38 results on '"Lauritzsen GF"'
Search Results
2. Upfront Autologuos Stem Cell Transplantation in Peripheral T-cell Lymphoma (NLG-T-01)
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D'Amore, Francesco Annibale, Relander, T, Lauritzsen, GF, Jantunen, E, Hagberg, H, Anderson, H, Holte, H, Ôsterborg, A, Merup, M, Brown, Peter De Nully, Kuittinen, O, Erlanson, M, Østenstad, B, Fagerli, U-M, Gadeberg, OV, Sundström, C, Delabie, J, Ralfkiær, Elisabeth Methner, Vornanen, M, and Toldbod, H
- Published
- 2012
3. High-dose chemotherapy and autologous stem cell transplantation in previously untreated peripheral T-cell lymphoma - final analysis of a large prospective multicenter study (NLG-T-01)
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D'Amore, Francesco Annibale, Relander, T, Lauritzsen, GF, Jantunen, E, Hagberg, H, Anderson, H, Holte, H, Østerborg, A, Merup, M, Brown, Peter De Nully, Østenstad, B, Kuittinen, O, Erlanson, M, Fagerli, UM, Gadeberg, O, Sundström, C, Delabie, J, Ralfkiaer, E, Vornanen, M, and Toldbod, H
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- 2012
4. Alemtuzumab does not affect hematopoietic recovery after autologous stem cell transplantation in T-cell lymphoma: Data from the ACT-1 trial
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Lauritzsen, GF, Gomes da Silva, M, Leppa, S, Pezzutto, A, Relander, T, Weidmann, E, van Gelder, M, Doorduijn, J, Hansen, PB, Altmann, B, Toldbod, Helle, and D'Amore, Francesco Annibale
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- 2011
5. First interim safety analysis of a phase III randomized trial in a newly diagnosed systemic peripheral T-cell lymphoma trated with CHOP chemotherapy with or without alemtuzumab and consolidated by autologous hematopoietic stem cell transplant
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D'Amore, Francesco Annibale, Gomes da Silva, M, Leppa, S, Relander, T, Pezzutto, A, Lauritzsen, GF, Weidmann, E, Van Gelder, M, Merup, M, Hagberg, H, Fagerli, UM, Brown, Peter De Nully, Boye Hansen, P, Mariz, JM, Jankovska, M, Walewski, J, Doorduijn, J, van Hoof, A, Christiansen, Ilse, Jyrkkiö, S, Kluin-Nelemans, JC, van Marwijk Kooy, M, Fijnheer, R, Stevens, W, Zijlstra, J, Böhmer, L, Lugtenburg, PJ, Grube, M, Prochazka, V, Salek, D, Greil, R, Trümper, L, Wulf, G, Altmann, B, Ziepert, M, Loeffler, M, Jantunen, E, Hopfinger, G, Van den Neste, E, and Toldbod, H
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- 2011
6. CHOEP-14 and autologous stem cell tranplantation (ASCT) in angioimmunoblastic T-cell lymphoma: a prospective study by the Nordic Lymphoma Group (NLG-T-01)
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Lauritzsen, GF, Relander, T, Jantunen, E, Hagberg, H, Anderson, H, Merup, M, Brown, P, Østenstad, B, Kuittinen, O, Erlanson, M, Fagerli, UM, Delabie, J, Sundström, C, Ralfkiaer, E, Vornanen, M, and D'Amore, Francesco Annibale
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- 2011
7. Pre-emptive treatment with rituximab of molecular relapse after autologous stem cell transplantation in mantle cell lymphoma.
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Andersen NS, Pedersen LB, Laurell A, Elonen E, Kolstad A, Boesen AM, Pedersen LM, Lauritzsen GF, Ekanger R, Nilsson-Ehle H, Nordström M, Fredén S, Jerkeman M, Eriksson M, Väärt J, Malmer B, and Geisler CH
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- 2009
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8. 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 Years.
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Kolstad A, Pedersen LB, Eskelund CW, Husby S, Grønbæk K, Jerkeman M, Laurell A, Räty R, Elonen E, Andersen NS, Brown PD, Kimby E, Bentzen H, Sundström C, Ehinger M, Karjalainen-Lindsberg ML, Delabie J, Ralfkiær E, Fagerli UM, Nilsson-Ehle H, Lauritzsen GF, Kuittinen O, Niemann C, and Geisler CH
- Subjects
- Adult, Aged, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm, Residual diagnosis, Neoplasm, Residual drug therapy, Recurrence, Scandinavian and Nordic Countries, Survival Analysis, Transplantation, Autologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Mantle-Cell therapy, Neoplasm, Residual prevention & control, Rituximab therapeutic use
- Abstract
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 rearrangements. 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., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2017
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9. 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau.
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Eskelund CW, Kolstad A, Jerkeman M, Räty R, Laurell A, Eloranta S, Smedby KE, Husby S, Pedersen LB, Andersen NS, Eriksson M, Kimby E, Bentzen H, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Ehinger M, Sundström C, Delabie J, Karjalainen-Lindsberg ML, Workman CT, Garde C, Elonen E, Brown P, Grønbaek K, and Geisler CH
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- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Biomarkers, Clinical Trials, Phase II as Topic, Female, Follow-Up Studies, Humans, Lymphoma, Mantle-Cell diagnosis, Male, Middle Aged, Mortality, Neoplasm Staging, Prognosis, Recurrence, Remission Induction, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Mantle-Cell drug therapy, Lymphoma, Mantle-Cell mortality
- Abstract
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 11·4 years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 12·7 and 8·5 years, 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 12 years, 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., (© 2016 John Wiley & Sons Ltd.)
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- 2016
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10. A national study on conditional survival, excess mortality and second cancer after high dose therapy with autologous stem cell transplantation for non-Hodgkin lymphoma.
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Smeland KB, Kiserud CE, Lauritzsen GF, Blystad AK, Fagerli UM, Falk RS, Fluge Ø, Fosså A, Kolstad A, Loge JH, Maisenhölder M, Østenstad B, Kvaløy S, and Holte H
- Subjects
- Adolescent, Adult, Aged, Combined Modality Therapy methods, Combined Modality Therapy mortality, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Lymphoma, Non-Hodgkin complications, Lymphoma, Non-Hodgkin mortality, Male, Middle Aged, Norway epidemiology, Recurrence, Registries, Survival Analysis, Transplantation, Autologous, Young Adult, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Non-Hodgkin therapy, Neoplasms, Second Primary etiology
- Abstract
This national population-based study aimed to investigate conditional survival and standardized mortality ratios (SMR) after high-dose therapy with autologous stem-cell transplantation (HDT-ASCT) for non-Hodgkin lymphoma (NHL), and to analyse cause of death, relapses and second malignancies. All patients ≥18 years treated with HDT-ASCT for NHL in Norway between 1987 and 2008 were included (n = 578). Information from the Cause of Death Registry and Cancer Registry of Norway were linked with clinical data. The 5-, 10- and 20-year overall survival was 61% (95% confidence interval [CI] 56-64%), 52% (95%CI 48-56%) and 45% (95%CI 40-50%), respectively. The 5-year survival conditional on having survived 2, 5 and 10 years after HDT-ASCT was 81%, 86% and 93%. SMRs were 12·3 (95%CI 11·0-13·9), 4·9 (95%CI 4·1-5·9), 2·4 (95%CI 1·8-3·2) and 1·0 (95%CI 0·6-1·8) for the entire cohort and for patients having survived 2, 5 and 10 years after HDT-ASCT respectively. Of the 281 deaths observed, 77% were relapse-related. Treatment-related mortality was 3·6%. The 10-year cumulative incidence of second malignancies was 7·9% and standardized incidence ratio was 2·0 (95%CI 1·5-2·6). NHL patients treated with HDT-ASCT were at increased risk of second cancer and premature death. The mortality was still elevated at 5 years, but after 10 years mortality equalled that of the general population., (© 2016 John Wiley & Sons Ltd.)
