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2. |
- Brattström, L, et al.
(author)
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Pyridoxine reduces cholesterol and low-density lipoprotein and increases antithrombin III activity in 80-year-old men with low plasma pyridoxal 5-phosphate
- 1990
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 50:8, s. 873-877
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Journal article (peer-reviewed)abstract
- We have previously observed that pyridoxine treatment reduced plasma total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol concentrations and increased antithrombin III (AT III) activity in atherosclerotic patients with subnormal plasma pyridoxal 5-phosphate (PLP) levels. In order to confirm these results, we selected 17 males with low plasma PLP levels from a group of 122 80-year-old males in whom PLP has been determined. After supplementation with 120 mg of pyridoxine per day for 8 weeks their mean plasma TC and LDL cholesterol concentrations were decreased by 10% (p less than 0.01) and 17% (p less than 0.001), respectively. There was no effect on high-density lipoprotein cholesterol and triglycerides but plasma AT III activity was increased by 6% (p less than 0.05). The mechanism by which pyridoxine acts is unclear but it is hypothesized that pyridoxine-derived PLP may enhance the catabolism of LDL and the activity of AT III by inhibiting their glycosylation.
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3. |
- Ekström, Ulf, et al.
(author)
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An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F)
- 1999
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In: Clinical Genetics. - : Wiley. - 0009-9163. ; 55:5, s. 332-339
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Journal article (peer-reviewed)abstract
- Familial hypercholesterolemia (FH) is caused by a defect in the function of the low density lipoprotein (LDL) receptor and inherited in an autosomal, codominant way. In this study we present a 13-year-old girl, compound heterozygote for the LDL receptor mutations C240F and Y167X. Fibroblasts from the patient showed very low cholesterol esterification rate, LDL uptake, and degradation compared to normal fibroblasts (< 2%, 8%, and < 2%, respectively). The C240F mutant was expressed in LDL receptor deficient CHOMldlA7 cells. Analysis of cell extracts by immunoblotting demonstrated delayed processing of the mutated LDL receptor, which was accumulated as a precursor protein of normal size. A high molecular weight form of the receptor was also detectable in these cells, which probably reflects cross-linking through the unpaired cysteine residue in the binding domain. Cells expressing the C240F mutant protein were unable to mediate uptake and degradation of LDL. The two siblings of the index case also carried the C240F mutation, but surprisingly one of them (a 17-year-old brother) showed no signs of hypercholesterolemia. This observation is consistent with the view that there may be cholesterol lowering mechanisms that can be activated, perhaps by mutations in known or hitherto unknown genes.
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4. |
- Elmståhl, Sölve, et al.
(author)
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Body composition and dietary habits in 80-year-old smoking men without cardiovascular disease
- 1991
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In: Aging (Milan, Italy). - 0394-9532. ; 3:3, s. 77-269
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Journal article (peer-reviewed)abstract
- Eighty-year-old male residents in the community of Malmö were questioned about smoking habits and the occurrence of cardiovascular disease (CVD). Of 1,280 subjects, 122 were selected for further studies and allocated into 4 groups: 1) no CVD, non-smokers; 2) no CVD, smokers; 3) CVD, smokers; and 4) CVD, non-smokers. The smokers had consumed on the average 13 g of tobacco daily for 59 years. Lean body mass (LBM), body fat (BF), % body fat (%BF), and total body water (TBW) were estimated by means of bioelectrical impedance analysis. The mean body weight (BW), LBM, and %BF for all subjects were 74.1 +/- 10.2 kg, 58.0 +/- 6.8 kg, and 21.3 +/- 5.9 kg, respectively. There were no significant differences between all subjects with and without CVD. A lower BW among smokers than in non-smokers was explained by lower BF and %BF in the former. Smokers who had lived predominantly in rural areas had lower BW (6.9 kg) and LBM (5.2 kg) than those from an urban area. A positive correlation was noted between the degree of physical activity and LBM and TBW. Seventeen percent of the smokers exercised regularly. The CVD group had higher plasma cholesterol concentrations than the non-CVD group. Plasma triglycerides showed a positive correlation with BF, %BF and BW, whereas HDL cholesterol was negatively correlated with BF, %BF and BW. It is concluded that smoking is one of several important factors related to body composition, and the penetrance of this factor is still apparent in elderly men.
