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2.
  • Almung, Magnus, et al. (författare)
  • I solitärens skugga : Nyttobyggnadens kreativa restaurering
  • 2015
  • Rapport (populärvet., debatt m.m.)abstract
    • Ekonomibyggnader har alltid behövts för de huvudbyggnader som finns inom våra bevarade kulturmiljöer. Några nyttobyggnader uppskattas och används fortfarande, andra betraktas som problematiska överloppsbyggnader, många rivs. Alltför få har dokumenterats eller fått sin historia klarlagd vilket undanhållit viktig kunskap om samhällets framväxt. Vi vill synliggöra och betona vikten av att bevara och utveckla hela bebyggelsemiljöer, ofta med ett antal hus utöver huvudbyggnaden och tillhörande yttre miljö i staden eller på landet. Denna rapport visar kursdeltagarnas projektarbeten om nyttobyggnader. De har dokumenterat med traditionella och nya arbetsmetoder, inventerat och intervjuat, läst och besökt arkiv, värderat, analyserat och därefter föreslagit hur man ska ta hand om och utveckla nyttobyggnaderna i sina kulturmiljöer.
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3.
  • Grabowski, Pawel, 1975-, et al. (författare)
  • Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status
  • 2005
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 105:12, s. 4807-4812
  • Tidskriftsartikel (refereegranskat)abstract
    • B-cell chronic lymphocytic leukemia (CLL) consists of 2 prognostic entities where cases with mutated immunoglobulin VH genes have better outcome than unmutated cases. VH-mutated CLLs display longer telomeres compared with unmutated cases and telomere length has been indicated to predict outcome, although the prognostic value of telomere length has not been fully established in CLL. We analyzed telomere length, VH gene mutation status, and clinical parameters in a large series of CLL. Telomere length was assessed by quantitative polymerase chain reaction (PCR), giving a very good correlation to telomere length estimated by Southern blotting (P < .001). The prognostic information given by mutation status (n = 282) and telomere length (n = 246) was significant (P < .001, respectively). Telomere length was a prognostic factor for stage A (P = .021) and stage B/C (P = .018) patients, whereas mutation status predicted outcome only in stage A patients (P < .001). Furthermore, mutated CLLs were subdivided by telomere length into 2 groups with different prognoses (P = .003), a subdivision not seen for unmutated cases (P = .232). Interestingly, the VH-mutated group with short telomeres had an overall survival close to that of the unmutated cases. Thus, by combining VH mutation status and telomere length, an improved subclassification of CLL was achieved identifying previously unrecognized patient groups with different outcomes.
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  • Hess, Georg, et al. (författare)
  • Phase III Study to Evaluate Temsirolimus Compared With Investigator's Choice Therapy for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
  • 2009
  • Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 27:23, s. 3822-3829
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, has shown clinical activity in mantle cell lymphoma (MCL). We evaluated two dose regimens of temsirolimus in comparison with investigator's choice single-agent therapy in relapsed or refractory disease. Patients and Methods In this multicenter, open-label, phase III study, 162 patients with relapsed or refractory MCL were randomly assigned (1: 1: 1) to receive one of two temsirolimus regimens: 175 mg weekly for 3 weeks followed by either 75 mg (175/75-mg) or 25 mg (175/25-mg) weekly, or investigator's choice therapy from prospectively approved options. The primary end point was progression-free survival (PFS) by independent assessment. Results Median PFS was 4.8, 3.4, and 1.9 months for the temsirolimus 175/75-mg, 175/25-mg, and investigator's choice groups, respectively. Patients treated with temsirolimus 175/75-mg had significantly longer PFS than those treated with investigator's choice therapy (P = .0009; hazard ratio = 0.44); those treated with temsirolimus 175/25-mg showed a trend toward longer PFS (P = .0618; hazard ratio = 0.65). Objective response rate was significantly higher in the 175/75-mg group (22%) compared with the investigator's choice group (2%; P = .0019). Median overall survival for the temsirolimus 175/75-mg group and the investigator's choice group was 12.8 months and 9.7 months, respectively (P = .3519). The most frequent grade 3 or 4 adverse events in the temsirolimus groups were thrombocytopenia, anemia, neutropenia, and asthenia. Conclusion Temsirolimus 175 mg weekly for 3 weeks followed by 75 mg weekly significantly improved PFS and objective response rate compared with investigator's choice therapy in patients with relapsed or refractory MCL.
