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  • 1.
    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)
  • 2. 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)
  • 3. Buckley, Patrick G.
    et al.
    Walsh, Sarah H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Laurell, Anna
    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.
    Roos, Göran
    Langford, Cordelia F.
    Dumanski, Jan P.
    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.
    Genome-wide microarray-based comparative genomic hybridization analysis of lymphoplasmacytic lymphomas reveals heterogeneous aberrations2009In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 50, no 9, p. 1528-34Article in journal (Refereed)
    Abstract [en]

    Lymphoplasmacytic lymphoma (LPL) is not a sharply delineated lymphoma entity, either morphologically, phenotypically, or clinically. The diagnosis is often made by excluding other small cell lymphomas with plasmacytic differentiation, thus a genetic diagnostic marker would be of great benefit. Conventional cytogenetic techniques have previously demonstrated a deletion of 6q in a proportion of cases, varying from 7 to 55%. In this report, we apply array-based comparative genomic hybridization on 11 LPL samples. Genomic aberrations were detected in 9 of 11 cases, and included gains and losses. In general, the number of genetic aberrations was relatively low (two to three abnormalities per case). Recurrent aberrations detected were deletion of 6q (two cases), deletion of chromosome 17 (two cases), gain of 3q (two cases), and gain of chromosome 7 (two cases). This report not only confirms the reported loss of 6q in a proportion of cases but also highlights the genetic heterogeneity of LPL, in accordance with the known immunophenotypical, morphological, and clinical diversity of the disease.

  • 4.
    Eskelund, Christian W.
    et al.
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Kolstad, Arne
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway..
    Jerkeman, Mats
    Univ Lund Hosp, Dept Oncol, Lund, Sweden..
    Raty, Riikka
    Univ Helsinki, Dept Haematol, Cent Hosp, Helsinki, Finland..
    Laurell, Anna
    Univ Uppsala Hosp, Dept Oncol, Uppsala, Sweden..
    Eloranta, Sandra
    Karolinska Inst, Clin Epidemiol Unit, Dept Med Solna, Stockholm, Sweden..
    Smedby, Karin E.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med Solna, Stockholm, Sweden..
    Husby, Simon
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Pedersen, Lone B.
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Andersen, Niels S.
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Eriksson, Mikael
    Univ Lund Hosp, Dept Oncol, Lund, Sweden..
    Kimby, Eva
    Karolinska Inst, Dept Haematol, Stockholm, Sweden..
    Bentzen, Hans
    Aarhus Univ Hosp, Dept Haematol, Aarhus, Denmark..
    Kuittinen, Outi
    Oulu Univ Hosp, Dept Radiotherapy & Oncol, Oulu, Finland..
    Lauritzsen, Grete F.
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway..
    Nilsson-Ehle, Herman
    Sahlgrens Univ Hosp, Sect Haematol & Coagulat Med, Gothenburg, Sweden..
    Ralfkiaer, Elisabeth
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Ehinger, Mats
    Univ Lund Hosp, Dept Pathol, Lund, Sweden..
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Univ Uppsala Hosp, Dept Genet & Pathol, Uppsala, Sweden..
    Delabie, Jan
    Oslo Univ Hosp, Dept Pathol, Oslo, Norway..
    Karjalainen-Lindsberg, Marja-Liisa
    Univ Helsinki, Dept Pathol, Cent Hosp, Helsinki, Finland..
    Workman, Christopher T.
    Tech Univ Denmark, Dept Syst Biol, Lyngby, Denmark.;Univ Copenhagen, Dept Hlth Sci, Copenhagen, Denmark..
    Garde, Christian
    Tech Univ Denmark, Dept Syst Biol, Lyngby, Denmark.;Univ Copenhagen, Dept Hlth Sci, Copenhagen, Denmark..
    Elonen, Erkki
    Univ Helsinki, Dept Haematol, Cent Hosp, Helsinki, Finland..
    Brown, Peter
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Gronbaek, Kirsten
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Geisler, Christian H.
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau2016In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 175, no 3, p. 410-418Article in journal (Refereed)
    Abstract [en]

    In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 114years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 127 and 85years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.

  • 5.
    Eskelund, Christian Winther
    et al.
    Rigshosp, Dept Hematol, Copenhagen, Denmark;Biotech Res & Innovat Ctr, Copenhagen, Denmark.
    Albertsson-Lindblad, Alexandra
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Oncol & Pathol, Lund, Sweden.
    Kolstad, Arne
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Raty, Riikka
    Helsinki Univ Hosp, Dept Hematol, Helsinki, Finland.
    Pedersen, Lone Bredo
    Rigshosp, Dept Hematol, Copenhagen, Denmark.
    Geisler, Christian Hartmann
    Rigshosp, Dept Hematol, Copenhagen, Denmark.
    Jerkeman, Mats
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Oncol & Pathol, Lund, Sweden.
    Gronbaek, Kirsten
    Rigshosp, Dept Hematol, Copenhagen, Denmark;Biotech Res & Innovat Ctr, Copenhagen, Denmark.
    Lenalidomide plus bendamustine-rituximab does not overcome the adverse impact of TP53 mutations in mantle cell lymphoma2018In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 103, no 11, p. E541-E543Article in journal (Other academic)
  • 6. Farnebo, Jacob
    et al.
    Gryback, Per
    Harmenberg, Ulrika
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Wersall, Peter
    Blomqvist, Lennart K.
    Ullen, Anders
    Sandstrom, Per
    Volumetric FDG-PET predicts overall and progression- free survival after 14 days of targeted therapy in metastatic renal cell carcinoma2014In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 14, p. 408-Article in journal (Refereed)
    Abstract [en]

