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  • 1.
    Abdul Qadhr, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Suurküla, Madis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Whole-body diffusion-weighted imaging compared with FDG-PET/CT in staging of lymphoma patients2011In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 52, no 2, p. 173-180Article in journal (Refereed)
    Abstract [en]

    Background:

    Diffusion-weighted imaging (DWI) has become increasingly valuable in lymph node imaging, yet the clinical utility of this technique in the staging of lymphoma has not been established.

    Purpose:

    To compare whole-body DWI with FDG-PET/CT in the staging of lymphoma patients.

    Material and Methods:

    Thirty-one patients, eight with Hodgkin lymphoma (HL) and 23 with non-Hodgkin's lymphoma (18 aggressive and five indolent) underwent both whole-body DWI, whole-body MRI (T1W and T2W-STIR) and FDG-PET/CT. Lesions on whole-body DWI were only considered positive if they correlated with lesions on T1W and T2W-STIR images. The staging given by each technique was compared, according to the Ann Arbor staging system. Differences in staging were solved using biopsy results, and clinical and CT follow-ups as standard of reference.

    Results:

    The staging was the same for DWI and FDG-PET/CT in 28 (90.3%) patients and different in three (9.7%). Of the 28 patients with the same staging, 11 had stage IV in both techniques and 17 had stages 0-III. No HL or aggressive non-Hodgkin's lymphoma patients had different staging. Three indolent small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) lymphoma had higher staging with DWI when compared with FDG-PET/CT. One small subcutaneous breast lymphoma was not seen but all other extranodal sites were detected by both techniques.

    Conclusion:

    Whole-body DWI is a promising technique for staging of both (aggressive and indolent) non-Hodgkin's lymphoma and HL.

  • 2.
    Adde, Magdalena
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Enblad, Gunilla
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hagberg, Hans
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sundström, Christer
    Department of Genetics and Pathology.
    Laurell, Anna
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Outcome for young high-risk aggressive B-cell lymphoma patients treated with CHOEP-14 and rituximab (R-CHOEP-14).2006In: Med Oncol, ISSN 1357-0560, Vol. 23, no 2, p. 283-93Article in journal (Refereed)
  • 3.
    Andersson, Anne
    et al.
    Department of Radiation Sciences, Oncology, Umeå University, Umeå.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Gustavsson, Anita
    Erlanson, Martin
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Tavelin, Björn
    Melin, Beatrice
    Long term risk of infections in Hodgkin lymphoma long-term survivors2011In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 154, no 5, p. 661-663Article in journal (Refereed)
  • 4.
    Berglund, Ake
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Nygren, Peter
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hagberg, Hans
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Pahlman, Lars
    Department of Surgical Sciences. Gastrointestinal Surgery.
    Sundin, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sundström, Christer
    Department of Genetics and Pathology.
    [Limit investigation in cancer of unknown primary site]2005In: Lakartidningen, ISSN 0023-7205, Vol. 102, no 41, p. 2946-8, 2950Article in journal (Other scientific)
  • 5.
    Berglund, Mattias
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Thunberg, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Amini, Rose-Marie
    Department of Genetics and Pathology.
    Book, Majlis
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Roos, Göran
    Erlanson, Martin
    Linderoth, Johan
    Dictor, Michael
    Jerkeman, Mats
    Cavallin-Ståhl, Eva
    Sundström, Christer
    Department of Genetics and Pathology.
    Rehn-Eriksson, Suzanne
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Backlin, Carin
    Department of Genetics and Pathology.
    Hagberg, Hans
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Rosenquist, Richard
    Department of Genetics and Pathology.
    Enblad, Gunilla
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Evaluation of immunophenotype in diffuse large B-cell lymphoma and its impact on prognosis.2005In: Mod Pathol, ISSN 0893-3952, Vol. 18, no 8, p. 1113-20Article in journal (Other scientific)
  • 6.
    Berglund, Åke
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ullen, Anders
    Karolinska Univ Hosp, Dept Oncol, Solna, Sweden..
    Lisyanskaya, Alla
    City Clin Oncol Ctr, St Petersburg State Healthcare Inst, St Petersburg, Russia..
    Orlov, Sergey
    St Petersburg State Med Univ, State Educ Inst Higher Profess Educ, St Petersburg, Russia..
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Tholander, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lewensohn, Rolf
    Karolinska Univ Hosp, Dept Oncol, Solna, Sweden..
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Spira, Jack
    Oncopeptides AB, Stockholm, Sweden..
    Harmenberg, Johan
    Oncopeptides AB, Stockholm, Sweden..
    Jerling, Markus
    Oncopeptides AB, Stockholm, Sweden..
    Alvfors, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ringbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Nordstrom, Eva
    Oncopeptides AB, Stockholm, Sweden..
    Soderlind, Karin
    Oncopeptides AB, Stockholm, Sweden..
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    First-in-human, phase I/IIa clinical study of the peptidase potentiated alkylator melflufen administered every three weeks to patients with advanced solid tumor malignancies2015In: Investigational new drugs, ISSN 0167-6997, E-ISSN 1573-0646, Vol. 33, no 6, p. 1232-1241Article in journal (Refereed)
    Abstract [en]

