| 1. |
- Nilsson-Ehle, Herman, et al.
(författare)
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Quality of life, physical function and MRI T2*in elderly low-risk MDS patients treated to a haemoglobin level of andgt;= 120 g/L with darbepoetin alfa +/- filgrastim or erythrocyte transfusions
- 2011
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Ingår i: European Journal of Haematology. - : John Wiley and Sons. - 0902-4441 .- 1600-0609. ; 87:3, s. 244-252
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin +/- granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of andgt; 120 g /L. Methods: Thirty-six elderly patients with low-and intermediate-1 risk MDS received darbepoetin (DA) 300 mu g/wk, with the addition of G-CSF if no response. If the Hb target was reached at 16 wk, treatment was maintained until week 26. Remaining patients were transfused to reach the target level for at least 8 wk. Results: Twenty-seven patients completed the study. Response rate to DA +/- G-CSF was 67% in evaluable patients and 56% according to intention to treat. Eighteen patients reached the target Hb level according to protocol. QoL scores for fatigue, dyspnoea, constipation, and physical, role and social functioning improved significantly during study, with similar results for transfused and untransfused patients. Maintaining Hb andgt; 120 g /L did not confer a higher transfusion rate, once the target was reached. In two of fourteen patients, magnetic resonance imaging T2* indicated cardiac iron overload, however, without association with ferritin levels. Conclusions: In elderly anaemic MDS patients, an increment in haemoglobin is associated with improved QoL, whether induced by growth factor treatment or transfusion therapy.
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| 2. |
- Abrahamsson, Anna, et al.
(författare)
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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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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 124:8, s. 1288-1295
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Andersen, Niels S., et al.
(författare)
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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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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 27:26, s. 4365-4370
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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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| 4. |
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| 5. |
- Bergman, Birgitta, 1941, et al.
(författare)
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Ocular changes, risk markers for eye disorders and effects of cataract surgery in elderly people: a study of an urban Swedish population followed from 70-97 years of age
- 2004
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 82, s. 166-74
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the prevalence of and potential risk factors for ocular disorders and the effects of timing of cataract surgery from age 70–97 years. Population: A representative population sample taken from within the Gerontological and Geriatric Population Studies (H 70) in Gothenburg, Sweden (n = 958). All subjects underwent eye examinations at age 70 years in 1971 and subsequently at ages 82, 88, 95 and 97 years. All inhabitants of Gothenburg aged 95 and 97 years were invited to participate in the study. Results: Decreased vision (visual acuity ≤ 0.5) was found in 20% and 80% of subjects at ages 82 and 97 years, respectively. Blood folate and physical activity at age 70 years correlated positively and body mass index (BMI) negatively to visual acuity (VA) ≥ 0.8 at ages 82 and 88 years. Smoking at age 70 years correlated to early age-related maculopathy (ARM). Cataract surgery had been performed in 40% of subjects at age 97 years. Surgery 2 years earlier led to a 15% increase in time spent with improved vision. Conclusions: The deterioration of vision in elderly people is a major health problem, for which ‘low’ folate status, smoking, ‘high’ BMI and low physical activity are potential risk factors. Early cataract surgery is also beneficial in very old patients.
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| 6. |
- Björkegren, Karin
(författare)
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Studies on Vitamin B12 and Folate Deficiency Markers in the Elderly : A Population-based Study
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of this study were to document the levels of cobalamin, folate, methylmalonic acid (MMA) and total homocysteine (tHcy) in serum and their relations to symptoms, clinical findings, and other factors in order to improve the possibilities of detecting early deficiency of vitamin B12 or folate, and to study the effects of cobalamin and folic acid treatment over a three-year period. The study population consisted of a 20% random sample of persons 70 years or older living in Älvkarleby in mid-Sweden. They were invited to a survey and 224 (88.4%) persons responded. Data were obtained by questionnaire, laboratory investigations and physical examination for the period 1993 – 1999. In a multivariate analysis performed at baseline, serum MMA and tHcy were significantly and independently correlated to age, serum cobalamin, and creatinine levels, and tHcy also to sex and serum folate. Neither serum cobalamin, folate, MMA nor tHcy had any significant correlation to haemoglobin or mean red cell volume. Almost half of the study population had signs of low tissue levels of vitamin B12 or folate. Among those who took multivitamin preparations, the proportion was much lower, 25%. Among traditional symptoms and clinical findings that have been linked to vitamin B12 or folate tissue deficiency, only changes in the tongue mucosa and mouth angle stomatitis were significantly associated with abnormal serum folate and tHcy levels. Traditional symptoms of vitamin deficiency may appear later in the course. 69 persons who had laboratory indications of early or overt tissue deficiency of vitamin B12 or folate and who had no ongoing vitamin treatment were given cobalamin for six months. Those whose MMA or tHcy levels did not normalise were given folic acid in addition to cobalamin. After further treatment for three months, all persons but one had normal levels. The laboratory effect still remained after three years of treatment. There was a tendency towards improvement of vibration sense, especially in the long nerve paths, and improvement of neurological symptoms and oral mucosa findings. Conclusion: A substantial proportion of elderly persons have laboratory signs of incipient tissue deficiency of vitamin B12 and folate. Treatment normalises lab parameters and some symptoms.
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| 7. |
- Bram Ednersson, Susanne, et al.
