| 1. |
- Cavalli-Björkman, Nina, et al.
(författare)
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Fatal adenovirus infection during alemtuzumab (anti-CD52 monoclonal antibody) treatment of a patient with fludarabine-refractory B-cell chronic lymphocytic leukemia
- 2002
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Ingår i: Medical Oncology. - 1357-0560 .- 1559-131X. ; 19:4, s. 277-80
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Tidskriftsartikel (refereegranskat)abstract
- Alemtuzumab (Campath-1H) is a humanized CD52 monoclonal antibody that targets normal as well as malignant B- and T-lymphocytes. Alemtuzumab has significant antitumor activity in chronic lymphocytic leukemia (B-CLL) but also induces immunosuppression. We describe a case of fatal adenovirus infection in a heavily pretreated patient with fludarabine-refractory B-CLL receiving alemtuzumab therapy, drawing attention to the fact that also viruses other than cytomegalovirus (CMV) and herpes simplex (HSV) need to be considered in B-CLL patients with fever of unknown origin while on alemtuzumab treatment.
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| 2. |
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| 3. |
- Erlandsson, Martin, et al.
(författare)
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Digital produktinformation baserat på datamallar : KONCEPTTEST MED MILJÖVARUDEKLARATIONER (EPD) OCH PRESTANDADEKLARATIONER (DOP) I WEBBTJÄNSTER (API)
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I framtiden måste vi bestämma oss för hur vi på ett rationellt, kvalitetssäkrat och digitalt sätt ska hantera produktinformation i byggsektorn. Visionen är att basera harmoniserad digital kvalitetsäkrad produktinformation på en internationellt användbar datamall.Grunderna för digitala datamallar och hur de tas fram beskrivs i standarderna ISO 23386/7 och ISO 23387.En ifylld datamall kallas ett datablad. I det här genomförda tillämpningstestet (proof of concept, PoC) av datamallar är syftet att kommunicera produktinformation digitalt i värdekedjan från materialtillverkan till dess att byggprodukten levererats till byggarbetsplatsen.I tillämpningstestet ingår flera materiatillverkare som har varit testpiloter för att ta fram datablad enligt datamalls-konceptet. Piloterna har tagit fram datablad för prestandadeklarationen (DoP) som är kopplat till produktens CE-märkning, samt för en EPD baserat på den globala datamallen som beskrivs i standarden ISO 22057.
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| 4. |
- Gunnarsson, Rebeqa, et al.
(författare)
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Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia
- 2011
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 96:8, s. 1161-1169
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Tidskriftsartikel (refereegranskat)abstract
- Background High-resolution genomic microarrays enable simultaneous detection of copy-number aberrations such as the known recurrent aberrations in chronic lymphocytic leukemia [del(11q), del(13q), del(17p) and trisomy 12], and copy-number neutral loss of heterozygosity. Moreover, comparison of genomic profiles from sequential patients' samples allows detection of clonal evolution. Design and Methods We screened samples from 369 patients with newly diagnosed chronic lymphocytic leukemia from a population-based cohort using 250K single nucleotide polymorphism-arrays. Clonal evolution was evaluated in 59 follow-up samples obtained after 5-9 years. Results At diagnosis, copy-number aberrations were identified in 90% of patients; 70% carried known recurrent alterations, including del(13q) (55%), trisomy 12 (10.5%), del(11q) (10%), and del(17p) (4%). Additional recurrent aberrations were detected on chromosomes 2 (1.9%), 4 (1.4%), 8 (1.6%) and 14 (1.6%). Thirteen patients (3.5%) displayed recurrent copy-number neutral loss of heterozygosity on 13q, of whom 11 had concurrent homozygous del(13q). Genomic complexity and large 13q deletions correlated with inferior outcome, while the former was linked to poor-prognostic aberrations. In the follow-up study, clonal evolution developed in 8/24 (33%) patients with unmutated IGHV, and in 4/25 (16%) IGHV-mutated and treated patients. In contrast, untreated patients with mutated IGHV (n=10) did not acquire additional aberrations. The most common secondary event, del(13q), was detected in 6/12 (50%) of all patients with acquired alterations. Interestingly, aberrations on, for example, chromosome 6q, 8p, 9p and 10q developed exclusively in patients with unmutated IGHV. Conclusions Whole-genome screening revealed a high frequency of genomic aberrations in newly diagnosed chronic lymphocytic leukemia. Clonal evolution was associated with other markers of aggressive disease and commonly included the known recurrent aberrations.
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| 6. |
- Hojjat-Farsangi, Mohammad, et al.
(författare)
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The tyrosine kinase receptor ROR1 is constitutively phosphorylated in chronic lymphocytic leukemia (CLL) cells
- 2013
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Ingår i: PLOS ONE. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1932-6203.
