MB, Canada..
    Wirk, Baldeep
    Penn State Canc Inst, Bone Marrow Transplant Program, Hershey, PA USA..
    Yoshimi, Ayami
    Univ Freiburg, Med Ctr, Dept Pediat & Adolescent Med, Div Pediat Hematol & Oncol, Freiburg, Germany..
    Khera, Nandita
    Mayo Clin, Dept Hematol Oncol, Phoenix, AZ USA..
    Wood, William A.
    Univ N Carolina, Dept Med, Div Hematol Oncol, Chapel Hill, NC USA..
    Hashmi, Shahrukh
    Mayo Clin, Dept Internal Med, Minneapolis, MN USA.;King Faisal Specialist Hosp & Res Ctr, Oncol Ctr, Riyadh, Saudi Arabia..
    Duncan, Christine N.
    Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Oncol, Boston Childrens Hosp, Boston, MA 02115 USA..
    Saber, Wael
    Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res CIBMTR, Inst Hlth & Equ, Milwaukee, WI 53226 USA..
    Neighborhood poverty and pediatric allogeneic hematopoietic cell transplantation outcomes: a CIBMTR analysis2021In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 137, no 4, p. 556-568Article in journal (Refereed)
    Abstract [en]

    Social determinants of health, including poverty, contribute significantly to health outcomes in the United States; however, their impact on pediatric hematopoietic cell transplantation (HCT) outcomes is poorly understood. We aimed to identify the association between neighborhood poverty and HCT outcomes for pediatric allogeneic HCT recipients in the Center for International Blood and Marrow Transplant Research database. We assembled 2 pediatric cohorts undergoing first allogeneic HCT from 2006 to 2015 at age 518 years, including 2053 children with malignant disease and 1696 children with nonmalignant disease. Neighborhood poverty exposure was defined a priori per the US Census definition as living in a high-poverty ZIP code (>= 20% of persons below 100% federal poverty level) and used as the primary predictor in all analyses. Our primary outcome was overall survival (OS), defined as the time from HCT until death resulting from any cause. Secondary outcomes included relapse and transplantation-related mortality (TRM) in malignant disease, acute and chronic graft-versus-host disease, and infection in the first 100 days post-HCT. Among children undergoing transplantation for nonmalignant disease, neighborhood poverty was not associated with any HCT outcome. Among children undergoing transplantation for malignant disease, neighborhood poverty conferred an increased risk of TRM but was not associated with inferior OS or any other transplantation outcome. Among children with malignant disease, a key secondary finding was that children with Medicaid insurance experienced inferior OS and increased TRM compared with those with private insurance. These data suggest opportunities for future investigation of the effects of household-level poverty exposure on HCT outcomes in pediatric malignant disease to inform care delivery interventions.

  • 31.
    Bornhauser, Beat C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Bonapace, Laura
    Lindholm, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Martinez, Rodrigo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Cario, Gunnar
    Schrappe, Martin
    Niggli, Felix K
    Schäfer, Beat W
    Bourquin, Jean-Pierre
    Low-dose arsenic trioxide sensitizes glucocorticoid-resistant acute lymphoblastic leukemia cells to dexamethasone via an Akt-dependent pathway2007In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 110, no 6, p. 2084-2091Article in journal (Refereed)
    Abstract [en]

    Incorporation of apoptosis-inducing agents into current therapeutic regimens is an attractive strategy to improve treatment for drug-resistant leukemia. We tested the potential of arsenic trioxide (ATO) to restore the response to dexamethasone in glucocorticoid (GC)–resistant acute lymphoblastic leukemia (ALL). Low-dose ATO markedly increased in vitro GC sensitivity of ALL cells from T-cell and precursor B-cell ALL patients with poor in vivo response to prednisone. In GC-resistant cell lines, this effect was mediated, at least in part, by inhibition of Akt and affecting downstream Akt targets such as Bad, a proapoptotic Bcl-2 family member, and the X-linked inhibitor of apoptosis protein (XIAP). Combination of ATO and dexamethasone resulted in increased Bad and rapid down-regulation of XIAP, while levels of the antiapoptotic regulator Mcl-1 remained unchanged. Expression of dominant-active Akt, reduction of Bad expression by RNA interference, or overexpression of XIAP abrogated the sensitizing effect of ATO. The inhibitory effect of XIAP overexpression was reduced when the Akt phosphorylation site was mutated (XIAP-S87A). These data suggest that the combination of ATO and glucocorticoids could be advantageous in GC-resistant ALL and reveal additional targets for the evaluation of new antileukemic agents.

