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  • 1. Abdulla, Maysaa
    et al.
    Hollander, Peter
    Pandzic, Tatjana
    Mansouri, Larry
    Ednersson, Susanne Bram
    Andersson, Per-Ola
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Fors, Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Petersen, Helga Munch
    Asmar, Fazila
    Gronbaek, Kirsten
    Enblad, Gunilla
    Cavelier, Lucia
    Rosenquist, Richard
    Amini, Rose-Marie
    Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma2020Ingår i: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 95, nr 1, s. 57-67Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC-based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non-GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression-free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression-free survival differed significantly. Importantly, patients assigned as non-GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome.

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  • 2.
    Andersson, Anne
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Enblad, Gunilla
    Department of Oncology, Radiology and Clinical immunology, Section of Oncology, Uppsala University, Uppsala.
    Gustavsson, Anita
    Department of Oncology, Skåne University Hospital, Lund University, Lund .
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hagberg, Hans
    Department of Oncology, Radiology and Clinical immunology, Section of Oncology, Uppsala University, Uppsala .
    Molin, Daniel
    Department of Oncology, Radiology and Clinical immunology, Section of Oncology, Uppsala University, Uppsala .
    Tavelin, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Melin, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Long term risk of infections in Hodgkin lymphoma long-term survivors2011Ingår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 154, nr 5, s. 661-663Artikel i tidskrift (Refereegranskat)
  • 3.
    Andersson, Anne
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Enblad, Gunilla
    Uppsala universitet.
    Gustavsson, Anita
    Lunds universitet.
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hagberg, Hans
    Uppsala universitet.
    Molin, Daniel
    Uppsala universitet.
    Tavelin, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Näslund, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Melin, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Cardiovascular side effects following treatment of Hodgkin’s lymphoma: comorbidity factors and a strategy for interventionManuskript (preprint) (Övrigt vetenskapligt)
  • 4. Berglund, Mattias
    et al.
    Enblad, Gunilla
    Thunberg, Ulf
    Amini, Rose-Marie
    Sundström, Christer
    Roos, Göran
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Erlanson, Martin
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Rosenquist, Richard
    Larsson, Catharina
    Lagercrantz, Svetlana
    Genomic imbalances during transformation from follicular lymphoma to diffuse large B-cell lymphoma.2007Ingår i: Modern Patholology, ISSN 0893-3952, Vol. 20, nr 1, s. 63-75Artikel i tidskrift (Refereegranskat)
  • 5. d'Amore, Francesco
    et al.
    Relander, Thomas
    Lauritzsen, Grete F.
    Jantunen, Esa
    Hagberg, Hans
    Anderson, Harald
    Holte, Harald Jr.
    Osterborg, Anders
    Merup, Mats
    Brown, Peter de Nully
    Kuittinen, Outi
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Ostenstad, Bjorn
    Fagerli, Unn-Merete
    Gadeberg, Ole
    Sundstrom, Christer
    Delabie, Jan
    Rafkiaer, Elisabeth
    Vornanen, Martine
    Toldbod, Helle
    High-dose chemotherapy and autologuos stem cell transplantation in previously untreated peripheral T-Cell Lymphoma: Final analysis of a large prospective multicenter study (NLG-T-01)2011Ingår i: 53rd ASH Annual Meeting and Exposition: Session: 731. Clinical Allogeneic and Autologous Transplantation - Results: Myeloma, Lymphomas and Multiple Sclerosis ; Monday, December 12, 2011: 7:00 AM Douglas Pavilion C (Manchester Grand Hyatt San Diego), washington, USA: American Society of Hematology , 2011, Vol. 118, nr 21, s. 155-156Konferensbidrag (Refereegranskat)
  • 6. d'Amore, Francesco
    et al.
    Relander, Thomas
    Lauritzsen, Grete F.
    Jantunen, Esa
    Hagberg, Hans
    Anderson, Harald
    Holte, Harald
    Osterborg, Anders
    Merup, Mats
    Brown, Peter
    Kuittinen, Outi
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Ostenstad, Bjorn
    Fagerli, Unn-Merete
    Gadeberg, Ole V.
    Sundstrom, Christer
    Delabie, Jan
    Ralfkiaer, Elisabeth
    Vornanen, Martine
    Toldbod, Helle E.
    Up-Front Autologous Stem-Cell Transplantation in Peripheral T-Cell Lymphoma: NLG-T-012012Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, nr 25, s. 3093-3099Artikel i tidskrift (Refereegranskat)
    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