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  • Laurell, Anna, et al. (författare)
  • Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma
  • 2017
  • Ingår i: Journal for Immunotherapy of Cancer. - : BMJ. - 2051-1426. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Accumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors. This concept doesn't require MHC-compatibility between injected cells and the patient and therefore introduces the possibility of using pre-produced and freeze-stored DCs from healthy blood donors as an off-the-shelf immune enhancer. The use of MHC-incompatible allogeneic DCs will further induce a local rejection process at the injection site that is expected to further enhance recruitment and maturation of endogenous bystander DCs. Methods: Twelve intermediate and poor risk patients with newly diagnosed metastatic renal cell carcinoma (mRCC) where included in a phase I/II study. Pro-inflammatory allogeneic DCs were produced from a leukapheresis product collected from one healthy blood donor and subsequently deep-frozen. A dose of 5-20 x 106 DCs (INTUVAX) was injected into the renal tumor twice with 2 weeks interval before planned nephrectomy and subsequent standard of care. Results: No INTUVAX-related severe adverse events were observed. A massive infiltration of CD8+ T cells was found in 5 out of 12 removed kidney tumors. No objective tumor response was observed and 6 out of 11 evaluable patients have subsequently received additional treatment with standard tyrosine kinase inhibitors (TKI). Three of these 6 patients experienced an objective tumor response including one sunitinib-treated patient who responded with a complete and durable regression of 4 brain metastases. Median overall survival (mOS) is still not reached (currently 42.5 months) but has already passed historical mOS in patients with unfavourable risk mRCC on standard TKI therapy. Conclusions: Our findings indicate that intratumoral administration of proinflammatory allogeneic DCs induces an antitumor immune response that may prolong survival in unfavourable risk mRCC-patients given subsequent standard of care. A randomized, multi-center, phase II mRCC trial (MERECA) with INTUVAX in conjuction with sunitinib has been initiated.
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  • Tobin, Gerard, et al. (författare)
  • Patients with chronic lymphocytic leukemia with mutated VH genes presenting with Binet stage B or C form a subgroup with a poor outcome
  • 2005
  • Ingår i: Haematologica. - 0390-6078 .- 1592-8721. ; 90:4, s. 465-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Objectives. The immunoglobulin VH gene mutation status is a strong prognostic indicator in B-cell chronic lymphocytic leukemia (CLL), since unmutated VH genes are correlated with short survival. However, the traditional cut-off level dividing mutated and unmutated cases, i.e. more or less than 2% mutations, has been questioned and other cut-offs have been suggested. We investigated whether an alternative cut-off should be applied and the relation of mutational status to another prognostic marker, Binet staging. Design and Methods. VH gene mutation status was assessed in 332 CLL cases by polymerase chain reaction amplification and nucleotide sequencing and was further correlated with overall survival using different VH mutation cut-offs (1-7%) and Binet stage. Results. After testing different mutation borders, the 2% cut-off remained the best discriminative level for determining prognosis. Interestingly, prognostic stratification was improved by combining the information on VH gene mutation status with that of Binet stage: unmutated cases (all stages, n=151, mutated cases with stage A (n=77), and mutated cases with stage B or C (n=37) had a median survival of 82, 179 and 74 months, respectively. Interpretation and Conclusions. CLL cases displaying mutated VH genes with Binet stage B or C had a survival similar to that of unmutated cases and significantly shorter than that of mutated stage A CLL. Our result reveals clinical heterogeneity within the VH mutated CLL group by inclusion of Binet stage data, a finding which is of importance when considering surrogate marker(s) for VH mutation status. ©2005 Ferrata Storti Foundation.
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  • Walsh, Sarah H, et al. (författare)
  • Telomere length and correlation with histopathogenesis in B-cell leukemias/lymphomas
  • 2007
  • Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 78:4, s. 283-289
  • Tidskriftsartikel (refereegranskat)abstract
    • Telomere length was recently reported to correlate with cellular origin of B-cell malignancies in relation to the germinal center (GC). In this report, we measured telomere length by quantitative-PCR in 223 B-cell lymphomas/leukemias and correlated results with immunoglobulin (Ig) mutation status and immunostainings for GC/non-GC subtypes of diffuse large B-cell lymphoma (DLBCL). Shortest telomeres were found in Ig-unmutated chronic lymphocytic leukemia (CLL) [median telomere to single copy gene value (T/S) 0.33], differing significantly to Ig-mutated CLL (0.63). Contrary to this, mantle cell lymphomas (MCLs) exhibited similar telomere lengths regardless of Ig mutation status (0.47). Telomere length differed significantly between GC-like (0.73) and non-GC-like DLBCLs (0.43), and follicular lymphomas (FLs) had shorter telomeres (0.53) than GC-DLBCL. Hairy cell leukemias, which display Ig gene intraclonal heterogeneity, had longer telomeres (0.62) than FLs and non-GC-DLBCL, but shorter than GC-DLBCL. We conclude that although DLBCL and CLL subsets can be clearly distinguished, telomere length reflects many parameters and may not simply correlate with GC-related origin.