    Purpose Melflufen (melphalan flufenamide, previously designated J1) is an optimized and targeted derivative of melphalan, hydrolyzed by aminopeptidases overexpressed in tumor cells resulting in selective release and trapping of melphalan, and enhanced activity in preclinical models. Methods This was a prospective, single-armed, open-label, first-in-human, dose-finding phase I/IIa study in 45 adult patients with advanced and progressive solid tumors without standard treatment options. Most common tumor types were ovarian carcinoma (n = 20) and non-small-cell lung cancer (NSCLC, n = 11). Results In the dose-escalating phase I part of the study, seven patients were treated with increasing fixed doses of melflufen (25-130 mg) Q3W. In the subsequent phase IIa part, 38 patients received in total 115 cycles of therapy at doses of 30-75 mg. No dose-limiting toxicities (DLTs) were observed at 25 and 50 mg; at higher doses DLTs were reversible neutropenias and thrombocytopenias, particularly evident in heavily pretreated patients, and the recommended phase II dose (RPTD) was set to 50 mg. Response Evaluation Criteria In Solid Tumors (RECIST) evaluation after 3 cycles of therapy (27 patients) showed partial response in one (ovarian cancer), and stable disease in 18 patients. One NSCLC patient received nine cycles of melflufen and progressed after 7 months of therapy. Conclusions In conclusion, melflufen can safely be given to cancer patients, and the toxicity profile was as expected for alkylating agents; RPTD is 50 mg Q3W. Reversible and manageable bone marrow suppression was identified as a DLT. Clinical activity is suggested in ovarian cancer, but modest activity in treatment of refractory NSCLC.

  • 7.
    Berglund, Åke
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Willen, Linda
    Grodeberg, Lina
    Skattum, Lillemor
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    The response to vaccination against influenza A(H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 9, p. 1212-1220Article in journal (Refereed)
    Abstract [en]

    It is debated whether cancer patients treated with chemotherapy can mount an adequate response to vaccination. Material and methods. Ninety-six adult outpatients with cancer, who were undergoing chemotherapy and/or monoclonal antibody, tyrosine kinase inhibitor, irradiation or corticosteroid treatments, were studied. Two doses of the pandemic influenza A(H1N1)/09 AS03-adjuvanted split virion vaccine, one dose of the seasonal influenza vaccine and one dose of the 23-valent pneumococcal polysaccharide vaccine were given. Serum haemagglutination inhibition (HI) assays were used to determine antibody titres against the influenza strains. For the pneumococcal vaccine 14 different serotype-specific anti-capsular antibodies were measured by bead assay xMAP (R). Results. Patients treated with rituximab did not respond to vaccination. For patients without rituximab treatment 4% had putatively protective antibodies before vaccination (HI >= 40) to the pandemic-like strain A/California7/2009HINI. After the first and second dose of vaccine, seroprotection rates (SPR) were 62% and 87%, and seroconversion rates (SCR) 62% and 84%, respectively. Before seasonal flu vaccination SPR against influenza A/Brisbane/59/2007H1N1 and A/Uruguay/10/2007H3N2 were 19% and 17%, respectively. After vaccination, SPR were 70% and 59% and SCR 42% and 50%, respectively. For the pneumococcal vaccine protective antibodies were found to 40% of the 14 strains before and to 68% after vaccination. The mean response to pneumococcal vaccination was to 44% of the 14 serotypes. A response to at least 50% of the 14 serotypes was found in 49% of the patients. No serious adverse events were reported. Conclusion. A substantial number of adult cancer patients with ongoing chemotherapy treatment could mount an adequate serological response to influenza and pneumococcal vaccination without severe adverse events. Thus, vaccination should be recommended. Adjuvanted vaccines may improve the vaccine response among this patient group. Patients recently treated with rituximab do not respond to vaccination.

  • 8.
    Blomstrand, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Erdheim-Chester disease presenting as periodontal disease: Experience of treatment with cladribine, interferon-a, local radiotherapy and anakinra2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 2, p. 248-250Article in journal (Refereed)
  • 9. Bosly, Andre
    et al.
    Grigg, Andrew
    Holte, Harald
    Gisselbrecht, Christian
    Radford, John
    Rossi, Andrea
    Lopez-Guillermo, Armando
    Trneny, Marek
    Sebban, Catherine
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    da Costa, Fernando Leal
    Colombat, Philippe
    Bron, Dominique
    Coiffier, Bertrand
    A Randomized Study of Interferon alpha-2b Versus No Treatment as Consolidation After High Dose Therapy and Autologous Stem Cell Transplantation for Patients With Relapsed Lymphoma2013In: The Oncologist, ISSN 1083-7159, E-ISSN 1549-490X, Vol. 18, no 11, p. 1189-1189Article in journal (Other academic)
    Abstract [en]

    Background. Patients with lymphoma who have experienced a first relapse or progression and have disease deemed sensitive to salvage chemotherapy nevertheless have a high likelihood of having a second relapse. To decrease the likelihood of a second relapse after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT), interferon (IFN) alpha-2b was given in a prospective randomized international trial. Methods. In this trial, 221 patients with varying histologic diagnoses (8 small lymphocytic, 37 follicular, 9 mantle, 90 diffuse large B-cell, 20 peripheral T-cell, 3 high-grade B-cell non-Hodgkin lymphoma, and 54 Hodgkin lymphoma) were randomly assigned to receive no further treatment (armA: 117 patients) or IFN alpha-2b, 3 MU three times weekly, for 18 months (arm B: 104 patients). Results. In arm B, 21 patients (20%) did not receive IFN alpha-2b because of early progression or absence of hematologic recovery, 29 patients (28%) completed the 18 months of treatment, and 54 patients (52%) interrupted treatment because of progression (23%) or toxicity (29%). Event-free survival and overall survival were not different between the two arms on an intent-to-treat analysis and also if analysis was restricted to patients who were a live and had not experienced disease progression three months after transplantation. The study was not sufficiently powered to evaluate effects in histologic subtypes. Conclusion. In this trial, post-autograft IFN alpha-2b did not improve outcomes in a heterogeneous group of patients with lymphoma.