  • 7. Ghez, D.
    et al.
    Fortpied, C.
    Mounier, N.
    Carde, P.
    Perrot, A.
    Khaled, H.
    Amorim, S.
    Ramadan, S.
    Bras, F. L.
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Herbaux, C.
    Marolleau, J-P
    Nicolas-Virelezier, E.
    Casasnovas, O.
    Stamatoullas-Bastard, A.
    Ferme, C.
    First-line escalated BEACOPP does not hinder stem cell collection and transplantation strategy in patients with relapsed/refractory Hodgkin's lymphoma2017Ingår i: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 52, nr 2, s. 310-312Artikel i tidskrift (Refereegranskat)
  • 8. Ghez, D.
    et al.
    Fortpied, C.
    Mounier, N.
    Carde, P.
    Perrot, A.
    Khaled, H.
    Amorim, S.
    Ramadan, S.
    Le Bras, F.
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Herbaux, C.
    Marolleau, J. P.
    Nicolas-Virelizier, E.
    Casasnovas, O.
    Stamatoullas-Bastard, A.
    Ferme, C.
    STEM CELL COLLECTION AFTER FAILURE OF UPFRONT ABVD OR BEACOPP IN PATIENTS WITH HIGH RISK ADVANCED STAGE III-IV HODGKIN'S LYMPHOMA2016Ingår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, nr S5, s. 50-50, artikel-id P091Artikel i tidskrift (Refereegranskat)
  • 9.
    Haider, Zahra
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Landfors, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Noren-Nyström, Ulrika
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Epigenetic and genetic distinctions between T-cell acute lymphoblastic leukemia and lymphomaManuskript (preprint) (Övrigt vetenskapligt)
  • 10. Hedström, Gustaf
    et al.
    Berglund, Mattias
    Molin, Daniel
    Fischer, Marie
    Nilsson, Gunnar
    Thunberg, Ulf
    Book, Majlis
    Sundström, Christer
    Rosenquist, Richard
    Roos, Göran
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Erlanson, Martin
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Amini, Rose-Marie
    Enblad, Gunilla
    Mast cell infiltration is a favourable prognostic factor in diffuse large B-cell lymphoma.2007Ingår i: Br J Haematol, ISSN 0007-1048, Vol. 138, nr 1, s. 68-71Artikel i tidskrift (Övrigt vetenskapligt)
  • 11. Holte, H.
    et al.
    Leppa, S.
    Bjorkholm, M.
    Fluge, O.
    Jyrkkio, S.
    Delabie, J.
    Sundstrom, C.
    Karjalainen-Lindsberg, M. -L
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Kolstad, A.
    Fossa, A.
    Ostenstad, B.
    Lofvenberg, E.
    Nordstrom, M.
    Janes, R.
    Pedersen, L. M.
    Anderson, H.
    Jerkeman, M.
    Eriksson, M.
    Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study2013Ingår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, nr 5, s. 1385-1392Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Many patients with aggressive B-cell lymphomas and high clinical risk score still die of lymphoma after conventional R-CHOP chemoimmunotherapy. We hypothesized that intensified chemoimmunotherapy including systemic central nervous system (CNS) prophylaxis improves outcome and reduces the incidence of CNS-related events. Patients and methods: Inclusion criteria were age 18-65 years, primary diffuse large B-cell lymphoma or grade III follicular lymphoma without clinical signs of CNS disease and negative cerebrospinal fluid cytology, age-adjusted International Prognostic Index 2-3 and WHO performance score 0-3. Treatment consisted of six courses of R-CHOEP-14 followed by a course of high-dose cytarabine and a course of high-dose methotrexate. Primary end point was failure-free survival (FFS) at 3 years. Results: A total of 156 eligible patients with a median age of 54 years (range 20-64) were included. Three toxic deaths were observed. Three-year overall survival (OS) and FFS rates (median observation time 52 months for survivors) were 81% and 65%, respectively. Seven patients experienced CNS relapse, all within 6 months. Conclusions: The results are promising with favorable 3-year OS and FFS rates, a low toxic death rate and a lower than expected number of CNS events. CNS progression might be further reduced by earlier CNS prophylaxis. CinicalTrials.gov.identifier: NCT01502982.

  • 12. Junlen, H. R.
    et al.
    Peterson, S.
    Kimby, E.
    Lockmer, S.
    Linden, O.
    Nilsson-Ehle, H.
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hagberg, H.
    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 Study2015Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 29, nr 3, s. 668-676Artikel i tidskrift (Refereegranskat)
    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.