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  • Adde, Magdalena, 1960- (författare)
  • Aggressive B-cell Lymphomas : Studies of Treatment, FDG-PET Evaluation and Prognostic Factors
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • To improve outcome in young, high-risk lymphoma patients, treatment was intensified, adding etoposide and rituximab to standard CHOP treatment. Granulocyte-colony stimulating factor (G-CSF) enabled treatment bi-weekly. Results were promising: overall (OS) and event-free survival (EFS) 79% and 60% respectively, median follow up 27 months. Single infusion Ara-C, contrary to expectations, did not prevent relapse in CNS. DLBCL were classified as germinal center (GC) or non-GC derived, using immunohistochemical markers, CD10, BCL6 and MUM1. We investigated the outcome for both phenotypes after adding rituximab to chemotherapy. For 106 patients treated with CHOP alone, the GC phenotype displayed significantly better OS and EFS. In contrast, GC phenotype did not predict outcome in 95 patients treated with immunochemotherapy . Thus, addition of rituximab seems to eliminate the prognostic value of immunohistochemically defined GC phenotypes in DLBCL. To improve evaluation and find non-responders, mid-treatment FDG-PET CT was incorporated into clinical routine for patients with high-risk aggressive lymphoma. For those with positive PET, biopsy followed by treatment intensification was recommended. Twenty-five patients were examined, five with positive PET. Two of these had lymphoma in the biopsy. Two had a negative biopsy, and one had a false positive investigation. Seven patients had increased uptake of uncertain significance. Two patients with uncertain PET, and two with negative PET have relapsed, giving a negative predictive value of 85%. In case of relapse of aggressive lymphoma or if not obtaining CR, high dose chemotherapy with autologous stem cell support (HDT) is standard treatment. HDT outcome for 38 patients with transformed follicular lymphoma was compared to outcome for 79 patients with de novo B-cell lymphoma. At median follow-up of 11.5 years both OS and EFS were superior in the transformed group, OS 67% and 33%, EFS 55% and 27% respectively. Treatment related mortality was less than reported in other studies.
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  • Adde, Magdalena, 1960-, et al. (författare)
  • Little usefullness of mid-treatment FDG-PET and biopsy for treatment intensification in patients with aggressive lymphoma
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose: To evaluate the experiences of introducing mid-treatment FDG-PET in patients with aggressive lymphoma, in a population based program with decentralized examinations, with emphasis on finding patients who would benefit from dose-escalation. Patients and Methods: Twenty-five patients with aggressive lymphoma were included. Twenty-four (95%) of these having an aggressive B-cell lymphoma (84% diffuse large B-cell lymphoma) were treated with CHOP-like treatment given at two week intervals + rituximab. One patient having an anaplastic T-cell lymphoma was treated with CHOEP-14. Mid-treatment FDG-PET was performed and assessed as positive, uncertain or negative for remaining lymphoma. The intention was to perform a biopsy in those with a positive FDG-PET, and, to change to a platina-containing therapy and consolidate with high-dose therapy if viable lymphoma was found. Retrospective review of the PET investigations was done. Living patients were followed for a median of 22 months. Results: At primary analysis five patients (20%) had positive uptake on FDG-PET. Two of them had biopsy-proven viable tumor but did not complete the planned salvage treatment, one due to chemotherapy toxicity and one due to progressive disease during salvage therapy. Two patients had a negative biopsy and one patient had no biopsy due to technical difficulties at diagnosis. These three patients remain in remission after standard treatment. Out of seven patients (28%) having “uncertain” uptake two relapsed. Thirteen patients (52%) were negative,two of whom relapsed giving a negative predictive value of 85%. Conclusion: Mid-treatment FDG PET-CT in order to find patients with biopsy-proven aggressive lymphoma, who can be salvaged with dose escalation, was not feasible in clinical routine.
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  • Adde, Magdalena, et al. (författare)
  • Superior outcome in transformed follicular lymphoma compared to de novo aggressive B-cell lymphoma treated with high-dose therapy and autologous stem-cell support
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose: To assess the outcome of high–dose therapy with autologous stem cell support (HDT) in patients with transformed follicular lymphoma compared to patients with de novo aggressive B-cell lymphoma, in a retrospective analysis of patients treated at two Swedish university hospitals. Patients and Methods: 117 patients, mean age 48 years (21-65), 79 with de novo aggressive B-cell lymphoma and 38 with transformed follicular lymphoma, were treated with high-dose-therapy (HDT) as consolidation. Thirteen patients with transformed follicular lymphoma had been treated with a single alkylating agent and 25 were chemonaive at transformation. After transformation, nine patients had HDT as part of first line aggressive therapy, and a further eight failed to obtain CR and had HDT upfront. Twenty-one patients received more than one treatment regimen before HDT. In the de novo aggressive lymphoma group five patients with high risk criteria, and 16 patients who failed to obtain CR, received HDT upfront (CR1), Fifty-eight patients received more than one regimen before HDT because of relapse. Rituximab was given as a single dose to five patients for in vivo purging of the stem cell graft. Results: With a median follow up of 11.5 years (8-20), event free survival (EFS) and overall survival (OS) were 35% and 44% respectively. When comparing the two groups, the ten- year EFS rates were 27% in the de novo group and 55% in the transformed group and the ten-year OS was 33 % and 67% respectively. Treatment related mortality was acceptable with 4% early and 3.5% late mortality. In a multivariate analysis, “transformed vs de novo aggressive” histopathology was the only factor significantly related to outcome. Conclusion: Both EFS and OS were much better in patients with transformed follicular lymphoma compared to patients with de novo aggressive B-cell lymphoma Although the introduction of rituximab certainly has improved the outcome in both groups, HDT should still be considered as a salvage strategy not only in cases of de novo aggressive B-cell lymphoma and especially in transformed follicular lymphoma relapsing after first line treatment..