  • 10.
    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.

  • 11. 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)
  • 12. d'Amore, Francesco
    et al.
    Relander, Thomas
    Lauritzsen, Grete F.
    Jantunen, Esa
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Anderson, Harald
    Holte, Harald
    Osterborg, Anders
    Merup, Mats
    Brown, Peter
    Kuittinen, Outi
    Erlanson, Martin
    Ostenstad, Bjorn
    Fagerli, Unn-Merete
    Gadeberg, Ole V.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Delabie, Jan
    Ralfkiaer, Elisabeth
    Vornanen, Martine
    Toldbod, Helle E.
    Up-Front Autologous Stem-Cell Transplantation in Peripheral T-Cell Lymphoma: NLG-T-012012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 25, p. 3093-3099Article in journal (Refereed)
    Abstract [en]

    Purpose Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large prospective phase II study in untreated systemic PTCL. This is the final report, with a 5-year median follow-up, of the NLG-T-01 study. Patients and Methods Treatment-naive patients with PTCL age 18 to 67 years (median, 57 years) were included. Anaplastic lymphoma kinase (ALK) -positive anaplastic large-cell lymphoma (ALCL) was excluded. An induction regimen of six cycles of biweekly CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) was administered (in patients age > 60 years, etoposide was omitted). If in complete or partial remission, patients proceeded to consolidation with HDT/ASCT. Results Of 166 enrolled patients, 160 had histopathologically confirmed PTCL. The majority presented with advanced-stage disease, B symptoms, and elevated serum lactate dehydrogenase. A total of 115 underwent HDT/ASCT, with 90 in complete remission at 3 months post-transplantation. Early failures occurred in 26%. Treatment-related mortality was 4%. At 60.5 months of median follow-up, 83 patients were alive. Consolidated 5-year overall and progression-free survival (PFS) were 51% (95% CI, 43% to 59%) and 44% (95% CI, 36% to 52%), respectively. Best results were obtained in ALK-negative ALCL. Conclusion Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44% of treatment-naive patients with PTCL. This represents an encouraging outcome, particularly considering the high median age and adverse risk profile of the study population. Therefore, dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL. J Clin Oncol 30: 3093-3099. (C) 2012 by American Society of Clinical Oncology

  • 13.
    Drott, Kristina
    et al.
    Skane Univ Hosp, Dept Oncol, Lasarettsg 23 A, SE-22185 Lund, Sweden.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Papworth, Karin
    Norrland Univ Hosp, Dept Oncol, Umea, Sweden.
    Relander, Thomas
    Skane Univ Hosp, Dept Oncol, Lasarettsg 23 A, SE-22185 Lund, Sweden.
    Jerkeman, Mats
    Skane Univ Hosp, Dept Oncol, Lasarettsg 23 A, SE-22185 Lund, Sweden.
    Valproate in combination with rituximab and CHOP as first-line therapy in diffuse large B-cell lymphoma (VALFRID)2018In: BLOOD ADVANCES, ISSN 2473-9529, Vol. 2, no 12, p. 1386-1392Article in journal (Refereed)
    Abstract [en]

    The aims of the present study were to establish the maximally tolerated dose (MTD) of the histone deacetylase inhibitor valproate together with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with diffuse large B-cell lymphoma (DLBCL). A phase 1 dose escalation study of valproate together with R-CHOP followed by a dose expansion study using the established MTD of valproate was performed. MTD of valproate together with R-CHOP was established at 60 mg/kg per day, as higher doses resulted in auditory adverse events (AEs). In the study population, 2-year progression-free survival was 84.7% (95% confidence interval [CI], 73.2%-98%). The 2-year overall survival (OS) was 96.8% (n = 31; 95% CI, 90.8%-100%). These data were compared with 2 risk-factor matched populations of R-CHOP-treated patients from the Swedish Lymphoma Registry (cohort A, n = 330 and B, n = 165). As compared with the matched cohorts, we observed a statistically significant (P = .034 and 0.028, respectively) beneficial effect of the addition of valproate to R-CHOP on the OS in the studied population. In conclusion, addition of valproate to R-CHOP is a feasible strategy in first-line treatment of DLBCL. The proposed phase 2 dose is 60 mg/kg per day together with prednisone. Auditory AEs were unexpected and warrant close monitoring. Our findings suggest that drugs that target histone deacetylation may add benefit and are tolerable when combined with standard R-CHOP in DLBCL.

  • 14.
    Drott, Kristina
    et al.
    Lund Univ, Dept Oncol, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Relander, Thomas
    Lund Univ, Dept Oncol, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Graffman, Cecilia
    Lund Univ, Dept Oncol, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Drott, Johan
    Respiratorius AB, Lund, Sweden..
    Jerkeman, Mats
    Lund Univ, Dept Oncol, Skane Univ Hosp, Lund, Sweden..
    Valproate in Combination with Rituximab and CHOP As First Line Therapy in Diffuse Large B-Cell Lymphoma (VALFRID): Preliminary Results from a Phase I Trial with a Dose Expansion Cohort2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 15. Ellin, Fredrik
    et al.
    Jerkeman, Mats
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Relander, Thomas
    Treatment outcome in T-cell lymphoblastic lymphoma in adults: a population-based study from the Swedish Lymphoma Registry2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 7, p. 927-934Article in journal (Refereed)
    Abstract [en]

