25 results on '"Fie Juhl Vojdeman"'
Search Results
2. Data from Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes
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Kostas Stamatopoulos, Paolo Ghia, Richard Rosenquist, Anastasia Hadzidimitriou, Frederic Davi, Chrysoula Belessi, Nikos Darzentas, Ioanna Chouvarda, Stephan Stilgenbauer, Diane F. Jelinek, Gianluca Gaidano, David Oscier, Nikos Maglaveras, Nicholas Chiorazzi, Elias Campo, Michael Hallek, Sarka Pospisilova, Anton W. Langerak, Hartmut Döhner, Carsten Niemann, Marco Montillo, Livio Trentin, Darko Antic, Ioannis Vlahavas, Achilles Anagnostopoulos, Gunnar Juliusson, Panagiotis Panagiotidis, Marie-Paule Lefranc, Véronique Giudicelli, Charles C. Chu, Karin E. Smedby, Larry Mansouri, Lone Bredo Pedersen, Christiane Pott, Jasmin Bahlo, Monica Facco, Maria Chatzouli, Dirk Kienle, Mark Catherwood, Teodora Karan-Djurasevic, Tatiana Tzenou, Silvio Veronese, Andrey Sudarikov, Niki Stavroyianni, Lydia Scarfo, Fie Juhl Vojdeman, Yorick Sandberg, Alba Navarro, Zadie Davis, Davide Rossi, Myriam Boudjogra, Karla Plevova, Tait Shanafelt, Xiao-Jie Yan, Eugen Tausch, Stavroula Ntoufa, Eva Minga, Lesley-Ann Sutton, Andreas Agathangelidis, Ioannis Kavakiotis, Panagiotis Baliakas, and Aliki Xochelli
- Abstract
Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication.Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34–expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes.Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively).Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management. Clin Cancer Res; 23(17); 5292–301. ©2017 AACR.
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- 2023
3. Table S1 from Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes
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Kostas Stamatopoulos, Paolo Ghia, Richard Rosenquist, Anastasia Hadzidimitriou, Frederic Davi, Chrysoula Belessi, Nikos Darzentas, Ioanna Chouvarda, Stephan Stilgenbauer, Diane F. Jelinek, Gianluca Gaidano, David Oscier, Nikos Maglaveras, Nicholas Chiorazzi, Elias Campo, Michael Hallek, Sarka Pospisilova, Anton W. Langerak, Hartmut Döhner, Carsten Niemann, Marco Montillo, Livio Trentin, Darko Antic, Ioannis Vlahavas, Achilles Anagnostopoulos, Gunnar Juliusson, Panagiotis Panagiotidis, Marie-Paule Lefranc, Véronique Giudicelli, Charles C. Chu, Karin E. Smedby, Larry Mansouri, Lone Bredo Pedersen, Christiane Pott, Jasmin Bahlo, Monica Facco, Maria Chatzouli, Dirk Kienle, Mark Catherwood, Teodora Karan-Djurasevic, Tatiana Tzenou, Silvio Veronese, Andrey Sudarikov, Niki Stavroyianni, Lydia Scarfo, Fie Juhl Vojdeman, Yorick Sandberg, Alba Navarro, Zadie Davis, Davide Rossi, Myriam Boudjogra, Karla Plevova, Tait Shanafelt, Xiao-Jie Yan, Eugen Tausch, Stavroula Ntoufa, Eva Minga, Lesley-Ann Sutton, Andreas Agathangelidis, Ioannis Kavakiotis, Panagiotis Baliakas, and Aliki Xochelli
- Abstract
Univariable and multivariable analysis for TTFT within M-CLL.
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- 2023
4. Figure S3A from Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes
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Kostas Stamatopoulos, Paolo Ghia, Richard Rosenquist, Anastasia Hadzidimitriou, Frederic Davi, Chrysoula Belessi, Nikos Darzentas, Ioanna Chouvarda, Stephan Stilgenbauer, Diane F. Jelinek, Gianluca Gaidano, David Oscier, Nikos Maglaveras, Nicholas Chiorazzi, Elias Campo, Michael Hallek, Sarka Pospisilova, Anton W. Langerak, Hartmut Döhner, Carsten Niemann, Marco Montillo, Livio Trentin, Darko Antic, Ioannis Vlahavas, Achilles Anagnostopoulos, Gunnar Juliusson, Panagiotis Panagiotidis, Marie-Paule Lefranc, Véronique Giudicelli, Charles C. Chu, Karin E. Smedby, Larry Mansouri, Lone Bredo Pedersen, Christiane Pott, Jasmin Bahlo, Monica Facco, Maria Chatzouli, Dirk Kienle, Mark Catherwood, Teodora Karan-Djurasevic, Tatiana Tzenou, Silvio Veronese, Andrey Sudarikov, Niki Stavroyianni, Lydia Scarfo, Fie Juhl Vojdeman, Yorick Sandberg, Alba Navarro, Zadie Davis, Davide Rossi, Myriam Boudjogra, Karla Plevova, Tait Shanafelt, Xiao-Jie Yan, Eugen Tausch, Stavroula Ntoufa, Eva Minga, Lesley-Ann Sutton, Andreas Agathangelidis, Ioannis Kavakiotis, Panagiotis Baliakas, and Aliki Xochelli
- Abstract
CLL with mutated IGHV4-34 receptors: shared and distinct clinical outcomes. B. IgG subsets #4 and #16 displayed significantly longer TTFT (p=0.00038) compared to M-CLL cases utilizing IGHV genes other than IGHV4-34.