    Background: To determine whether changes in the metabolism of metastatic renal cell carcinoma (mRCC) assessed by F18-FDG-PET after 14 and 28 days of treatment with tyrosine kinase inhibitors can predict overall and progression-free patient survival. Methods: Thirty-nine consecutive patients with mRCC were included prospectively and underwent PET examinations prior to and after 14 and 28 days of standard treatment with sunitinib (n = 18), sorafenib (n = 19) or pazopanib (n = 2). The PET response was analyzed in terms of SUVmax, SULpeak, and total lesion glycolysis and a positive response (defined as a 30% reduction) compared to overall and progression-free survival. Results: Thirty-five patients with at least one metabolically active metastatic lesion prior to treatment underwent additional FDG-PET examinations after 14 (n = 32) and/or 28 days (n = 30) of treatment. Changes in either SULpeak or total lesion glycolysis were correlated to both progression-free and overall survival (for TLG2.5 responders, HR = 0.38 (95% CI: 0.18-0.83) and 0.22 (95% CI: 0.09-0.53), and for TLG50 responders, HR = 0.25 (0.10-0.62) and 0.25 (95% CI: 0.11-0.57) and for SULpeak responders, HR = 0.39 (95% CI: 0.17-0.91) and 0.38 (95% CI: 0.15-0.93), respectively). In contrast SUVmax response did not predict progression-free or overall survival (HR = 0.43 (95% CI: 0.18-1.01) and 0.50 (95% CI: 0.21-1.19), respectively). Conclusions: Assessment of early changes in SULpeak and total lesion glycolysis undergoing treatment with tyrosine kinase inhibitors by FDG-PET can possibly predict progression-free and overall survival in patients with mRCC.

  • 7. Flordal Thelander, Emma
    et al.
    Ichimura, Koichi
    Collins, V. Peter
    Walsh, Sarah H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Barbany, Gisela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Hagberg, Anette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Larsson, Catharina
    Lagercrantz, Svetlana
    Detailed assessment of copy number alterations revealing homozygous deletions in 1p and 13q in mantle cell lymphoma2007In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 31, no 9, p. 1219-1230Article in journal (Refereed)
    Abstract [en]

    Mantle cell lymphoma (MCL) is characterized by over-expression of cyclin Dl as a result of the characteristic t(11;14)(q13;q32). However, this translocation alone has proven not to be sufficient for lymphomagenesis, suggesting the involvement of additional alterations. We have characterized 35 cases of MCL by array comparative genomic hybridization with an average resolution of 0.97Mb distributed over the complete human genome. The most common alterations were losses in 1p13.2–p31.1, 6q16.2–q27, 8p21.3, 9p13.2–p24.3, 9q13–q31.3, 11q14.3–q23.3, 13q14.13–q21.31, 13q33.1–q34, and 22q11.23–q13.33 and gains involving 3q21.2–q29, 7p12.1–p22.3, 8q24.13–q24.23, and 18q21.33–q22.3. Four homozygous deletions were identified in totally three patients; two overlapping at 1p32.3, and two adjacent at 13q32.3. The homozygous deletions at 1p32.3 cover the CDKN2C locus (coding for p18), while the region at 13q32.3 does not encompass any known tumor suppressor genes. A gain in 3q was significantly associated with shorter survival (P=0.047).

  • 8. Geisler, Christian H.
    et al.
    Kolstad, Arne
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Jerkeman, Mats
    Raty, Riikka
    Andersen, Niels S.
    Pedersen, Lone B.
    Eriksson, Mikael
    Nordstrom, Marie
    Kimby, Eva
    Bentzen, Hans
    Kuittinen, Outi
    Lauritzsen, Grete F.
    Nilsson-Ehle, Herman
    Ralfkiaer, Elisabeth
    Ehinger, Mats
    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
    Karjalainen-Lindsberg, Marja-Liisa
    Brown, Peter
    Elonen, Erkki
    Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC plus autologous stem-cell support: still very long survival but late relapses do occur2012In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 158, no 3, p. 355-362Article in journal (Refereed)
    Abstract [en]

    Mantle cell lymphoma (MCL) is a heterogenic non-Hodgkin lymphoma entity, with a median survival of about 5 years. In 2008 we reported the early based on the median observation time of 4 years results of the Nordic Lymphoma Group MCL2 study of frontline intensive induction immunochemotherapy and autologous stem cell transplantation (ASCT), with more than 60% event-free survival at 5 years, and no subsequent relapses reported. Here we present an update after a median observation time of 6.5 years. The overall results are still excellent, with median overall survival and response duration longer than 10 years, and a median event-free survival of 7.4 years. However, six patients have now progressed later than 5 years after end of treatment. The international MCL Prognostic Index (MIPI) and Ki-67-expression were the only independent prognostic factors. Subdivided by the MIPI-Biological Index (MIPI + Ki-67, MIPI-B), more than 70% of patients with low-intermediate MIPI-B were alive at 10 years, but only 23% of the patients with high MIPI-B. These results, although highly encouraging regarding the majority of the patients, underline the need of a risk-adapted treatment strategy for MCL.

  • 9. Grabowski, Pawel
    et al.
    Hultdin, Magnus
    Karlsson, Karin
    Tobin, Gerard
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Åleskog, Anna
    Department of Medical Sciences.
    Thunberg, Ulf
    Department of Oncology, Radiology and Clinical Immunology.
    Laurell, Anna
    Department of Oncology, Radiology and Clinical Immunology.
    Sundström, Christer
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Rosenquist, Richard
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Roos, Göran
    Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status.2005In: Blood, ISSN 0006-4971, Vol. 105, no 12, p. 4807-12Article in journal (Refereed)
  • 10.
    Halldórsdóttir, Anna Margret
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Lundin, A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Murray, Fiona
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Knuutila, S
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ehrencrona, H
    Sander, B
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Impact of TP53 mutation and 17p deletion in mantle cell lymphoma2011In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551Article in journal (Refereed)
  • 11. Haugnes, Hege S.
    et al.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Stierner, Ulrika
    Bremnes, Roy M.
    Dahl, Olav
    Cavallin-Stahl, Eva
    Cohn-Cedermark, Gabriella
    High-dose chemotherapy with autologous stem cell support in patients with metastatic non-seminomatous testicular cancer: a report from the Swedish Norwegian Testicular Cancer Group (SWENOTECA)2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 2, p. 168-176Article in journal (Refereed)
    Abstract [en]