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

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

  • 33.
    Chatzilari, Elisavet
    et al.
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Xochelli, Aliki
    Ctr Res & Technol Hellas, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Maronidis, Anastasios
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Vardi, Anna
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Mattsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Larsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Douka, Vassiliki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Iskas, Michail
    George Papanicolaou Gen Hosp, Hematol BMT Unit, Thessaloniki, Greece..
    Karavalakis, George
    G Papanicolaou Hosp, BMT Unit, Dept Hematol, Thessaloniki, Greece..
    Papalexandri, Apostolia
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Niemann, Carsten
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Montillo, Marco
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Davi, Frederic
    Hop La Pitie Salpetriere, Dept Biol Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Ghia, Paolo
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Hadzidimitriou, Anastasia
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Nikolopoulos, Spiros
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Kompatsiaris, Yannis
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Personalized Modeling of Disease Evolution in CLL: Does Statistical Significance Translate into Predictive Accuracy?2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 34.
    Chatzilari, Elisavet
    et al.
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Xochelli, Aliki
    Ctr Res & Technol Hellas, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Maronidis, Anastasios
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Vardi, Anna
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Mattsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Larsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Douka, Vassiliki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Iskas, Michail
    George Papanicolaou Gen Hosp, Hematol BMT Unit, Thessaloniki, Greece..
    Karavalakis, George
    G Papanicolaou Hosp, BMT Unit, Dept Hematol, Thessaloniki, Greece..
    Papalexandri, Apostolia
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Niemann, Carsten
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Montillo, Marco
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Davi, Frederic
    Hop La Pitie Salpetriere, Dept Biol Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Ghia, Paolo
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Hadzidimitriou, Anastasia
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Nikolopoulos, Spiros
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Kompatsiaris, Yannis
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Personalized Modeling of Disease Evolution in CLL: Does Statistical Significance Translate into Predictive Accuracy?2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 35. Chen, Leslie Y.
    et al.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Gwilliam, Rhian
    Bentley, David
    Deloukas, Panos
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Gamma-glutamyl carboxylase (GGCX) microsatellite and warfarin dosing2005In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 106, no 10, p. 3673-4Article in journal (Refereed)
  • 36.
    Chen, Robert
    et al.
    City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplant, 1500 E Duarte Rd, Duarte, CA 91010 USA.
    Zinzani, Pier Luigi
    Univ Bologna, Inst Hematol Seragnoli, Dept Expt Diagnost & Specialty Med, Bologna, Italy.
    Lee, Hun Ju
    Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA.
    Armand, Philippe
    Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
    Johnson, Nathalie A.
    Jewish Gen Hosp, Dept Hematol, Montreal, PQ, Canada.
    Brice, Pauline
    Hop St Louis, Dept Hematol Oncol, Paris, France.
    Radford, John
    Univ Manchester, Div Canc Sci, Manchester, Lancs, England;Christie NHS Fdn Trust, Manchester, Lancs, England.
    Ribrag, Vincent
    Inst Gustave Roussy, Dept Drug Dev & Hematol, Villejuif, France.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Vassilakopoulos, Theodoros P.
    Gen Hosp Athens, Dept Hematol & Bone Marrow Transplantat, Athens, Greece.
    Tomita, Akihiro
    Fujita Hlth Univ, Sch Med, Dept Hematol, Toyoake, Aichi, Japan.
    von Tresckow, Bastian
    Univ Cologne, Dept Internal Med, Cologne, Germany;Univ Hosp Cologne, Cologne, Germany.
    Shipp, Margaret A.
    Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
    Lin, Jianxin
    Merck & Co Inc, Med Oncol, Kenilworth, NJ USA.
    Kim, Eunhee
    Merck & Co Inc, Med Oncol, Kenilworth, NJ USA.
    Nahar, Akash
    Merck & Co Inc, Med Oncol, Kenilworth, NJ USA.
    Balakumaran, Arun
    Merck & Co Inc, Med Oncol, Kenilworth, NJ USA.
    Moskowitz, Craig H.
    Univ Miami, Dept Med, Sylvester Comprehens Canc Ctr, Miami, FL USA.
    Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-0872019In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 134, no 14, p. 1144-1153Article in journal (Refereed)
    Abstract [en]