  • 13. Junlen, Henna Riikka
    et al.
    Peterson, Stefan
    Kimby, Eva
    Lockmer, Sandra
    Linden, Ola
    Nilsson-Ehle, Herman
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hagberg, Hans
    Radlund, Anders
    Hagberg, Oskar
    Wahlin, Björn E.
    Follicular Lymphoma Survival in Sweden in the Rituximab Era2014Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, nr 21Artikel i tidskrift (Övrigt vetenskapligt)
  • 14. Kasteng, Frida
    et al.
    Erlanson, Martin
    Norrlands University Hospital, Umeå, Sweden.
    Hagberg, Hans
    Kimby, Eva
    Relander, Thomas
    Lundkvist, Jonas
    Cost-effectiveness of maintenance rituximab treatment after second line therapy in patients with follicular lymphoma in Sweden2008Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 47, nr 6, s. 1029-1036Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Rituximab has significantly improved the prognosis for patients with both indolent and aggressive non-Hodgkin's lymphoma. An economic evaluation was carried out to assess the cost-effectiveness in Sweden of rituximab as maintenance therapy for patients with follicular lymphoma in remission after second line therapy.

    MATERIALS AND METHODS: The incremental cost and effectiveness of rituximab maintenance therapy versus observation were evaluated in a health-state transition model. Primary effect measures were quality-adjusted life-years (QALY) and life-years gained (LYG). Model state transitions were calculated based on progression-free and overall survival data from the EORTC20981 trial. The analysis was made from the perspective of the healthcare provider, including direct medical costs presented in euro, 2007 value. Effects and costs were discounted at a 3% annual rate. The stability of the base case results were tested in one-way and probabilistic sensitivity analyses.

    RESULTS: The evaluation assessed rituximab maintenance therapy to be associated with an incremental cost per QALY gained of euro 12,600 and an incremental cost per LYG of euro 11,200. The average discounted life expectancy for patients on rituximab maintenance was 1.0 year longer than for patients on observation (5.96 vs. 4.94 years). Rituximab maintenance was associated with an additional 0.9 QALY, and total costs per patient were euro 11,500 higher in the treatment arm, compared to observation.

    DISCUSSION: The results indicate that rituximab maintenance treatment after successful induction therapy for patients with relapsed/refractory follicular lymphoma in Sweden is cost-effective compared to observation.

  • 15. Kimby, Eva
    et al.
    Östenstad, Björn
    Brown, Peter de Nully
    Holte, Harald, Jr.
    Hagberg, Hans
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Linden, Ola
    Nordström, Marie
    Sundström, Christer
    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 Group2012Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 120, nr 21Artikel i tidskrift (Övrigt vetenskapligt)
  • 16. Kolstad, Arne
    et al.
    Madsbu, Ulf
    Dahle, Jostein
    Stokke, Caroline
    Bach-Gansmo, Tore
    Londalen, Ayca Muftuler
    Holtedahl, Jon Erik
    Revheim, Mona Elisabeth
    Bruland, Oyvind
    Bolstad, Bjorg
    Bolstad, Nils
    Tierens, Anne
    Larsen, Roy Hartvig
    Alfheim, Jan Alan
    Delabie, Jan
    Signe, Spetalen
    Erlanson, Martin
    Ruda, Stine Nygaard
    Holte, Harald
    A Phase I Study of (177)lu-DOTA-HH1 (Betalutin) Radioimmunotherapy for Patients with Relapsed CD37+Non-Hodgkin's B Cell Lymphoma2014Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, nr 21Artikel i tidskrift (Övrigt vetenskapligt)
  • 17. Lagerlöf, Ingemar
    et al.
    Holte, Harald
    Glimelius, Ingrid
    Björkholm, Magnus
    Enblad, Gunilla
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Fluge, Oystein
    Fohlin, Helena
    Fosså, Alexander
    Goldkuhl, Christina
    Gustavsson, Anita
    Johansson, Ann Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Linderoth, Johan
    Nome, Ole
    Palma, Marzia
    Åkesson, Lisa
    Ostenstad, Bjorn
    Raud, Cecilia
    Glimelius, Bengt
    Molin, Daniel
    No excess long-term mortality in stage I-IIA Hodgkin lymphoma patients treated with ABVD and limited field radiotherapy2020Ingår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 188, nr 5, s. 685-691Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    When treating limited stage classical Hodgkin lymphoma (cHL), balancing treatment efficacy and toxicity is important. Toxicities after extended-field radiotherapy are well documented. Investigators have aimed at reducing toxicity without compromising efficacy, mainly by using combined modality treatment (CMT), i.e. chemotherapy and limited-field radiotherapy. In some clinical trials, radiotherapy has been omitted. We evaluated 364 patients with stage I-IIA cHL treated between 1999 and 2005. Patients were treated with two or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) according to presence of risk factors, followed by 30 Gy limited-field (reduced compared to involved-field) radiotherapy. After a median follow-up of 16 years for survival, freedom from progression at five and ten years was 93% and overall survival at 5 and 10 years was 98% and 96%, respectively. Only two relapses, out of 27, occurred after more than 5 years. There was no excess mortality compared to the general population. Of the analysed subgroups, only patients with progression within five years showed significant excess mortality. The absence of excess mortality questions the concept of omitting radiotherapy after short-term chemotherapy, a strategy that has been associated with an elevated risk of relapse but not yet with a proven reduced long-term excess mortality.