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- 2016
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11. Conditional survival and excess mortality after high-dose therapy with autologous stem cell transplantation for adult refractory or relapsed Hodgkin lymphoma in Norway.
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Smeland KB, Kiserud CE, Lauritzsen GF, Fagerli UM, Falk RS, Fluge Ø, Fosså A, Kolstad A, Loge JH, Maisenhölder M, Kvaløy S, and Holte H
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- Cohort Studies, Female, Hematopoietic Stem Cell Transplantation trends, Humans, Male, Neoplasms, Second Primary diagnosis, Norway epidemiology, Recurrence, Registries, Survival Rate trends, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation mortality, Hodgkin Disease mortality, Hodgkin Disease therapy, Neoplasms, Second Primary mortality
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- 2015
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12. High dose chemotherapy with autologous stem cell transplant for patients with transformed B-cell non-Hodgkin lymphoma in the rituximab era.
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Blaker YN, Eide MB, Liestøl K, Lauritzsen GF, Kolstad A, Fosså A, Smeland EB, and Holte H
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- Adult, Aged, Antibodies, Monoclonal, Murine-Derived administration & dosage, Disease Progression, Female, Follow-Up Studies, Humans, Lymphoma, Non-Hodgkin mortality, Male, Middle Aged, Neoplasm Grading, Neoplasm Staging, Remission Induction, Retrospective Studies, Rituximab, Transplantation, Autologous, Treatment Outcome, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation, Lymphoma, Non-Hodgkin pathology, Lymphoma, Non-Hodgkin therapy
- Abstract
High dose chemotherapy with autologous stem cell transplant (HD-ASCT) is a recommended procedure for patients with transformed indolent B-cell lymphoma from the pre-rituximab era. In this retrospective single-center study, we present our experience with HD-ASCT in patients with histologically verified transformed indolent B-cell lymphoma in the rituximab era. Forty-two patients were included, of whom 28 with chemosensitive disease proceeded to HD-ASCT. Twenty patients (71%) achieved a complete response (CR) and five (18%) a partial response (PR) after HD-ASCT. With a median observation time of 49 months for the survivors, the median progression-free survival (PFS) and overall survival (OS) for patients with HD-ASCT were 39 months and 57 months, respectively. Patients who were rituximab-naive at transformation had a significantly better OS compared to patients previously treated with rituximab, both in the whole patient cohort and among the HD-ASCT-treated patients (p = 0.036 and p = 0.039, respectively). Furthermore, male sex influenced survival negatively, whereas time from diagnosis to transformation was positively associated with survival, both with borderline significance, in HD-ASCT-treated patients. In conclusion, HD-ASCT remains an effective treatment for transformed indolent lymphomas in the rituximab era.
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- 2014
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13. Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma.
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Kolstad A, Laurell A, Jerkeman M, Grønbæk K, Elonen E, Räty R, Pedersen LB, Loft A, Bogsrud TV, Kimby E, Hansen PB, Fagerli UM, Nilsson-Ehle H, Lauritzsen GF, Lehmann AK, Sundstrom C, Karjalainen-Lindsberg ML, Ralfkiaer E, Ehinger M, Delabie J, Bentzen H, Schildt J, Kostova-Aherdan K, Frederiksen H, Brown Pde N, and Geisler CH
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- Adult, Aged, Carmustine administration & dosage, Combined Modality Therapy, Cyclophosphamide administration & dosage, Cytarabine administration & dosage, Disease-Free Survival, Etoposide administration & dosage, Female, Humans, Kaplan-Meier Estimate, Male, Melphalan administration & dosage, Middle Aged, Multivariate Analysis, Neoplasm, Residual diagnosis, Prognosis, Radioimmunotherapy, Time Factors, Transplantation, Autologous, Treatment Outcome, Antibodies, Monoclonal therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Mantle-Cell therapy, Stem Cell Transplantation methods
- Abstract
The main objective of the MCL3 study was to improve outcome for patients not in complete remission (CR) before transplant by adding (90)Y-ibritumomab-tiuxetan (Zevalin) to the high-dose regimen. One hundred sixty untreated, stage II-IV mantle cell lymphoma patients <66 years received rituximab (R)-maxi-CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) alternating with R-high-dose cytarabine (6 cycles total), followed by high-dose BEAM/C (bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan or cyclophosphamide) and autologous stem cell transplantation from 2005 to 2009. Zevalin (0.4 mCi/kg) was given to responders not in CR before transplant. Overall response rate pretransplant was 97%. The outcome did not differ from that of the historic control: the MCL2 trial with similar treatment except for Zevalin. Overall survival (OS), event-free survival (EFS), and progression-free survival (PFS) at 4 years were 78%, 62%, and 71%, respectively. For responding non-CR patients who received Zevalin, duration of response was shorter than for the CR group. Inferior PFS, EFS, and OS were predicted by positron emission tomography (PET) positivity pretransplant and detectable minimal residual disease (MRD) after transplant. In conclusion, positive PET and MRD were strong predictors of outcome. Intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant. This trial was registered at www.clinicaltrials.gov as #NCT00514475.
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- 2014
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14. Multimodal treatment with ALL-like chemotherapy, Auto-SCT and radiotherapy for lymphoblastic lymphoma.
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Bersvendsen H, Kolstad A, Blystad AK, Aurlien E, Fosså A, Kvaløy SO, Holte H, and Lauritzsen GF
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- Adolescent, Adult, Aged, Female, Hematopoietic Stem Cell Transplantation methods, Humans, Induction Chemotherapy methods, Kaplan-Meier Estimate, Maintenance Chemotherapy methods, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Radiotherapy methods, Retrospective Studies, Treatment Outcome, Young Adult, Combined Modality Therapy methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Background: Recommended treatment for lymphoblastic lymphomas, a highly aggressive, relatively rare lymphoma entity predominantly seen in teenagers and young adults, includes acute lymphoblastic leukemia (ALL)-like induction chemotherapy. Whether these patients should be consolidated with maintenance chemotherapy or autologous stem cell transplantation (Auto-SCT) and the use of radiotherapy are matters of debate., Methods: We reviewed treatment and outcome for 25 consecutive patients above the age of 15 years with lymphoblastic lymphoma (T-lineage; T-LBL, n = 19; B-lineage; B-LBL, n = 6) seen at a single center during a 12-year period (1999-2011). Patients were given an ALL-like chemotherapy induction regimen, and responding patients were consolidated with Auto-SCT and local radiotherapy when applicable., Results: Median age at diagnosis was 33 years (range 15-65). Seventeen of the T-LBL patients had a mediastinal mass, three patients had central nervous system (CNS) involvement. Chemotherapy with intensified CNS prophylaxis induced an overall response rate of 92% (CR 84%, PR 8%). In total 23/25 (92%) patients underwent Auto-SCT in first remission while 13 of 14 eligible patients with mediastinal involvement received local radiotherapy. Twenty percent of the patients had hepatotoxicity grade 3-4 and 32% thromboembolic events (TE). Two patients (8%) died of treatment-related toxicity. One patient had progressive disease and died of lymphoma. Three patients have relapsed, but two of these (both B-LBL) are currently alive in second CR after Allo-SCT. With a median follow-up of 98 months (range 1-163) the 5- and 8-year PFS and OS are 76% and 84%, respectively., Conclusions: Combined intensive ALL-like induction and early consolidation chemotherapy followed by Auto-SCT and local radiation therapy resulted in high sustained cure rates.