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- 2023
5. Dihydropyrimidine dehydrogenase (DPD) genotype and phenotype among Danish cancer patients:prevalence and correlation between DPYD-genotype variants and P-uracil concentrations
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Niels Herluf Paulsen, Camilla Qvortrup, Fie Juhl Vojdeman, Peter Plomgaard, Stig Ejdrup Andersen, Anne Ramlov, Birgitte Bertelsen, Maria Rossing, Claus Gyrup Nielsen, Elke Hoffmann-Lücke, Eva Greibe, Hanne Spangsberg Holm, Heidi Hvid Nielsen, Ihab Bishara Yousef Lolas, Jonna Skov Madsen, Marianne Lerbaek Bergmann, Morten Mørk, Palle B. Nielsen Fruekilde, Pernille Bøttger, Peter Clausager Petersen, Peter Henrik Nissen, Søren Feddersen, Troels K. Bergmann, Per Pfeiffer, and Per Damkier
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Phenotype ,Dihydrouracil Dehydrogenase (NADP)/genetics ,Genotype ,Oncology ,Prevalence ,Humans ,Radiology, Nuclear Medicine and imaging ,Fluorouracil ,Hematology ,General Medicine ,Uracil ,Neoplasms/epidemiology ,Denmark/epidemiology - Published
- 2022
6. Dihydropyrimidine dehydrogenase (DPD) genotype and phenotype among Danish cancer patients: prevalence and correlation between
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Niels Herluf, Paulsen, Camilla, Qvortrup, Fie Juhl, Vojdeman, Peter, Plomgaard, Stig Ejdrup, Andersen, Anne, Ramlov, Birgitte, Bertelsen, Maria, Rossing, Claus Gyrup, Nielsen, Elke, Hoffmann-Lücke, Eva, Greibe, Hanne, Spangsberg Holm, Heidi Hvid, Nielsen, Ihab Bishara Yousef, Lolas, Jonna Skov, Madsen, Marianne Lerbaek, Bergmann, Morten, Mørk, Palle B Nielsen, Fruekilde, Pernille, Bøttger, Peter Clausager, Petersen, Peter Henrik, Nissen, Søren, Feddersen, Troels K, Bergmann, Per, Pfeiffer, and Per, Damkier
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Phenotype ,Genotype ,Neoplasms ,Denmark ,Prevalence ,Humans ,Fluorouracil ,Uracil ,Dihydrouracil Dehydrogenase (NADP) - Published
- 2022
7. Vitamin D levels and the risk of prostate cancer and prostate cancer mortality
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John Thomas Helgstrand, Klaus Brasso, Martin Andreas Røder, Hein Vincent Stroomberg, Fie Juhl Vojdeman, Anne-Marie Heegaard, Christian M. Madsen, Anne Tjønneland, Anja Olsen, Henrik L. Jørgensen, Peter Schwarz, and Bent Lind
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Male ,Oncology ,medicine.medical_specialty ,Biopsy ,vitamin D ,prostatic neoplasms ,030218 nuclear medicine & medical imaging ,Bone remodeling ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,Epidemiology ,medicine ,Vitamin D and neurology ,Humans ,Radiology, Nuclear Medicine and imaging ,Vitamin D ,risk ,business.industry ,Prostatic Neoplasms ,Prostate cancer mortality ,Hematology ,General Medicine ,medicine.disease ,mortality ,Logistic Models ,030220 oncology & carcinogenesis ,epidemiology ,Observational study ,business - Abstract
BACKGROUND: Vitamin D has a role in bone turnover and potentially bone-metastatic spread of prostate cancer (PCa). The aim of this observational study was to address the association between levels of serum vitamin D, diagnosis of PCa and subsequent mortality in men who underwent a biopsy of the prostate.METHODS: All men who underwent prostatic biopsy in the Danish PCa Registry (DaPCaR) and who had a serum vitamin D measurement during the period 2004 to 2010 (n = 4,065) were identified. Men were categorized by clinical cut-offs based on seasonally adjusted serum vitamin D levels in 75 nmol/L (high) serum vitamin D. Logistic regression model for association between vitamin D and risk of PCa diagnosis and multivariate survival analyses were applied.RESULTS: No association between serum vitamin D and risk of PCa was found. Overall survival was lowest for serum vitamin D deficiency and a significantly higher PCa specific mortality (HR: 2.37, 95%CI: 1.45-3.90, p CONCLUSION: No association was found between serum vitamin D categories and risk of PCa in men who underwent biopsy of the prostate. Men with PCa and serum vitamin D deficiency had a higher overall and PCa specific mortality compared to men with a sufficient level of serum vitamin D.
- Published
- 2020
8. Chronic lymphocytic leukaemia clones are detectable decades before diagnosis
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Fie Juhl Vojdeman, Stig E. Bojesen, Jens Helby, Børge G. Nordestgaard, Carsten Utoft Niemann, Michael A. E. Andersen, Christian Brieghel, and Lone Bredo Pedersen
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Lymphocytic leukaemia ,Neoplasm, Residual ,Time Factors ,business.industry ,DNA Mutational Analysis ,Hematology ,Leukemia, Lymphocytic, Chronic, B-Cell ,Clonal Evolution ,Immunology ,Mutation ,Biomarkers, Tumor ,Medicine ,Humans ,business ,Early Detection of Cancer - Published
- 2021
9. Comorbidity and mortality after hip fracture in nineteen thousand six hundred and eighty two patients aged eighteen to sixty five years in Denmark from 1996 to 2012
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Adam Omari, Jes B. Lauritzen, Henrik L. Jørgensen, Fie Juhl Vojdeman, and Christian M. Madsen
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Heart Diseases ,Heart disease ,Denmark ,Comorbidity ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Orthopedics and Sports Medicine ,Registries ,Aged ,030203 arthritis & rheumatology ,030222 orthopedics ,Hip fracture ,Hip Fractures ,business.industry ,Mortality rate ,Hazard ratio ,Age Factors ,Middle Aged ,medicine.disease ,Confidence interval ,Orthopedic surgery ,Female ,Surgery ,business - Abstract
This nationwide study assessed associations between comorbidity and mortality after hip fracture in young and middle-aged patients. Data on 19,682 patients aged 18 to 65 years were extracted from Danish registries out of 154,047 patients who experienced a hip fracture between 1996 and 2012. Mortality and comorbidity were assessed using information on vital status, hospital admissions, and prescriptions. Of the 19,682 patients 17,722 (90.0%) were middle-aged (40–65 years) and 1960 (10.0%) were young (18–39 years). The 30-day mortality rates were 3.2% (n = 570) and 1.6% (n = 32), respectively. Indicators of multi-trauma (hazard ratio (HR), 3.5 95% confidence interval (CI) [1.6–7.8], n = 2056) and having diabetes (HR, 4.4 [1.2–11.3], n = 59) and heart disease (HR, 4.4[1.3–14.8], n = 57) increased 30-day mortality in the young patients, while having cancer (HR, 5.0 [4.2–5.9], n = 1958) increased 30-day mortality in the middle-aged patients. Heart disease and diabetes were associated with high mortality in the young patients while having cancer was associated with high mortality in the middle-aged patients.
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- 2019
10. [The Danish screening programme for haemoglobinopathies]
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Andreas, Glenthøj, Mie, Samson, Nina, Toft, Birgitte Rode, Diness, Nikolaj, Askj R, Fie Juhl, Vojdeman, Henrik, Birgens, Morten Beck, Sørensen, and Jesper, Petersen
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Europe ,Hemoglobinopathies ,Pregnancy ,Denmark ,Prenatal Diagnosis ,Amniocentesis ,Humans ,Female - Abstract
The prevalence of people in Denmark descending from areas with a high prevalence of haemoglobinopathies is approximately one tenth and increasing. Since 1995, the Danish Health Authority has recommended haemoglobinopathy screening of pregnant women with ethnic roots outside Northern Europe. Partners of pregnant haemoglobinopathy carriers are also tested. Carrier state in both parents leads to genetic counselling, and prenatal diagnostics of the foetus (chorionic villus biopsy or amniocentesis) is offered, which can lead to abortion and/or preimplantation genetic screening for future pregnancies, as discussed in this review.
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- 2021
11. The Danish screening programme for haemoglobinopathies
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Andreas Glenthøj, Mie Samson, Nina Toft, Birgitte Rode Diness, Nikolaj Askj R, Fie Juhl Vojdeman, Henrik Birgens, Morten Beck Sørensen, and Jesper Petersen
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Europe ,Pregnancy ,Prenatal Diagnosis ,Amniocentesis ,Hemoglobinopathies/diagnosis ,Humans ,Female ,Denmark/epidemiology - Abstract
The prevalence of people in Denmark descending from areas with a high prevalence of haemoglobinopathies is approximately one tenth and increasing. Since 1995, the Danish Health Authority has recommended haemoglobinopathy screening of pregnant women with ethnic roots outside Northern Europe. Partners of pregnant haemoglobinopathy carriers are also tested. Carrier state in both parents leads to genetic counselling, and prenatal diagnostics of the foetus (chorionic villus biopsy or amniocentesis) is offered, which can lead to abortion and/or preimplantation genetic screening for future pregnancies, as discussed in this review.