(författare)
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Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma patients
- 2018
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 181:6, s. 770-781
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse large B cell lymphoma (DLBCL) patients with early relapse or refractory disease have a very poor outcome. Immunochemotherapy resistance will probably, also in the era of targeted drugs, remain the major cause of treatment failure. We used proteomic mass spectrometry to analyse the global protein expression of micro-dissected formalin-fixed paraffin-embedded tumour tissues from 97 DLBCL patients: 44 with primary refractory disease or relapse within 1year from diagnosis (REF/REL), and 53 who were progression-free more than 5years after diagnosis (CURED). We identified 2127 proteins: 442 were found in all patients and 102 were differentially expressed. Sixty-five proteins were overexpressed in REF/REL patients, of which 46 were ribosomal proteins (RPs) compared with 2 of the 37 overexpressed proteins in CURED patients (P=76x10(-10)). Twenty of 37 overexpressed proteins in CURED patients were associated with actin regulation, compared with 1 of 65 in REF/REL patients (P=14x10(-9)). Immunohistochemical staining showed higher expression of RPS5 and RPL17 in REF/REL patients while MARCKS-like protein, belonging to the actin network, was more highly expressed in CURED patients. Even though functional studies aimed at individual proteins and protein interactions to evaluate potential clinical effect are needed, our findings suggest new mechanisms behind immunochemotherapy resistance in DLBCL.
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| 8. |
- Bram Ednersson, Susanne, et al.
(författare)
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Proteomic analysis in diffuse large B-cell lymphoma identifies dysregulated tumor microenvironment proteins in non-GCB/ABC subtype patients
- 2021
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 62:10, s. 2360-2373
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Tidskriftsartikel (refereegranskat)abstract
- The complexity of the activated B-cell like (ABC) diffuse large B-cell lymphoma (DLBCL) subtype is probably not only explained by genetic alterations and methods to measure global protein expression could bring new knowledge regarding the pathophysiology. We used quantitative proteomics to analyze the global protein expression of formalin-fixed paraffin-embedded (FFPE) tumor tissues from 202 DLBCL patients. We identified 6430 proteins and 498 were significantly regulated between the germinal center B-cell like (GCB) and non-GCB groups. A number of proteins previously not described to be upregulated in non-GCB or ABC DLBCL was found, e.g. CD64, CD85A, guanylate-binding protein 1 (GBP1), interferon-induced proteins with tetratricopeptide repeat (IFIT)2, and mixed lineage kinase domain-like protein (MLKL) and immunohistochemical staining showed higher expression of GBP1 and MLKL. A cluster analysis revealed that the most prominent cluster contained proteins involved in the tumor microenvironment and regulation of the immune system. Our data suggest that the therapeutic focus should be expanded toward the tumor microenvironment in non-GCB/ABC subtype patients.
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| 9. |
- Bram Ednersson, Susanne, et al.
(författare)
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TBLR1 and CREBBP as potential novel prognostic immunohistochemical biomarkers in diffuse large B-cell lymphoma
- 2020
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 61:11, s. 2595-2604
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have identified prognostic mutational clusters for diffuse large B-cell lymphoma (DLBCL) patients, both within and outside the original cell-of-origin (COO) classification. For many of these mutations, there is limited information regarding the corresponding protein expression. With the aim to determine the relationship of protein expression and intensity to COO and prognosis, we used digital image analysis to quantitate immunohistochemical staining of CREBBP, IRF8, EZH2, and TBLR1 in 209 DLBCL patients. We found that patients with strong nuclear expression of TBLR1 had inferior progression-free survival (PFS) and overall survival (OS) in univariable analysis and inferior PFS in multivariable analysis. Patients with higher proportion of intermediate to strong nuclear CREBBP expression had a worse PFS and OS in univariable analysis. CREBBP was expressed with stronger intensity in non-GCB patients and the prognostic impact was restricted to this subgroup. These findings suggest that high nuclear protein expression of TBLR1 and CREBBP is negatively associated with prognosis in DLBCL.
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| 10. |
- Ekberg, Sara, et al.
(författare)
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Trends in the prevalence, incidence and survival of non-Hodgkin lymphoma subtypes during the 21st century - a Swedish lymphoma register study
- 2020
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 189:6, s. 1083-1092
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Tidskriftsartikel (refereegranskat)abstract
- Non-Hodgkin lymphoma (NHL) prognosis has improved in recent years, yet the number of patients living with the diagnosis, i.e. the prevalence, has seldom been reported. The prevalence provides a measure of the burden of disease, useful for healthcare planning and to optimise resource allocation. We provide a systematic presentation of temporal trends in absolute numbers of prevalent patients by NHL subtypes, linking them to trends in incidence, survival and mortality. Patients diagnosed 2000-2016 were identified in the national Swedish lymphoma register. Incidence and mortality rates, relative survival and prevalence were estimated for NHL overall and for major clinical and morphological subtypes. Poisson regression was used to test for temporal trends. Increasing incidence and improved survival have led to a 47% increase in the five-year prevalence of NHL overall in 2016 compared to 2004. An increasing prevalence was observed for all investigated subtypes during the study period, but most notably for diffuse large B cell lymphomas among aggressive subtypes (66%), and marginal zone lymphomas among indolent subtypes (135%). This dramatic increase in NHL prevalence underscores the need to develop and evaluate alternative follow-up schemes to use resources efficiently and still ensure optimal care of lymphoma survivors.
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