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- 2014
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15. High-dose therapy with autologous stem cell support for lymphoma--from experimental to standard treatment.
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Smeland KB, Kiserud CE, Lauritzsen GF, Fosså A, Hammerstrøm J, Jetne V, Kolstad A, Kvalheim G, Loge JH, Løkeland T, Tangen JM, Holte H, and Kvaløy S
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- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy history, Critical Pathways, History, 20th Century, Humans, Lymphoma history, Norway, Practice Guidelines as Topic, Transplantation, Autologous history, Antineoplastic Combined Chemotherapy Protocols history, Hematopoietic Stem Cell Transplantation history, Lymphoma therapy
- Abstract
High-dose therapy with autologous stem cell support (HDT) has been a therapeutic option for lymphomas in Norway since as far back as 1987. By restoring bone marrow function through reinfusion of the patient's own stem cells, it is possible to administer cancer treatment in higher and otherwise lethal doses, and thereby achieve better treatment results. Originally stem cells were harvested from bone marrow and the high-dose therapy included total body irradiation, but since the mid 1990s stem cells have been harvested by apheresis and the high-dose therapy has consisted of chemotherapy alone (BEAM chemotherapy). In 1995 the treatment was regionalised and since then it has been performed in all health regions. The HDT procedure was introduced as an experimental treatment in clinical studies with international collaboration. The indications have changed over time, and this is now established treatment for a number of types of lymphoma.
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- 2013
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16. High-dose therapy with autologous stem cell support for lymphoma in Norway 1987-2008.
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Smeland KB, Kiserud CE, Lauritzsen GF, Blystad AK, Fagerli UM, Fluge Ø, Fosså A, Hammerstrøm J, Kolstad A, Loge JH, Maisenhølder M, Østenstad B, Kvaløy S, and Holte H
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- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy statistics & numerical data, Female, Humans, Lymphoma mortality, Male, Middle Aged, Norway epidemiology, Survival Rate, Transplantation, Autologous statistics & numerical data, Young Adult, Hematopoietic Stem Cell Transplantation statistics & numerical data, Lymphoma therapy
- Abstract
Background: High-dose therapy with autologous stem cell support (HDT) has been a treatment option for lymphomas in Norway for 25 years. The purpose of the article was to describe the use of the therapy for lymphomas for the country as a whole and by health region, and to reveal the overall survival rate., Method: All lymphoma patients ≥ 18 years who received HDT in Norway in the period 1987-2008 are included. Patients, diagnostics and treatment are identified for each hospital. Data for the population base have been retrieved from Statistics Norway., Results: Altogether 726 lymphoma patients received HDT in Norway in the period 1987-2008, with an annual average of 0.72 per 100,000 inhabitants. The annual number of treatments increased until 2004 and has since been stable. The average number of treatments per 100,000 inhabitants per year was 0.94 for Northern Norway Health Region, 0.80 for South-Eastern Norway Health Region, 0.58 for Central Norway Health Region and 0.55 for Western Norway Health Region. Early mortality (death within 100 days) was 6%. Ten-year overall survival was 55% (95% CI 51-59%), and Hodgkin's lymphoma had the best survival of the lymphoma groups (p = 0.01)., Interpretation: The annual number of HDT increased gradually until 2004. The use of the treatment varied according to the patients' place of residence at the time of diagnosis, and was most frequently used for patients belonging to Northern Norway Health Region. More than half of the lymphoma patients are alive ten years after the treatment.
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- 2013
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17. Ultra-short course sirolimus contributes to effective GVHD prophylaxis after reduced-intensity allogeneic hematopoietic cell transplantation.
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Fløisand Y, Brinch L, Gedde-Dahl T, Tjønnfjord GE, Dybedal I, Holte H, Heldal D, Torfoss D, Aurlien E, Lauritzsen GF, Fosså A, Lehne G, Baggerød E, Kvalheim G, Egeland T, Bishop MR, Fowler DH, and Kolstad A
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- Adult, Aged, Antibodies, Monoclonal, Murine-Derived administration & dosage, Combined Modality Therapy, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Etoposide administration & dosage, Female, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Hodgkin Disease drug therapy, Hodgkin Disease surgery, Humans, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Non-Hodgkin surgery, Male, Middle Aged, Prednisolone administration & dosage, Rituximab, Transplantation, Homologous, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Vincristine administration & dosage, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation methods, Hodgkin Disease therapy, Immunosuppressive Agents administration & dosage, Lymphoma, Non-Hodgkin therapy, Sirolimus administration & dosage, Transplantation Conditioning methods
- Abstract
Reduced-intensity conditioning (RIC) allo-SCT is a potentially curative treatment approach for patients with relapsed Hodgkin's or non-Hodgkin's lymphoma. In the present study, 37 patients underwent RIC allo-SCT after induction treatment with EPOCH-F(R) using a novel form of dual-agent immunosuppression for GVHD prophylaxis with CsA and sirolimus. With a median follow-up of 28 months among survivors, the probability for OS at 3 and 5 years was 56%. Treatment-related mortality was 16% at day +100 and 30% after 1 year of transplant. Acute GVHD grades II-IV developed in 38% of patients, suggesting that the regimen consisting of CsA and an ultra-short course of sirolimus is effective in the prevention of acute GVHD.
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- 2012
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18. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01.
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d'Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, Holte H, Österborg A, Merup M, Brown P, Kuittinen O, Erlanson M, Østenstad B, Fagerli UM, Gadeberg OV, Sundström C, Delabie J, Ralfkiaer E, Vornanen M, and Toldbod HE
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Chemotherapy, Adjuvant, Cyclophosphamide administration & dosage, Disease Progression, Disease-Free Survival, Doxorubicin administration & dosage, Etoposide administration & dosage, Europe, Female, Humans, Kaplan-Meier Estimate, Lymphoma, T-Cell, Peripheral mortality, Lymphoma, T-Cell, Peripheral pathology, Male, Middle Aged, Multivariate Analysis, Neoadjuvant Therapy, Prednisone administration & dosage, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, Transplantation, Autologous, Treatment Outcome, Vincristine administration & dosage, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, T-Cell, Peripheral therapy, Stem Cell Transplantation adverse effects, Stem Cell Transplantation mortality
- Abstract
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.
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- 2012
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19. Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem-cell support: still very long survival but late relapses do occur.