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorylation of receptor tyrosine kinases (RTKs) has a key role in cellular functions contributing to the malignant phenotype of tumor cells. We and others have previously demonstrated that RTK ROR1 is overexpressed in chronic lymphocytic leukemia (CLL). Silencing siRNA downregulated ROR1 and induced apoptosis of CLL cells. In the present study we analysed ROR1 isoforms and the phosphorylation pattern in CLL cells (n=38) applying western blot and flow-cytometry using anti-ROR1 antibodies and an anti-phospho-ROR1 antibody against the TK domain. Two major ROR1 bands with the size of 105 and 130 kDa respectively were identified, presumably representing unglycosylated (immature) and glycosylated (mature) ROR1 respectively as well as a 260 kDa band which may represent dimerized ROR1. A ROR1 band of 64 kDa that may correspond to a C-terminal fragment was also noted, present only in the nucleus. The 105 kDa ROR1 isoform was more frequently expressed in non-progressive as compared to progressive CLL patients (p=0.03). The 64, 105, 130 and 260 kDa bands were constitutively phosphorylated both at tyrosine and serine residues. Phosphorylation intensity of the mature (130 kDa) isoform was significantly higher in progressive than in non-progressive disease (p<0.001). Incubation of CLL cells with a mouse anti-ROR1 KNG or an anti-ROR1 CRD mAb respectively induced dephosphorylation of ROR1 before entering apoptosis. In conclusion CLL cells expressed different isoforms of ROR1 which were constitutively phosphorylated. The mature, phosphorylated ROR1 isoform was associated with a progressive disease stage. Targeting ROR1 by mAbs induced specific dephosphorylation and leukemic cell death. ROR1 might be an interesting therapeutic target.
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| 7. |
- Linden, Karolina, 1982, et al.
(författare)
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Initial Validation of the Diabetes and Breastfeeding Management Questionnaire (DBM-Q)
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - Basel, Switzerland : MDPI. - 1661-7827 .- 1660-4601. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- Women with pre-gestational diabetes face additional challenges after birth as they struggle with breastfeeding and managing unpredictable blood glucose levels. The aim of this study is to validate the Diabetes and Breastfeeding Management Questionnaire (DBM-Q). In total, 142 mothers with type 1 diabetes mellitus answered the questionnaire, which initially consisted of 11 items. The response rate was 82.5% (n = 128) at two months, and 88.4% (n = 137) at six months postpartum. The measurement properties of the Diabetes and Breastfeeding Management Questionnaire were tested according to the Rasch measurement theory (RMT). One item showed both disordered thresholds and several model misfits and was removed. Two items showed disordered thresholds which were resolved by collapsing response categories. This resulted in a 10-item questionnaire with all the fit residuals within the range of +2.5, minor significant dierential item functioning, well-targeted items and a person separation index of 0.73. Evaluating the DBM-Q according to the RMT is a strength, as it evaluates data against strict measurement criteria. This study provides an initial validation of the questionnaire. The DBM-Q shows good measurement properties for measuring diabetes and breastfeeding management postpartum in women with pre-gestational diabetes. Further studies are needed to identify cutos for when professional support is needed.
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| 8. |
- Lundin, Jeanette
(författare)
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Targeted CD52 therapy in lymphoid malignancies : a clinical and immunological study
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is a great need for developing new treatment alternatives in low grade non Hodgkin's lymphoma (NHL) including chronic lymphocytic leukemia (CLL). The CD52 antigen, which is expressed on almost all lymphoid malignancies, can be utilized as a target for CD52-directed monoclonal antibody therapy (alemtuzumab, Campath-1 H). The aim of this thesis is to evaluate the clinical, safety and immunological effects of alemtuzumab in low grade NHL or CLL. In the first trial, 50 patients with low grade NHL received alemtuzumab as i.v. infusions (30 mg tiw). The 0 R rate was 20%; marked anti-tumor effects were observed in blood (CR 94%) and bone marrow (CR 32% and PR 24%). At the time of initiating this study, antiviral and antibacterial prophylaxis was not routinely given and grade III-IV infections developed in one third of the patients. The trial served as the basis for alemtuzumab's subsequent development in lymphocytic leukemias and T-cell lymphomas. In the second study, 41 patients were received subcutaneous (s.c.) alemtuzumab therapy for up to 18 weeks. The OR rate was 8 1% (intention to treat). Median time to treatment failure was 18+ months. CR or nodular PR in bone marrow was achieved in 66%, which often required 18 weeks of therapy. Grade 1-2 local injection site reactions was observed in most patients, but disappeared within 2 weeks upon continued therapy. Four cases of CMV reactivation were observed (fever without pneumonitis, rapidly responding to ganciclovir). This trial shows a considerably higher response rate on alemtuzumab than in advanced B-CLL. A prolonged duration of therapy appears to be important for maximal efficacy. S.c. administration seemed to reduce the incidence and severity of general "first dose" side effects and may also reduce the costs of therapy. In the third study, B cells from healthy volunteers and patients with previously untreated B-CLL were analyzed by flow cytometry (MESF units) to quantify receptor intensity of CD20, CD22 and CD52 (which all are potential therapeutic target antigens). Receptor intensity analysis revealed that the expression of CD52 was >30 times greater than that of