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- 2021
12. The HOVON68 CLL trial revisited: performance status and comorbidity affect survival in elderly patients with chronic lymphocytic leukemia
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Ka L. Wu, Marinus H. J. van Oers, Mars B. van 't Veer, Maija Itälä-Remes, Eva Kimby, Christian H. Geisler, Jeanette K. Doorduijn, Fie Juhl Vojdeman, Aaron Polliack, Martine C. J. Abrahamse-Testroote, Tomas Kozak, Shulamiet Wittebol, Geir E. Tjønnfjord, Jan Walewski, Wendimagegn Ghidey Alemayehu, Hematology, and Clinical Haematology
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Male ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,Cyclophosphamide ,Chronic lymphocytic leukemia ,elderly ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Cause of Death ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,alemtuzumab ,Humans ,Transplantation, Homologous ,performance status ,Mortality ,Survival analysis ,Aged ,Aged, 80 and over ,Clinical Trials as Topic ,Performance status ,business.industry ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Hematology ,ta3121 ,medicine.disease ,Comorbidity ,Combined Modality Therapy ,Leukemia, Lymphocytic, Chronic, B-Cell ,Fludarabine ,comorbidity ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Alemtuzumab ,Female ,chemo-immunotherapy ,business ,CLL ,030215 immunology ,medicine.drug - Abstract
In the HOVON68 CLL trial, patients 65 to 75 years of age had no survival benefit from the addition of low-dose alemtuzumab to fludarabine and cyclophosphamide (FC) in contrast to younger patients. The reasons are explored in this 5-year trial update using both survival analysis and competing risk analysis on non-CLL-related mortality. Elderly FCA patients died more frequently from causes not related to CLL, and more often related to comorbidity (mostly cardiovascular) than to infection. In a Cox multivariate analysis, del(17p), performance status >0, and comorbidity were associated with a higher non-CLL-related mortality in the elderly independent of the treatment modality. Thus, while the ‘fit’ elderly with no comorbidity or performance status of 0 might potentially benefit from chemo-immunotherapy with FC, caution is warranted, when considering alemtuzumab treatment in elderly patients with cardiovascular comorbidity.
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- 2017
13. Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes
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Véronique Giudicelli, Lesley-Ann Sutton, Panagiotis Baliakas, Anastasia Hadzidimitriou, David Oscier, Kostas Stamatopoulos, Michael Hallek, Eugen Tausch, Marco Montillo, Achilles Anagnostopoulos, Elias Campo, Yorick Sandberg, Silvio Veronese, Šárka Pospíšilová, Dirk Kienle, Karin E. Smedby, Xiao-Jie Yan, Lydia Scarfò, Andreas Agathangelidis, Nikos Darzentas, Richard Rosenquist, Stavroula Ntoufa, Larry Mansouri, Darko Antic, Niki Stavroyianni, Aliki Xochelli, Tait D. Shanafelt, Tatiana Tzenou, Andrey Sudarikov, Charles C. Chu, Anton W. Langerak, Marie-Paule Lefranc, Nicholas Chiorazzi, Eva Minga, Carsten Utoft Niemann, Ioanna Chouvarda, Nikos Maglaveras, Gianluca Gaidano, Maria Chatzouli, Karla Plevová, Mark Catherwood, Hartmut Döhner, Chrysoula Belessi, Myriam Boudjogra, Zadie Davis, Ioannis Kavakiotis, Gunnar Juliusson, Livio Trentin, Frederic Davi, Davide Rossi, Jasmin Bahlo, Diane F. Jelinek, Monica Facco, Christiane Pott, Lone Bredo Pedersen, Panagiotis Panagiotidis, Fie Juhl Vojdeman, Stephan Stilgenbauer, Teodora Karan-Djurasevic, Alba Navarro, Paolo Ghia, Ioannis Vlahavas, Immunology, Xochelli, Aliki, Baliakas, Panagioti, Kavakiotis, Ioanni, Agathangelidis, Andrea, Sutton, Lesley-Ann, Minga, Eva, Ntoufa, Stavroula, Tausch, Eugen, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Boudjogra, Myriam, Rossi, Davide, Davis, Zadie, Navarro, Alba, Sandberg, Yorick, Vojdeman, Fie Juhl, Scarfo, Lydia, Stavroyianni, Niki, Sudarikov, Andrey, Veronese, Silvio, Tzenou, Tatiana, Karan-Djurasevic, Teodora, Catherwood, Mark, Kienle, Dirk, Chatzouli, Maria, Facco, Monica, Bahlo, Jasmin, Pott, Christiane, Pedersen, Lone Bredo, Mansouri, Larry, Smedby, Karin E, Chu, Charles C, Giudicelli, Véronique, Lefranc, Marie-Paule, Panagiotidis, Panagioti, Juliusson, Gunnar, Anagnostopoulos, Achille, Vlahavas, Ioanni, Antic, Darko, Trentin, Livio, Montillo, Marco, Niemann, Carsten, Döhner, Hartmut, Langerak, Anton W, Pospisilova, Sarka, Hallek, Michael, Campo, Elia, Chiorazzi, Nichola, Maglaveras, Niko, Oscier, David, Gaidano, Gianluca, Jelinek, Diane F, Stilgenbauer, Stephan, Chouvarda, Ioanna, Darzentas, Niko, Belessi, Chrysoula, Davi, Frederic, Hadzidimitriou, Anastasia, Rosenquist, Richard, Ghia, Paolo, and Stamatopoulos, Kostas
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Chronic lymphocytic leukemia ,B-cell receptor ,Immunoglobulin Variable Region ,Somatic hypermutation ,Immunogenetics ,Disease ,Biology ,03 medical and health sciences ,hemic and lymphatic diseases ,medicine ,Humans ,Amino Acid Sequence ,breakpoint cluster region ,Chronic Lymphocytic Leukemia B cell receptor BCR Immunoglobulin ,medicine.disease ,ADP-ribosyl Cyclase 1 ,Leukemia, Lymphocytic, Chronic, B-Cell ,3. Good health ,Gene Expression Regulation, Neoplastic ,Leukemia ,030104 developmental biology ,Oncology ,Immunology ,biology.protein ,Female ,Somatic Hypermutation, Immunoglobulin ,Antibody ,Immunoglobulin Heavy Chains - Abstract
Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34–expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management. Clin Cancer Res; 23(17); 5292–301. ©2017 AACR.
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- 2017
14. [Diagnosing von Willebrand disease]
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Fie Juhl, Vojdeman, Malou, Philips, Eva, Funding, and Jens Peter, Gøtze
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von Willebrand Diseases ,Denmark ,von Willebrand Factor ,Prevalence ,Humans - Abstract
Von Willebrand disease (VWD) is an inherited bleeding disorder with abnormal primary haemostasis due to defects in, or decreased concentration of the glycoprotein von Willebrand factor. In Denmark, the estimated prevalence of VWD is 1% corresponding to approximately 50,000 patients, but only a few hundred have been diagnosed, mostly due to prolonged bleeding after a trauma or during surgery. Thus, VWD is underdiagnosed in the general population. Improved anamnestic screening for bleeding disorders such as VWD in certain high-risk groups can facilitate institution of prophylactic treatment.