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  • Albertsson-Lindblad, Alexandra, et al. (författare)
  • Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma
  • 2016
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:14, s. 1814-1820
  • Tidskriftsartikel (refereegranskat)abstract
    • For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter, open-label phase 1/2 trial, we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment for elderly patients with MCL. Patients >65 years with untreated MCL, stages II-IV were eligible for inclusion. Primary end points were maximally tolerable dose (MTD) of LEN and progression-free survival (PFS). Patients received 6 cycles every four weeks of L-B-R (L D1-14, B 90 mg/m(2) IV, days 1-2 and R 375 mg/m(2) IV, day 1) followed by single LEN (days 1-21, every four weeks, cycles 7-13). Fifty-one patients (median age 71 years) were enrolled from 2009 to 2013. In phase 1, the MTD of LEN was defined as 10 mg in cycles 2 through 6, and omitted in cycle 1. After 6 cycles, the complete remission rate (CRR) was 64%, and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3-year overall survival was 73%. Infection was the most common nonhematologic grade 3 to 5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in 3 patients: 2 Pneumocystis carinii pneumonia and 1 cytomegalovirus retinitis. Second primary malignancies (SPM) were observed in 8 patients (16%). LEN could safely be combined with R-B when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs, which may limit its use. This trial is registered at www.Clinicaltrials.gov as #NCT00963534.
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  • Albertsson-Lindblad, Alexandra, et al. (författare)
  • Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years, the Nordic Lymphoma Group phase I+II trial NLG-MCL4
  • 2016
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 128:14, s. 1814-1820
  • Tidskriftsartikel (refereegranskat)abstract
    • For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years with untreated MCL, stage II-IV were eligible for inclusion. Primary endpoints were maximally tolerable dose (MTD) of LEN, and progression-free survival (PFS). Patients received six cycles q4w of L-B-R (L D1-14, B 90 mg/m(2) iv D1-2 and R 375 mg/m(2) iv D1) followed by single LEN (D1-21, q4w, cycles 7-13). 51 patients (median age 71 years) were enrolled 2009-2013. In phase I, the MTD of LEN was defined as 10 mg in cycles 2-6, and omitted in cycle 1. After six cycles, the complete remission rate (CRR) was 64% and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3 year overall survival was 73%. Infection was the most common non-hematological grade 3-5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in three patients; 2 PCP and 1 CMV retinitis. Second primary malignancies (SPM) were observed in eight patients (16%). LEN could safely be combined with R-B, when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs which may limit its use. http://clinicaltrials.gov: NCT00963534.
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20.
  • Andersen, Niels S., et al. (författare)
  • Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma
  • 2009
  • Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 27:26, s. 4365-4370
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT). Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks. Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR. Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.
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  • Andersson, Johanna, 1990-, et al. (författare)
  • Depressive symptoms, functional impairment, and health-related quality of life in idiopathic normal pressure hydrocephalus : a population-based study
  • 2024
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:Maximising quality of life is a central goal for all healthcare, especially when dealing with dementing disorders. In this study we aimed to compare health-related quality of life (HRQoL), depressive symptoms and functional impairment between individuals with and without idiopathic normal pressure hydrocephalus (iNPH) from the general population.Methods: A total of 122 individuals, 30 with iNPH (median age 75 years, 67 females) underwent neurological examinations and computed tomography of the brain with standardised rating of imaging findings and clinical symptoms. The participants completed the Geriatric Depression Scale (GDS-15) and the HRQoL instrument EQ5D-5L. In addition, the modified Rankin Scale (mRS) was used to evaluate functional impairment.Results: Compared with participants without iNPH, those with iNPH reported a higher score on GDS-15 (median 3 vs 1) and mRS (median 2 vs 1) (p < 0.05). Further, those with iNPH rated lower on EQ5D-5L (index 0.79, VAS 70) than those without iNPH (index 0.86, VAS 80) (p < 0.05). In logistic regression models, low HRQoL was associated with more depressive symptoms, a higher degree of iNPH symptoms, and lower functional status.Conclusions: In this population-based sample, those with iNPH had more depressive symptoms, lower functional status, and worse quality of life compared to those without iNPH. The strongest association with low HRQoL was found for depressive symptoms, functional level, and degree of iNPH symptoms. These results underline the value of shunt surgery because of its potential to reduce symptoms and disability in iNPH and therefore improve HRQoL.
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24.
  • Berglund, Torkel, et al. (författare)
  • Nicotinamide; antioxidative and DNA hypomethylation effects in plant cells
  • 2017
  • Ingår i: Plant physiology and biochemistry (Paris). - : Elsevier. - 0981-9428 .- 1873-2690. ; 118, s. 551-560
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of nicotinamide (NIC) and its natural plant metabolites nicotinic acid (NIA) and trigonelline (TRIG) were studied with respect to defense in plant cell cultures. NIC and NIA could protect against oxidative stress damage caused by 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH), which generates free radicals. Damage was analyzed as DNA strand breaks in cell cultures of Pisum sativum (garden pea), Daucus carota (carrot), Populus tremula L. × P. tremuloides (hybrid aspen) and Catharanthus roseus (Madagascar periwinkle), monitored by single cell gel electrophoresis (comet assay), and assays of cell leakage in C. roseus. The activities of aconitase and fumarase enzymes, which have key roles in energy metabolism, were analyzed in P. sativum cultures after treatment with NIC or NIA. Aconitase activity was increased by NIA, and fumarase activity was increased by both compounds. These compounds were shown to promote glutathione metabolism in P. sativum cultures, and NIC was shown to have a global DNA hypomethylating effect. Neither TRIG nor poly(ADP-ribose) polymerase (PARP) inhibitor 3-aminobenzamide offered any protection against DNA damage or cell leakage, nor did they promote aconitase or fumarase activities, or glutathione metabolism. By this broad approach addressing multiple biochemical factors and different plant species, we demonstrate that NIC and NIA protect plant cells from oxidative stress, and that NIC clearly exerts an epigenetic effect; decreased DNA methylation. This indicates that these compounds have important roles in the regulation of metabolism in plant cells, especially in connection to stress.