  • 18. Linderholm, B
    et al.
    Andersson, J
    Lindh, Birgitta
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Beckman, L
    Erlanson, Martin
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Edin, K
    Tavelin, Björn
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Grankvist, Kjell
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Henriksson, Roger
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Overexpression of c-erbB-2 is related to a higher expression of vascular endothelial growth factor (VEGF) and constitutes an independent prognostic factor in primary node-positive breast cancer after adjuvant systemic treatment2004Ingår i: Eur J Cancer, ISSN 0959-8049, Vol. 40, nr 1, s. 33-42Artikel i tidskrift (Refereegranskat)
  • 19. Linderoth, Johan
    et al.
    Edén, Patrik
    Ehinger, Mats
    Valcich, Jeanette
    Jerkeman, Mats
    Bendahl, Pär-Ola
    Berglund, Mattias
    Enblad, Gunilla
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Cavallin-Ståhl, Eva
    Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma2008Ingår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 141, nr 4, s. 423-432Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In order to identify genes associated with primary chemotherapy-resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B-cell lymphoma (DLBCL), stage II-IV, either in continuous complete remission (n = 24) or with progressive disease during primary treatment (n = 13), were examined using spotted 55K oligonucleotide arrays. Immunohistochemistry was used for confirmation at the protein level. The top 86 genes that best discriminated between the two cohorts were chosen for further analysis. Only seven of 86 genes were overexpressed in the refractory cohort, e.g. RABGGTB and POLE, both potential targets for drug intervention. Seventy-nine of 86 genes were overexpressed in the cured cohort and mainly coded for proteins expressed in the tumour microenvironment, many of them involved in proteolytic activity and remodelling of extra cellular matrix. Furthermore, major histocompatibility complex class I molecules, CD3D and ICAM1 were overexpressed, indicating an enhanced immunological reaction. Immunohistochemistry confirmed the GEP results. The frequency of tumour infiltrating lymphocytes, macrophages, and reactive cells expressing ICAM-1, lysozyme, cathepsin D, urokinase plasminogen activator receptor, signal transducer and activator of transcription 1, and galectin-3 was higher in the cured cohort. These findings indicate that a reactive microenvironment has an impact on the outcome of chemotherapy in DLBCL.