    Background. The SWENOTECA IV protocol from 1995 is a prospective population-based study in metastatic non-seminomatous germ cell testicular cancer (NSGCT), designed for early identification of patients with poor response to standard cisplatin-based chemotherapy. A slow tumor marker decline (HCG T(1/2) > 3 days, AFP T(1/2) > 7 days) after BEP or BEP plus ifosfamide was regarded as poor response. The aim of this study was to present survival and toxicity data for patients treated with high-dose chemotherapy (HDCT) within the SWENOTECA IV cancer care program. Material and methods. In total 882 adult men diagnosed with metastatic NSGCT between July 1995 and June 2007 in Sweden and Norway (except one center) were included in SWENOTECA IV and treated accordingly. Among these, 55 men (6.2%) were treated with HDCT according to three different indications in the protocol: A) poor response to standard-dose intensified chemotherapy (BEP plus ifosfamide); B) vital cancer at surgery after intensified chemotherapy; and C) selected relapses after previous chemotherapy. In situation A and C two HDCT cycles and in situation B one HDCT cycle was recommended. Situation A was the reason for HDCT in 36 patients, B in seven and C in 12 patients. The first HDCT cycle consisted of carboplatin 28 x (GFR + 25) mg, cyclofosfamide 6000 mg/m(2) and etoposide 1750 mg/m(2), administered over four days. In cycle two, etoposide was replaced by tiotepa 480 mg/m(2). Results. After a median follow-up of 7.5 years, overall survival was 72%, 100% and 58%, while failure-free survival was 64%, 71% and 42% in situation A, B and C, respectively. Three patients (5.5%) died during HDCT (renal failure or intracerebral hemorrhage). Nephrotoxicity was the most common non-hematological grade 4 toxicity (n = 5, 9%). Conclusion. The population-based SWENOTECA strategy, selecting patients who do not respond adequately to primary standard-dose chemotherapy for immediate treatment intensification with HDCT, is feasible and might be advantageous.

  • 12.
    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
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. 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.

  • 13.
    Hellström, Vivan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wallgren, AnnaCarin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Loskog, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Tötterman, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Bengtsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lundberg, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Holmström, B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    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, Transplantation Surgery.
    Donor Derived and BK Virus Positive Urologic Cancers After Renal Transplantation2017In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 17, no S3, p. 472-472, article id A188Article in journal (Other academic)
  • 14.
    Hoster, E.
    et al.
    Univ Hosp Munich, Dept Internal Med 3, Munich, Germany.;Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany..
    Geisler, C. H.
    Rigshosp, Hematol Dept, DK-2100 Copenhagen, Denmark..
    Doorduijn, J.
    Erasmus MC Canc Inst, Dept Hematol, Rotterdam, Netherlands..
    van der Holt, B.
    Erasmus MC Canc Inst, Clin Trial Ctr, HOVON Data Ctr, Rotterdam, Netherlands..
    Walewski, J.
    Maria Sklodowska Curie Mem Inst & Oncol Ctr, Dept Lymphoid Malignancies, Warsaw, Poland..
    Bloehdorn, J.
    Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany..
    Ribrag, V.
    Inst Gustave Roussy, Villejuif, France..
    Salles, G.
    Univ Lyon 1, Hosp Civils Lyon, Pierre Benite, France..
    Hallek, M.
    Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany..
    Pott, C.
    Univ Hosp Schleswig Holstein, Med Dept 2, Campus Kiel, Kiel, Germany..
    Szymczyk, M.
    Maria Sklodowska Curie Mem Inst & Oncol Ctr, Dept Lymphoid Malignancies, Warsaw, Poland..
    Kolstad, A.
    Norwegian Radium Hosp, Oncol Dept, Oslo, Norway..
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Raty, R.
    Univ Helsinki, Cent Hosp, Dept Hematol, Helsinki, Finland..
    Jerkeman, M.
    Skane Univ Hosp, Dept Oncol, Lund, Sweden..
    van't Veer, M.
    Erasmus MC Canc Inst, Dept Hematol, Rotterdam, Netherlands..
    Kluin-Nelemans, J. C.
    Univ Groningen, Univ Med Ctr Groningen, Dept Hematol, Groningen, Netherlands..
    Klapper, W.
    Univ Kiel, Dept Pathol, Hematopathol Sect, Kiel, Germany.;Univ Kiel, Lymph Node Registry, Kiel, Germany..
    Unterhalt, M.
    Univ Hosp Munich, Dept Internal Med 3, Munich, Germany..
    Dreyling, M.
    Univ Hosp Munich, Dept Internal Med 3, Munich, Germany..
    Hermine, O.
    Univ Paris 05, Hop Necker, AP HP, Dept Hematol, Paris, France.;Univ Sorbonne Paris Cite, INSERM U1163, Paris, France.;Univ Sorbonne Paris Cite, CNRS 8254, Imagine Inst, Paris, France..
    Total body irradiation after high-dose cytarabine in mantle cell lymphoma: a comparison of Nordic MCL2, HOVON-45, and European MCL Younger trials2016In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 30, no 6, p. 1428-1430Article in journal (Refereed)
  • 15. Husby, Simon
    et al.
    Pedersen, Lone Bredo
    Ralfkiaer, Ulrik
    Garde, Christian
    Ek, Sara
    Kolstad, Arne
    Jerkeman, Mats
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Raety, Riikka
    Pedersen, Anja
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Karjalainen-Lindsberg, Marja-Liisa
    Delabie, Jan
    Clasen-Linde, Erik
    Workman, Christopher
    Geisler, Christian H.
    Gronbaek, Kirsten
    Diagnostic Tumor Mirna Profiling Predicts Molecular Relapse in Mantle Cell Lymphoma Patients Prospectively Followed for Minimal Residual Disease. Results from the Nordic MCL2-3 Trials2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 16. Husby, Simon
    et al.
    Ralfkiaer, Ulrik
    Garde, Christian
    Zandi, Roza
    Ek, Sara
    Kolstad, Arne
    Jerkeman, Mats
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Raety, Riikka
    Pedersen, Lone B.
    Pedersen, Anja
    Ehinger, Mats
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Karjalainen-Lindsberg, Marja-Liisa
    Delabie, Jan
    Clasen-Linde, Erik
    Brown, Peter
    Cowland, Jack B.
    Workman, Christopher T.
    Geisler, Christian H.
    Gronbaek, Kirsten
    miR-18b overexpression identifies mantle cell lymphoma patients with poor outcome and improves the MIPI-B prognosticator2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 125, no 17, p. 2669-2677Article in journal (Refereed)
    Abstract [en]