    Background. T-cell lymphoblastic lymphoma (T-LBL) is a rare neoplasm of precursor lymphoblast origin, for which there is no standard treatment for adults. Results of current treatment strategies in selected populations do exist but are largely unreported for unselected series. Here, we aimed to investigate treatment outcome in a population-based cohort. Material and methods. Patients were identified through the Swedish Lymphoma Registry and data was retrospectively collected for all adult (>= 18 years) Swedish T-LBL patients diagnosed during 2000-2009. Results. A total of 39 patients with median age 40 years (range 18-78) were identified with females being significantly older than males (median age 66 vs. 37, p = 0.027). The five-year overall survival for all patients was 42%. Female gender was associated with shorter survival also when adjusted for treatment strategy and age [hazard ratio (HR) 4.29; p = 0.002]. Thirty patients received intensive chemotherapy, otherwise used for treatment of acute lymphoblastic leukemia (ALL), which resulted in an overall response rate of 97% and a five-year progression-free survival (PFS) of 49%. In this group only CNS involvement at diagnosis predicted shorter PFS (HR 13.3; p = 0.03). Among patients treated with hyper-CVAD the addition of mediastinal irradiation resulted in prolonged time to progression compared to patients receiving only chemotherapy (p = 0.047). The major reason for treatment failure was relapse and in this series 18-fluoro-deoxyglucose positron emission tomography (PET) did not predict this risk. Conclusion. This population-based study indicates that all fit T-LBL patients should be considered for intensive treatment. Our results also suggest a beneficial effect of mediastinal irradiation in combination with hyper-CVAD treatment. Relapsing patients have a dismal outcome irrespective of salvage treatment.

  • 16.
    Enblad, Gunilla
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Hagberg, Hans
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Erlanson, Martin
    Lundin, Jeanette
    MacDonald, Anja Porwit
    Repp, Roland
    Schetelig, Johannes
    Seipelt, Gernot
    Osterborg, Anders
    A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas.2004In: Blood, ISSN 0006-4971, Vol. 103, no 8, p. 2920-4Article in journal (Other scientific)
  • 17.
    Enblad, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Karlsson, Hannah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Wenthe, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Wikström, Kristina I.
    Karolinska Hosp, VECURA, Huddinge, Sweden..
    Essand, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Savoldo, Barbara
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Dotti, Gianpietro
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Brenner, Malcolm K.
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Loskog, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    A Clinical Trial Using Third Generation CD19 Targeting CAR T Cells for Relapsed Lymphoma and Leukemia2016In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 24, p. S295-S296Article in journal (Other academic)
  • 18.
    Enblad, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Karlsson, Hannah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Wikström, Kristina
    Karolinska Univ Hosp, VECURA, Stockholm, Sweden..
    Essand, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Savoldo, Barbara
    Baylor Collage Med, Ctr Cell & Gene Therapy, Houston, TX USA..
    Brenner, Malcolm K.
    Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.;Houston Methodist Hosp, Houston, TX USA..
    Dotti, Gianpietro
    Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.;Houston Methodist Hosp, Houston, TX USA..
    Hallböök, Helene
    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.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Loskog, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Third Generation CD19-CAR T Cells for Relapsed and Refractory Lymphoma and Leukemia Report from the Swedish Phase I/IIa Trial2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 19.
    Enblad, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Karlsson, Hannah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Wikström, Kristina I.
    Karolinska Univ Hosp, VECURA, Huddinge, Sweden..
    Essand, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Savoldo, Barbara
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Brenner, Malcolm K.
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Dotti, Gianpietro
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Loskog, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    CD19-targeting third generation CAR T cells for relapsed and refractory lymphoma and leukemia: report from the Swedish phase Ulla trial2016In: CANCER IMMUNOLOGY RESEARCH, ISSN 2326-6066, Vol. 4, no 1Article in journal (Other academic)
  • 20.
    Enblad, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Martinsson, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Population-based experience on primary central nervous system lymphoma 2000-2012: the incidence is increasing2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 4, p. 599-607Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Primary central nervous system lymphomas (PCNSL) are rare lymphomas with a poor prognosis. Recently, an increased incidence has been reported. The present study is a population-based study of all patients with PCNSL in the Uppsala/Örebro region of middle Sweden.

    PATIENTS AND METHODS: All patients diagnosed with a PCNSL at Uppsala University Hospital 2000-2012 were identified. Altogether, 96 patients (50 women and 46 men) were included. The median age at diagnosis was 66 years (17-95).

    RESULTS: There was a statistically significant increase in age-standardized incidence during the study period, 30 patients were diagnosed in the first half and 66 in the second half of the period. No patient had an HIV-infection. Two patients had undergone kidney transplantation and were treated with immunosuppressive drugs. A high proportion of the patients, 29%, had a history of an autoimmune or inflammatory disease. The prognosis was poor with a median survival of only four months. In the 70 (73%) patients treated with curative intention the median survival was 12 months. Patients treated with high-dose methotrexate, radiotherapy and/or temozolomide appeared to have a better survival. There was no improvement in survival during the study period or after the introduction of rituximab. There also was no difference in any of the analyzed variables that could explain the increased incidence.

    CONCLUSION: In this population-based study we could confirm the previously described increased incidence of PCNSL. The prognosis remains poor despite the inclusion of treatment with rituximab during the study period. A high proportion of the patients had a history of an autoimmune or inflammatory disease not previously described but there was no increase during the study period.