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8. |
- Nilsson, A, et al.
(author)
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Transient hypertriglyceridemia of infancy
- 1996
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In: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 85:12, s. 1508-1510
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Journal article (peer-reviewed)abstract
- A premature boy who had suffered from IRDS, bronchopulmonary dysplasia and retinopathy of prematurity developed massive hypertriglyceridemia (48.1 mmol/L) together with moderate hypercholesterolemia (12.6 mmol/L) at 5 months of age. Lipoprotein electrophoresis revealed a marked elevation of the level of the very low density lipoprotein fraction. There was a moderate decrease in the activity of a lipolytic enzyme, lipoprotein lipase (LPL). The child had neither liver or renal disorder nor any inflammatory disease. The hyperlipidemia disappeared spontaneously at the age of 3 years. The cause of the decreased LPL activity could not be established. A partial genetic deficiency in lipoprotein lipase appears the most likely explanation, since no signs of secondary lowering of LPL activity could be found.
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10. |
- Nilsson, Peter, et al.
(author)
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Effects of smoking cessation on insulin and cardiovascular risk factors--a controlled study of 4 months' duration
- 1996
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In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 240:4, s. 189-194
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To investigate the effects on serum lipids, plasma fibrinogen, plasma insulin, plasma C-peptide and blood glucose, of smoking cessation after 4 months. To develop a group-based smoking intervention programme in primary health care. SETTING: Twenty health centres in primary health care in southern Sweden. SUBJECTS: Four hundred habitual smokers (> 10 cigarettes per day-1, > 10 years), recruited by advertisement in local papers. INTERVENTION: The smokers were randomized, after stratification for age and sex, to one intervention group (n = 200) and one control group (n = 200). The intervention group was offered supportive group sessions and free nicotine supplementation (patches, chewing gum). MAIN OUTCOME MEASURES: All participants were investigated at the start and after 4 months (medical history, physical examination, laboratory evaluation). Blood samples were drawn for determination of glucose, insulin and C-peptide, both in the fasting state and during an oral glucose tolerance test (OGTT), and for measurement of lipoproteins, fibrinogen, nicotine and cotinine. RESULTS: In the intervention group 98 of the subjects (48%) had quit smoking after 4 months. They were compared with the 156 subjects in the control group (91%) who were still daily smokers during the whole period. There were no significant differences in any variable between the two (total) experimental groups at baseline. Plasma nicotine and cotinine decreased (P < 0.001) in the intervention group following smoking cessation, and weight increased by 2.7 kg. In the intervention group HDL-cholesterol increased by 11% (P < 0.001), whereas HbA1c increased by 2% (P < 0.05) only in the control group. No changes occurred in levels of glucose, insulin, C-peptide and fibrinogen. CONCLUSION: The smoking cessation programme had a success rate of almost 50% over 4 months. Smoking cessation was associated with a marked increase in HDL-cholesterol levels but did not affect glucose tolerance. A concomitant weight increase may have blunted any independent beneficial effect of smoking cessation on glucose metabolism.
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11. |
- Abrahamsson, Anna, et al.
(author)
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Real world data on primary treatment for mantle cell lymphoma: a Nordic Lymphoma Group observational study.
- 2014
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 124:8, s. 1288-1295
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Journal article (peer-reviewed)abstract
- There is consensus that young patients with mantle cell lymphoma (MCL) should receive intensive immunochemotherapy regimens, but optimal treatment of elderly patients as well for as patients with limited or indolent disease is not defined. Our aim was to evaluate and compare outcome in relation to prognostic factors and first-line treatment in patients with MCL in a population-based data set. Data were collected from the Swedish and Danish Lymphoma Registries from the period of 2000-2011. A total of 1389 patients were diagnosed with MCL. During this period, age-standardized incidence MCL increased, most prominently among males. Furthermore, male gender was associated with inferior overall survival (OS) in multivariate analysis (HR 1.36; p=0.002). Forty-three (3.6%) patients with stage I-II disease received radiotherapy with curative intent, showing a 3 year OS of 93%. Twenty-nine (2.4%) patients followed a watch-and-wait approach and showed a 3 year OS of 79.8%. Among patients receiving systemic treatment, rituximab (n=766; HR 0.66; p=0.001) and autologous stem cell transplant (ASCT) (n=273; HR 0.55; p=0.004) were independently associated with improved overall survival in multivariate analysis. Hence, by a population-based approach, we were able to provide novel data on prognostic factors and primary treatment of MCL, applicable to routine clinical practice.