    Recent studies show that mantle cell lymphoma (MCL) express aberrant microRNA (miRNA) profiles; however, the clinical effect of miRNA expression has not previously been examined and validated in large prospective homogenously treated cohorts. We performed genome-wide miRNA microarray profiling of 74 diagnostic MCL samples from the Nordic MCL2trial (screening cohort). Prognosticmi RNAs were validated in diagnostic MCL samples from 94 patients of the independent Nordic MCL3 trial (validation cohort). Three miRNAs (miR-18b, miR-92a, and miR-378d) were significantly differentially expressed in patients who died of MCL in both cohorts. MiR-18b was superior to miR-92a and miR-378d in predicting high risk. Thus, we generated a new biological MCL International Prognostic Index (MIPI-B)-miR prognosticator, combining expression levels of miR-18b with MIPI-B data. Compared to the MIPI-B, this prognosticator improved identification of high-risk patients with regard to cause-specific, overall, and progression free survival. Transfection of 2 MCL cell lines with miR-18b decreased their proliferation rate without inducing apoptosis, suggesting that miR-18b may render MCL cells resistant to chemotherapy by decelerating cell proliferation. We conclude that overexpression of miR-18b identifies patients with poor prognosis in 2 large prospective MCL cohorts and adds prognostic information to the MIPI-B. MiR-18b may reduce the proliferation rate of MCL cells as a mechanism of chemoresistance.

  • 17.
    Jerkeman, Mats
    et al.
    Lund Univ, Inst Clin Sci, Dept Oncol, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Eskelund, Christian Winther
    Rigshosp, Dept Haematol, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth Sci, Biotech Res & Innovat Ctr, Copenhagen, Denmark..
    Hutchings, Martin
    Rigshosp, Dept Haematol, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth Sci, Biotech Res & Innovat Ctr, Copenhagen, Denmark..
    Raty, Riikka
    Helsinki Univ Hosp, Dept Haematol, Helsinki, Finland..
    Wader, Karin Fahl
    St Olavs Univ Hosp, Dept Oncol, Trondheim, Norway..
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Toldbod, Helle
    Aarhus Univ Hosp, Clin Trial Off, Dept Haematol, Aarhus, Denmark..
    Pedersen, Lone Bredo
    Rigshosp, Dept Haematol, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth Sci, Biotech Res & Innovat Ctr, Copenhagen, Denmark..
    Niemann, Carsten Utoft
    Rigshosp, Dept Haematol, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth Sci, Biotech Res & Innovat Ctr, Copenhagen, Denmark..
    Dahl, Christina
    Danish Canc Soc, Res Ctr, Copenhagen, Denmark..
    Kuitunen, Hanne
    Oulu Univ Hosp, Dept Oncol, Oulu, Finland..
    Geisler, Christian H.
    Rigshosp, Dept Haematol, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth Sci, Biotech Res & Innovat Ctr, Copenhagen, Denmark..
    Gronbaek, Kirsten
    Rigshosp, Dept Haematol, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth Sci, Biotech Res & Innovat Ctr, Copenhagen, Denmark..
    Kolstad, Arne
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway..
    Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial2018In: Tha Lancet Haematology, ISSN 2352-3026, Vol. 5, no 3, p. E109-E116Article in journal (Refereed)
    Abstract [en]

    Background Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone. Methods In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients aged 18 years or older with relapsed or refractory mantle cell lymphoma who had previously been treated with at least one rituximab-containing regimen, an Eastern Cooperative Oncology Group performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56 days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m(2)) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle, whereas oral lenalidomide (15 mg once a day) was given on days 1-21. The primary endpoint was overall response assessed in the intention-totreat population according to Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment. The trial is ongoing, but is no longer accruing patients, and is registered with ClinicalTrials. gov, number NCT02460276. Findings Between April 30, 2015, and June 1, 2016, we enrolled 50 patients with relapsed or refractory mantle cell lymphoma at ten centres in Sweden, Finland, Norway, and Denmark. At a median follow-up of 17.8 months (IQR 14.7-20.9), 38 (76%, 95% CI 63-86) patients had an overall response, including 28 (56%, 42-69) patients who had a complete response and ten (20%, 11-33) who had a partial response. The most common grade 3-4 adverse events were neutropenia (in 19 [38%] of 50 patients), infections (in 11 [22%] patients), and cutaneous toxicity (in seven [14%] patients). There were three treatment-related deaths during the study, two due to sepsis and one due to embolic stroke. Interpretation Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomised controlled trial.