  • 21.
    Frisk, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Mandahl, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Lönnerholm, Gudmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Cataracts after autologous bone marrow transplantation in children2000In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 89, no 7, p. 814-819Article in journal (Refereed)
    Abstract [en]

    We recorded the incidence and degree of posterior subcapsular cataract (PSC) in 29 children who had undergone autologous (n = 28) or syngeneic (n = 1) bone marrow transplantation (BMT) due to haematologic or lymphoid malignancy. Conditioning prior to transplantation consisted either of a combination of chemotherapy and total body irradiation (TBI) (n = 21) or of chemotherapy only (n = 8). TBI was given in one fraction of 7.5 Gy. Nine patients had received previous cranial irradiation. The patients were followed for 4-10 y (median 8y) after transplantation. Of 29 patients, 22 developed PSC, all within 4 y after BMT. With the exception of one patient who developed unilateral PSC, all had received TBI. Conversely, 100% of those who received TBI developed PSC. In this group (+TBI), eight patients (38%) developed significant PSC, defined as best corrected visual acuity < 0.8 in either eye. Six patients (10 eyes) have since needed surgical repair consisting of extracapsular cataract extraction and intraocular lens implantation. There was no clear relationship between previous cranial irradiation and cataract development, nor any other obvious baseline differences between those in the +TBI group who developed significant PSC and those who did not. Although effects of previous therapy cannot be ruled out, TBI appears to be the main cause of PSC in this group of patients. Twelve patients in the +TBI group had well-preserved visual acuity throughout the study, reflecting a slow progression of PSC. This compares favourably with previous reports of allogeneic BMT, possibly owing to less need for corticosteroids after autologous BMT.

    We conclude that the incidence of PSC was high after autologous BMT where the conditioning regimen included total body irradiation.

  • 22. Gisselbrecht, Christian
    et al.
    Schmitz, Norbert
    Mounier, Nicolas
    Gill, Devinder Singh
    Linch, David C.
    Trneny, Marek
    Bosly, Andre
    Milpied, Noel J.
    Radford, John
    Ketterer, Nicolas
    Shpilberg, Ofer
    Duehrsen, Ulrich
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ma, David D.
    Viardot, Andreas
    Lowenthal, Ray
    Briere, Josette
    Salles, Gilles
    Moskowitz, Craig H.
    Glass, Bertram
    Rituximab Maintenance Therapy After Autologous Stem-Cell Transplantation in Patients With Relapsed CD20(+) Diffuse Large B-Cell Lymphoma: Final Analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 36, p. 4462-4469Article in journal (Refereed)
    Abstract [en]

    Purpose The standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL) is salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT). The impact of maintenance rituximab after ASCT is not known. Patients and Methods In total, 477 patients with CD20(+) DLBCL who were in their first relapse or refractory to initial therapy were randomly assigned to one of two salvage regimens. After three cycles of salvage chemotherapy, the responding patients received high-dose chemotherapy followed by ASCT. Then, 242 patients were randomly assigned to either rituximab every 2 months for 1 year or observation. Results After ASCT, 122 patients received rituximab, and 120 patients were observed only. The median follow-up time was 44 months. The 4-year event-free survival (EFS) rates after ASCT were 52% and 53% for the rituximab and observation groups, respectively (P=.7). Treatment with rituximab was associated with a 15% attributable risk of serious adverse events after day 100, with more deaths (six deaths v three deaths in the observation arm). Several factors affected EFS after ASCT (P<.05), including relapsed disease within 12 months (EFS: 46% v 56% for relapsed disease after 12 months), secondary age-adjusted International Prognostic Index (saaIPI) more than 1 (EFS: 37% v 61% for saaIPI < 1), and prior treatment with rituximab (EFS: 47% v 59% for no prior rituximab). A significant difference in EFS between women (63%) and men (46%) was also observed in the rituximab group. In the Cox model for maintenance, the saaIPI was a significant prognostic factor (P<.001), as was male sex (P=.01). Conclusion In relapsed DLBCL, we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT.

  • 23. Hagberg, H
    et al.
    Siegbahn, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Prognostic value of serum lactic dehydrogenase in non-Hodgkin's lymphoma.1983In: Scand J Haematol, ISSN 0036-553X, Vol. 31, no 1, p. 49-56Article in journal (Other scientific)
  • 24.
    Hagberg, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hogberg, K.
    Jensen, B. A.
    Leppa, S.
    Munksgaard, L.
    Szatkowski, D.
    Retrospective Analysis of Primary Chemoimmunotherapy with Bendamustine in Combination with Rituximab in Patients with Indolent and Mantle-Cell Lymphomas2014In: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, no S1, p. 692-692Article in journal (Other academic)
  • 25.
    Hall, Kirsten Sundby
    et al.
    Oslo Univ Hosp, Norwegian Radium Hosp, Dept Oncol, Oslo, Norway.
    Bruland, Oyvind S.
    Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway;Oslo Univ Hosp, Norwegian Radium Hosp, Dept Oncol, Oslo, Norway.
    Bjerkehagen, Bodil
    Oslo Univ Hosp, Norwegian Radium Hosp, Dept Pathol, Oslo, Norway.
    Zaikova, Olga
    Oslo Univ Hosp, Div Orthopaed Surg, Oslo, Norway.
    Engellau, Jacob
    Oslo Univ Hosp, Norwegian Radium Hosp, Dept Pathol, Oslo, Norway.
    Hagberg, Oskar
    Reg Canc Ctr South, Lund, Sweden.
    Hansson, Lina
    Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ahlstrom, Marie
    Lund Univ, Lund, Sweden;Skane Univ Hosp, Dept Oncol, Lund, Sweden.
    Knobel, Heidi
    St Olavs Univ Hosp, Dept Oncol, Trondheim, Norway.
    Papworth, Karin
    Norrlands Univ Hosp, Dept Oncol, Umea, Sweden.
    Zemmler, Maja
    Linkoping Univ Hosp, Dept Oncol, Linkoping, Sweden.
    Goplen, Dorota
    Haukeland Hosp, Dept Musculoskeletal Tumour Serv Oncol, Bergen, Norway.
    Bauer, Henrik C. F.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Eriksson, Mikael
    Lund Univ, Lund, Sweden;Skane Univ Hosp, Dept Oncol, Lund, Sweden.
    Adjuvant chemotherapy and postoperative radiotherapy in high-risk soft tissue sarcoma patients defined by biological risk factors-A Scandinavian Sarcoma Group study (SSG XX)2018In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 99, p. 78-85Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the outcome following adjuvant doxorubicin and ifosfamide in a prospective non-randomised study based on a soft tissue sarcoma (STS) patient subgroup defined by specific morphological characteristics previously shown to be at a high-risk of metastatic relapse. The expected 5-year cumulative incidence of metastases in patients with this risk profile has previously been reported to be about 50% without adjuvant chemotherapy.