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- 2019
15. Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark
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Darshana Durup, Fie Juhl Vojdeman, Anja Olsen, Peter Schwarz, Christian M. Madsen, Anne Tjønneland, Kirsten Frederiksen, Louise Hansen, Henrik L. Jørgensen, Anne-Marie Heegaard, and Bent Lind
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,cancer incidence ,Denmark ,03 medical and health sciences ,0302 clinical medicine ,Prostate ,Neoplasms ,Internal medicine ,Epidemiology ,medicine ,Vitamin D and neurology ,Humans ,Registries ,Vitamin D ,Lung cancer ,business.industry ,Incidence ,Incidence (epidemiology) ,Cancer ,Middle Aged ,medicine.disease ,vitamin D levels ,primary health care ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Population study ,Female ,Skin cancer ,business - Abstract
Vitamin D has been linked to cancer development in both pre-clinical and epidemiological studies. Our study examines the association between serum levels of vitamin D and cancer incidence in the Capital Region of Denmark. Individuals who had vitamin D analyzed at The Copenhagen General Practitioners Laboratory between April 2004 and January 2010 were linked to Danish registries with end of follow-up date at Dec 31st 2014, excluding individuals with pre-existing cancer. Cox regression models adjusted for age in one-year intervals, sex, month of sampling, and Charlson Comorbidity Index were applied. The study population of 217,244 individuals had a median vitamin D level of 46 nmol/L (IQR 27–67 nmol/L). Non-melanoma skin cancer was the most frequent form of cancer, followed by breast-, lung-, and prostate cancers. No associations were found between increments of 10 nmol/L vitamin D and incidence of breast, colorectal, urinary, ovary or corpus uteri cancer. However, higher levels of vitamin D were associated with higher incidence of non-melanoma (HR 1.09 [1.09–1.1]) and melanoma skin cancer (HR 1.1 [1.08–1.13]) as well as prostate (HR 1.05 [1.03–1.07]) and hematological cancers (HR 1.03 [1.01–1.06]), but with lower incidence of lung cancer (HR 0.95 [0.93–0.97]). In our study, vitamin D levels are not associated with the incidence of several major cancer types, but higher levels are significantly associated with a higher incidence of skin, prostate, and hematological cancers as well as a lower incidence of lung cancer. These results do not support an overall protective effect against cancer by vitamin D.
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- 2019
16. Excess mortality following hip fracture in patients with diabetes according to age: a nationwide population-based cohort study of 154,047 hip fracture patients
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Jes B. Lauritzen, Bo Abrahamsen, Debbie Norring-Agerskov, Christopher Jantzen, Christian M. Madsen, Fie Juhl Vojdeman, and Henrik L. Jørgensen
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Male ,Aging ,medicine.medical_specialty ,Denmark ,Population ,fragility fracture ,survival ,Diabetes Complications ,endocrinology ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Epidemiology ,Medicine ,Humans ,030212 general & internal medicine ,Registries ,education ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Hip fracture ,education.field_of_study ,business.industry ,Hip Fractures ,Hazard ratio ,Age Factors ,General Medicine ,Middle Aged ,medicine.disease ,osteoporosis ,Comorbidity ,Diabetes Mellitus, Type 2 ,ageing ,epidemiology ,Female ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
OBJECTIVE: to test the hypothesis that excess mortality conferred by diabetes following hip fracture decreases with advancing age.METHODS: a nationwide population-based cohort study including 154,047 patients who were admitted with a hip fracture in Denmark from 1996 to 2012. Information on hip fracture diagnosis, diabetes, other comorbidities, and the primary outcome all-cause mortality was collected using the national Danish health registries. The association between diabetes and all-cause mortality according to age was assessed using Cox proportional hazards regression in the age categories: RESULTS: during a median follow-up of 3 years (interquartile range: 1-6 years, 603,091 person-years) 114,990 died from any cause. In total, 8% (n = 12,158) of the patients had diabetes at baseline and had unadjusted, and age, sex and Charlson Comorbidity Index adjusted hazard ratios for all-cause mortality of 1.19 (95% confidence interval: 1.16-1.21) and 1.14 (1.12-1.17) as compared to patients without diabetes. The sex and Charlson Comorbidity Index adjusted hazard ratios according to age were 1.64 (1.34-2.02) for patients CONCLUSIONS: diabetes is associated with excess mortality following hip fracture across all ages, but the excess mortality decreases with advancing age.
- Published
- 2018
17. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy
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Tatiana Tzenou, Richard Rosenquist, Marie-Paule Lefranc, Karla Plevová, Charles C. Chu, Yorick Sandberg, Gunnar Juliusson, Véronique Giudicelli, Livio Trentin, Mark Catherwood, Frederic Davi, Šárka Pospíšilová, Xiao-Jie Yan, Silvio Veronese, Lesley-Ann Sutton, Carsten Utoft Niemann, Nikos Darzentas, Kostas Stamatopoulos, Achilles Anagnostopoulos, Diane F. Jelinek, David Oscier, Mattias Mattsson, Nicholas Chiorazzi, Karin E. Smedby, Panagiotis Panagiotidis, Chrysoula Belessi, Florence Nguyen-Khac, Marco Montillo, Eva Minga, Paolo Ghia, Anton W. Langerak, Lydia Scarfò, Andreas Agathangelidis, Tait D. Shanafelt, Panagiotis Baliakas, Niki Stavroyianni, Larry Mansouri, Anastasia Hadzidimitriou, Zadie Davis, Fie Juhl Vojdeman, Uppsala Universitet [Uppsala], Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden, Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece, Department of Immunology, Genetics and Pathology [Uppsala, Sueden] (IGP), Uppsala University, Department of Hematology [Uppsala], Università Vita-Salute San Raffaele, Milan, Italy., Strategic Research Program in CLL, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy, Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden, Università Vita e Salute, San Raffaele, Milano, Italy, Strategic Research Program in CLL, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK., The Feinstein Institute for Medical Research, CEITEC-Central European Institute of Technology, MasarykBrno, Czech Republic., Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Hematology, Rigshospitalet, Copenhagen, Denmark, First Department of Propaedeutic Medicine, University of Athens, Athens, Greece, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Medicine Solna, Clinical Epidemiology Unit, Karolinska Institutet, and Hematology Center, Karolinska University Hospital, Stockholm, Sweden, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hematology and Transplantation, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece, Universita degli Studi di Padova, Venetian Institute Molecular Medicine (VIMM), Department of Hemato-Oncology, Belfast City Hospital, Belfast, UK, University Hospital Brno, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Immunology, Mayo Clinic, Rochester, MV, USA, Mayo Clinic [Rochester], Hematology Department, Nikea General Hospital, Piraeus, Greece, Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden., Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece., Institute of Applied Biosciences, Thessaloniki, Greece., Department of Immunology, Baliakas, Panagioti, Mattsson, Mattia, Hadzidimitriou, Anastasia, Minga, Eva, Agathangelidis, Andrea, Sutton, Lesley-Ann, Scarfo, Lydia, Davis, Zadie, Yan, Xiao-Jie, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie J, Tzenou, Tatiana, Chu, Charles C, Veronese, Silvio, Mansouri, Larry, Smedby, Karin E, Giudicelli, Véronique, Nguyen-Khac, Florence, Panagiotidis, Panagioti, Juliusson, Gunnar, Anagnostopoulos, Achille, Lefranc, Marie-Paule, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Niemann, Carsten U, Langerak, Anton W, Pospisilova, Sarka, Stavroyianni, Niki, Chiorazzi, Nichola, Oscier, David, Jelinek, Diane F, Shanafelt, Tait, Darzentas, Niko, Belessi, Chrysoula, Davi, Frederic, Ghia, Paolo, Rosenquist, Richard, Stamatopoulos, Kostas, and Immunology
- Subjects
Adult ,Male ,chemorefractorine ,Oncology ,medicine.medical_specialty ,Cyclophosphamide ,Chronic lymphocytic leukemia ,[SDV]Life Sciences [q-bio] ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Drug Therapy ,Chemoimmunotherapy ,Internal medicine ,medicine ,Humans ,Chronic Lymphocytic Leukemia ,[INFO]Computer Science [cs] ,stereotyped subsets ,Online Only Articles ,Survival rate ,ComputingMilieux_MISCELLANEOUS ,Aged ,Retrospective Studies ,Aged, 80 and over ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Hematology ,business.industry ,Middle Aged ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,3. Good health ,Fludarabine ,Survival Rate ,Leukemia ,030220 oncology & carcinogenesis ,Female ,Rituximab ,Immunotherapy ,business ,030215 immunology ,medicine.drug - Abstract
The overall survival (OS) of patients with chronic lymphocytic leukemia (CLL) has improved over the last decades mainly due to advances in the understanding of the disease biology and the introduction of novel therapeutic approaches(1). In the present retrospective study we investigated trends in OS in subgroups of cases defined by genetic and immunogenetic features aiming at addressing the question whether advances in chemoimmunotherapy had a uniform impact across all CLL patients. We found that such advances have translated into prolonged OS in all prognostic subgroups examined except those carrying TP53 abnormalities, as expected, but also those assigned to stereotyped subsets #1 and #2, that are generally devoid of such gene aberrations. This latter finding, reported here for the first time, indicates the need for alternative treatment options for these patients.