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Geisler CH, Kolstad A, Laurell A, Jerkeman M, Räty R, Andersen NS, Pedersen LB, Eriksson M, Nordström M, Kimby E, Bentzen H, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Ehinger M, Sundström C, Delabie J, Karjalainen-Lindsberg ML, Brown P, and Elonen E
- Subjects
- Aged, Antibodies, Monoclonal, Murine-Derived administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Carmustine administration & dosage, Cyclophosphamide administration & dosage, Cytarabine administration & dosage, Disease-Free Survival, Etoposide administration & dosage, Female, Humans, Immunotherapy, Lymphoma, Mantle-Cell drug therapy, Lymphoma, Mantle-Cell immunology, Lymphoma, Mantle-Cell pathology, Male, Melphalan administration & dosage, Middle Aged, Podophyllotoxin administration & dosage, Prognosis, Recurrence, Rituximab, Survival Rate, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Mantle-Cell therapy
- Abstract
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. The study was registered at www.isrctn.org as ISRCTN 87866680., (© 2012 Blackwell Publishing Ltd.)
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- 2012
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20. Two escalated followed by six standard BEACOPP in advanced-stage high-risk classical Hodgkin lymphoma: high cure rates but increased risk of aseptic osteonecrosis.
- Author
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Fosså A, Fiskvik IH, Kolstad A, Lauritzsen GF, Aurlien E, Blystad AK, Hole KH, Ikonomou IM, and Holte H
- Subjects
- Adolescent, Adult, Bleomycin administration & dosage, Bleomycin adverse effects, Chemotherapy, Adjuvant, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Disease Progression, Dose-Response Relationship, Drug, Doxorubicin administration & dosage, Doxorubicin adverse effects, Drug Administration Schedule, Etoposide administration & dosage, Etoposide adverse effects, Female, Follow-Up Studies, Hodgkin Disease diagnosis, Hodgkin Disease mortality, Hodgkin Disease pathology, Humans, Male, Middle Aged, Neoplasm Staging, Osteonecrosis diagnosis, Osteonecrosis etiology, Osteonecrosis mortality, Practice Guidelines as Topic standards, Prednisone administration & dosage, Prednisone adverse effects, Procarbazine administration & dosage, Procarbazine adverse effects, Retrospective Studies, Risk, Survival Analysis, Vincristine administration & dosage, Vincristine adverse effects, Young Adult, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Hodgkin Disease drug therapy, Osteonecrosis chemically induced
- Abstract
Background: From 1999, Norwegian guidelines recommend two escalated (esc) BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) followed by six standard (s) BEACOPP for patients with advanced-stage classical Hodgkin lymphoma (HL) with an international prognostic score (IPS) ≥ 4. We evaluated retrospectively the experience with this recommendation at the Norwegian Radium Hospital, also including all IPS 3 patients treated with the same regimen., Patients and Methods: Forty-seven patients were treated between June 1999 and December 2008. IPS was 3 in 10 patients and ≥ 4 in 37., Results: Thirty-five patients received eight cycles of BEACOPP, 12 patients received one to six cycles only, mainly due to toxicity. Sixty percent of patients had dose reductions. With median follow-up of survivors of 89 months, 5-year progression-free and overall survival are 84% [95% confidence interval (CI) 73% to 95%] and 91% (95% CI 82% to 100%), respectively. Toxicity was considerable with grade 3 or more infections/febrile neutropenia in 66% of patients, including one death and three cases of Pneumocystis jiroveci pneumonia. Of note, 10 patients (21%) experienced symptomatic aseptic osteonecrosis, of whom 3 have had hip replacement surgery after treatment., Conclusion: Two escBEACOPP plus six sBEACOPP is efficacious in advanced-stage high-risk HL. We document a high incidence of aseptic bone necrosis, possibly related to prednisolone.
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- 2012
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21. High dose chemotherapy with autologous stem cell support for patients with histologically transformed B-cell non-Hodgkin lymphomas. A Norwegian multi centre phase II study.
- Author
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Eide MB, Lauritzsen GF, Kvalheim G, Kolstad A, Fagerli UM, Maisenhölder M, Østenstad B, Fluge Ø, Delabie J, Aarset H, Liestøl K, and Holte H
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bone Marrow Purging methods, Disease Progression, Drug Administration Schedule, Epidemiologic Methods, Female, Humans, Lymphoma, Follicular pathology, Lymphoma, Large B-Cell, Diffuse pathology, Male, Middle Aged, Recurrence, Salvage Therapy methods, Tissue and Organ Harvesting methods, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
We present a prospective phase II study of patients with relapse after chemotherapy showing transformation of follicular lymphoma to diffuse large B-cell lymphoma, performed before rituximab was included in standard treatment. Patients in complete (CR) or partial remission (PR) after salvage chemotherapy were eligible for high-dose chemotherapy with autologous stem cell support (HDT). Forty-seven patients from five Norwegian centres were included, of whom 30 (63%) received HDT. Eighteen (60%) achieved CR, seven (23%) PR and five (10%) had progressive disease following HDT. Median follow-up for the surviving patients was 75 months; median progression-free (PFS) and overall survival (OS) were 26 and 47 months, respectively. Median OS for all patients was 43 months, compared to only 10 months for patients not eligible for HDT. Patients receiving CD34(+) enriched/B-cell depleted grafts had inferior PFS and a trend for inferior OS compared to patients receiving non-purged grafts (Log Rank 0·025 and 0·151, respectively). In conclusion, two thirds of patients with transformation of follicular lymphoma were eligible for HDT. The majority of patients achieved CR and a considerable number had prolonged OS. The use of in vitro purged grafts did not result in a survival benefit compared to that of non-purged grafts., (© 2011 Blackwell Publishing Ltd.)
- Published
- 2011
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22. Dose-intensified treatment of Burkitt lymphoma and B-cell lymphoma unclassifiable, (with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma) in young adults (<50 years): a comparison of two adapted BFM protocols.
- Author
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Tauro S, Cochrane L, Lauritzsen GF, Baker L, Delabie J, Roberts C, Mahendra P, and Holte H
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cohort Studies, Cyclophosphamide administration & dosage, Cytarabine administration & dosage, Dexamethasone administration & dosage, Doxorubicin administration & dosage, Etoposide administration & dosage, Female, Granulocyte Colony-Stimulating Factor administration & dosage, Humans, Ifosfamide administration & dosage, Lymphoma, B-Cell classification, Male, Methotrexate administration & dosage, Middle Aged, Neoplasm Staging, Prednisolone administration & dosage, Survival Analysis, Vincristine administration & dosage, Vindesine administration & dosage, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Burkitt Lymphoma drug therapy, Lymphoma, B-Cell drug therapy
- Abstract
The chemotherapy dose-intensity in two adapted German BFM paediatric protocols (BFM 90 and NHL 86) was compared in contemporaneously treated adults <50 years with Burkitt lymphoma and B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (collectively referred to as BL). In BFM 90, primary prophylaxis with Granulocyte-colony-stimulating factor was used, postinduction treatment was started at granulocytes > or =0.5 x 10(9)/L (> or =1.0 x 10(9)/L in NHL 86) with a higher mean methotrexate dose (2.9 g/m(2)/cycle, n = 23; 1.6 g/m(2)/cycle in NHL 86, n = 22, P < 0.001). Intervals between consecutive treatment-cycles were shorter in BFM 90 (P < 0.001) with no additional toxicity. However, the two-year failure-free survival with BFM 90 (82%) was similar to that achieved with NHL 86 (72%, P = 0.33). We conclude that BFM 90 enables safe intensification of therapy in young adults with BL compared to NHL 86, but registry-based studies are required to further evaluate the antineoplastic effects and cost-effectiveness of the two therapeutic approaches.
- Published
- 2010
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23. The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the International Prognostic Index (IPI) in predicting survival following intensive first-line immunochemotherapy and autologous stem cell transplantation (ASCT).