    Methods: High-risk STS was defined as high-grade morphology (according to the Federation Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade II-III) and either vascular invasion or at least two of the following criteria: tumour size >= 8.0 cm, infiltrative growth and necrosis. Six cycles of doxorubicin (60 mg/m(2)) and ifosfamide (6 g/m(2)) were given. Postoperative accelerated radiotherapy was applied and scheduled between cycles 3 and 4.

    Results: For the 150 eligible patients, median follow-up time for metastases-free survival was 3.9 years (range 0.2-8.7). Five-year metastases-free survival (MFS) was 70.4% (95% confidence interval [CI]: 63.1-78.4) with a local recurrence rate of 14.0% (95% CI: 7.8-20.2). For overall survival (OS), the median follow-up time was 4.4 years (range: 0.2-8.7). The five-year OS was 76.1% (95% CI: 68.8-84.2). Tumour size, deep location and reduced dose intensity (<80%) had a negative impact on survival. Toxicity was moderate with no treatment-related death.

    Conclusions: A benefit of adjuvant chemotherapy, compared to similar historical control groups, was demonstrated in STS patients with defined poor prognostic factors. Vascular invasion, tumour size, growth pattern and necrosis may identify patients in need of adjuvant chemotherapy.

  • 26.
    Hellström, Vivan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Enström, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Nyberg, Filippa
    Karolinska Institutet.
    Bäckman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Opelz, Gerhard
    Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
    Döhler, Bernd
    department of Transplant Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
    Holmberg, Lars
    Regional Cancer Centre Uppsala Örebro, Uppsala University, Uppsala.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Malignancies in transplanted patients: Multidisciplinary evaluation and switch to mTOR inhibitors after kidney transplantation - experiences from a prospective, clinical, observational study2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 6, p. 774-781Article in journal (Refereed)
    Abstract [en]

    Background Solid organ transplant recipients are at increased risk of developing malignancies. The objective of this prospective, observational, one-armed study was to study the feasibility to add a mammalian target of rapamycin (mTOR) inhibitor to the immunosuppressive regimen in transplanted patients with post-transplant malignancies. During the trial the need to improve identification of post-transplant malignancies and to reassure adequate oncological treatment of these patients became evident. Multidisciplinary team (MDT) evaluation of oncological and immunosuppressive treatments was implemented for all patients with malignancies after renal or combined renal and pancreas transplantation because of the trial.Material and methods At Uppsala University Hospital, Sweden, a MDT consisting of transplant surgeons, nephrologists, oncologists and dermatologists evaluated 120 renal or combined renal and pancreas-transplanted recipients diagnosed with malignancies from September 2006 to July 2012. To identify all malignancies, the population was linked to the Regional Tumor Registry (RTR). We recorded to which extent a switch to mTOR inhibitors was possible and how often the originally planned oncological managements were adjusted. All patients were followed for three years. (ClinicalTrials.gov: NCT02241564).Results In 76 of 120 patients (63%) a switch to mTOR inhibitors was possible. Immunosuppression was interrupted in seven patients (6%), reduced in three patients (2%) and remained unchanged in 34 of 120 patients (28%). Identification of post-transplant malignancies increased significantly after linkage to RTR (p=0.015). The initially recommended oncological treatment was adjusted in 23 of 44 patients (52%) with solid or hematological malignancies; 36 of these patients (82%) were treated according to national guidelines.Conclusion In two thirds of the patients the immunosuppressive treatment could be changed to an mTOR inhibitor with anti-tumor effects in transplanted patients with post-transplant malignancies. The use of regional tumor registers considerably improved the identification of patients with post-transplant malignancies indicating that post-transplant malignancies might be timely underreported in transplant registers.

  • 27. Junlen, H. R.
    et al.
    Peterson, S.
    Kimby, E.
    Lockmer, S.
    Linden, O.
    Nilsson-Ehle, H.
    Erlanson, M.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Radlund, A.
    Hagberg, O.
    Wahlin, B. E.
    Follicular lymphoma in Sweden: nationwide improved survival in the rituximab era, particularly in elderly women: a Swedish Lymphoma Registry Study2015In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 29, no 3, p. 668-676Article in journal (Refereed)
    Abstract [en]

    Treatment for follicular lymphoma (FL) improved with rituximab. In Sweden, first-line rituximab was gradually introduced between 2003 and 2007, with regional differences. The first national guidelines for FL were published in November 2007, recommending rituximab in first-line therapy. Using the population-based Swedish Lymphoma Registry, 2641 patients diagnosed with FL from 2000 to 2010 were identified and characterized by year and region of diagnosis, age (median, 65 years), gender (50% men), first-line therapy and clinical risk factors. Overall and relative survivals were estimated by calendar periods (2000-2002, 2003-2007 and 2008-2010) and region of diagnosis. With each period, first-line rituximab use and survival increased. Survival was superior in regions where rituximab was quickly adopted and inferior where slowly adopted. These differences were independent in multivariable analyses. Ten-year relative survival for patients diagnosed 2003-2010 was 92%, 83%, 78% and 64% in the age groups 18-49, 50-59, 60-69 and. 70, respectively. With increasing rituximab use, male sex emerged as an adverse factor. Survival improved in all patient categories, particularly in elderly women. The introduction and the establishment of rituximab have led to a nationwide improvement in FL survival. However, rituximab might be inadequately dosed in younger women and men of all ages.