    Programmed death-1 inhibitors are approved for patients with relapsed or refractory classic Hodgkin lymphoma (RRcHL). We present the 2-year follow-up of the phase 2 KEYNOTE-087 study of pembrolizumab in 210 patients, based on HL progression after autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV; cohort 1); salvage chemotherapy and BV, with ineligibility for SCT owing to chemorefractory disease (cohort 2); and progression after SCT without BV (cohort 3). With a median follow-up of 27.6 months, the objective response rate (ORR) by blinded independent central review was 71.9% (95% CI, 65.3-77.9), the complete response rate (CRR) was 27.6%, and the partial response (PR) rate was 44.3%. Median duration of response was 16.5months (range, 0.0+ to 27.0+ [+, no progressive disease at last assessment]) in all patients, 22.1months in cohort 1, 11.1 months in cohort 2, and 24.4 months in cohort 3. Median progression-free survival was not reached in all patients with CR: 13.8 months (95% CI, 12.0-22.1) for patients with PR and 10.9 months (95% CI, 5.6-11.1) for patients with stable disease. Median overall survival was not reached in all patients or in any cohort. Treatment-related adverse events (TRAEs) of any grade occurred in 153 (72.9%) patients; grades 3 and 4 occurred in 25 (12.0%) patients; none resulted in death. Results confirmed effective antitumor activity, durability of response, and manageable safety of pembrolizumab monotherapy in RRcHL, regardless of prior treatment and including chemoresistant cHL.

  • 37.
    Cherif, Honar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Influenza A H1N1 2009 Vaccine in Patients with Hematological Diseases: Good Safety and Immunogenicity Even in Heavily Chemotherapy-Treated Patients2012In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 120, no 21, p. 1054-Article in journal (Refereed)
  • 38. Chiang, Samuel C. C.
    et al.
    Theorell, Jakob
    Entesarian, Miriam
    Meeths, Marie
    Mastafa, Monika
    Al-Herz, Waleed
    Frisk, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Gilmour, Kimberly C.
    Ifversen, Marianne
    Langenskiold, Cecilia
    Machaczka, Maciej
    Naqvi, Ahmed
    Payne, Jeanette
    Perez-Martinez, Antonio
    Sabel, Magnus
    Unal, Ekrem
    Unal, Sule
    Winiarski, Jacek
    Nordenskjold, Magnus
    Ljunggren, Hans-Gustaf
    Henter, Jan-Inge
    Bryceson, Yenan T.
    Comparison of primary human cytotoxic T-cell and natural killer cell responses reveal similar molecular requirements for lytic granule exocytosis but differences in cytokine production2013In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 121, no 8, p. 1345-1356Article in journal (Refereed)
    Abstract [en]

    Cytotoxic lymphocytes, encompassing cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, kill pathogen-infected, neoplastic, or certain hematopoietic cells through the release of perforin-containing lytic granules. In the present study, we first performed probability-state modeling of differentiation and lytic granule markers on CD8(+) T cells to enable the comparison of bona fide CTLs with NK cells. Analysis identified CD57(bright) expression as a reliable phenotype of granule marker-containing CTLs. We then compared CD3(+)CD8(+)CD57(bright) CTLs with NK cells. Healthy adult peripheral blood CD3(+)CD8(+)CD57(bright) CTLs expressed more granzyme B but less perforin than CD3(-)CD56(dim) NK cells. On stimulation, such CTLs degranulated more readily than other T-cell subsets, but had a propensity to degranulate that was similar to NK cells. Remarkably, the CTLs produced cytokines more rapidly and with greater frequency than NK cells. In patients with biallelic mutations in UNC13D, STX11, or STXBP2 associated with familial hemophagocytic lymphohistiocytosis, CTL and NK cell degranulation were similarly impaired. Therefore, cytotoxic lymphocyte subsets have similar requirements for Munc13-4, syntaxin-11, and Munc18-2 in lytic granule exocytosis. The present results provide a detailed comparison of human CD3(+)CD8(+)CD57(bright) CTLs and NK cells and suggest that analysis of CD57(bright) CTL function may prove useful in the diagnosis of primary immunodeficiencies including familial hemophagocytic lymphohistiocytosis.

  • 39. Chigrinova, Ekaterina
    et al.
    Rinaldi, Andrea
    Kwee, Ivo
    Rossi, Davide
    Rancoita, Paola M. V.
    Strefford, Jonathan C.
    Oscier, David
    Stamatopoulos, Kostas
    Papadaki, Theodora
    Berger, Francoise
    Young, Ken H.
    Murray, Fiona
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Rosenquist, Richard Brandell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Greiner, Timothy C.
    Chan, Wing C.
    Orlandi, Ester M.
    Lucioni, Marco
    Marasca, Roberto
    Inghirami, Giorgio
    Ladetto, Marco
    Forconi, Francesco
    Cogliatti, Sergio
    Votavova, Nana
    Swerdlow, Steven H.
    Stilgenbauer, Stephan
    Piris, Miguel A.
    Matolcsy, Andras
    Spagnolo, Dominic
    Nikitin, Eugene
    Zamo, Alberto
    Gattei, Valter
    Bhagat, Govind
    Ott, German
    Zucca, Emanuele
    Gaidano, Gianluca
    Bertoni, Francesco
    Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome2013In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, no 15, p. 2673-2682Article in journal (Refereed)
    Abstract [en]