- Published
- 2018
18. Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations
- Author
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Eva Minga, Karin E. Smedby, Lesley-Ann Sutton, Nicholas Chiorazzi, Myriam Boudjogra, Kostas Stamatopoulos, Karla Plevová, Lone Bredo Pedersen, Zadie Davis, Lydia Scarfò, Andreas Agathangelidis, Monica Facco, Achilles Anagnostopoulos, Maria Chatzouli, Chrysoula Belessi, Athina Tsanousa, Panagiotis Baliakas, Kirsten van Lom, Lefteris Angelis, Yorick Sandberg, Gunnar Juliusson, Diane F. Jelinek, Fie Juhl Vojdeman, Anne Gardiner, Panagiotis Panagiotidis, Anton W. Langerak, Florence Nguyen-Khac, Hana Skuhrová Francová, Frederic Davi, Denis Moreno, Silvio Veronese, Richard Rosenquist, Marie-Paule Lefranc, Nikos Darzentas, Šárka Pospíšilová, Véronique Giudicelli, Xiao-Jie Yan, Charles C. Chu, Christian H. Geisler, Larry Mansouri, David Oscier, Mark Catherwood, Marco Montillo, Anastasia Hadzidimitriou, Livio Trentin, Paolo Ghia, Tait D. Shanafelt, Tatiana Tzenou, Baliakas, P, Agathangelidis, A, Hadzidimitriou, A, Sutton, La, Minga, E, Tsanousa, A, Scarfò, L, Davis, Z, Yan, Xj, Shanafelt, T, Plevova, K, Sandberg, Y, Vojdeman, Fj, Boudjogra, M, Tzenou, T, Chatzouli, M, Chu, Cc, Veronese, S, Gardiner, A, Mansouri, L, Smedby, Ke, Pedersen, Lb, Moreno, D, Van Lom, K, Giudicelli, V, Francova, H, Nguyen Khac, F, Panagiotidis, P, Juliusson, G, Angelis, L, Anagnostopoulos, A, Lefranc, Mp, Facco, M, Trentin, L, Catherwood, M, Montillo, M, Geisler, Ch, Langerak, Aw, Pospisilova, S, Chiorazzi, N, Oscier, D, Jelinek, Df, Darzentas, N, Belessi, C, Davi, F, Ghia, PAOLO PROSPERO, Rosenquist, R, Stamatopoulos K. Ghia P., is Co senior author, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden, Università Vita-Salute San Raffaele, Milan, Italy, Division of Molecular Oncology and Department of Onco-Hematology, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute, Milan, Italy, Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece, Department of Informatics, Aristotle University of Thessaloniki, Thessaloniki, Greece, Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom, The Feinstein Institute for Medical Research, Mayo Clinic [Rochester], Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Hematology, Rigshospitalet, Copenhagen, Denmark, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), First Department of Propaedeutic Medicine, University of Athens, Athens, Greece, Hematology Department, Nikea General Hospital, Piraeus, Greece, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, Hematology Department and Hematopoietic Cell Transplantation Unit, Georgios Papanicolaou Hospital, Thessaloniki, Greece, Universita degli Studi di Padova, Department of Hemato-Oncology, Belfast City Hospital, Belfast, United Kingdom, Immunology, and Hematology
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Male ,Oncology ,medicine.medical_specialty ,Chronic lymphocytic leukemia ,Immunology ,B-cell receptor ,Gene Rearrangement, B-Lymphocyte, Heavy Chain ,Antineoplastic Agents ,Biology ,Biochemistry ,Time-to-Treatment ,Genetic Heterogeneity ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,10. No inequality ,ComputingMilieux_MISCELLANEOUS ,Survival analysis ,Aged ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,B-Lymphocytes ,0303 health sciences ,Lymphoid Neoplasia ,Hematology ,Gene Expression Regulation, Leukemic ,Genetic heterogeneity ,Cell Biology ,Middle Aged ,Prognosis ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Survival Analysis ,Treatment Outcome ,030220 oncology & carcinogenesis ,biology.protein ,Immunoglobulin heavy chain ,Female ,Somatic Hypermutation, Immunoglobulin ,Antibody ,Immunoglobulin Heavy Chains ,IGHV@ - Abstract
An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset # 2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset # 2. Within subset # 2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset # 2/IGHV3-21 was enriched for IGHV-unmutated cases (P =.002). Subset # 2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset # 2/IGHV3-21 (22 vs 60 months, P =.001). No such difference was observed between non-subset # 2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset # 2 emerges as uniformly aggressive, contrasting non-subset # 2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.