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26.
  • Bergström, Lisa, et al. (författare)
  • One-Year Incidence, Time Trends, and Predictors of Recurrent Ischemic Stroke in Sweden From 1998 to 2010 An Observational Study
  • 2017
  • Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 48:8, s. 2046-2051
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: Recent data on the incidence, time trends, and predictors of recurrent ischemic stroke are limited for unselected patient populations.Methods: Data for ischemic stroke patients were obtained from The Swedish Stroke Register (Riksstroke) between 1998 and 2009 and merged with The Swedish National Inpatient Register. A reference group of patients was created by Statistics Sweden. The ischemic stroke patient cohort was divided into 4 time periods. Recurrent ischemic stroke within 1 year was recorded until 2010. Kaplan-Meier and Cox regression analyses were performed to study time trends and predictors of ischemic stroke recurrence.Results: Of 196 765 patients with ischemic stroke, 11.3% had a recurrent ischemic stroke within 1 year. The Kaplan-Meier estimates of the 1-year cumulative incidence of recurrent ischemic stroke decreased from 15.0% in 1998 to 2001 to 12.0% in 2007 to 2010 in the stroke patient cohort while the cumulative incidence of ischemic stroke decreased from 0.7% to 0.4% in the reference population. Age > 75 years, prior ischemic stroke or myocardial infarction, atrial fibrillation without warfarin treatment, diabetes mellitus, and treatment with beta-blockers or diuretics were associated with a higher risk while warfarin treatment for atrial fibrillation, lipid-lowering medication, and antithrombotic treatment (acetylsalicylic acid, dipyridamole) were associated with a reduced risk of recurrent ischemic stroke.Conclusions: The risk of recurrent ischemic stroke decreased from 1998 to 2010. Well-known risk factors for stroke were associated with a higher risk of ischemic stroke recurrence; whereas, secondary preventive medication was associated with a reduced risk, emphasizing the importance of secondary preventive treatment.
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28.
  • Buckley, Patrick G., et al. (författare)
  • Genome-wide microarray-based comparative genomic hybridization analysis of lymphoplasmacytic lymphomas reveals heterogeneous aberrations
  • 2009
  • Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 50:9, s. 1528-34
  • Tidskriftsartikel (refereegranskat)abstract
    • Lymphoplasmacytic lymphoma (LPL) is not a sharply delineated lymphoma entity, either morphologically, phenotypically, or clinically. The diagnosis is often made by excluding other small cell lymphomas with plasmacytic differentiation, thus a genetic diagnostic marker would be of great benefit. Conventional cytogenetic techniques have previously demonstrated a deletion of 6q in a proportion of cases, varying from 7 to 55%. In this report, we apply array-based comparative genomic hybridization on 11 LPL samples. Genomic aberrations were detected in 9 of 11 cases, and included gains and losses. In general, the number of genetic aberrations was relatively low (two to three abnormalities per case). Recurrent aberrations detected were deletion of 6q (two cases), deletion of chromosome 17 (two cases), gain of 3q (two cases), and gain of chromosome 7 (two cases). This report not only confirms the reported loss of 6q in a proportion of cases but also highlights the genetic heterogeneity of LPL, in accordance with the known immunophenotypical, morphological, and clinical diversity of the disease.
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29.
  • Canalias, Carlota, et al. (författare)
  • High-resolution domain imaging on the nonpolar y-face of periodically poled KTiOPO4 by means of atomic force microscopy
  • 2003
  • Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 83:4, s. 734-736
  • Tidskriftsartikel (refereegranskat)abstract
    • The inverse piezoelectric effect is used to produce high-resolution images of ferroelectric domains in periodically poled KTiOPO4 crystals on their nonpolar y-face using atomic force microscopy. We demonstrate that the technique is convenient for studying the nucleation and growth of domains in a periodically poled KTiOPO4 sample.
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30.