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12. |
- Andersen, Niels S., et al.
(author)
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Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma
- 2009
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In: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 27:26, s. 4365-4370
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Journal article (peer-reviewed)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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14. |
- Asp, N G, et al.
(author)
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Wheat bran increases high-density-lipoprotein cholesterol in the rat
- 1981
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In: British Journal of Nutrition. - 0007-1145. ; 46:3, s. 93-385
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Journal article (peer-reviewed)abstract
- 1. Five groups of male Sprague Dawley rats were given for 6 months a diet with high protein and fat contents but a very low dietary fibre content (group B), and this diet mixed with (g/kg) 50 low-methoxyl pectin (group L), 50 high-methoxyl pectin (group H), 50 guar gum (group G) and 200 wheat bran (group WB, corresponding to 100 wheat fibre) respectively. 2. The weight increment was significantly lower in group G than in the other groups. Assuming no energy value of the dietary fibre, the weight increment (/kJ) was the same in groups B, L and H, lower in group G and higher in group WB, indicating that a proportion of the bran fibre might in fact be available as a source of energy. 3. Wheat bran increased total plasma cholesterol and high-density-lipoprotein cholesterol after 6, 12 and 26 weeks. Group G had significantly lowered plasma cholesterol after 12 weeks. Pectin on the other hand did not significantly influence total or HDL-cholesterol levels. It is therefore possible that the plasma cholesterol lowering effect of pectin previously demonstrated in the rat is dependent on the presence of significant amounts of dietary cholesterol as our diets did not contain added cholesterol. Plasma triglycerides decreased with age but were similar in all groups.
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15. |
- Ekbom, Tord, et al.
(author)
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Decrease in high density lipoprotein cholesterol during prolonged storage. CELL Study Group
- 1996
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 56:2, s. 97-101
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Journal article (peer-reviewed)abstract
- Different studies on the stability of high density lipoprotein cholesterol (HDL) in frozen serum or plasma have yielded conflicting results, namely increase, decrease, or no change at all during prolonged storage under freezing conditions. As part of a major trial on lipid-lowering strategies we statistically demonstrated a time-related decrease in HDL cholesterol during storage up to 46 months at -20 degrees C. We therefore re-analysed 85 frozen samples that had been analysed fresh and then stored from 26 to 46 months, using the dextran sulphate 500/Mg2+ method. A linear regression analysis of change in HDL cholesterol on time was performed. The slope was significantly negative (p < 0.0005). The regression equation was (decrease in HDL) = 0.05 - 0.008 x (time in months), i.e. after 6 months' storage at -20 degrees C there was almost a 1% decrease in the HDL cholesterol concentration per month of storage.
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16. |
- Ekelund, Mats, et al.
(author)
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Effects of total parenteral nutrition on lipid metabolism in rats
- 1994
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In: JPEN. - : Wiley. - 0148-6071. ; 18:6, s. 503-509
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Journal article (peer-reviewed)abstract
- BACKGROUND: The pathophysiologic mechanisms behind the development of liver steatosis during total parenteral nutrition (TPN) and the possible relationship to alterations of lipoprotein lipase activities in different tissues are not fully known. It is also unknown whether continuous and discontinuous administration of TPN affect lipid metabolism differently. METHODS: TPN, including 8.4 g of triglycerides per kilogram per day, was given for 10 days to two groups of male Sprague-Dawley rats that received the infusions discontinuously and continuously, respectively. Freely fed rats were used as controls. RESULTS: TPN led to hyperlipidemia and accumulation of triglycerides in the liver. High-density lipoproteins were enriched in triglycerides, whereas high-density lipoprotein cholesterol and phospholipid levels were low. The activities of hepatic lipase were markedly decreased, and lipoprotein lipase activities in adipose tissue and in cardiac muscle were both up-regulated. The increased levels of cholesterol and phospholipids in the serum of TPN animals were more pronounced after discontinuous administration. CONCLUSIONS: TPN including lipids interferes with the normal regulation of lipid metabolism. Although the mechanisms remain obscure, the elevation of lipoprotein lipase activities seems functionally important to accommodate the increased input of triglycerides during TPN. Possibly, the observed alterations in lipase activities may be attributed to a state of hypothyroidism.