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Geisler CH, Kolstad A, Laurell A, Räty R, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Nilsson-Ehle H, Kuittinen O, Lauritzsen GF, Ralfkiaer E, Ehinger M, Sundström C, Delabie J, Karjalainen-Lindsberg ML, Brown P, and Elonen E
- Subjects
- Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, Ki-67 Antigen biosynthesis, Lymphoma, Mantle-Cell metabolism, Male, Risk Factors, Survival Rate, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Lymphoma, Mantle-Cell mortality, Lymphoma, Mantle-Cell therapy, Stem Cell Transplantation
- Abstract
Mantle cell lymphoma (MCL) has a heterogeneous clinical course. The recently proposed Mantle Cell Lymphoma International Prognostic Index (MIPI) predicted the survival of MCL better than the International Prognostic Index in MCL patients treated with conventional chemotherapy, but its validity in MCL treated with more intensive immunochemotherapy has been questioned. Applied here to 158 patients of the Nordic MCL2 trial of first-line intensive immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation, the MIPI and the simplified MIPI (s-MIPI) predicted survival significantly better (P < .001) than the International Prognostic Index (P > .004). Both the MIPI and the s-MIPI mainly identified 2 risk groups, low and intermediate versus high risk, with the more easily applied s-MIPI being just as powerful as the MIPI. The MIPI(B) (biological), incorporating Ki-67 expression, identified almost half of the patients as high risk. We suggest that also a simplified MIPI(B) is feasible.
- Published
- 2010
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24. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group.
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Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, and Elonen E
- Subjects
- Adult, Aged, Combined Modality Therapy, Disease-Free Survival, Female, Humans, Ki-67 Antigen, Male, Middle Aged, Multivariate Analysis, Time Factors, Treatment Outcome, Bone Marrow Purging, Immunotherapy, Lymphoma, Mantle-Cell drug therapy, Stem Cells cytology
- Abstract
Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R + high-dose cytarabine. Responders received high-dose chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL-1 trial, the event-free, overall, and progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680.
- Published
- 2008
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25. Mantle cell lymphoma with partial involvement of the mantle zone: an early infiltration pattern of mantle cell lymphoma?
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Bassarova A, Tierens A, Lauritzsen GF, Fosså A, and Delabie J
- Subjects
- Adult, Aged, Axilla, Cyclin D1 metabolism, Female, Humans, Male, Lymph Nodes pathology, Lymphoma, Mantle-Cell pathology
- Abstract
Most patients with mantle cell lymphoma present with a diffuse or nodular infiltration of the involved organs at diagnosis. We present two patients with a rare morphological variant, displaying a partial involvement of the mantle zone. Patient 1 presented with an enlarged inguinal lymph node, which showed marked follicular hyperplasia with singly spread Cyclin D1+ small lymphoid cells in the mantle zones. An additional lymph node biopsy taken 3 months later showed the same pattern. Patient 2 presented with a classical mantle cell lymphoma with lymph node, bone marrow and gastro-intestinal involvement. However, revision of an appendectomy specimen taken 4 years earlier showed pronounced follicular hyperplasia with singly spread Cyclin D1+ small lymphoid cells in the mantle zones. Mantle cell lymphoma with partial involvement of the mantle zone has rarely been reported and many represent an early manifestation of mantle cell lymphoma. Our cases also illustrate that the inclusion of an anti-cyclin D1 antibody in the diagnostic panel of antibodies to study unexplained follicular hyperplasia, might be advised.
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- 2008
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26. Clinical effect of buffy-coat vs. apheresis platelet concentrates in patients with severe thrombocytopenia after intensive chemotherapy.
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Akkök CA, Brinch L, Lauritzsen GF, Solheim BG, and Kjeldsen-Kragh J
- Subjects
- Adolescent, Adult, Anemia, Aplastic complications, Anemia, Aplastic drug therapy, Female, Humans, Male, Middle Aged, Neoplasms complications, Neoplasms drug therapy, Prospective Studies, Thrombocytopenia etiology, Time Factors, Blood Banks, Blood Preservation adverse effects, Platelet Transfusion, Plateletpheresis methods, Thrombocytopenia therapy
- Abstract
Background and Objectives: Therapeutic or prophylactic use of platelet concentrates (PC) is essential for patients with thrombocytopenia due to intensive chemotherapy for various malignancies. PC quality has been improved after introduction of storage containers that are more oxygen permeable than the second-generation PC containers. Consequently, shelf life of PCs at our blood bank has been extended to 6.5 days after monitoring each PC for bacterial contamination. In this prospective observational study, we compared apheresis PCs harvested by Amicus cell separator with buffy-coat (BC) PCs during storage for up to 6.5 days., Materials and Methods: All PCs were collected from healthy volunteer donors and were prepared for routine clinical use. A total of 446 transfusion episodes with 688 PCs for 77 adult patients with oncological and haematological diseases were registered during a 13-month period. Outcome measures were corrected count increment after 1 h (CCI-1), after 18-24 h (CCI-2), and transfusion intervals. Transfusions were carried out after storage from 1.5 to 6.5 days., Results: Both CCI and the transfusion intervals decreased statistically significantly by increasing storage time after transfusions with apheresis PCs or BC PCs. However, less than 4% of the variation in CCI and transfusion interval could be explained by platelet storage time. There were no significant differences between BC PCs and apheresis PCs, regarding CCI and transfusion intervals., Conclusion: We can conclude that BC PCs are not inferior to apheresis PCs, and may serve the clinical purposes as well as apheresis PCs harvested by Amicus.
- Published
- 2007
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27. Tobramycin once versus three times daily, given with penicillin G, to febrile neutropenic cancer patients in Norway: a prospective, randomized, multicentre trial.
- Author
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Torfoss D, Høiby EA, Tangen JM, Holte H, Bø K, Meyer P, Grøttum K, Weyde K, Lauritzsen GF, Sandstad B, Jacobsen AB, Olsen H, and Kvaløy S
- Subjects
- Adolescent, Adult, Aged, Anti-Bacterial Agents administration & dosage, Antineoplastic Agents adverse effects, Antineoplastic Agents therapeutic use, Drug Therapy, Combination, Female, Fever etiology, Humans, Male, Middle Aged, Neutropenia chemically induced, Norway, Penicillin G administration & dosage, Prospective Studies, Sample Size, Tobramycin administration & dosage, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Fever drug therapy, Neoplasms complications, Neutropenia complications, Penicillin G therapeutic use, Tobramycin therapeutic use
- Abstract
Objectives: Penicillin G with an aminoglycoside is the standard initial empirical treatment in febrile neutropenia in Norway. It has been argued that giving the aminoglycoside once daily to neutropenic patients with Gram-negative bacteraemia may be hazardous when penicillin G is the beta-lactam antibiotic. We questioned this argument and hypothesized that tobramycin once daily was as efficacious as three times daily., Methods: We conducted a randomized prospective multicentre study, comparing the efficacy of tobramycin 6 mg/kg once (arm A) versus three times (arm B) daily, plus penicillin G 5 million IU x 4, in febrile neutropenic cancer patients., Primary Outcome: modification of the antibiotic regimen., Results: One hundred and seventy-four patients were evaluable for intention-to-treat analyses. One hundred and fifty-five patients had lymphoma or leukaemia as the underlying cancer diagnosis. In arm A, 35 of 88 patients and in arm B, 34 of 86 patients, that is 40% in both arms had no modification of the antibiotic regimen. No patients died while participating in the study. Upon modification of the antibiotic regimen, all patients were successfully treated. The increase in serum creatinine was modest and similar in the two treatment groups., Conclusions: When administered with penicillin G, tobramycin given once daily was as efficacious and safe as tobramycin given three times daily in cancer patients with febrile neutropenia in Norway, provided the regimen was modified according to the clinical response.