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- 2015
19. Brief Report: CD52 Expression on CD4+ T Cells in HIV-Positive Individuals on cART
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Fie Juhl Vojdeman, Malene Hove-Skovsgaard, Marco Gelpi, Anders Elm Pedersen, Julie C. Gaardbo, Susanne Dam Nielsen, and Hans J. Hartling
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Cart ,Adult ,CD4-Positive T-Lymphocytes ,Male ,CD52 ,Stimulation ,HIV Infections ,CD38 ,Peripheral blood mononuclear cell ,Flow cytometry ,Andrology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Antiretroviral Therapy, Highly Active ,Medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Membrane Glycoproteins ,medicine.diagnostic_test ,biology ,business.industry ,Flow Cytometry ,ADP-ribosyl Cyclase 1 ,CD4 Lymphocyte Count ,Infectious Diseases ,Anti-Retroviral Agents ,CD52 Antigen ,Cohort ,biology.protein ,Leukocytes, Mononuclear ,Female ,Antibody ,business ,030215 immunology - Abstract
BACKGROUND HIV persists in a latent state in quiescent CD4 T cells preventing eradication of HIV. CD52 is a surface molecule modulated by HIV. We aimed at examining factors related to CD52 expression on CD4 T cells in HIV-positive individuals and the impact of initiation of combination antiretroviral therapy (cART). METHODS Peripheral blood mononuclear cells from 18 HIV-positive individuals and 10 uninfected age- and sex-matched controls were examined by flow cytometry for CD38 and CD52 expression on CD4 T cells. Stimulation assays were performed on 8 healthy blood donors to determine a cutoff for CD52 expression. RESULTS All examined CD4 T cells expressed CD52. However, both CD4 T cells with higher (CD52) and with lower CD52 expression (CD52dim) were found in HIV-positive individuals compared to uninfected controls. Two % CD52dim cells defined groups of high and low CD52: the group of individuals with high CD52 had higher CD4 counts at baseline (447 vs. 54 cells/µL, P = 0.02) and higher increase in CD4 counts during follow-up compared with low CD52 (P = 0.02). After 12 months of cART, CD52 increased (median fluorescence intensity 4846 vs. 5621, P < 0.05), whereas CD38 decreased (median fluorescence intensity 1519 vs. 730, P < 0.0001). CONCLUSIONS All HIV-positive individuals in this cohort had CD4 T cells that expressed CD52. Higher CD4 counts were found in those with high CD52. Furthermore, an increase in CD52 was found after 12 months of cART, indicating that anti-CD52 antibodies may be more efficient for depletion of CD4 T cells in HIV-positive individuals on cART.
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- 2017
20. Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia is a predictor of early death
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Ole Weis Bjerrum, Michael Asger Andersen, Mette K. Andersen, Carsten Utoft Niemann, Fie Juhl Vojdeman, Peter de Nully Brown, and Christian H. Geisler
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,Chronic lymphocytic leukemia ,Newly diagnosed ,Infections ,Gastroenterology ,Hypogammaglobulinemia ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Agammaglobulinemia ,hemic and lymphatic diseases ,Internal medicine ,Cause of Death ,medicine ,Humans ,Stage (cooking) ,Gene Rearrangement, B-Lymphocyte ,Cause of death ,Aged ,Aged, 80 and over ,Chromosome Aberrations ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Leukemia, Lymphocytic, Chronic, B-Cell ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Female ,Neoplasm Grading ,business ,IGHV@ ,Biomarkers ,030215 immunology ,Follow-Up Studies - Abstract
Hypogammaglobulinemia is the most common immune deficiency in chronic lymphocytic leukemia (CLL). However, the prognostic significance in terms of morbidity and mortality remains controversial. We here evaluate the significance of hypogammaglobulinemia in terms of infections, treatment-free survival (TFS), and overall survival (OS). A total of 159 consecutive, newly diagnosed patients were included for analysis. Twenty-five patients (16%) had a moderate or severe infection within one year of diagnosis, but no associations were found between low immunoglobulin (Ig) levels and infections. In multivariate analysis, we found age (>65), high Binet stage, high β2-microglobulin, and Ig deficiency to be associated with shorter OS. Decreased levels of IgM, deletion of chromosome 17p and unmutated IGHV status had independent negative impact on TFS. Thus, patients with hypogammaglobulinemia did not suffer more from infections early in the disease course, and decreased Ig had independent negative prognostic impact in CLL.
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- 2016
21. Abstract 1200: 25OH vitamin D concentrations are associated with both higher and lower incidence of specific cancers
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Darshana Durup, Anne-Marie Heegaard, Anja Olsen, Peter Schwarz, Louise Hansen, Kirsten Frederiksen, Bent Lind, Christian M. Madsen, Anne Tjønneland, Henrik L. Jørgensen, and Fie Juhl Vojdeman
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Cancer Research ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Incidence (epidemiology) ,Population ,Cancer ,medicine.disease ,Cancer registry ,Oncology ,Internal medicine ,medicine ,Vitamin D and neurology ,Population study ,Skin cancer ,education ,business ,Blood sampling - Abstract
This study examined the association between concentrations of 25OH vitamin D and cancer incidence in individuals from the Capital Region of Denmark who had 25OH vitamin D analyzed in serum via their general practitioner between April 2004 and January 2010 (CopD). CopD data were linked to the Danish Cancer Registry, the National Patient Registry and the Danish Civil Registration System as of December 2014. CopD consists of 246,858 individuals with 25OH vitamin D analyses. Individuals diagnosed with cancer prior to their 25OH vitamin D analysis (N=29,614) were excluded. The population analyzed in the study (217,244 individuals) had a mean level of 25OH vitamin D of 50.2 nmol/L, a mean age of 49.1 years (SD 20.1), female predominance (65.3%), and low comorbidity burden (Charlson Comorbidity index (CCI) ≥1 in 20.5%). Cox regression models with time since blood sampling as the underlying time scale adjusted for age in one year intervals, sex, month of sampling, and CCI as strata variables were performed in SAS 9.4 (SAS Institute, Cary, USA). P-values less than 0.05 were considered statistically significant. The study population experienced a total of 18,359 incident cancers during the follow-up period. Non-melanoma skin cancer was the most frequent form of cancer, followed by breast-, lung-, and prostate cancer (Table). In the adjusted analysis higher levels of 25OH vitamin D in increments of 10 nmol/L were associated with higher incidence of non-melanoma- and melanoma skin cancer, as well as prostate- and hematological cancers, but lower incidence of lung cancer. Excluding those diagnosed with cancer within 5 years of blood sampling, revealed similar results (Table). In conclusion, higher concentrations of 25OH vitamin D are associated with both higher and lower incidence of cancer depending on cancer type in CopD. Thus, in a population from general practice we find higher 25OH vitamin D concentrations are associated with the incidence of skin-, prostate and hematological cancers. Hazard ratios (HR) per 10nmol/L increase in 25OH vitamin D.Adjusted HR for allHR for cancer after 5+ yearsN casesHR95% ClpN casesHR95% ClpSkin cancerNon-melanoma50451.091.09-1.10 Citation Format: Fie J. Vojdeman, Christian M. Madsen, Darshana Durup, Kirsten Frederiksen, Anja Olsen, Louise Hansen, Anne-Marie Heegaard, Bent S. Lind, Anne Tjønneland, Henrik L. Jørgensen, Peter Schwarz. 25OH vitamin D concentrations are associated with both higher and lower incidence of specific cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1200.