  • 28. Junlen, Henna Riikka
    et al.
    Peterson, Stefan
    Kimby, Eva
    Lockmer, Sandra
    Linden, Ola
    Nilsson-Ehle, Herman
    Erlanson, Martin
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Radlund, Anders
    Hagberg, Oskar
    Wahlin, Bjorn E.
    Follicular Lymphoma Survival in Sweden in the Rituximab Era2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 29. Kimby, Eva
    et al.
    Martinelli, Giovanni
    Ostenstad, Bjorn
    Mey, Ulrich J. M.
    Rauch, Daniel
    Wahlin, Bjorn E.
    Hitz, Felicitas
    Hernberg, Micaela
    Johansson, Ann-Sofie
    Brown, Peter de Nully
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ferreri, Andres J. M.
    Lohri, Andreas
    Novak, Urban
    Zander, Thilo
    Bersvendsen, Hanne
    Bargetzi, Mario
    Mingrone, Walter
    Krasniqi, Fatime
    Dirnhofer, Stephan
    Hawle, Hanne
    Berardi, Simona
    Demmel, Steffi
    Rondeau, Stephanie
    Zucca, Emanuele
    Rituximab Plus Lenalidomide Improves the Complete Remission Rate in Comparison with Rituximab Monotherapy in Untreated Follicular Lymphoma Patients in Need of Therapy. Primary Endpoint Analysis of the Randomized Phase-2 Trial SAKK 35/102014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 30. Kimby, Eva
    et al.
    Ostenstad, Bjorn
    Brown, Peter de Nully
    Holte, Harald, Jr.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Erlanson, Martin
    Linden, Ola
    Nordstrom, Marie
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Rituximab (R) in Combination with Interferon-a2a (IFN) Versus Single R in Patients with Follicular or Other CD20+Low-Grade (indolent) Lymphoma: Final Results From a Randomized Phase III Study From the Nordic Lymphoma Group2012In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 120, no 21, p. 794-Article in journal (Refereed)
  • 31. Kimby, Eva
    et al.
    Östenstad, Björn
    Brown, Peter
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Erlanson, Martin
    Holte, Harald
    Linden, Ola
    Johansson, Ann-Sofie
    Ahlgren, Tomas
    Wader, Karin
    Wahlin, Björn Engelbrekt
    Delabie, Jan
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Two courses of four weekly infusions of rituximab with or without interferon-α2a: final results from a randomized phase III study in symptomatic indolent B-cell lymphomas2015In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 56, no 9, p. 2598-2607Article in journal (Refereed)
    Abstract [en]

    Patients with advanced CD20 + indolent lymphoma, requiring therapy, were randomized to rituximab (four weekly infusions of 375 mg/m(2)) or to rituximab combined with 5 weeks of interferon-α2a (IFN-α2a) (3-4.5 MIU daily) as priming. Responding patients were eligible for a second cycle with the same allocated treatment. In total, 156 patients were randomized to rituximab and 157 to rituximab + IFN-α2a. In the intention-to treat (ITT) population, 244 patients (78%) responded to cycle 1. After a second cycle the complete remission/complete remission unconfirmed (CR/CRu) rate was 41% with the combination versus 24% with monotherapy (p = 0.005). The median time to treatment failure (primary endpoint) in ITT patients was 28 vs. 21.5 months, respectively (p = 0.302). After a long median follow-up (61 months), 33% (42% of patients responding to cycle 1) were still failure-free with an overall survival rate of 88% and with no difference between the treatment groups. The trial was registered at ClinicalTrials.gov Identifier: NCT01609010.

  • 32.
    Lövgren, Tanja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Wenthe, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Karlsson, S. C. Hannah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Gammelgård, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala Univ Hosp, Dept Oncol, Uppsala, Sweden.
    Essand, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Savoldo, Barbara
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Dotti, Gianpietro
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Uppsala Univ Hosp, Sect Hematol, Uppsala, Sweden..
    Brenner, Malcolm K.
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala Univ Hosp, Dept Oncol, Uppsala, Sweden..
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala Univ Hosp, Dept Oncol, Uppsala, Sweden..
    Loskog, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Immunological biomarkers correlate to survival in CAR19-treated patients2017In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 337-337Article in journal (Other academic)
  • 33.
    Molin, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Suurküla, Madis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Change of initial staging at early remission evaluation with FDG-PET/CT in Hodgkin lymphoma: A report of two cases2010In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 49, no 4, p. 526-528Article in journal (Refereed)
  • 34.
    Morth, Charlott
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Malarsjukhuset, Dept Oncol, S-63188 Eskilstuna, Sweden..
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Successful intraperitoneal rituximab treatment in a patient with therapy-resistant malignant ascites due to mantle cell lymphoma2015In: Annals of Hematology, ISSN 0939-5555, E-ISSN 1432-0584, Vol. 94, no 10, p. 1757-1758Article in journal (Refereed)
  • 35. Pulczynski, Elisa J.
    et al.
    Kuittinen, Outi
    Erlanson, Martin
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Fossa, Alexander
    Eriksson, Mikael
    Nordstrom, Marie
    Ostenstad, Bjorn
    Fluge, Oystein
    Leppa, Sirpa
    Fiirgaard, Bente
    Bersvendsen, Hanne
    Fagerli, Unn-Merete
    Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by The Nordic Lymphoma Group2015In: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, no 4, p. 537-543Article in journal (Refereed)
    Abstract [en]