- Published
- 2007
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28. Standard CHOP-21 as first line therapy for elderly patients with Hodgkin's lymphoma.
- Author
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Kolstad A, Nome O, Delabie J, Lauritzsen GF, Fossa A, and Holte H
- Subjects
- Aged, Aged, 80 and over, Cohort Studies, Cyclophosphamide therapeutic use, Disease-Free Survival, Doxorubicin therapeutic use, Female, Humans, Male, Middle Aged, Prednisone therapeutic use, Remission Induction, Survival Rate, Vincristine therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy
- Abstract
There is no consensus on the optimal chemotherapy regimen for Hodgkin's lymphoma patients > or = 60 years. We present our institution's results of 5 years, using CHOP-21 as standard for this patient group. Twenty-nine patients with a median age of 71 years (range, 60 - 91) were included in this cohort. Fifty-five percent had known co-morbidities. Stage I/IIA patients (38%) were treated with 2 - 4 cycles of CHOP followed by radiotherapy. Stage IIB - IV patients (62%) received 6 - 8 cycles of CHOP and for the majority (13/18 pts) no radiotherapy. Two treatment-related deaths occurred. Febrile neutropenia was the most common toxicity (31%). The complete response rate after CHOP +/- radiotherapy was 93%. With a median follow-up of 41 months, five patients have relapsed and four have died from Hodgkin's lymphoma. So far, no relapses have occurred after 2 years from the end of therapy. Overall survival and progression-free survival at 3 years were 79% and 76%, respectively. We conclude that CHOP-21 is a well-tolerated and effective treatment for elderly patients with Hodgkin's lymphoma.
- Published
- 2007
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29. Pneumocystis jirovecii pneumonia in B-cell lymphoma patients treated with the rituximab-CHOEP-14 regimen.
- Author
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Kolstad A, Holte H, Fosså A, Lauritzsen GF, Gaustad P, and Torfoss D
- Subjects
- Adult, Antibodies, Monoclonal, Murine-Derived, Bronchoalveolar Lavage Fluid, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Humans, Lymphoma, B-Cell drug therapy, Microscopy, Fluorescence, Middle Aged, Pneumonia, Pneumocystis drug therapy, Polymerase Chain Reaction, Prednisone administration & dosage, Rituximab, Vincristine administration & dosage, Antibodies, Monoclonal administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Lymphoma, B-Cell complications, Pneumocystis metabolism, Pneumonia, Pneumocystis complications
- Abstract
We report six cases of Pneumocystis jirovecii pneumonia (PCP) verified by immunoflourescence/polymerase chain reaction of bronchoalveolar fluid among 46 lymphoma patients (13%) who received rituximab-CHOEP-14 at our institution. PCP prophylaxis should be standard management for this group of patients and also considered for patients treated with rituximab-CHOP-14, CHOP-14 or CHOEP-14.
- Published
- 2007
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30. Peripheral T-cell lymphoma with involvement of the expanded mantle zone.
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Ikonomou IM, Tierens A, Troen G, Aamot HV, Heim S, Lauritzsen GF, Vålerhaugen H, and Delabie J
- Subjects
- Adult, Biomarkers, Tumor metabolism, CD4 Antigens metabolism, Combined Modality Therapy, DNA-Binding Proteins metabolism, Fatal Outcome, Female, Germinal Center pathology, Humans, Lymphoma, Mantle-Cell metabolism, Lymphoma, Mantle-Cell therapy, Lymphoma, T-Cell, Peripheral metabolism, Lymphoma, T-Cell, Peripheral therapy, Male, Middle Aged, Proto-Oncogene Proteins c-bcl-6, Remission Induction, Lymph Nodes pathology, Lymphoma, Mantle-Cell pathology, Lymphoma, T-Cell, Peripheral pathology
- Abstract
Peripheral T-cell lymphoma (PTCL) with a nodular architecture is rare. Recently, two variants have been described with infiltration of the B-cell follicle, one variant that localizes to the marginal zone with a so-called perifollicular growth pattern, and a variant that localizes to the germinal center. These lymphomas have a CD4+ phenotype and may express Bcl-6. We have studied five similar cases of PTCL with involvement of the B-cell follicle. However, our cases differ from the cases previously described by their predominant and frequently patchy involvement of the expanded mantle zone of the B-cell follicle at onset. Later biopsies in three of the cases show diffuse infiltration of the lymph node, without features of angioimmunoblastic TCL (AILT). All cases expressed Bcl-6 in addition to CD4. Cytogenetics was available in four of the cases but revealed no recurrent chromosomal aberrations or changes associated with other types of PTCL. No mutations of the BCL-6 gene were observed. Together, the cases seem to have an intermediately aggressive clinical behavior. Whether our cases are part of a spectrum of PTCLs that encompasses previously described variants with predominant marginal zone or germinal center infiltration or they represent a separate T-cell lymphoma type remains to be demonstrated by a study of more of such cases.
- Published
- 2006
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31. Treatment of Burkitt's/Burkitt-like lymphoma in adolescents and adults: a 20-year experience from the Norwegian Radium Hospital with the use of three successive regimens.
- Author
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Smeland S, Blystad AK, Kvaløy SO, Ikonomou IM, Delabie J, Kvalheim G, Hammerstrøm J, Lauritzsen GF, and Holte H
- Subjects
- Adolescent, Adult, Aged, Antibiotics, Antineoplastic administration & dosage, Burkitt Lymphoma mortality, Cancer Care Facilities statistics & numerical data, Doxorubicin administration & dosage, Female, Humans, Male, Methotrexate administration & dosage, Middle Aged, Neoplasm Staging, Norway, Retrospective Studies, Stem Cell Transplantation, Survival Analysis, Survival Rate, Transplantation, Autologous, Treatment Outcome, Antibiotics, Antineoplastic therapeutic use, Burkitt Lymphoma therapy, Doxorubicin therapeutic use, Methotrexate therapeutic use
- Abstract
Background: Burkitt's/Burkitt-like lymphoma (BL/BLL) are highly aggressive lymphomas mainly affecting children and young adults. We report the results in adolescent and adult patients with the use of three successive regimens., Patients and Methods: Forty-nine patients aged 15-70 years admitted to the Norwegian Radium Hospital in the period 1982-2001 with a diagnosis of BL/BLL on histological review and who were given chemotherapy with curative intent are included in this analysis. Up to 1987 patients were given doxorubicin-based chemotherapy supplemented with intravenous and intrathecal methotrexate (MmCHOP). From 1987 to 1994, patients who obtained complete remission upon this regimen were consolidated with high-dose therapy with stem-cell support (MmCHOP + HDT). In 1995 we introduced as frontline therapy the German Berlin-Frankfurt-Munster (BFM) regimen., Results: By intention to treat analyses, the progression-free survival rates for patients who received MmCHOP (n=13), MmCHOP + HDT (n=17) or BFM therapy (n=19) are 30.8%, 70.6% and 73.7%, respectively. In the groups of patients who received either the BFM regimen or MmCHOP + HDT, all patients who obtained complete remission upon induction therapy are continuously disease free. There was no treatment-related death., Conclusions: BL/BLL in adolescents and adults can successfully be treated with 5-day blocks of intensified chemotherapy such as the BFM regimen or CHOP/methotrexate-based chemotherapy consolidated with high-dose therapy. Using the BFM regimen, continuous remissions are obtained without additional myeloablative chemotherapy.