- Published
- 2018
22. Plasma alemtuzumab levels in patients with chronic lymphocytic leukemia treated with alemtuzumab combined with chemotherapy reflect the efficacy of the treatment: a hypothesis
- Author
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Jesper Jurlander, Mars B. van ’t Veer, Marinus H. J. van Oers, Fie Juhl Vojdeman, Jan Walewski, Aaron Polliack, Eva Kimby, Christian H. Geisler, Nikolai Kirkby, Michela Montagna, Maija Itälä-Remes, Geir E. Tjønnfjord, Tomas Kozak, Mario Regazzi, Amsterdam institute for Infection and Immunity, Cancer Center Amsterdam, and Clinical Haematology
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Oncology ,Cancer Research ,medicine.medical_specialty ,Combination therapy ,Cyclophosphamide ,medicine.medical_treatment ,Chronic lymphocytic leukemia ,Antibodies, Monoclonal, Humanized ,Pharmacokinetics ,Internal medicine ,Lymphopenia ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Alemtuzumab ,Chemotherapy ,business.industry ,Hematology ,Induction Chemotherapy ,medicine.disease ,Prognosis ,Leukemia, Lymphocytic, Chronic, B-Cell ,Fludarabine ,Treatment Outcome ,Immunology ,Lymphocytopenia ,business ,medicine.drug - Abstract
In the HOVON68 trial comparing subcutaneous low-dose alemtuzumab (LD-A) used together with fludarabine (F) and cyclophosphamide (C) with FC alone in high-risk chronic lymphocytic leukemia (CLL), LD-AFC resulted in significantly more clinical and molecular responses than FC, but also in more opportunistic infections. In a subgroup analysis of alemtuzumab trough levels during treatment by a sensitive enzyme-linked immunosorbent assay (ELISA) method, detectable levels were found in 4/6 complete and 0/3 partial responders. A relationship between alemtuzumab plasma levels, response and duration of lymphocytopenia was evident. We hypothesize that following combination therapy, the response may not be a function of the alemtuzumab levels, but the opposite, that plasma alemtuzumab levels are a function of the efficacy of the entire treatment, and the fewer leukemic target cells that are remaining, the higher are the levels of plasma alemtuzumab. This concept may well provide a guide for alemtuzumab dosage in future trials.
- Published
- 2012
23. CLL with Mutated IGHV4-34 Antigen Receptors Is Clinically Heterogeneous: Antigen Receptor Stereotypy Makes the Difference
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Alba Navarro, Panagiotis Baliakas, Lone Bredo Pedersen, Richard Rosenquist, Stephan Stilgenbauer, Véronique Giudicelli, Yorick Sandberg, Elias Campo, Tatiana Tzenou, Gunnar Juliusson, Monica Facco, Andrey Sudarikov, Niki Stavroyianni, Teodora Karan-Djurasevic, Nikos Darzentas, Charles C. Chu, Eva Minga, Karla Plevová, Frederic Davi, Maria Chatzouli, Chrysoula Belessi, Livio Trentin, Paolo Ghia, Marie-Paule Lefranc, Davide Rossi, Xiao J. Yan, Šárka Pospíšilová, Diane F. Jelinek, Carsten Utoft Niemann, Jasmin Bahlo, Karin E. Smedby, Myriam Boudjogra, Mark Catherwood, Larry Mansouri, Darko Antic, Silvio Veronese, Lydia Scarfò, Andreas Agathangelidis, Marco Montillo, Zadie Davis, Anastasia Hadzidimitriou, Michael Hallek, Tait D. Shanafelt, Hartmut Döhner, Kostas Stamatopoulos, Achilles Anagnostopoulos, David Oscier, Nicholas Chiorazzi, Gianluca Gaidano, Eugen Tausch, Fie Juhl Vojdeman, Panagiotis Panagiotidis, Dirk Kienle, Aliki Xochelli, Lesley-Ann Sutton, and Anton W. Langerak
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0303 health sciences ,medicine.medical_specialty ,Mutation ,Hematology ,biology ,Immunology ,Cell Biology ,CD38 ,medicine.disease_cause ,Biochemistry ,3. Good health ,03 medical and health sciences ,Stereotypy (non-human) ,0302 clinical medicine ,Antigen ,Immunoglobulin M ,Internal medicine ,biology.protein ,medicine ,Gene ,Antigen receptors ,030304 developmental biology ,030215 immunology - Abstract
The IGHV4-34 gene is very frequent (~10%) in the B cell receptor immunoglobulin (BcR IG) gene repertoire of chronic lymphocytic leukemia (CLL). Over 30% of IGHV4-34 CLL cases can be assigned to different subsets with stereotyped BcR IG. The largest is subset #4 which represents ~1% of all CLL and ~10% of IGHV4-34 CLL and is considered a prototype for indolent disease. The BcR IG of a great majority (~85%) of IGHV4-34 CLL cases carry a significant load of somatic hypermutation (SHM), often with distinctive SHM patterns. This holds especially true for stereotyped subsets and is suggestive of particular modes of interactions with the selecting antigen(s). In detail, subsets #4 and #16, both involving IgG-switched cases (IgG-CLL), exhibit the greatest sequence similarity in SHM profiles, whereas they differ in this respect from IgM/D subsets #29 and #201. Prompted by these observations, here we explored the extent that these subset-biased SHM profiles in different IGHV4-34 stereotyped subsets were reflected in distinct demographics, clinical presentation, genomic aberrations and outcomes. Within a multi-institutional series of 20,331 CLL patients, 1790 (8.8%) expressed IGHV4-34 BcR IG. Following established bioinformatics approaches for the identification of BcR IG stereotypy, 573/1790 IGHV4-34 CLL cases (32%) were assigned to stereotyped subsets; of these, 340 cases (19% of all IGHV4-34 CLL and 60% of stereotyped IGHV4-34 cases) belonged to subsets #4, #16, #29 and #201, all concerning IGHV-mutated CLL (M-CLL). Clinicobiological information was available for 275/340 patients: #4, n=150; #16, n=44; #29, n=39; and #201, n=42. Comparisons between subsets revealed no differences in gender and age distribution. Interestingly, however, 36-43% of each subset cases were young for CLL (defined as patients aged ≤55 years), which is higher compared to general CLL cohorts, where young patients generally account for ~25% of cases. In contrast, significant differences were identified between subsets regarding: (i) disease stage at diagnosis, with >90% of IgG subsets #4 and #16 diagnosed at Binet stage A versus 83% in subset #201 and 74% in subset #29 (p=0.029); (ii) CD38 expression, ranging from 1% in subset #4 to 10% in subset #201 (p=0.013); (iii) the distribution of del(13q), peaking at a remarkable 92% in subset #29 versus only 37% in subset #16 (p Disclosures Tausch: Gilead: Other: Travel support. Shanafelt:Glaxo-Smith_Kline: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Polyphenon E Int'l: Research Funding; Hospira: Research Funding; Janssen: Research Funding; Pharmactckucs: Research Funding; Cephalon: Research Funding. Niemann:Gilead: Consultancy; Janssen: Consultancy; Roche: Consultancy; Novartis: Other: Travel grant. Langerak:InVivoScribe: Patents & Royalties: Licensing of IP and Patent on BIOMED-2-based methods for PCR-based Clonality Diagnostics.; DAKO: Patents & Royalties: Licensing of IP and Patent on Split-Signal FISH. Royalties for Dept. of Immunology, Erasmus MC, Rotterdam, NL; Roche: Other: Lab services in the field of MRD diagnostics provided by Dept of Immunology, Erasmus MC (Rotterdam). Hallek:Celgene: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; AbbVie: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Roche: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Boehringher Ingelheim: Honoraria, Other: Speakers Bureau and/or Advisory Boards; Pharmacyclics: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Mundipharma: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Janssen: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Gilead: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding. Ghia:Janssen Pharmaceuticals: Research Funding.