CD20 and CD22. A substantial variability over the time was seen and most pronounced for CD20. The effects of in vivo cytokine (interleukin-4) therapy on receptor density were also studied but a clear impact on receptor intensity expression could not be observed. Thus, effects described in vitro in other studies were not easily translated into the in vivo situation. In the fourth trial, 22 patients with advanced mycosis fungoides/Sezary's syndrome (MF/SS) were treated with alemtuzumab for 12 weeks. The OR rate was 55%, including 32% CRs. Less heavily pre-treated patients had an OR rate of 80% vs. 33% in refractory patients. Itching, self-assessed by VAS was reduced from a median of 8 before treatment to 2 at end of the therapy. CMV reactivation occurred in 4 patients (18%) and 3 patients had fever of unknown origin, which resolved following i.v. antibiotics. Except for CMV, all serious infectious adverse events occurred in the refractory patients. This study shows that alemtuzumab has a major activity in MF/SS patients. In a last study, immunological cell subpopulations were studied before and after therapy as well as during long-term unmaintained follow-up in CLL patients who had received alemtuzumab as first line therapy. CD4 and CD8 T cells were profoundly depleted from blood and remained at <25% of the baseline levels for >6 months in most patients. Also normal B cells, NK-, and NK-T cell populations were markedly suppressed. Monocytes and granulocytes were less affected by the therapy. The degree of suppression and time to recovery appeared not to be dose-dependent. No late occurring infections were observed. Antigen (CD52) negative T-cell populations were detected in blood and persisted for a prolonged period of time. Alemtuzumab is a new monoclonal antibody with significant effect in lymphoid malignancies, it induces long-lasting immune suppression and antibiotic prophylaxis is needed to prevent infectous complications.
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| 9. |
- Melin, Jeanette, et al.
(författare)
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An off-target scale limits the utility of Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS) as a measure of well-being in public health surveys
- 2022
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Ingår i: Public Health. - : Elsevier BV. - 0033-3506 .- 1476-5616. ; 202, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess the utility and measurement properties for the well-being scale Short Warwick–Edinburgh Mental Well-Being Scale (SWEMWBS) in a Swedish general population survey. Study design: A cross-sectional survey study. Methods: Data were retrieved from the 2018 public health survey in Stockholm County, containing a random sample of 22 856 persons stratified to be representative for the municipalities and districts within the region. The data were analyzed according to Rasch Measurement Theory. Results: Person attribute values are positively skewed (mean 2.32, SD 1.85), with wide gaps in the item threshold attribute values. Overall item fit statistics were acceptable, and person measurement separation reliability was 0.83, indicating three statistically distinct ranges in the estimated well-being values. Conclusion: While the SWEMWBS items indicated acceptable fit to the Rasch measurement model, targeting of items to sample is skewed toward lower levels of well-being, and there is a ceiling effect. Thus, we suggest a careful reconsideration of SWEMWBS as a tool for use in general public health surveys, especially for assessing change over time and group differences, as there are large measurement uncertainties for the majority of cases when the population as a whole is sampled. We encourage revisions applying a coherent and comprehensive ordinal construct theory for well-being to fill the gaps in the upper end of the SWEMWBS scales' item thresholds. The addition of more challenging items would improve targeting for population-based surveys, increase reliability, and provide more actionable information that could be useful in improving individuals' well-being. © 2021 The Authors
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| 10. |
- Palma, Marzia, et al.
(författare)
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Ibrutinib induces rapid down-regulation of inflammatory markers and altered transcription of chronic lymphocytic leukaemia-related genes in blood and lymph nodes
- 2018
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Ingår i: British Journal of Haematology. - : WILEY. - 0007-1048 .- 1365-2141. ; 183:2, s. 212-224
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Tidskriftsartikel (refereegranskat)abstract
- In chronic lymphocytic leukaemia (CLL) patients, treatment with the Bruton tyrosine kinase inhibitor ibrutinib induces a rapid shift of tumour cells from lymph nodes (LN) to peripheral blood (PB). Here, we characterized in depth the dynamics of ibrutinib-induced inflammatory, transcriptional and cellular changes in different compartments immediately after treatment initiation in seven relapsed/refractory CLL patients. Serial PB and LN samples were taken before start and during the first 29 days of treatment. Changes in plasma inflammation-related biomarkers, CLL cell RNA expression, B-cell activation and migration markers expression, and PB mononuclear cell populations were assessed. A significant reduction of 10 plasma inflammation markers, the majority of which were chemokines and not CLL-derived, was observed within hours, and was paralleled by very early increase of CD19(+) circulating cells. At the RNA level, significant and continuous changes in transcription factors and signalling molecules linked to B-cell receptor signalling and CLL biology was observed in both PB and LN CLL cells already after 2 days of treatment. In conclusion, ibrutinib seems to instantly shut off an ongoing inflammatory response and interfere with diverse sensitive pathways in the LN.
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