- Published
- 2004
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32. Clonal deletion of thymocytes as a tumor escape mechanism.
- Author
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Lauritzsen GF, Hofgaard PO, Schenck K, and Bogen B
- Subjects
- Animals, Apoptosis physiology, Clone Cells, Dendritic Cells immunology, Immune Tolerance, Lymphocyte Activation immunology, Mice, Mice, Inbred BALB C, Mice, Transgenic, Multiple Myeloma pathology, Myeloma Proteins metabolism, Plasmacytoma immunology, Plasmacytoma pathology, Receptors, Antigen, T-Cell immunology, Thymus Gland cytology, Tumor Cells, Cultured, CD4-Positive T-Lymphocytes immunology, Multiple Myeloma immunology, Tumor Escape immunology
- Abstract
Clonal deletion of thymocytes is a major event in T-cell tolerance and might represent a tumor escape mechanism. Previously, we have shown that class II-restricted, Id-specific, CD4+ T cells in T-cell receptor (TCR)-transgenic mice confer resistance against the MOPC315 plasmacytoma. In this report, we have investigated whether monoclonal immunoglobulin (Ig) produced by a plasmacytoma can induce deletion of thymocytes specific for the variable parts of Ig, i.e., the idiotype (Id). Large numbers of MOPC315 tumor cells were injected s.c. in the TCR-transgenic mice to overwhelm the CD4+ T-cell-mediated protection. When the MOPC315 plasmacytomas reached a weight of approximately 0.5 g (serum myeloma protein M315 about 50 microg/ml), immature CD4+ 8+ and mature CD4+ transgenic thymocytes became progressively deleted. Apoptotic thymocytes were already detectable when tumors were 2 mm in diameter (serum M315: 5 microg/ml, or 0.03 microM). The negative selection was Id-specific, because an Id-negative plasmacytoma failed to induce deletion. Injection of purified MOPC315-myeloma protein (M315) i.p. caused a profound reduction of Id-specific thymocytes. Enriched thymic dendritic cells (DC) from tumor-bearing animals were found to be primed with lambda2(315) and induced apoptosis of thymocytes in vitro. Our results indicate that circulating myeloma protein is processed and presented by thymic antigen-presenting cells (APC), and induces deletion of Id-specific thymocytes. Deletion of tumor-specific thymocytes may represent a tumor escape mechanism in patients with cancers that secrete or shed tumor antigens. The possibility that vaccination with tumor Ig or genes encoding for it may induce tolerance instead of protection should be taken into consideration.
- Published
- 1998
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33. Naive CD4+ T cells confer idiotype-specific tumor resistance in the absence of antibodies.
- Author
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Bogen B, Munthe L, Sollien A, Hofgaard P, Omholt H, Dagnaes F, Dembic Z, and Lauritzsen GF
- Subjects
- Animals, CD8-Positive T-Lymphocytes immunology, Female, Gene Rearrangement, B-Lymphocyte genetics, Gene Rearrangement, T-Lymphocyte genetics, Immunoglobulins blood, Immunoglobulins genetics, Immunotherapy, Adoptive methods, Lymphoid Tissue immunology, Male, Mice, Mice, Inbred BALB C, Mice, SCID, Mice, Transgenic, Neoplasms, Experimental prevention & control, Receptors, Antigen, T-Cell genetics, Antibodies, Anti-Idiotypic immunology, CD4-Positive T-Lymphocytes immunology, Neoplasm Transplantation immunology, Neoplasms, Experimental immunology
- Abstract
CD4+ T cells can recognize a processed idiotypic peptide derived from the mouse lambda 2(315) immunoglobulin light chain. The idiotypic peptide is presented on the I-E(d) class II major histocompatibility complex molecule. Mice made transgenic for a lambda 2(315)-specific alpha beta T cell receptor have been demonstrated to be specifically resistant against a tumor challenge with the MOPC315 (alpha,lambda 2(315)) plasmacytoma (Lauritzsen, G. F., Weiss, S., Dembic, Z. and Bogen, B., Proc. Natl. Acad. Sci. USA 1994, 91: 5700). That study, however, did not rule out a role of either anti-Id antibodies or T cells expressing nontransgenic specificities due to expression of endogenous T cell receptor (TcR) alpha chains. Also, the role of different T cell subsets in protection was unclear. To remove these ambiguities, we have now made the transgenic mice homozygous for the scid mutation, known to inhibit both Ig and TcR gene rearrangements. Such transgenic SCID mice lack B cells and antibodies while they still have plenty of CD4+ and CD4-8- cells expressing the transgenic alpha beta T cell receptor. The number of CD8+ T cell is dramatically reduced. Even so, transgenic SCID mice are protected against a challenge with MOPC315 plasmacytoma cells. Therefore, B cells, as well as novel T cell receptor specificities created by rearrangements of endogenous alpha-chain genes, are both dispensable for effective immunosurveillance in our system. Surprisingly, we found that transgenic CD8+ and CD4-8- cells are idiotype-specific and I-E(d) restricted. However, these T cell subsets are not required for resistance because adoptive transfer experiments demonstrated that highly purified transgenic SCID CD4+ cells suffice for tumor protection.
- Published
- 1995
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34. Naive idiotype-specific CD4+ T cells and immunosurveillance of B-cell tumors.
- Author
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Lauritzsen GF, Weiss S, Dembic Z, and Bogen B
- Subjects
- Animals, B-Lymphocytes immunology, Cytokines metabolism, Dose-Response Relationship, Immunologic, Immunization, Passive, Immunoglobulin lambda-Chains immunology, Lymph Nodes immunology, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, SCID, Mice, Transgenic, CD4-Positive T-Lymphocytes immunology, Immunoglobulin Idiotypes immunology, Lymphoma, B-Cell immunology, Monitoring, Immunologic, Plasmacytoma immunology, Receptors, Antigen, T-Cell, alpha-beta immunology
- Abstract
The immunosurveillance hypothesis suggests that lymphocytes can recognize tumor-specific antigens expressed by transformed cells and initiate their elimination. Immunosurveillance implies that lymphocytes of naive phenotype can home to a tumor site and become activated by tumor-specific antigens. In this study, we have employed T-cell receptor transgenic mice as a source of naive, tumor-specific T cells. The transgenic, CD4+ T cells recognize a 91- to 101-residue fragment of the lambda 2(315) immunoglobulin light chain presented by I-Ed class II molecules. Such naive, idiotype-specific, CD4+ T cells protected against tumor development of a class II negative plasmacytoma (MOPC315) and a class II positive B lymphoma (F9), which both secrete lambda 2(315) immunoglobulin. Adoptive transfer experiments demonstrated that 2 x 10(6) lymph node cells were sufficient for protection against MOPC315. Depletion of T-cell subsets indicated that transgenic CD4+ cells were indispensable for tumor resistance. However, an additional role of CD8+ T cells is not ruled out. In contrast to the resistance against the secreting MOPC315 and F9 cells, transgenic mice were not protected against B lymphoma cells (F67), which do not secrete lambda 2(315) but express a truncated lambda 2(315) chain intracellularly. The results suggest that lambda 2(315) is processed and presented by host antigen-presenting cells, which in turn activate naive, idiotype-specific T cells.