    Richter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). Although RS, usually represented by the histologic transformation to a diffuse large B-cell lymphoma (DLBCL), is associated with a very poor outcome, especially when clonally related to the preexisting CLL, the mechanisms leading to RS have not been clarified. To better understand the pathogenesis of RS, we analyzed a series of cases including 59 RS, 28 CLL phase of RS, 315 CLL, and 127 de novo DLBCL. RS demonstrated a genomic complexity intermediate between CLL and DLBCL. Cell-cycle deregulation via inactivation of TP53 and of CDKN2A was a main mechanism in the histologic transformation from CLL phase, being present in approximately one half of the cases, and affected the outcome of the RS patients. A second major subgroup was characterized by the presence of trisomy 12 and comprised one third of the cases. Although RS shared some of the lesions seen in de novo DLBCL, its genomic profile was clearly separate. The CLL phase preceding RS had not a generalized increase in genomic complexity compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions.

  • 40.
    Christoffersson, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Vågesjö, Evelina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Vandooren, Jennifer
    Liden, Majken
    Massena, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Reinert, RB
    Brissova, M
    Powers, AC
    Opdenakker, Ghislain
    Phillipson, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    VEGF-A recruits a proangiogenic MMP-9-delivering neutrophil subset that induces angiogenesis in transplanted hypoxic tissue2012In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 120, no 23, p. 4653-4662Article in journal (Refereed)
    Abstract [sv]

    Recruitment and retention of leukocytes at a site of blood vessel growth are crucial for proper angiogenesis and subsequent tissue perfusion. Although critical for many aspects of regenerative medicine, the mechanisms of leukocyte recruitment to and actions at sites of angiogenesis are not fully understood. In this study, we investigated the signals attracting leukocytes to avascular transplanted pancreatic islets and leukocyte actions at the engraftment site. Expression of the angiogenic stimulus VEGF-A by mouse pancreatic islets was elevated shortly after syngeneic transplantation to muscle. High levels of leukocytes, predominantly CD11b+/Gr-1+/CXCR4hi neutrophils, were observed at the site of engraftment, whereas VEGF-A–deficient islets recruited only half of the amount of leukocytes when transplanted. Acute VEGF-A exposure of muscle increased leukocyte extravasation but not the levels of SDF-1α. VEGF-A–recruited neutrophils expressed 10 times higher amounts of MMP-9 than neutrophils recruited to an inflammatory stimulus. Revascularization of islets transplanted to MMP-9–deficient mice was impaired because blood vessels initially failed to penetrate grafts, and after 2 weeks vascularity was still disturbed. This study demonstrates that VEGF-A recruits a proangiogenic circulating subset of CD11b+/Gr-1+ neutrophils that are CXCR4hi and deliver large amounts of the effector protein MMP-9, required for islet revascularization and functional integration after transplantation.