    The Nordic Lymphoma Group has conducted a phase ll trial in newly diagnosed primary central nervous system lymphoma patients applying an age-adjusted multi-agent immunochemotherapy regimen, which in elderly patients included temozolomide maintenance treatment. Patients aged 18-75 years were eligible. Thirty-nine patients aged 18-65 years and 27 patients aged 66-75 years were enrolled. The median age of the two age groups was 55 and 70 years, respectively. The overall response rate was 73.8% for the entire cohort: 69.9% in the younger and 80.8% in the elderly subgroup. With a median follow up of 22 months, the 2-year overall survival probability was 60.7% in patients aged 65 years or under and 55.6% in patients aged over 65 years (P=0.40). The estimated progression-free survival at two years was 33.1% (95% CI: 19.1%-47.9%) in patients aged under 65 years and 44.4% (95% CI: 25.6%-61.8%) in the elderly subgroup (P=0.74). Median duration of response was ten months in the younger subgroup, and not reached in the elderly patient subgroup (P=0.33). Four patients aged 64-75 years (6%) died from treatment-related complications. Survival in the two age groups was similar despite a de-escalation of induction treatment in patients aged over 65 years. Duration of response in elderly patients receiving maintenance temozolomide was longer than in the younger age subgroup. While toxicity during induction is still of concern, especially in the elderly patients, we conclude from these data that de-escalation of induction therapy in elderly primary central nervous system lymphoma patients followed by maintenance treatment seems to be a promising treatment strategy.

  • 36.
    Thorsélius, Mia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Walsh, Sarah H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Thunberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Heterogeneous somatic hypermutation status confounds the cell of origin in hairy cell leukemia2005In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 29, no 2, p. 153-158Article in journal (Refereed)
    Abstract [en]

    Hairy cell leukemia (HCL) is thought to arise from a post-germinal center (GC) B-cell, however the exact normal counterpart remains unclear. We performed VH gene analysis of 32 HCL cases, revealing somatically mutated VH genes (<98% homology) in 27 cases and unmutated VH genes in five cases, four of which displayed germline VH genes. Intraclonal heterogeneity was evident in the majority of eight mutated HCLs investigated, although at a lower level compared to GC-derived lymphomas. A novel finding of preferential VH3-30 gene usage was detected (19% of HCLs). Our data confounds the postulated post-GC origin in HCL considering (1) the finding of unmutated HCLs, generally correlating with a pre-GC origin, and (2) the presence of intraclonal variation in mutated HCLs. The latter suggests that the transformed B-cell was frozen when it still had an active mutation process, implying a closer relation to the GC than previously assumed. Furthermore, restricted VH3-30 usage indicates that antigen selection could be a promoting factor in HCL development.

  • 37. Wahlin, Björn Engelbrekt
    et al.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Holte, Harald
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Erlanson, Martin
    Nilsson-Ehle, Herman
    Lindén, Ola
    Nordström, Marie
    Ostenstad, Bjørn
    Geisler, Christian H
    Brown, Peter de Nully
    Lehtinen, Tuula
    Maisenhölder, Martin
    Tierens, Anne M
    Sander, Birgitta
    Christensson, Birger
    Kimby, Eva
    T cells in tumors and blood predict outcome in follicular lymphoma treated with rituximab2011In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 17, no 12, p. 4136-4144Article in journal (Refereed)
    Abstract [en]

    Purpose:

    T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown.

    Experimental Design:

    Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-α2a–rituximab combinations.

    Results:

    In univariate analysis, higher levels of CD3+, CD4+, and CD8+ T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3+ (P = 0.011) and blood-CD4+ (P = 0.029) cells were independent. CD4+ cells were favorable regardless of treatment arm, but CD8+ cells were favorable only in patients treated with single rituximab, because IFN-α2a improved responses especially in patients with low CD8+ cell levels. Higher levels of blood-CD3+ (P = 0.003) and blood-CD4+ (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8+ cells longer times to next treatment (P = 0.046).

    Conclusions:

    We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4+ and CD8+ cells are both favorable in patients treated with rituximab. IFN-α2a abrogates the negative impact of few CD8+ cells.

  • 38. Wästerlid, Tove
    et al.
    Jonsson, Björn
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Jerkeman, Mats
    Population based study of prognostic factors and treatment in adult Burkitt lymphoma: a Swedish Lymphoma Registry study2011In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 52, no 11, p. 2090-2096Article in journal (Refereed)
    Abstract [en]

    Burkitt lymphoma (BL) is a rare neoplasm constituting 1-2% of adult lymphomas. Our aims in this study were to establish prognostic factors for overall survival in adult BL and evaluate the efficacy of different chemotherapy regimens in a population based setting. The study population was collected from the Swedish Lymphoma Registry 2000-2010. During this period, 156 adult patients with BL were identified. In multivariate analysis, age and performance status (PS) were significant adverse prognostic factors for overall survival. A modified prognostic index, based on: age >40 years, PS >1, and lactate dehydrogenase > upper limit of normal (ULN) was proposed. Patients with a score of 0-1, 2, and 3 were found to have a 2-year survival of 91.2%, 58.4%, and 27.5%, respectively. High-intensity regimens were associated with more favorable overall survival. Rituximab addition was not significantly associated with improvement in survival. A modified prognostic index may be valuable for adult BL, as proposed.

1 - 38 of 38
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