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1. De novo accelerated phase of chronic myeloid leukemia should be recognized even in the era of tyrosine kinase inhibitors

Author

Hornak, Tomas, primary, Mayer, Jiri, additional, Cicatkova, Petra, additional, Semerad, Lukas, additional, Kvetkova, Anezka, additional, Klamova, Hana, additional, Faber, Edgar, additional, Belohlavkova, Petra, additional, Karas, Michal, additional, Stejskal, Lukas, additional, Cmunt, Eduard, additional, Cerna, Olga, additional, Srbova, Dana, additional, Zizkova, Hana, additional, Vrablova, Lucia, additional, Skoumalova, Ivana, additional, Voglova, Jaroslava, additional, Jurkova, Tereza, additional, Chrapava, Marika, additional, Jurcek, Tomas, additional, Jeziskova, Ivana, additional, Jarosova, Marie, additional, Machova Polakova, Katerina, additional, Papajik, Tomas, additional, Zak, Pavel, additional, Jindra, Pavel, additional, and Zackova, Daniela, additional

Published
2024
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2. P669: ANALYSIS OF FACTORS INFLUENCING THE DECISION TO STOP TKI TREATMENT IN CML PATIENTS IN DEEP MOLECULAR RESPONSE

Author

Semerad, Lukas, primary, Žáčková, Daniela, additional, Belohlavkova, Petra, additional, Voglova, Jaroslava, additional, Žák, Pavel, additional, Faber, Edgar, additional, Papajik, Tomas, additional, Skoumalova, Ivana, additional, Karas, Michal, additional, Jindra, Pavel, additional, Klamová, Hana, additional, Salek, Cyril, additional, Srbová, Dana, additional, Zizkova, Hana, additional, Stejskal, Lukas, additional, Cerna, Olga, additional, Cmunt, Eduard, additional, Cicatkova, Petra, additional, Kvetkova, Anezka, additional, Hornak, Tomas, additional, Jeziskova, Ivana, additional, Jurcek, Tomas, additional, Weinbergerová, Barbora, additional, Prochazkova, Jirina, additional, Machova Polakova, Katerina, additional, Svobodnik, Adam, additional, Stepanova, Radka, additional, and Mayer, Jiri, additional

Published
2023
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3. Real World Population- Based Data from Nationwide Registry Support the Existence of Accelerated Phase in Newly Diagnosed Chronic Myeloid Leukemia (CML) Patients Even in Tyrosine Kinase Inhibitors (TKIs) Era

Author

Hornak, Tomas, Mayer, Jiri, Cicatkova, Petra, Semerad, Lukas, Kvetkova, Anezka, Klamova, Hana, Faber, Edgar, Belohlavkova, Petra, Karas, Michal, Stejskal, Lukas, Cmunt, Eduard, Cerna, Olga, Srbova, Dana, Zizkova, Hana, Vrablova, Lucia, Skoumalova, Ivana, Voglova, Jaroslava, Jurkova, Tereza, Chrapava, Marika, Jurcek, Tomas, Jeziskova, Ivana, Jarosova, Marie, Machova Polakova, Katerina, Papajik, Tomas, Zak, Pavel, Jindra, Pavel, and Zackova, Daniela

Published
2023
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4. Current survival measures reliably reflect modern sequential treatment in CML: Correlation with prognostic stratifications

Author

Pavlik, Tomas, Janousova, Eva, Mayer, Jiri, Indrak, Karel, Jarosova, Marie, Klamova, Hana, Zackova, Daniela, Voglova, Jaroslava, Faber, Edgar, Karas, Michal, Polakova, Katerina Machova, Racil, Zdenek, Demeckova, Eva, Demitrovicova, Ludmila, Tothova, Elena, Chudej, Juraj, Markuljak, Imrich, Cmunt, Eduard, Kozak, Tomas, Muzik, Jan, and Dusek, Ladislav

Published
2013
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6. Insulin resistance is an underlying mechanism of impaired glucose metabolism during nilotinib therapy

Author

Racil, Zdenek, primary, Koritakova, Eva, additional, Sacha, Tomasz, additional, Klamova, Hana, additional, Belohlavkova, Petra, additional, Faber, Edgar, additional, Rea, Delphine, additional, Malaskova, Ludmila, additional, Prochazkova, Jirina, additional, Zackova, Daniela, additional, Voglova, Jaroslava, additional, Wącław, Joanna, additional, Cetkovsky, Petr, additional, Zak, Pavel, additional, and Mayer, Jiri, additional

Published
2018
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8. Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib.