  • 41.
    Claesson-Welsh, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gremlin: vexing VEGF receptor agonist2010In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 116, no 18, p. 3386-3387Article in journal (Other academic)
  • 42.
    Condoluci, Adalgisa
    et al.
    Univ Svizzera Italiana, Oncol Res Inst, Bellinzona, Switzerland.;Oncol Inst Southern Switzerland, Bellinzona, Switzerland..
    di Bergamo, Lodovico Terzi
    Univ Svizzera Italiana, Oncol Res Inst, Bellinzona, Switzerland..
    Langerbeins, Petra
    Univ Cologne, Cologne Bonn & German CLL Study Grp, Ctr Integrated Oncol, Cologne, Germany..
    Hoechstetter, Manuela A.
    German CLL Study Grp, Hosp Munich Schwabing, Munich, Germany..
    Herling, Carmen D.
    Univ Cologne, Cologne Bonn & German CLL Study Grp, Ctr Integrated Oncol, Cologne, Germany..
    De Paoli, Lorenzo
    Univ Piemonte Orientale, Dept Translat Med, Div Hematol, Novara, Italy..
    Delgado, Julio
    Hosp Clin Barcelona, Barcelona, Spain..
    Rabe, Kari G.
    Mayo Clin, Rochester, MN USA..
    Gentile, Massimo
    Azienda Osped Cosenza, Cosenza, Italy..
    Doubek, Michael
    Masaryk Univ, Interni Hematol & Onkol Klin IHOK, Univ Hosp Brno, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic.;Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Mauro, Francesca R.
    Sapienza Univ, Div Hematol, Rome, Italy..
    Chiodin, Giorgia
    Univ Southampton, Canc Sci Div, Southampton, Hants, England..
    Mattsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Bahlo, Jasmin
    Univ Cologne, Cologne Bonn & German CLL Study Grp, Ctr Integrated Oncol, Cologne, Germany..
    Cutrona, Giovanna
    IRCCS Osped Policlin San Martino, Genoa, Italy..
    Kotaskova, Jana
    Masaryk Univ, Interni Hematol & Onkol Klin IHOK, Univ Hosp Brno, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic.;Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Deambrogi, Clara
    Univ Piemonte Orientale, Dept Translat Med, Div Hematol, Novara, Italy..
    Smedby, Karin E.
    Karolinska Inst, Stockholm, Sweden. Nanjing Med Univ, Affiliated Hosp 1, Jiangsu Prov Hosp, Nanjing, Peoples R China..
    Spina, Valeria
    Univ Svizzera Italiana, Oncol Res Inst, Bellinzona, Switzerland..
    Bruscaggin, Alessio
    Univ Svizzera Italiana, Oncol Res Inst, Bellinzona, Switzerland..
    Wu, Wei
    Univ Svizzera Italiana, Oncol Res Inst, Bellinzona, Switzerland.;IRCCS Osped Policlin San Martino, Genoa, Italy..
    Moia, Riccardo
    Univ Piemonte Orientale, Dept Translat Med, Div Hematol, Novara, Italy..
    Bianchi, Elena
    Oncol Inst Southern Switzerland, Bellinzona, Switzerland..
    Gerber, Bernhard
    Oncol Inst Southern Switzerland, Bellinzona, Switzerland..
    Zucca, Emanuele
    Oncol Inst Southern Switzerland, Bellinzona, Switzerland..
    Gillessen, Silke
    Oncol Inst Southern Switzerland, Bellinzona, Switzerland..
    Ghielmini, Michele
    Oncol Inst Southern Switzerland, Bellinzona, Switzerland..
    Cavalli, Franco
    Oncol Inst Southern Switzerland, Bellinzona, Switzerland..
    Stussi, Georg
    Oncol Inst Southern Switzerland, Bellinzona, Switzerland..
    Hess, Mark A.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA..
    Baumann, Tycho S.
    Hosp Clin Barcelona, Barcelona, Spain..
    Neri, Antonino
    Univ Milan, Dept Oncol & Hematooncol, Milan, Italy..
    Ferrarini, Manlio
    Univ Genoa, Dept Expt Med, Genoa, Italy..
    Rosenquist, Richard
    Karolinska Inst, Stockholm, Sweden. Nanjing Med Univ, Affiliated Hosp 1, Jiangsu Prov Hosp, Nanjing, Peoples R China..
    Forconi, Francesco
    Univ Southampton, Canc Sci Div, Southampton, Hants, England.;Southampton Univ Hosp Trust, Southampton, Hants, England..
    Foa, Robin
    Sapienza Univ, Div Hematol, Rome, Italy..
    Pospisilova, Sarka
    Masaryk Univ, Interni Hematol & Onkol Klin IHOK, Univ Hosp Brno, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic.;Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Morabito, Fortunato
    Biotechnol Res Unit Aprigliano, Cosenza, Italy.;Augusta Victoria Hosp, Jerusalem, Israel..
    Stilgenbauer, Stephan
    Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany..
    Doehner, Hartmut
    Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany..
    Parikh, Sameer A.
    Mayo Clin, Rochester, MN USA..
    Wierda, William G.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA..
    Montserrat, Emili
    Hosp Clin Barcelona, Barcelona, Spain.;Univ Barcelona, Inst Hematol & Oncol, Barcelona, Spain..
    Gaidano, Gianluca
    Univ Piemonte Orientale, Dept Translat Med, Div Hematol, Novara, Italy..
    Hallek, Michael
    Univ Cologne, Cologne Bonn & German CLL Study Grp, Ctr Integrated Oncol, Cologne, Germany..
    Rossi, Davide
    Univ Svizzera Italiana, Oncol Res Inst, Bellinzona, Switzerland.;Oncol Inst Southern Switzerland, Bellinzona, Switzerland..
    International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia2020In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 135, no 21, p. 1859-1869Article in journal (Refereed)
    Abstract [en]

    Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early-stage disease and managed with active surveillance. The individual course of patients with early-stage CLL is heterogeneous, and their probability of needing treatment is hardly anticipated at diagnosis. We aimed at developing an international prognostic score to predict time to first treatment (TTFT) in patients with CLL with early, asymptomatic disease (International Prognostic Score for Early-stage CLL [IPS-E]). Individual patient data from 11 international cohorts of patients with early-stage CLL (n = 4933) were analyzed to build and validate the prognostic score. Three covariates were consistently and independently correlated with TTFT: unmutated immunoglobulin heavy variable gene (IGHV), absolute lymphocyte count higher than 15 x 10(9)/L, and presence of palpable lymph nodes. The IPS-E was the sum of the covariates (1 point each), and separated low-risk (score 0), intermediate-risk (score 1), and high-risk (score 2-3) patients showing a distinct TTFT. The score accuracy was validated in 9 cohorts staged by the Binet system and 1 cohort staged by the Rai system. The C-index was 0.74 in the training series and 0.70 in the aggregate of validation series. By meta-analysis of the training and validation cohorts, the 5-year cumulative risk for treatment start was 8.4%, 28.4%, and 61.2% among low-risk, intermediate-risk, and high-risk patients, respectively. The IPS-E is a simple and robust prognostic model that predicts the likelihood of treatment requirement in patients with early-stage CLL. The IPS-E can be useful in clinical management and in the design of early intervention clinical trials.

  • 43. Cuccuini, Wendy
    et al.
    Briere, Josette
    Mounier, Nicolas
    Voelker, Hans-Ullrich
    Rosenwald, Andreas
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Cogliatti, Sergio
    Hirchaud, Edouard
    Ysebaert, Loic
    Bron, Dominique
    Soulier, Jean
    Gaulard, Philippe
    Houlgatte, Remi
    Gisselbrecht, Christian
    Thieblemont, Catherine
    MYC+ diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation2012In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 119, no 20, p. 4619-4624Article in journal (Refereed)
    Abstract [en]

    Approximately 5-10% of diffuse large B-cell lymphomas (DLBCL) harbor a 8q24/MYC rearrangement (MYC+). We determined the prognostic significance of MYC rearrangement in patients with relapsed/refractory DLBCL prospectively treated by R-ICE or R-DHAP followed by highdose therapy and autologous stem cell transplantation. Twenty-eight (17%) of the 161 patients analyzed presented a MYC+ rearrangement, targeted as either simple hit (25%) or complex hits (n = 75%) including MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6. Results were statistically highly concordant in matched primary and relapsed biopsies (n = 45). Compared to the MYC+ DLBCL patients, the MYC+ DLBCL patients presented with a more elevated lactico-deshydrogenase level (P = .0006) and a more advanced age adjusted international prognostic index (P = .0039). The 4-year PFS and OS were significantly lower in the MYC+ DLBCL patients than those in the MYC- DLBCL patients, with rates of 18% vs 42% (P = .0322), and of 29% vs 62% (P = .0113), respectively. Type of treatment, R-DHAP or R-ICE, had no impact on survivals, with 4-year PFS rates of 17% vs 19% and 4-year OS rates of 26% vs 31%. In conclusion, MYC rearrangement is an early event in DLBCL. MYC+ DLBCL patients have a significant inferior prognosis than MYC- DLBCL patients. Their outcome was not influenced by the proposed salvage therapy.

  • 44. Dahlen, Torsten
    et al.
    Edgren, Gustaf
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lambe, Mats
    Bjorkholm, Magnus
    Sandin, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sjalander, Anders
    Richter, Johan
    Ohm, Lotta
    Back, Magnus
    Stenke, Leif
    Increased Risk of Cardiovascular Events Associated with TKI Treatment in Chronic Phase Chronic Myeloid Leukemia. Data from Swedish Population-Based Registries2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 45.
    Dahlin, Joakim S.
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Ekoff, Maria
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Grootens, Jennine
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Löf, Liza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ungerstedt, Johanna S.
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden.;Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden..
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Nilsson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden.
    KIT signaling is dispensable for human mast cell progenitor development2017In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 130, no 16, p. 1785-1794Article in journal (Refereed)
    Abstract [en]

    Human hematopoietic progenitors are generally assumed to require stem cell factor (SCF) and KIT signaling during differentiation for the formation of mast cells. Imatinib treatment, which inhibits KIT signaling, depletes mast cells in vivo. Furthermore, the absence of SCF or imatinib treatment prevents progenitors from developing into mast cells in vitro. However, these observations do not mean that mast cell progenitors require SCF and KIT signaling throughout differentiation. Here, we demonstrate that circulating mast cell progenitors are present in patients undergoing imatinib treatment. In addition, we show that mast cell progenitors from peripheral blood survive, mature, and proliferate without SCF and KIT signaling in vitro. Contrary to the prevailing consensus, our results show that SCF and KIT signaling are dispensable for early mast cell development.