  • 20. Linderoth, Johan
    et al.
    Ehinger, Mats
    Jerkeman, Mats
    Bendahl, Pär-Ola
    Åkerman, Måns
    Berglund, Mattias
    Enblad, Gunilla
    Erlanson, Martin
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Roos, Göran
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Cavallin-Ståhl, Eva
    CD40 expression identifies a prognostically favourable subgroup of diffuse large B-cell lymphoma.2007Ingår i: Leuk Lymphoma, ISSN 1042-8194, Vol. 48, nr 9, s. 1774-1779Artikel i tidskrift (Refereegranskat)
  • 21. Linderoth, Johan
    et al.
    Ehinger, Mats
    Åkerman, Måns
    Cavallin-Ståhl, Eva
    Enblad, Gunilla
    Erlanson, Martin
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Jerkeman, Mats
    Tissue microarray is inappropriate for analysis of BCL6 expression in diffuse large B-cell lymphoma.2007Ingår i: Eur J Haematol, ISSN 0902-4441, Vol. 79, nr 2, s. 146-149Artikel i tidskrift (Refereegranskat)
  • 22. Mansouri, Larry
    et al.
    Noerenberg, Daniel
    Young, Emma
    Mylonas, Elena
    Abdulla, Maysaa
    Frick, Mareike
    Asmar, Fazila
    Ljungstroem, Viktor
    Schneider, Markus
    Yoshida, Kenichi
    Skaftason, Aron
    Pandzic, Tatjana
    Gonzalez, Blanca
    Tasidou, Anna
    Waldhueter, Nils
    Rivas-Delgado, Alfredo
    Angelopoulou, Maria
    Ziepert, Marita
    Arends, Christopher Maximilian
    Couronne, Lucile
    Lenze, Dido
    Baldus, Claudia D.
    Bastard, Christian
    Okosun, Jessica
    Fitzgibbon, Jude
    Doerken, Bernd
    Drexler, Hans G.
    Roos-Weil, Damien
    Schmitt, Clemens A.
    Munch-Petersen, Helga D.
    Zenz, Thorsten
    Hansmann, Martin-Leo
    Strefford, Jonathan C.
    Enblad, Gunilla
    Bernard, Olivier A.
    Ralfkiaer, Elisabeth
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Korkolopoulou, Penelope
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Papadaki, Theodora
    Gronbaek, Kirsten
    Lopez-Guillermo, Armando
    Ogawa, Seishi
    Kuppers, Ralf
    Stamatopoulos, Kostas
    Stavroyianni, Niki
    Kanellis, George
    Rosenwald, Andreas
    Campo, Elias
    Amini, Rose-Marie
    Ott, German
    Vassilakopoulos, Theodoros P.
    Hummel, Michael
    Rosenquist, Richard
    Damm, Frederik
    Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma2016Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 128, nr 23, s. 2666-2670Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We recently reported a truncating deletion in the NFKBIE gene, which encodes IkB epsilon, a negative feedback regulator of NF-kB, in clinically aggressive chronic lymphocytic leukemia (CLL). Because preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, we screened a large patient cohort (n = 1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal zone lymphoma, and T-cell acute lymphoblastic leukemia (< 2%), slightly higher frequencies were seen in diffuse large B- cell lymphoma, mantle cell lymphoma, and primary central nervous system lymphoma (3% to 4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases [22.7%]) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases [27.3%]). NFKBIE-deleted PMBL patients were more often therapy refractory (P =.022) and displayed inferior outcome compared with wild- type patients (5-year survival, 59% vs 78%; P = .034); however, they appeared to benefit from radiotherapy P = .022) and rituximab-containing regimens (P = .074). NFKBIE aberrations remained an independent factor in multivariate analysis (P =.003) and when restricting the analysis to immunochemotherapy-treated patients (P = .008). Whole-exome sequencing and gene expression profiling verified the importance of NF-kB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL.

  • 23.
    Norrback, Karl-Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Enblad, Gunilla
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Sundström, Christer
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Telomerase activity in Hodgkin's disease1998Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 92, nr 2, s. 567-573Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Telomere maintenance executed by the action of telomerase seems to be a prerequisite for immortalization. Telomerase is found in most cell lines and malignant tumors. A telomerase-independent mechanism for telomere maintenance in Hodgkin's disease has been proposed in the absence of detectable telomerase activity. In this study, telomerase activity was detected in 31 of 77 Hodgkin's disease samples and a strong correlation between eosinophilia and absence of detectable telomerase activity was found. Purified eosinophils and specifically eosinophil-derived neurotoxin and eosinophilic cationic protein, both ribonucleases, were found to degrade telomerase. Purified neutrophils also exhibited weak telomerase degradative activity. Reanalysis of previously telomerase-negative Hodgkin's disease samples with eosinophilia using ribonuclease inhibitors resulted in the detection of telomerase activity. Ribonuclease-containing cells in vivo thus have a considerable impact on the detectability of telomerase. In Hodgkin's disease samples without eosinophilia, 24 of 27 exhibited telomerase activity at decreased levels compared with non-Hodgkin's lymphomas and at increased levels compared with reactive nodes indicative of a telomerase positive tumor component in Hodgkin's disease. Telomerase positivity of the Hodgkin's and Reed-Sternberg cells in vivo was also supported by high levels of telomerase expression in Hodgkin's disease cell lines. Based on our data, Hodgkin's lymphomas are potential targets for antitelomerase therapy.