  • Einarsson, Sandra, 1981-, et al. (författare)
  • Mapping the impact of malnutrition as defined by the Global Leadership Initiative on Malnutrition and nutrition impact symptoms on the possibility of returning to work after treatment for head and neck cancer
  • 2024
  • Ingår i: Supportive Care in Cancer. - : Springer. - 0941-4355 .- 1433-7339. ; 32
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: This study aimed to investigate whether malnutrition or nutrition impact symptoms (NIS) affect the possibility of returning to work after treatment for head and neck cancer.Methods: Patients of working age with head and neck cancer were followed up from treatment initiation to 3 months (n = 238), 1 year (n = 182), and 2 years (n = 130) after treatment completion. The observed decrease in the number of patients over time was due to retirement, lack of follow-up, or death. Returning to work was dichotomised as yes or no. Malnutrition was diagnosed 7 weeks after treatment initiation using the Global Leadership Initiative on Malnutrition (GLIM) criteria. This time-point corresponds to the end of chemoradiotherapy or radiotherapy (with or without prior surgery), except for patients who underwent exclusive surgery. NIS were scored on a Likert scale (1-5) at each follow-up using the Head and Neck Patient Symptom Checklist (c) (HNSC (c)). Nonparametric tests were used to analyse the ability of patients with/without malnutrition and high/low NIS scores to return to work.Results: At 3 months, 1 year, and 2 years after treatment completion, 135/238 (56.7%), 49/182 (26.9%), and 23/130 (17.7%) patients had not returned to work. Patients with malnutrition at 7 weeks after treatment initiation were more likely to not return to work at 3 months than those without malnutrition, 70.5% compared to 47.1% (p < 0.001). At all three follow-up time-points, patients reporting high scores for a number of NIS had more often not returned to work, with this pattern being most distinct at 2 years.Conclusion: Malnutrition according to the GLIM criteria at 7 weeks after treatment initiation and NIS assessed by the HNSC (c) at subsequent follow-ups were predictors of the return-to-work process after treatment for up to 2 years.
  •  
31.
  • Eskelund, Christian W., et al. (författare)
  • 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2) : prolonged remissions without survival plateau
  • 2016
  • Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 175:3, s. 410-418
  • Tidskriftsartikel (refereegranskat)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 114years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 127 and 85years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.
  •  
32.
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33.
  • Farnebo, Jacob, et al. (författare)
  • Volumetric FDG-PET predicts overall and progression- free survival after 14 days of targeted therapy in metastatic renal cell carcinoma
  • 2014
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14, s. 408-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To determine whether changes in the metabolism of metastatic renal cell carcinoma (mRCC) assessed by F18-FDG-PET after 14 and 28 days of treatment with tyrosine kinase inhibitors can predict overall and progression-free patient survival. Methods: Thirty-nine consecutive patients with mRCC were included prospectively and underwent PET examinations prior to and after 14 and 28 days of standard treatment with sunitinib (n = 18), sorafenib (n = 19) or pazopanib (n = 2). The PET response was analyzed in terms of SUVmax, SULpeak, and total lesion glycolysis and a positive response (defined as a 30% reduction) compared to overall and progression-free survival. Results: Thirty-five patients with at least one metabolically active metastatic lesion prior to treatment underwent additional FDG-PET examinations after 14 (n = 32) and/or 28 days (n = 30) of treatment. Changes in either SULpeak or total lesion glycolysis were correlated to both progression-free and overall survival (for TLG2.5 responders, HR = 0.38 (95% CI: 0.18-0.83) and 0.22 (95% CI: 0.09-0.53), and for TLG50 responders, HR = 0.25 (0.10-0.62) and 0.25 (95% CI: 0.11-0.57) and for SULpeak responders, HR = 0.39 (95% CI: 0.17-0.91) and 0.38 (95% CI: 0.15-0.93), respectively). In contrast SUVmax response did not predict progression-free or overall survival (HR = 0.43 (95% CI: 0.18-1.01) and 0.50 (95% CI: 0.21-1.19), respectively). Conclusions: Assessment of early changes in SULpeak and total lesion glycolysis undergoing treatment with tyrosine kinase inhibitors by FDG-PET can possibly predict progression-free and overall survival in patients with mRCC.
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34.
  • Fathali, Anna, 1981, et al. (författare)
  • Hydrothermal Aging-Induced Changes in Washcoats of Commercial Three-Way Catalysts
  • 2013
  • Ingår i: Topics in Catalysis. - : Springer Science and Business Media LLC. - 1572-9028 .- 1022-5528. ; 56:1-8, s. 323-328
  • Konferensbidrag (refereegranskat)abstract
    • In order to quantify hydrothermal aging effects on the mono- and bi-metallic Pd and Rh supported on cerium-zirconium promoted alumina commercial three-way catalysts (TWCs), the catalysts were tested both fresh and after accelerated hydrothermal aging. The catalytic tests showed clear deactivation of the aged samples and influence on TWC's property, such as: light-off temperature, specific surface area (BET), dispersion of noble metals, oxygen storage capacity, oxygen storage capacity complete and labile oxygen storage capacity. Water inhibition have been investigated and confirmed for the performance of NOx reduction of the fresh catalyst. X-ray photoelectron spectroscopy was used to study changes in the oxidation state of the Pd and Rh present in the washcoat of the catalyst, before and after hydrothermal aging. Element maps by SEM-EDX analysis was perform in order to characterize the catalysts morphology, the surface's composition and element distribution.
  •  
35.