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17. |
- Eskelund, Christian W., et al.
(author)
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15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2) : prolonged remissions without survival plateau
- 2016
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 175:3, s. 410-418
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Journal article (peer-reviewed)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.
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18. |
- Eskelund, Christian Winther, et al.
(author)
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Detailed Long-Term Follow-Up of Patients Who Relapsed After the Nordic Mantle Cell Lymphoma Trials : MCL2 and MCL3
- 2021
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In: HemaSphere. - : Wolters Kluwer. - 2572-9241. ; 5:1
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Journal article (peer-reviewed)abstract
- Mantle cell lymphoma (MCL) is an incurable disease with a highly variable clinical course. The prognosis after relapse is generally poor, and no standard of care exists. We investigated the postrelapse outcomes of 149 patients who were initially treated in the Nordic Lymphoma Group trials, MCL2 or MCL3, both representing intensive cytarabine-containing frontline regimens including autologous stem cell transplant. Patients with progression of disease before 24 months (POD24, n = 51, 34%) displayed a median overall survival of 6.6 months compared with 46 months for patients with later POD (n = 98, 66%; P < 0.001). MCL international prognostic index, cell proliferation marker, blastoid morphology, and TP53 mutations showed independent prognostic value irrespective of POD24, and in a combined, exploratory risk score, patients with 0, 1, 2-3, or 4-5 high-risk markers, respectively, displayed a 5-year overall survival of 62%, 39%, 31%, and 0%. By a comparison of median progression-free survival of the different salvage therapies in the relapse setting, bendamustine-rituximab was superior to all other combination chemotherapy regimens; however, it was also associated with longer responses to last line of therapy. Collectively, we confirm the prognostic impact of POD24 and highlight the relevance of other biomarkers, and we emphasize the importance of novel therapies for patients with high-risk features at first POD.
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19. |
- Fagher, B, et al.
(author)
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L-carnitine and haemodialysis: double blind study on muscle function and metabolism and peripheral nerve function
- 1985
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - 1502-7686. ; 45:2, s. 169-178
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Journal article (peer-reviewed)abstract
- Twenty-eight haemodialysis patients were randomized to L-carnitine, 2 g i.v. three times a week, and saline over a 6-week period. No obvious deficiency of carnitine was found in vastus lateralis with a median value of 12.9 mmol/kg dry weight; range 6.2-21.4. Female patients had lower total plasma carnitine compared to female controls, p less than 0.002, whereas no decrease was found in males. No relationship was found between muscle and total plasma carnitine. After carnitine administration the muscle carnitine level increased about 60%, p less than 0.01, and the total plasma carnitine level more than tenfold, whereas the initially high degree of acylation decreased, p less than 0.02. Maximum dynamic muscular strength was reduced with a mean value of 44% compared with healthy controls. Total metabolic activity of isolated skeletal muscle fibres, measured as heat production with a new technique using a perfusion microcalorimeter, showed a median value of 0.40 mW/g, 25% lower than normal, p less than 0.02. Carnitine administration had no effect on several different tests of muscular function. Neurophysiologically, discrete improvements in the temperature responses were recorded, but no changes in sensory and motor nerve conduction velocities or in vibration thresholds were noted. No symptomatic improvement was observed even in patients with the lowest carnitine levels prior to treatment. Our data do not support the hypothesis that carnitine deficiency contributes to muscle and nerve dysfunction in patients on chronic haemodialysis.
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20. |
- Geisler, Christian H., et al.
(author)
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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
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 112:7, s. 2687-93
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Journal article (peer-reviewed)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.
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21. |
- Geisler, Christian H., et al.
(author)
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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
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 158:3, s. 355-362
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Journal article (peer-reviewed)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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22. |
- Geisler, Christian H., et al.
(author)
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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)
- 2010
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:8, s. 1530-1533
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Journal article (peer-reviewed)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.
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