  • 46.
    Dahlin, Joakim S
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Öhrvik, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hallgren, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lineage- CD34hi CD117int/hi FcϵRI+ cells in human blood constitute a rare population of mast cell progenitors2016In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 127, no 4, p. 383-391Article in journal (Refereed)
    Abstract [en]

    Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34(+) progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered. To our knowledge, this is the first report of human lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7 and developed a mast cell-like phenotype, although with a slow cell division capacity in vitro. Isolated lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) blood cells had an immature mast cell-like appearance and expressed high levels of many mast cell-related genes as compared with human blood basophils in whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A mRNA transcripts were detected by quantitative RT-PCR. Altogether, we propose that the lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) blood mast cell progenitors than asthmatics with normal lung function.

  • 47. Daikeler, Thomas
    et al.
    Labopin, Myriam
    Ruggeri, Annalisa
    Crotta, Alessandro
    Abinun, Mario
    Hussein, Ayad Ahmed
    Carlson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Cornillon, Jerome
    Diez-Martin, Jose L.
    Gandemer, Virginie
    Faraci, Maura
    Lindemans, Caroline
    O'Meara, Anne
    Mialou, Valerie
    Renard, Marleen
    Sedlacek, Petr
    Sirvent, Anne
    Socie, Gerard
    Sora, Federica
    Varotto, Stefania
    Sanz, Jaime
    Voswinkel, Jan
    Vora, Ajay
    Yesilipek, M. Akif
    Herr, Andree-Laure
    Gluckman, Eliane
    Farge, Dominique
    Rocha, Vanderson
    New autoimmune diseases after cord blood transplantation: a retrospective study of EUROCORD and the Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation2013In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 121, no 6, p. 1059-1064Article in journal (Refereed)
    Abstract [en]

    To describe the incidence, risk factors, and treatment of autoimmune diseases (ADs) occurring after cord blood transplantation (CBT), we analyzed both CBT recipients reported to EUROCORD who had developed at least 1 new AD and those who had not. Fifty-two of 726 reported patients developed at least 1 AD within 212 days (range, 27-4267) after CBT. Cumulative incidence of ADs after CBT was 5.0% +/- 1% at 1 year and 6.6% +/- 1% at 5 years. Patients developing ADs were younger and had more nonmalignant diseases (P < .001). ADs target hematopoietic (autoimmune hemolytic anemia, n = 20; Evans syndrome, n = 9; autoimmune thrombocytopenia, n = 11; and immune neutropenia, n = 1) and other tissues (thyroiditis, n = 3; psoriasis, n = 2; Graves disease, n = 1; membranous glomerulonephritis, n = 2; rheumatoid arthritis, n = 1; ulcerative colitis, n = 1; and systemic lupus erythematosus, n = 1). Four patients developed 2 ADs (3 cases of immune thrombocytopenia followed by autoimmune hemolytic anemia and 1 Evans syndrome with rheumatoid arthritis). By multivariate analysis, the main risk factor for developing an AD was nonmalignant disease as an indication for CBT (P = .0001). Hematologic ADs were most often treated with steroids, rituximab, and cyclosporine. With a median follow-up of 26 months (range, 2-91), 6 of 52 patients died as a consequence of ADs. We conclude that CBT may be followed by potentially life-threatening, mainly hematologic ADs.