  • Flordal Thelander, Emma, et al. (författare)
  • Detailed assessment of copy number alterations revealing homozygous deletions in 1p and 13q in mantle cell lymphoma
  • 2007
  • Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 31:9, s. 1219-1230
  • Tidskriftsartikel (refereegranskat)abstract
    • Mantle cell lymphoma (MCL) is characterized by over-expression of cyclin Dl as a result of the characteristic t(11;14)(q13;q32). However, this translocation alone has proven not to be sufficient for lymphomagenesis, suggesting the involvement of additional alterations. We have characterized 35 cases of MCL by array comparative genomic hybridization with an average resolution of 0.97Mb distributed over the complete human genome. The most common alterations were losses in 1p13.2–p31.1, 6q16.2–q27, 8p21.3, 9p13.2–p24.3, 9q13–q31.3, 11q14.3–q23.3, 13q14.13–q21.31, 13q33.1–q34, and 22q11.23–q13.33 and gains involving 3q21.2–q29, 7p12.1–p22.3, 8q24.13–q24.23, and 18q21.33–q22.3. Four homozygous deletions were identified in totally three patients; two overlapping at 1p32.3, and two adjacent at 13q32.3. The homozygous deletions at 1p32.3 cover the CDKN2C locus (coding for p18), while the region at 13q32.3 does not encompass any known tumor suppressor genes. A gain in 3q was significantly associated with shorter survival (P=0.047).
  •  
36.
  • Fragemann, Anna, et al. (författare)
  • Broadband nondegenerate optical parametric amplification in the mid infrared with periodically poled KTiOPO4
  • 2005
  • Ingår i: Optics Letters. - 0146-9592 .- 1539-4794. ; 30:17, s. 2296-2298
  • Tidskriftsartikel (refereegranskat)abstract
    • We theoretically and experimentally demonstrate that the bandwidth in a nondegenerate optical parametric amplifier can be substantially increased by noncollinear interaction in a quasi-phase-matched single-periodicity structure. Broadband amplification of signals between 1540 and 1720 nm was realized in periodically poled KTiOPO4. The achieved signal bandwidth of 6.9 THz at 1680 nm is large enough to accommodate sub-100 fs optical pulses.
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37.
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38.
  •  
39.
  • Fragemann, Anna, et al. (författare)
  • Frequency converters from visible to mid-infrared with periodically poled RbTiOPO4
  • 2003
  • Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 83:15, s. 3090-3092
  • Tidskriftsartikel (refereegranskat)abstract
    • Electric-field poling has been used to fabricate quasi-phase-matched frequency converters in RbTiOPO4. A more accurate Sellmeier equation has been obtained for wavelengths between 0.43 and 3.4 mum. The dispersion of the thermo-optic coefficient for n(z) refractive index has been derived in the near- to mid-infrared spectral region. The nonlinear performance of periodically poled RbTiOPO4 obtained in the infrared optical parametric devices is comparable to that of periodically poled KTiOPO4.
  •  
40.
  • Fragemann, Anna, et al. (författare)
  • High-peak power nanosecond optical parametric amplifier with periodically poled KTP
  • 2003
  • Ingår i: Optics Express. - 1094-4087. ; 11:11, s. 1297-1302
  • Tidskriftsartikel (refereegranskat)abstract
    • A two-stage optical parametric amplifier generating 5 ns 208 kW peak power pulses in the spectral region at 1.535 mum in a diffraction-limited beam was realized in a single periodically poled KTP crystal. The maximum small-signal gain for the two stages reached 75dB and the total conversion efficiency was 30%. An analysis of the small-signal gain dependence on the M-2 of the pump beam is presented for the collinear and noncollinear OPA. Efficient spectral broadening of the signal was demonstrated in short pieces of single-mode telecommunication fiber.
  •  
41.
  • Fragemann, Anna, et al. (författare)
  • Optical parametric amplification of a gain-switched picosecond laser diode
  • 2005
  • Ingår i: Optics Express. - 1094-4087. ; 13:17, s. 6482-6489
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical parametric amplification, employing periodically poled KTiOPO4 as the gain medium, was used to amplify radiation emitted by a gain-switched laser diode. The pulses, which had durations between 20 ps and 2 ns, were amplified with up to 50 dB in a double stage set-up and reached pulse energies of 1 and 23 mu J, respectively.
  •  
42.
  • Fragemann, Anna, et al. (författare)
  • Optical parametric amplification of a picosecond pulsed laser diode at 975 nm
  • 2005
  • Ingår i: Conference on Lasers and Electro-Optics Europe. - 0780389743 - 9780780389748
  • Konferensbidrag (refereegranskat)abstract
    • Optical parametric amplification, employing periodically poled KTiOPO 4 as the gain medium, was used to amplify picosecond pulses at 975 nm emitted by a laser diode. A gain of 35 dB was achieved.
  •  
43.