  • 18. Kolstad, Arne
    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
    Grønbæk, Kirsten
    Elonen, Erkki
    Räty, Riikka
    Pedersen, Lone Bredo
    Loft, Annika
    Bogsrud, Trond Velde
    Kimby, Eva
    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 MCL-3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 123, no 19, p. 2953-2959Article in journal (Refereed)
    Abstract [en]

    The main objective of the MCL3 study was to improve outcome for patients not in CR before transplant by adding (90)Y-ibritumomab-tiuxetan (Zevalin) to the high-dose regimen. 160 consecutive, untreated stage II-IV MCL patients < 66 years received rituximab (R)- maxi-CHOP alternating with R-high-dose Ara-C (6 cycles total), followed by high-dose BEAM or BEAC and autologous stem cell transplantation 2005-2009. Zevalin (0.4 mCi/kg) was given to responders in only CRu/PR prior to high-dose therapy. The overall response rate (ORR) pre-transplant was 97%. After a median follow-up of 4.4 years the outcome did not differ from that of the historic control, the MCL2 trial with the same treatment except for Zevalin. Overall (OS), event free (EFS), and progression-free survival (PFS) at 4 years were 78, 62 and 71%, respectively. For patients in CRu/PR before transplant who received Zevalin duration of response was shorter than in the CR group. Inferior PFS, EFS- and OS were predicted by PET-positivity pre-transplant and detectable minimal residual disease (MRD) before and after transplant. In conclusion, a positive PET prior to transplant and MRD are strong predictors of outcome. Late intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant.

  • 19.
    Kolstad, Arne
    et al.
    Oslo Univ Hosp, Radiumhospitalet, Dept Oncol, Oslo, Norway..
    Pedersen, Lone Bredo
    Copenhagen Univ Hosp, Rigshospitalet, Dept Hematol, Copenhagen, Denmark..
    Eskelund, Christian W.
    Copenhagen Univ Hosp, Rigshospitalet, Dept Hematol, Copenhagen, Denmark..
    Husby, Simon
    Copenhagen Univ Hosp, Rigshospitalet, Dept Hematol, Copenhagen, Denmark..
    Gronbaek, Kirsten
    Copenhagen Univ Hosp, Rigshospitalet, Dept Hematol, Copenhagen, Denmark..
    Jerkeman, Mats
    Skane Univ Hosp, Dept Oncol, Lund, Sweden..
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Raty, Riikka
    Univ Helsinki, Cent Hosp, Dept Hematol & Oncol, Helsinki, Finland..
    Elonen, Erkki
    Univ Helsinki, Cent Hosp, Dept Hematol & Oncol, Helsinki, Finland..
    Andersen, Niels Smedegaard
    Copenhagen Univ Hosp, Rigshospitalet, Dept Hematol, Copenhagen, Denmark..
    Brown, Peter deNully
    Copenhagen Univ Hosp, Rigshospitalet, Dept Hematol, Copenhagen, Denmark..
    Kimby, Eva
    Karolinska Inst, Dept Hematol, S-10401 Stockholm, Sweden..
    Bentzen, Hans
    Aarhus Univ Hosp, Dept Hematol, DK-8000 Aarhus, Denmark..
    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..
    Ehinger, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Karjalainen-Lindsberg, Marja-Liisa
    Skane Univ Hosp, Dept Pathol, Lund, Sweden..
    Delabie, Jan
    Helsinki Univ Cent Hosp, Dept Pathol, Helsinki, Finland..
    Ralfkiaer, Elisabeth
    Copenhagen Univ Hosp, Rigshospitalet, Dept Hematol, Copenhagen, Denmark.;Oslo Univ Hosp, Dept Pathol, Oslo, Norway..
    Fagerli, Unn-Merete
    Copenhagen Univ Hosp, Rigshospitalet, Dept Pathol, Copenhagen, Denmark..
    Nilsson-Ehle, Herman
    St Olavs Univ Hosp, Dept Oncol, Trondheim, Norway..
    Lauritzsen, Grete Fossum
    Oslo Univ Hosp, Radiumhospitalet, Dept Oncol, Oslo, Norway..
    Kuittinen, Outi
    Sahlgrens Univ Hosp, Dept Hematol, Gothenburg, Sweden. Oulu Univ Hosp, Dept Oncol, Oulu, Finland..
    Niemann, Carsten
    Copenhagen Univ Hosp, Rigshospitalet, Dept Hematol, Copenhagen, Denmark..
    Geisler, Christian Hartman
    Copenhagen Univ Hosp, Rigshospitalet, Dept Hematol, Copenhagen, Denmark..
    Molecular Monitoring after Autologous Stem Cell Transplantation and Preemptive Rituximab Treatment of Molecular Relapse; Results from the Nordic Mantle Cell Lymphoma Studies (MCL2 and MCL3) with Median Follow-Up of 8.5 Years2017In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 23, no 3, p. 428-435Article in journal (Refereed)
    Abstract [en]

    The main objectives of the present study were to monitor minimal residual disease (MRD) in the bone marrow of patients with mantle cell lymphoma (MCL) to predict clinical relapse and guide preemptive treatment with rituximab. Among the patients enrolled in 2 prospective trials by the Nordic Lymphoma Group, 183 who had completed autologous stem cell transplantation (ASCT) and in whom an MRD marker had been obtained were included in our analysis. Fresh samples of bone marrow were analyzed for MRD by a combined standard nested and quantitative real-time PCR assay for Bcl-1/immunoglobulin heavy chain gene (IgH) and clonal IgH rear-rangements. Significantly shorter progression-free survival (PFS) and overall survival (OS) was demonstrated for patients who were MRD positive pre-ASCT (54 patients) or in the first analysis post-ASCT (23 patients). The median PFS was only 20 months in those who were MRD-positive in the first sample post-ASCT, compared with 142 months in the MRD-negative group (P <.0001). OS was 75% at 10 years and median not reached in the MRD-negative group, compared with only 35 months in the MRD-positive group (P <.0001). Of the 86 patients (47%) who remained in continuous molecular remission, 73% were still in clinical remission after 10 years. For all patients, the median time from ASCT to first molecular relapse was 55 months, with a continuous occurrence of late molecular relapses. Fifty-eight patients who experienced MRD relapse received rituximab as preemptive treatment on 1 or more occasions, and in this group, the median time from first molecular relapse to clinical relapse was 55 months. In most cases, rituximab converted patients to MRD negativity (87%), but many patients became MRD-positive again later during follow-up (69%). By multivariate analysis, high-risk Mantle Cell Lymphoma International Prognostic Index score and positive MRD status pre-ASCT predicted early molecular relapse. In conclusion, preemptive rituximab treatment converts patients to MRD negativity and likely postpones clinical relapse. Molecular monitoring offers an opportunity to select some patients for therapeutic intervention and to avoid unnecessary treatment in others. MRD-positive patients in the first analysis post-ASCT have a dismal prognosis and thus are in need of novel strategies.