- Published
- 1994
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35. The role of idiotype-specific, CD4+ T cells in tumor resistance against major histocompatibility complex class II molecule negative plasmacytoma cells.
- Author
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Lauritzsen GF and Bogen B
- Subjects
- Animals, Lymphocyte Activation immunology, Lymphoma, B-Cell immunology, Male, Mice, Mice, Inbred BALB C, Tumor Cells, Cultured, Antigen-Presenting Cells immunology, CD4-Positive T-Lymphocytes immunology, Histocompatibility Antigens Class II immunology, Immunoglobulin Idiotypes immunology, Plasmacytoma immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
It is known that immunoglobulins can be processed and that idiotypic peptides are presented on MHC class II molecules to T cells. It has also been demonstrated that T cells can recognize a complex of an Id-peptide/MHC molecule as a tumor-specific antigen on B lymphoma cells. However, plasmacytomas, an important type of B cell malignancies, most often lack class II molecules and are thus expected to be poor targets for Id-specific, CD4+ T cells. Nevertheless, we now demonstrate that cloned, MHC class II restricted T cells, specific for a lambda 2(315) idiotypic peptide, convey protection in vivo (Winn assay) against the class II molecule-negative MOPC315 (alpha, lambda 2(315)) plasmacytoma. T cells can also inhibit the growth of MOPC315 cells in vitro provided that MHC compatible (H-2d) splenocytes and extra lambda 2(315) are added. Based on these data we suggest that the myeloma protein secreted by MOPC315 cells attains such a high local concentration in vivo that it is processed and presented by neighboring host APC to the Id-specific T cells. Such activated T cells secrete lymphokines which may directly affect the growth of MOPC315 cells in the vicinity. Alternatively, lymphokines from activated T cells stimulate local host cells, like macrophages, to become tumoricidal.
- Published
- 1993
- Full Text
- View/download PDF
36. Anti-tumour activity of idiotype-specific, MHC-restricted Th1 and Th2 clones in vitro and in vivo.
- Author
-
Lauritzsen GF, Weiss S, and Bogen B
- Subjects
- Animals, Clone Cells, Lymphocyte Activation, Lymphokines pharmacology, Male, Mice, Mice, Inbred BALB C, Histocompatibility Antigens Class II immunology, Immunoglobulin Idiotypes immunology, Lymphoma, B-Cell immunology, T-Lymphocytes, Helper-Inducer immunology
- Abstract
Idiotypes (Id) can serve as individual markers on B cells; therefore, cytotoxic Id-specific T cells may play a significant role in immunological surveillance of Id+ B-cell tumours. We have investigated the anti-tumour activity of CD4+ BALB/c Th1 and Th2 clones which recognize a processed Id of the syngeneic lambda 2(315) L chain in the context of the class II MHC molecule I-Ed. Id-specific T cells and A20/46 B lymphoma cells transfected with the lambda 2(315) gene were injected s.c. into the same site of BALB/c mice (Winn assay). The results show that both Th1 and Th2 clones can protect against tumour development. The protection was Id-specific because T cells did not influence tumour development by an A20/46 B lymphoma cell line transfected with the pSV2neo expression vector alone. In vitro studies showed that the Th1 clones were cytotoxic to lambda 2(315)-transfected B lymphoma cells; by contrast, the Th2 clone was not cytotoxic in 51Cr-release assay even though the Th2 cells inhibited the growth of lambda 2(315) B lymphoma cells. The anti-lymphoma properties of both the Th1 and Th2 clones appear to involve as yet undefined cytotoxic and growth inhibiting molecules.
- Published
- 1993
- Full Text
- View/download PDF
37. Idiotype-specific, major histocompatibility complex restricted T cells are of both Th1 and Th2 type.
- Author
-
Lauritzsen GF and Bogen B
- Subjects
- Animals, Antigens, Differentiation, T-Lymphocyte immunology, CD3 Complex, Clone Cells, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Lymphocyte Activation, Lymphokines biosynthesis, Mice, Mice, Inbred BALB C, Receptors, Antigen, T-Cell immunology, CD4-Positive T-Lymphocytes immunology, Immunoglobulin Idiotypes immunology, Major Histocompatibility Complex immunology, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Helper-Inducer immunology
- Abstract
The lymphokine secretion patterns of seven independent 91-101.lambda 2(315)/I-Ed specific, CD4+ T-cell clones have been investigated. Six of the clones are of the Th1 type as they secrete IL2 and IFN gamma, but not IL4. Some of these six Th1 clones produce TNF alpha/beta, and some produce minor amounts of IL5 and IL6. One clone is of the Th2 type as it produces IL4, IL5, and large amounts of IL6, but not IL2, IFN gamma or TNF. The Th1/Th2 classification does not have any stringent relationship to immunization protocol, fine specificity and V alpha/V beta gene segment utilization. The immunoregulatory significance of our findings for Id/MHC-dependent T-B cell interaction is discussed.
- Published
- 1991
- Full Text
- View/download PDF
38. A stimulatory monoclonal antibody detecting T cell receptor diversity among idiotype-specific, major histocompatibility complex-restricted T cell clones.
- Author
-
Bogen B, Lauritzsen GF, and Weiss S
- Subjects
- Animals, Antibodies, Monoclonal biosynthesis, Antibody Specificity, Clone Cells, Epitopes immunology, Genetic Variation, Interferon-gamma metabolism, Interleukin-2 metabolism, Interleukin-3 metabolism, Lymphocyte Activation immunology, Mice, Mice, Inbred BALB C, Receptors, Antigen, T-Cell genetics, Antibodies, Monoclonal immunology, Histocompatibility Antigens immunology, Receptors, Antigen, T-Cell immunology, T-Lymphocytes immunology
- Abstract
A panel of independent BALB/c T cell clones responding to a peptide of the lambda 2(315) immunoglobulin light chain (residues 91-101), in the context of I-Ed, has previously been described. A monoclonal antibody (mAb; GB113) to the T cell receptor (TcR) of one of the clones, 4B2A1 (V alpha 1, J alpha 19; V beta 8.2, D beta 1.1, J beta 1.2) precipitates the alpha/beta heterodimer from 4B2A1. However, GB113 does not bind DO11-10.2 cells bearing a similar alpha/beta heterodimer (V alpha 1.1, J alpha TT11; V beta 8.2, D beta 1.1, J beta 1.1). GB113 does not cross-react with the TcR of the six other clones in the panel. Furthermore, the mAb does not bind polyclonal lambda 2(315)-specific T cell lines except 4.4% of cells of line 4 from which 4B2A1 was cloned. The mAb only binds a negligible number (0.5%) of BALB/c thymocytes and peripheral T cells. Therefore, the epitope detected by GB113 is very rarely expressed on 91-101. lambda 2(315)-specific TcR or on TcR of normal T cells. Soluble GB113 induces T cell activation [measured as proliferation and interleukin (IL) 2, IL3 and interferon-gamma production]. GB113-induced T cell activation is enhanced by soluble anti-CD4 and anti-Thy-1 mAb.
- Published
- 1990
- Full Text
- View/download PDF
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