  • Fragemann, Anna (författare)
  • Optical parametric amplification with periodically poled KTiOPO4
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis explores the use of engineered nonlinear crystals from the KTiOPO4 (KTP) family as the gain material in optical parametric amplifiers (OPAs), with the aim to achieve more knowledge about the benefits and limitations of these devices. The work aims further at extending the possible applications of OPAs by constructing and investigating several efficient and well performing amplifiers. An OPA consists of a strong pump source, which transfers its energy to a weak seed beam while propagating through a nonlinear crystal. The crystals employed in this work are members of the KTP family, which are attractive due to their large nonlinear coefficients, high resistance to damage and wide transparency range. The flexibility of OPAs with respect to different wavelength regions and pulse regimes was examined by employing various dissimilar seed and pump sources. The possibility to adapt an OPA to a specific pump and seed wavelength and achieve efficient energy conversion between the beams, originates from quasi-phasematching, which is achieved in periodically poled (PP) nonlinear crystals. Quasi-phasematched samples can be obtained by changing the position of certain atoms in a ferroelectric crystal and thereby reversing the spontaneous polarisation. In this thesis several material properties of PP crystals from the KTP family were examined. The wavelength and temperature dispersion of the refractive index were determined for PP RbTiOPO4, which is essential for future use of this material. Another experiment helped to increase the insight into the volumes close to domain walls in PP crystals Further, several OPAs were built and their ability to efficiently amplify the seed beam without changing its spectral or spatial properties was studied. Small signal gains of up to 55 dB and conversion efficiencies of more than 35 % were achieved for single pass arrangements employing 8 mm long PPKTP crystals. Apart from constructing three setups, which generated powerful nanosecond, picosecond and femtosecond pulses, the possibility to amplify broadband signals was investigated. An increase of the OPA bandwidth by a factor of approximately three was achieved in a noncollinear configuration.
  •  
44.
  • Fragemann, Anna, et al. (författare)
  • Second-order nonlinearities in the domain walls of periodically poled KTiOPO4
  • 2004
  • Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 85:3, s. 375-377
  • Tidskriftsartikel (refereegranskat)abstract
    • The domain wall regions in periodically poled KTiOPO4 crystals were examined and found to give rise to phasematched second harmonic generation in the Cerenkov directions. This phenomenon is caused by the nonlinear coefficients d(11) and d(12), which are not present in single domain regions, but are nonzero at and close to domain walls. The appearance of these nonlinearities is attributed to strain, produced by the domain inversion process and results in the creation of a dc piezoelectric field.
  •  
45.
  •  
46.
  •  
47.
  • Fransson, Linda, et al. (författare)
  • Minor Enantiomer Recycling-Effect of Two Reinforcing Catalysts on Product Yield and Enantiomeric Excess
  • 2010
  • Ingår i: ChemCatChem. - : Wiley. - 1867-3880 .- 1867-3899. ; 2:6, s. 683-693
  • Tidskriftsartikel (refereegranskat)abstract
    • Kinetic modeling of a recycling procedure in which the minor product enantiomer from an enantioselective catalytic reaction is selectively retransformed to starting material by a second chiral catalyst demonstrates that the enantiomeric excess of the product is not affected by the relative amounts of the two catalysts, but that the yield increases when the amount of the catalyst for the product-forming reaction is increased. The yield, but not the enantiomeric excess, is also affected by the initial substrate concentration. The recycling process is compared to sequential processes in which either the second catalyst is added after completion of the first reaction or in which the two catalysts are added simultaneously. In the sequential processes, high enantioselectivity can be obtained at the expense of product yield, whereas under recycling conditions both high enantiomeric excess and high yield can be achieved. Experimental data from a recycling procedure providing qualitative support for results from kinetic modeling are presented.
  •  
48.
  • Frisk, Sofia, et al. (författare)
  • Early activating somatic PIK3CA mutations promote ectopic muscle development and upper limb overgrowth
  • 2019
  • Ingår i: Clinical Genetics. - : WILEY. - 0009-9163 .- 1399-0004. ; 96:2, s. 118-125
  • Tidskriftsartikel (refereegranskat)abstract
    • PIK3CA-related overgrowth spectrum is a group of rare genetic disorders with asymmetric overgrowth caused by somatic mosaic PIK3CA mutations. Here, we report clinical data and molecular findings from two patients with congenital muscular upper limb overgrowth and aberrant anatomy. During debulking surgery, numerous ectopic muscles were found in the upper limbs of the patients. DNA sequencing, followed by digital polymerase chain reaction, was performed on DNA extracted from biopsies from hypertrophic ectopic muscles and identified the somatic mosaic PIK3CA hotspot mutations c.3140A > G, p.(His1047Arg) and c.1624G > A, p.(Glu542Lys) in a male (patient 1) and a female (patient 2) patient, respectively. Patient 1 had four ectopic muscles and unilateral isolated muscular overgrowth while patient 2 had 13 ectopic muscles and bilateral isolated muscular overgrowth of both upper limbs, indicating that her mutation occurred at early pre-somitic mesoderm state. The finding of PIK3CA mutations in ectopic muscles highlights the importance of PIK3CA in cell fate in early human embryonic development. Moreover, our findings provide evidence that the disease phenotype depends on the timing of PIK3CA mutagenesis during embryogenesis and confirm the diagnostic entity PIK3CA-related muscular overgrowth with ectopic accessory muscles.
  •  
49.
  • Geisler, Christian H., et al. (författare)
  • 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
  • 2008
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 112:7, s. 2687-93
  • Tidskriftsartikel (refereegranskat)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.
  •  
50.
  • Geisler, Christian H., et al. (författare)
  • Nordic MCL2 trial update : six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC plus autologous stem-cell support: still very long survival but late relapses do occur
  • 2012
  • Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 158:3, s. 355-362
  • Tidskriftsartikel (refereegranskat)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.
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