  • 48. d'Amore, Francesco
    et al.
    Leppa, Sirpa
    da Silva, Maria Comes
    Relander, Thomas
    Brown, Peter De Nully
    Weidmann, Eckhart
    Lauritzsen, Grete Fossum
    Pezzutto, Antonio
    Van Hoof, Achiel
    van Gelder, Michel
    Doorduijn, Jeanette K.
    Wu, Ka Lung
    Kluin-Nelemans, J. C.
    Lugtenburg, P. J.
    Jankovska, Milada
    Merup, Mats
    Fagerli, Unn-Merete
    Walewski, Jan
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mariz, Jose Mario
    Hansen, Per Boye
    Noesslinger, Thomas
    Janssens, Ann
    Brandefors, Lena
    Demuynck, Hilde
    Schaafsma, Martyn Ronald
    Christiansen, Ilse
    Salek, David
    Jyrkkio, Sirkku
    Prochazka, Vit
    Zijlstra, Josee
    Bohmer, L.
    Greil, Richard
    Stevens, Wendy
    Fijnheer, Rob
    Kooy, Marinus van Marwijk
    Grube, Matthias
    Hopfinger, Georg
    Van den Neste, Eric
    Jantunen, Esa
    Truemper, Lorenz
    Wulf, Gerald
    Altmann, Bettina
    Ziepert, Marita
    Loeffler, Markus
    Toldbod, Helle
    First Interim Efficacy and Safety Analysis of an International Phase III Randomized Trial in Newly Diagnosed Systemic Peripheral T-Cell Lymphoma Treated with Chemotherapy with or without Alemtuzumab and Consolidated by High Dose Therapy2012In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 120, no 21, p. 57-Article in journal (Refereed)
  • 49. De Bruyne, Elke
    et al.
    Bos, Tomas J.
    Schuit, Frans
    Van Valckenborgh, Els
    Menu, Eline
    Thorrez, Lieven
    Atadja, Peter
    Jernberg-Wiklund, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Vanderkerken, Karin
    IGF-1 suppresses Bim expression in multiple myeloma via epigenetic and posttranslational mechanisms2010In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 115, no 12, p. 2430-2440Article in journal (Refereed)
    Abstract [en]

    Insulin-like growth factor-1 (IGF-1) is an important growth and survival factor in multiple myeloma (MM). Here, we demonstrate that IGF-1 induces significant down-regulation of the proapoptotic BH3-only protein Bim in MM cells. Reduced Bim levels by RNA interference (RNAi) protected cells from drug-induced cell death. The IGF-1-mediated down-regulation of Bim was the result of (1) reduced transcription by activation of the Akt pathway and inactivation of the transcription factor FoxO3a, (2) increased proteasome-mediated degradation of the Bim extra-long protein by activation of the mitogen-activated protein kinase pathway, and (3) epigenetic regulation of both the Bim and the FoxO3a promoter. Treatment of cells with the histone deacetylase inhibitor LBH589 resulted in a clear up-regulation in the expression of Bim. Furthermore, the methylation inhibitor 5-aza-2'deoxycytidine (decitabine) significantly increased the effects of LBH589. On IGF-1 treatment, the Bim promoter region was found to be unmethylated, whereas chromatin immunoprecipitation analysis of the IGF-1-treated cells showed both a reduced histone H3 tail Lys9 (H3K9) acetylation and an increased H3K9 dimethylation, which contributed actively to its silencing. These data identify a new mechanism in the IGF-1-dependent survival of MM cells and emphasize the need for IGF-1-targeted drug therapy.

  • 50. de Miranda, Noel F. C. C.
    et al.
    Georgiou, Konstantinos
    Chen, Longyun
    Wu, Chenglin
    Gao, Zhibo
    Zaravinos, Apostolos
    Lisboa, Susana
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Teixeira, Manuel R.
    Zeng, Yixin
    Peng, Roujun
    Pan-Hammarstrom, Qiang
    Exome sequencing reveals novel mutation targets in diffuse large B-cell lymphomas derived from Chinese patients2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 16, p. 2544-2553Article in journal (Refereed)
    Abstract [en]

    Next-generation sequencing studies on diffuse large B-cell lymphomas (DLBCLs) have revealed novel targets of genetic aberrations but also high intercohort heterogeneity. Previous studies have suggested that the prevalence of disease subgroups and cytogenetic profiles differ between Western and Asian patients. To characterize the coding genome of Chinese DLBCL, we performed whole-exome sequencing of DNA derived from 31 tumors and respective peripheral blood samples. The mutation prevalence of B2M, CD70, DTX1, LYN, TMSB4X, and UBE2A was investigated in an additional 105 tumor samples. We discovered 11 novel targets of recurrent mutations in DLBCL that included functionally relevant genes such as LYN and TMSB4X. Additional genes were found mutated at high frequency (>= 10%) in the Chinese cohort including DTX1, which was the most prevalent mutation target in the Notch pathway. We furthermore demonstrated that mutations in DTX1 impair its function as a negative regulator of Notch. Novel and previous unappreciated targets of somatic mutations in DLBCL identified in this study support the existence of additional/alternative tumorigenic pathways in these tumors. The observed differences with previous reports might be explained by the genetic heterogeneity of DLBCL, the germline genetic makeup of Chinese individuals, and/or exposure to distinct etiological agents.

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