  • 24. Pulczynski, Elisa Jacobsen
    et al.
    Kamper, Peter
    Fagerli, Unn-Merete
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Kuittinen, Outi
    Fossa, Alexander
    Östenstad, Björn
    Fluge, Oystein
    Maisenhölder, Martin
    Hagberg, Hans
    Eriksson, Mikael
    Nordström, Marie
    Leppa, Sirpa
    Age-adjusted combined immunochemotherapy without radiotherapy in newly diagnosed PCNSL: A phase II trial of the Nordic Lymphoma Group2011Ingår i: 53rd ASH Anual Meeting and Exposition: Program: Oral and Poster AbstractsSession: 623. Lymphoma - Chemotherapy, excluding Pre-Clinical Models: Poster I Saturday, December 10, 2011, 5:30 PM-7:30 PM Hall GH (San Diego Convention Center), 2011, Vol. 118, nr 21, s. 696-696Konferensbidrag (Refereegranskat)
    Abstract [en]

    Patients and Methods: From May 2007 to October 2010, 66 newly diagnosed primary central nervous system lymphoma (PCNSL) patients (M/F ratio 1:1) were enrolled. Younger patients (≤65 yrs; N=39) received 6 three-weekly cycles of chemotherapy consisting of: high-dose (HD)-methotrexate (MTX) (cycles 1, 2, 4 and 5), HD-cytosine arabinoside (AraC) (cycles 3 and 6) in addition to Rituximab (cycle 1 only), ifosfamide (cycles 1 and 4), cyclophosphamide (cycles 2 and 5), vincristine (cycles 2 and 5), vindesine (cycles 3 and 6), and dexamethasone (all 6 cycles). Depocyte® was delivered intratechally during the HD-MTX cycles. Elderly patients (66-75 yrs; N=27) received an identical Rituximab-containing 1st cycle. Cyclophosphamide and ifosfamide were replaced by temozolamide (cycles 2 to 6), which was also given as maintenance in patients with chemosensitive disease, and vincristine was omitted. No radiotherapy was given. Response was determined after the 2nd, 4th and 6thchemotherapy cycle by cerebral MRI and assessed according to International Primary CNS Lymphoma Coordinating Group criteria. The primary endpoint was overall survival (OS), secondary endpoints were progression-free survival (PFS), overall response rate (ORR), systemic toxicity and neurotoxicity assessed as Mini Mental State Examination (MMSE) and Functional Independence Measure (FIM).

    Results: The median age was 64 yrs overall, 55 yrs (range 40-65) for younger and 70 yrs (range 66-75 years) for elderly patients. In 56 patients, the International Extranodal Lymphoma Study Group prognostic score was: 0-1 (N=5), 2-3 (N=36) and 4-5 (N=15). In the remaining 10 patients, lumbar puncture was not performed in five and spinal fluid protein concentration not reported in additional five cases. Response assessment after completion of induction treatment was performed in 43 out of 66 patients and showed complete remission (CR/CRu) in 30 patients, partial remission (PR) in 5 and progressive disease (PD) in 8. The ORR was 53 %. In 23 patients, response could not be evaluated due to early progression (n=8), toxic death (n=4), poor performance (n=3), neurotoxicity (n=5), or other causes (n=3). Of the 27 elderly patients, 15 continued to maintenance therapy. Of these, 14 have completed the maintenance schedule. Remission status at month 3 was CR in 13 and PD in 1 patient.

    With a median follow-up of 11.1 months (range 0.6-40.2) the 3-yr OS was 54.6% with no significant difference between younger and elderly patients (56.4% vs 51.9% respectively, p=0.32). The 3-yr PFS was 35.1% (32.9% in younger and 38.2 % in elderly patients; p=0.96). There were four septic deaths. Grade 3-4 hematological toxicity was seen in 79 % of the patients. Arachnoditis-like symptoms occurred in 13 patients. In all but two patients, the symptoms resolved within less than a week. MMSE and FIM were recorded both before and after therapy in 32 patients. Scores improved in 18 and 20 patients, respectively.

    Conclusion: In conclusion, the schedule applied in the present study led to a 3 yr PFS of 35%. Surprisingly, no significant outcome difference was found between the younger and the elderly patients. The majority of treatment failures were due to early progressive disease under induction therapy. Although the follow-up of our study is short, de-escalation of induction treatment intensity by introduction of a less toxic agent as temozolomide, and its subsequent use in a maintenance schedule may explain a possible survival benefit of this strategy in elderly patients.

    Disclosures: No relevant conflicts of interest to declare.

  • 25. Wahlin, Björn Engelbrekt
    et al.
    Sundström, Christer
    Holte, Harald
    Hagberg, Hans
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    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 Rituximab2011Ingår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 17, nr 12, s. 4136-4144Artikel i tidskrift (Refereegranskat)
    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.

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