- Published
- 2015
24. Clinical Impact of Stereotyped Antigen Receptors in Chronic Lymphocytic Leukemia
- Author
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Karin E. Smedby, Monica Facco, Nicholas Chiorazzi, Anastasia Hadzidimitriou, Yorick Sandberg, Christian H. Geisler, Myriam Boudjoghra, Larry Mansouri, Florence Nguyen-Khac, Lesley-Ann Sutton, Diane F. Jelinek, Gunnar Juliusson, E. Minga, Silvio Veronese, Anne Gardiner, Frederic Davi, Šárka Pospíšilová, Anton W. Langerak, Lydia Scarfò, Andreas Agathangelidis, Zadie Davis, Marco Montillo, Nikos Darzentas, David Oscier, J. Yan, Richard Rosenquist, Lone Bredo Pedersen, Charles C. Chu, Fie Juhl Vojdeman, Kirsten van Lom, Athina Tsanousa, Kostas Stamatopoulos, Achilles Anagnostopoulos, Tatiana Tzenou, Panagiotis Baliakas, Paolo Ghia, Hana Skuhrová Francová, Karla Plevová, Marie-Paule Lefranc, Denis Moreno, Panagiotis Panagiotidis, Maria Chatzouli, Chrysoula Belessi, Livio Trentin, Mark Catherwood, Lefteris Angelis, Tait D. Shanafelt, and Véronique Giudicelli
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medicine.medical_specialty ,Hematology ,Chronic lymphocytic leukemia ,Immunology ,breakpoint cluster region ,Clone (cell biology) ,Cell Biology ,Biology ,medicine.disease ,Biochemistry ,Somatic evolution in cancer ,Stereotypy (non-human) ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Chromosome abnormality ,IGHV@ - Abstract
In chronic lymphocytic leukemia (CLL), the molecular features of the clonotypic B-cell receptor immunoglobulins (BcR IG) are set from the birth of the clone and in contrast to genetic aberrations, remain stable overtime, rendering the BcR IG a reference biomarker that is usually not significantly affected by clonal evolution. Approximately 30% of CLL cases carry quasi-identical BcR IGs and can be assigned to distinct stereotyped subsets. While preliminary evidence alludes to BcR IG stereotypy being relevant from a clinical viewpoint, this aspect has never been explored systematically or in a cohort of adequate size to enable meaningful conclusions. In order to assess the clinical implications of BcR IG stereotypy, we evaluated clinicobiological data from 8593 CLL patients, particularly focusing on 14 major stereotyped subsets of cases with unmutated (U-CLL) or mutated IGHV genes (M-CLL). The largest subset was #2 (n=254, 3%), within which 156 and 98 cases were M-CLL and U-CLL, respectively, followed by U-CLL subsets #1 (n=173, 2%) and #7 (n=123, 1.4%). Amongst M-CLL, the largest subsets were #4 (n=94, 1.1%) and #148 (n=92, 1%). Stereotyped subsets, even of the same mutational category i.e. U-CLL or M-CLL, exhibited significant clinicobiological differences regarding: age at diagnosis (median age ranging from 53-68 years, p75% in M-CLL subsets #77 and #148 (p Disclosures Montillo: Janssen: Honoraria.
25. Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: A retrospective multicentre study
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Karin E. Smedby, Panagiotis Panagiotidis, Larry Mansouri, Marie-Paule Lefranc, Lydia Scarfò, Anastasia Hadzidimitriou, Yorick Sandberg, Andreas Agathangelidis, Mark Catherwood, Gunnar Juliusson, Diane F. Jelinek, Nikos Darzentas, Livio Trentin, Tait D. Shanafelt, Anne Gardiner, Frederic Davi, Monica Facco, Silvio Veronese, Šárka Pospíšilová, Xiao-Jie Yan, Véronique Giudicelli, Florence Nguyen-Khac, Kirsten van Lom, Michele Nichelatti, Paolo Ghia, Eva Minga, Richard Rosenquist, Marco Montillo, Charles C. Chu, Panagiotis Baliakas, David Oscier, Lone Bredo Pedersen, Nicholas Chiorazzi, Maria Chatzouli, Chrysoula Belessi, Athina Tsanousa, Christian H. Geisler, Anton W. Langerak, Lesley-Ann Sutton, Lefteris Angelis, Tatiana Tzenou, Karla Plevová, Myriam Boudjogra, Zadie Davis, Kostas Stamatopoulos, Achilles Anagnostopoulos, Hana Skuhrová Francová, and Fie Juhl Vojdeman
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Oncology ,stereotyped B-cell receptor, chronic lymphocytic leukemia ,medicine.medical_specialty ,Hematology ,business.industry ,Chronic lymphocytic leukemia ,Cancer ,stereotyped B-cell receptor ,medicine.disease ,Clinical trial ,Stereotypy (non-human) ,Internal medicine ,Immunology ,Cohort ,medicine ,chronic lymphocytic leukemia ,media_common.cataloged_instance ,Immunoglobulin heavy chain ,European union ,business ,media_common - Abstract
Summary Background About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi-identical B-cell receptor immunoglobulins and can be assigned to distinct stereotyped subsets. Although preliminary evidence suggests that B-cell receptor immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has never been explored in a systematic manner or in a cohort of adequate size that would enable clinical conclusions to be drawn. Methods For this retrospective, multicentre study, we analysed 8593 patients with CLL for whom immunogenetic data were available. These patients were followed up in 15 academic institutions throughout Europe (in Czech Republic, Denmark, France, Greece, Italy, Netherlands, Sweden, and the UK) and the USA, and data were collected between June 1, 2012, and June 7, 2013. We retrospectively assessed the clinical implications of CLL B-cell receptor immunoglobulin stereotypy, with a particular focus on 14 major stereotyped subsets comprising cases expressing unmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain variable genes. The primary outcome of our analysis was time to first treatment, defined as the time between diagnosis and date of first treatment. Findings 2878 patients were assigned to a stereotyped subset, of which 1122 patients belonged to one of 14 major subsets. Stereotyped subsets showed significant differences in terms of age, sex, disease burden at diagnosis, CD38 expression, and cytogenetic aberrations of prognostic significance. Patients within a specific subset generally followed the same clinical course, whereas patients in different stereotyped subsets—despite having the same immunoglobulin heavy variable gene and displaying similar immunoglobulin mutational status—showed substantially different times to first treatment. By integrating B-cell receptor immunoglobulin stereotypy (for subsets 1, 2, and 4) into the well established Dohner cytogenetic prognostic model, we showed these, which collectively account for around 7% of all cases of CLL and represent both U-CLL and M-CLL, constituted separate clinical entities, ranging from very indolent (subset 4) to aggressive disease (subsets 1 and 2). Interpretation The molecular classification of chronic lymphocytic leukaemia based on B-cell receptor immunoglobulin stereotypy improves the Dohner hierarchical model and refines prognostication beyond immunoglobulin mutational status, with potential implications for clinical decision making, especially within prospective clinical trials. Funding European Union; General Secretariat for Research and Technology of Greece; AIRC; Italian Ministry of Health; AIRC Regional Project with Fondazione CARIPARO and CARIVERONA; Regione Veneto on Chronic Lymphocytic Leukemia; Nordic Cancer Union; Swedish Cancer Society; Swedish Research Council; and National Cancer Institute (NIH).
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