  • 20.
    Laurell, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Kolstad, Arne
    Jerkeman, Mats
    Raty, Riikka
    Geisler, Christian H.
    High dose cytarabine with rituximab is not enough in first-line treatment of mantle cell lymphoma with high proliferation: early closure of the Nordic Lymphoma Group Mantle Cell Lymphoma 5 trial2014In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 55, no 5, p. 1206-1208Article in journal (Refereed)
  • 21.
    Laurell, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Brekkan, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Tolf, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Wallgren, Anna Carin
    Karolinska Inst, Dept Pathol, Stockholm, Sweden.
    Andersson, Bengt
    Univ Gothenburg, Dept Microbiol & Immunol, Gothenburg, Sweden.
    Adamson, Lars
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Kiessling, Rolf
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Karlsson-Parra, Alex
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Immunicum AB, Gothenburg, Sweden.
    Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma.2017In: Journal for immunotherapy of cancer, ISSN 2051-1426, Vol. 5, article id 52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Accumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors. This concept doesn't require MHC-compatibility between injected cells and the patient and therefore introduces the possibility of using pre-produced and freeze-stored DCs from healthy blood donors as an off- the-shelf immune enhancer. The use of MHC-incompatible allogeneic DCs will further induce a local rejection process at the injection site that is expected to further enhance recruitment and maturation of endogenous bystander DCs.

    METHODS: Twelve intermediate and poor risk patients with newly diagnosed metastatic renal cell carcinoma (mRCC) where included in a phase I/II study. Pro-inflammatory allogeneic DCs were produced from a leukapheresis product collected from one healthy blood donor and subsequently deep-frozen. A dose of 5-20 × 10(6) DCs (INTUVAX) was injected into the renal tumor twice with 2 weeks interval before planned nephrectomy and subsequent standard of care.

    RESULTS: No INTUVAX-related severe adverse events were observed. A massive infiltration of CD8+ T cells was found in 5 out of 12 removed kidney tumors. No objective tumor response was observed and 6 out of 11 evaluable patients have subsequently received additional treatment with standard tyrosine kinase inhibitors (TKI). Three of these 6 patients experienced an objective tumor response including one sunitinib-treated patient who responded with a complete and durable regression of 4 brain metastases. Median overall survival (mOS) is still not reached (currently 42.5 months) but has already passed historical mOS in patients with unfavourable risk mRCC on standard TKI therapy.

    CONCLUSIONS: Our findings indicate that intratumoral administration of proinflammatory allogeneic DCs induces an anti-tumor immune response that may prolong survival in unfavourable risk mRCC-patients given subsequent standard of care. A randomized, multi-center, phase II mRCC trial (MERECA) with INTUVAX in conjuction with sunitinib has been initiated.

    TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01525017.

  • 22.
    Magnusson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wallgren, AnnaCarin
    Brekkan, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Karlsson-Parra, Alex
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Long-term survival in unfavorable-risk mRCC patients after intratumoral administration of a cell-based allogeneic vaccine adjuvant.2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 15Article in journal (Other academic)
  • 23. Nordström, Lena
    et al.
    Sernbo, Sandra
    Eden, Patrik
    Grønbaek, Kirsten
    Kolstad, Arne
    Räty, Riikka
    Karjalainen, Marja-Liisa
    Geisler, Christian
    Ralfkiaer, Elisabeth
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Delabie, Jan
    Ehinger, Mats
    Jerkeman, Mats
    Ek, Sara
    SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma: a Nordic Lymphoma Group study2014In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 166, no 1, p. 98-108Article in journal (Refereed)
    Abstract [en]

    Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3 protocols. In 2008, a MCL international prognostic index (MIPI) was created to enable stratification of the clinical diverse MCL patients into three risk groups. So far, use of the MIPI in clinical routine has been limited, as it has been shown that it inadequately separates low and intermediate risk group patients. To improve outcome and minimize treatment-related morbidity, additional parameters need to be evaluated to enable risk-adapted treatment selection. We have investigated the individual prognostic role of the MIPI and molecular markers including SOX11, TP53 (p53), MKI67 (Ki-67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating an improved prognostic tool by combining the MIPI with information on molecular markers. SOX11 was shown to significantly add prognostic information to the MIPI, but in multivariate analysis TP53 was the only significant independent molecular marker. Based on these findings, we propose that TP53 and SOX11 should routinely be assessed and that a combined TP53/MIPI score may be used to guide treatment decisions.

  • 24.
    Stenman, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lindskog, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Prognostic significance of serum albumin in patients with metastatic renal cell carcinoma2014In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 31, no 3, p. 841-Article in journal (Refereed)
    Abstract [en]

    Systemic inflammation has been suggested to impact on the prognosis of metastatic renal cell carcinoma (mRCC). We undertook a retrospective analysis of patients with mRCC treated at Akademiska University Hospital in Sweden during the years 2005-2012 to assess the possible prognostic significance of inflammation-related factors including serum albumin, platelet count, weight loss and C-reactive protein (CRP). The Memorial Sloan-Kettering Cancer Center (MSKCC) criteria for prognosis of mRCC and ECOG performance status were assessed for all patients. Overall survival (OS) and progression-free survival (PFS) were calculated according to Kaplan-Meier, and Cox proportional hazards regression was used for uni- and multivariate analyses. The median OS of all patients (n=84) was 20 months. Univariate analysis identified low serum albumin (HR=4.17, p<0.001), elevated platelet count (HR=2.98, p<0.001) and patient-reported weight loss prior to diagnosis of mRCC (HR=2.73, p<0.001), in addition to MSKCC (HR=3.35, p=0.0088) to be associated with shorter OS. CRP did not significantly affect OS. Serum albumin retained prognostic significance for OS in multivariate analysis (HR=2.72, p=0.015). In patients treated with an angiogenesis-targeted agent (n=47), low serum albumin level (HR=4.63, p<0.001) and elevated platelet count (HR=2.11, p=0.022) were associated with shorter PFS. In contrast, CRP, weight loss and MSKCC risk group did not significantly affect PFS. In multivariate analysis serum albumin remained associated with PFS (HR=3.92, p=0.0035). Our findings identify serum albumin as an independent prognostic factor for patients with mRCC treated with angiogenesis-targeted therapy.

  • 25.
    Stenman, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Staehler, Michael
    Deparment of Urology, Ludwig-Maximilians University, Munich Germany.
    Szabados, Bernadett
    Deparment of Urology, Ludwig-Maximilians University, Munich Germany.
    Sandström, Per
    Department of Oncology-Pathology, Karolinska Institute, Sweden.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lindskog, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Harmenberg, Ulrika
    Department of Oncology-Pathology, Karolinska Institute, Sweden.
    Metastatic papillary renal cell carcinoma in the era of targeted therapy: a retrospective study from three European academic centres2019In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 3, p. 306-312Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Metastatic papillary renal cell carcinoma (mPRCC) is understudied. The disease is often aggressive and specific treatment options are lacking.

    PATIENTS AND METHODS: mPRCC patients (n = 86) referred to three academic centres in Sweden and Germany in the years 2005-2015 were retrospectively identified from medical records. Statistical analyses included Kaplan-Meier curves and calculation of Cox proportional hazards, generating hazard ratios with 95% confidence intervals. The aim of the study was to evaluate overall survival (OS) of mPRCC patients treated outside of clinical trials in the era of targeted agents (TA) and to identify clinically useful prognostic factors.

    RESULTS: Median OS of all mPRCC patients was 11.2 months. TA were used in 77% of the patients and associated with younger age and better Eastern Cooperative Oncology Group performance status (PS). Brain metastases were common (28%). Patients with synchronous or metachronous metastases had similar OS. Variables independently associated with risk of death included age ≥60 years, worse PS and ≥3 metastatic sites. The MSKCC criteria did not provide additional prognostic information. A subgroup analysis of TA-treated patients revealed an association of lymph node metastasis with risk of death in addition to the other prognostic factors.

    CONCLUSION: OS in mPRCC remained short in the era of targeted agents. Age, PS, and number of metastatic sites provided independent prognostic information.

  • 26. Tandstad, T.
    et al.
    Stahl, O.
    Hakansson, U.
    Dahl, O.
    Haugnes, H. S.
    Klepp, O. H.
    Langberg, C. W.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Oldenburg, J.
    Solberg, A.
    Soderstrom, K.
    Cavallin-Stahl, E.
    Stierner, U.
    Wahlquist, R.
    Wall, N.
    Cohn-Cedermark, G.
    One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded results from the SWENOTECA group2014In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 25, no 11, p. 2167-2172Article in journal (Refereed)
    Abstract [en]

    The SWENOTECA group treated 517 clinical stage I nonseminoma patients with one course of adjuvant BEP in a prospective study. The median follow-up is 7.9 years. One course of adjuvant BEP reduced the risk of relapse by over 90%. The relapse rates were 1.6% in low-risk disease and 3.2% in high-risk disease. One course of adjuvant BEP should be considered a standard adjuvant treatment option.SWENOTECA has since 1998 offered patients with clinical stage I (CS I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and cisplatin (BEP). The aim has been to reduce the risk of relapse, sparing patients the need of toxic salvage treatment. Initial results on 312 patients treated with one course of adjuvant BEP, with a median follow-up of 4.5 years, have been previously published. We now report mature and expanded results. In a prospective, binational, population-based risk-adapted treatment protocol, 517 Norwegian and Swedish patients with CS I nonseminoma received one course of adjuvant BEP. Patients with lymphovascular invasion (LVI) in the primary testicular tumor were recommended one course of adjuvant BEP. Patients without LVI could choose between surveillance and one course of adjuvant BEP. Data for patients receiving one course of BEP are presented in this study. At a median follow-up of 7.9 years, 12 relapses have occurred, all with IGCCC good prognosis. The latest relapse occurred 3.3 years after adjuvant treatment. The relapse rate at 5 years was 3.2% for patients with LVI and 1.6% for patients without LVI. Five-year cause-specific survival was 100%. The updated and expanded results confirm a low relapse rate following one course of adjuvant BEP in CS I nonseminoma. One course of adjuvant BEP should be considered a standard treatment in CS I nonseminoma with LVI. For patients with CS I nonseminoma without LVI, one course of adjuvant BEP is also a treatment option.

  • 27. Thelander, Emma Flordal
    et al.
    Walsh, Sarah H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Thorselius, Mia
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Laurell, Anna
    Department of Oncology, Radiology and Clinical Immunology.
    Landgren, Ola
    Larsson, Catharina
    Rosenquist, Richard
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Lagercrantz, Svetlana
    Mantle cell lymphomas with clonal immunoglobulin V(H)3-21 gene rearrangements exhibit fewer genomic imbalances than mantle cell lymphomas utilizing other immunoglobulin V(H) genes.2005In: Mod Pathol, ISSN 0893-3952, Vol. 18, no 3, p. 331-9Article in journal (Other scientific)
  • 28.
    Thorselius, Mia
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Kröber, Alexander
    Murray, Fiona
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Thunberg, Ulf
    Department of Oncology, Radiology and Clinical Immunology.
    Tobin, Gerard
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Buhler, Andreas
    Kienle, Dirk
    Albesiano, Emilia
    Maffei, Rossana
    Dao-Ung, Lan-Phuong
    Wiley, James
    Vilpo, Juhani
    Laurell, Anna
    Department of Oncology, Radiology and Clinical Immunology.
    Merup, Mats
    Roos, Göran
    Karlsson, Karin
    Chiorazzi, Nicholas
    Marasca, Roberto
    Döhner, Hartmut
    Stilgenbauer, Stephan
    Rosenquist, Richard
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status.2006In: Blood, ISSN 0006-4971, Vol. 107, no 7, p. 2889-94Article in journal (Refereed)
  • 29.
    Tobin, Gerard
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Skogsberg, Åsa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Thunberg, Ulf
    Department of Oncology, Radiology and Clinical Immunology.
    Laurell, Anna
    Department of Oncology, Radiology and Clinical Immunology.
    Åleskog, Anna
    Department of Medical Sciences.
    Merup,
    Sundström, Christer
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Roos,
    Nilsson, Kenneth
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Rosenquist, Richard
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Mcl-1 gene promoter insertions do not correlate with disease outcome, stage or V(H) gene mutation status in chronic lymphocytic leukaemia.2005In: Leukemia, ISSN 0887-6924, p. 871-873Article in journal (Refereed)
  • 30.
    Tobin, Gerard
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Thunberg, Ulf
    Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Karlsson, Karin
    Murray, Fiona
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Laurell, Anna
    Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Willander, Kerstin
    Enblad, Gunilla
    Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Merup, Mats
    Vilpo, Juhani
    Juliusson, Gunnar
    Sundström, Christer
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Söderberg, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Roos, Göran
    Rosenquist, Richard
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia.2004In: Blood, ISSN 0006-4971, Vol. 104, no 9, p. 2879-85Article in journal (Refereed)
    Abstract [en]

    Pseudohypoaldosteronism type I (PHA1) is a condition associated with salt wasting leading to dehydration, hypotension, hyperkalemia, and metabolic acidosis. Sporadic cases and two familial forms, one autosomal dominant and one autosomal recessive form, have been described. The autosomal dominant or sporadic form manifests milder salt wasting that remits with age. Mutations in the gene encoding the mineralocorticoid receptor (MR) have been identified in patients with the autosomal dominant inheritance. However, recent studies suggest that the autosomal dominant and sporadic forms are genetically heterogeneous and that additional genes might be involved. We report on the study of 15 members of a Swedish five-generation family with the autosomal dominant form of PHA1. Interestingly, neuropathy was found in two of five affected individuals. A novel heterozygous nonsense mutation C436X in exon 2 was identified in the index patient by linkage analysis, PCR, and direct sequencing of the MR gene. Analysis of the family demonstrated that the mutation segregated with PHA1 in the family. It is unclear whether the neuropathy is associated with the mutation found. Our results together with previously published data suggest that loss-of-function mutations of the MR gene located at 4q31.1, commonly are associated with the autosomal dominant form of PHA1.

  • 31.
    Tobin, Gerard
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Thunberg, Ulf
    Department of Oncology, Radiology and Clinical Immunology.
    Laurell, Anna
    Department of Oncology, Radiology and Clinical Immunology.
    Karlsson, Karin
    Åleskog, Anna
    Department of Medical Sciences.
    Willander, Kerstin
    Söderberg, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Merup, Mats
    Vilpo, Juhani
    Hultdin, Magnus
    Sundström, Christer
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Roos, Göran
    Rosenquist, Richard
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Patients with chronic lymphocytic leukemia with mutated VH genes presenting with Binet stage B or C form a subgroup with a poor outcome.2005In: Haematologica, ISSN 1592-8721, Vol. 90, no 4, p. 465-9Article in journal (Refereed)
  • 32.
    Walsh, Sarah H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Grabowski, Pawel
    Berglund, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Thunberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Thorsélius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Tobin, Gerard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Åleskog, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Karlsson, Karin
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Roos, Göran
    Telomere length and correlation with histopathogenesis in B-cell leukemias/lymphomas2007In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 78, no 4, p. 283-289Article in journal (Refereed)
    Abstract [en]

    Telomere length was recently reported to correlate with cellular origin of B-cell malignancies in relation to the germinal center (GC). In this report, we measured telomere length by quantitative-PCR in 223 B-cell lymphomas/leukemias and correlated results with immunoglobulin (Ig) mutation status and immunostainings for GC/non-GC subtypes of diffuse large B-cell lymphoma (DLBCL). Shortest telomeres were found in Ig-unmutated chronic lymphocytic leukemia (CLL) [median telomere to single copy gene value (T/S) 0.33], differing significantly to Ig-mutated CLL (0.63). Contrary to this, mantle cell lymphomas (MCLs) exhibited similar telomere lengths regardless of Ig mutation status (0.47). Telomere length differed significantly between GC-like (0.73) and non-GC-like DLBCLs (0.43), and follicular lymphomas (FLs) had shorter telomeres (0.53) than GC-DLBCL. Hairy cell leukemias, which display Ig gene intraclonal heterogeneity, had longer telomeres (0.62) than FLs and non-GC-DLBCL, but shorter than GC-DLBCL. We conclude that although DLBCL and CLL subsets can be clearly distinguished, telomere length reflects many parameters and may not simply correlate with GC-related origin.

  • 33.
    Åleskog, Anna
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Tobin, Gerard
    Department of Genetics and Pathology.
    Laurell, Anna
    Department of Oncology, Radiology and Clinical Immunology.
    Thunberg, Ulf
    Department of Oncology, Radiology and Clinical Immunology.
    Lindhagen, Elin
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Roos, Göran
    Nilsson, Kenneth
    Department of Genetics and Pathology.
    Nygren, Peter
    Department of Oncology, Radiology and Clinical Immunology.
    Sundström, Christer
    Department of Genetics and Pathology.
    Höglund, Martin
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Rolf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Rosenquist, Richard
    Department of Genetics and Pathology.
    VH gene mutation status and cellular drug resistance in chronic lymphocytic leukemia2004In: Eur J Haematol, Vol. 73, p. 407-411Article in journal (Refereed)
1 - 33 of 33
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