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service d'hématologie, Gullaksen, Stein-Erik, Skavland, Jørn, Gavasso, Sonia, Tosevski, Vinko, Warzocha, Krzysztof, Dumrese, Claudia, Ferrant, Augustin, Gedde-Dahl, Tobias, Hellmann, Andrzej, Janssen, Jeroen, Labar, Boris, Lang, Alois, Majeed, Waleed, Mihaylov, Georgi, Stentoft, Jesper, Stenke, Leif, Thaler, Josef, Thielen, Noortje, Verhoef, Gregor, Voglova, Jaroslava, Ossenkoppele, Gert, Hochhaus, Andreas, Hjorth-Hansen, Henrik, Mustjoki, Satu, Sopper, Sieghart, Giles, Francis, Porkka, Kimmo, Wolf, Dominik, Gjertsen, Bjørn Tore, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service d'hématologie, Gullaksen, Stein-Erik, Skavland, Jørn, Gavasso, Sonia, Tosevski, Vinko, Warzocha, Krzysztof, Dumrese, Claudia, Ferrant, Augustin, Gedde-Dahl, Tobias, Hellmann, Andrzej, Janssen, Jeroen, Labar, Boris, Lang, Alois, Majeed, Waleed, Mihaylov, Georgi, Stentoft, Jesper, Stenke, Leif, Thaler, Josef, Thielen, Noortje, Verhoef, Gregor, Voglova, Jaroslava, Ossenkoppele, Gert, Hochhaus, Andreas, Hjorth-Hansen, Henrik, Mustjoki, Satu, Sopper, Sieghart, Giles, Francis, Porkka, Kimmo, Wolf, Dominik, and Gjertsen, Bjørn Tore

Abstract

Monitoring of single cell signal transduction in leukemic cellular subsets has been proposed to provide deeper understanding of disease biology and prognosis, but has so far not been tested in a clinical trial of targeted therapy. We developed a complete mass cytometry analysis pipeline for characterization of intracellular signal transduction patterns in the major leukocyte subsets of chronic phase chronic myeloid leukemia. Changes in phosphorylated Bcr-Abl1 and the signaling pathways involved were readily identifiable in peripheral blood single cells already within three hours of the patient receiving oral nilotinib. The signal transduction profiles of healthy donors were clearly distinct from those of the patients at diagnosis. Furthermore, using principal component analysis, we could show that phosphorylated transcription factors STAT3 (Y705) and CREB (S133) within seven days reflected BCR-ABL1 at three and six months. Analyses of peripheral blood cells longitudinally collected from patients in the ENEST1st clinical trial showed that single cell mass cytometry appears to be highly suitable for future investigations addressing tyrosine kinase inhibitor dosing and effect. ().

Published
2017

9. Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib

Author

Gullaksen, Stein-Erik, primary, Skavland, Jørn, additional, Gavasso, Sonia, additional, Tosevski, Vinko, additional, Warzocha, Krzysztof, additional, Dumrese, Claudia, additional, Ferrant, Augustin, additional, Gedde-Dahl, Tobias, additional, Hellmann, Andrzej, additional, Janssen, Jeroen, additional, Labar, Boris, additional, Lang, Alois, additional, Majeed, Waleed, additional, Mihaylov, Georgi, additional, Stentoft, Jesper, additional, Stenke, Leif, additional, Thaler, Josef, additional, Thielen, Noortje, additional, Verhoef, Gregor, additional, Voglova, Jaroslava, additional, Ossenkoppele, Gert, additional, Hochhaus, Andreas, additional, Hjorth-Hansen, Henrik, additional, Mustjoki, Satu, additional, Sopper, Sieghart, additional, Giles, Francis, additional, Porkka, Kimmo, additional, Wolf, Dominik, additional, and Gjertsen, Bjørn Tore, additional

Published
2017
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10. Single-Cell Immune Signatures in Patients with Chronic Phase Chronic Myeloid Leukemia (CML) Treated with Nilotinib: An ENEST1st Sub Study

Author

Gullaksen, Stein-Erik, primary, Skavland, Jørn, additional, Warzocha, Krzysztof, additional, Gavasso, Sonia, additional, Tosevski, Vinko, additional, Thielen, Noortje, additional, Voglova, Jaroslava, additional, Ferrant, Augustin, additional, Linkesch, Werner, additional, Thaler, Josef, additional, Lang, Alois, additional, Stentoft, Jesper, additional, Gedde-Dahl, Tobias, additional, Hjorth-Hansen, Henrik, additional, Majeed, Waleed, additional, Verhoef, Gregor, additional, Hellmann, Andrzej, additional, Mihaylov, Georgi G., additional, Dumrese, Claudia, additional, Giles, Frank, additional, Hochhaus, Andreas, additional, Sopper, Sieghart, additional, Stenke, Leif, additional, Labar, Boris, additional, Janssen, Jeroen, additional, Porkka, Kimmo, additional, Ossenkoppele, Gert J., additional, Mustjoki, Satu, additional, Wolf, Dominik, additional, and Gjertsen, Bjorn T., additional

Published
2015
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11. Outcome and management of pregnancies in severe chronic neutropenia patients by the European branch of the severe chronic neutropenia international registry

Author

UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique, Zeidler, Cornelia, Grote, Ulrike A. H., Nickel, Anna, Brand, Beate, Carlsson, Göran, Cortesão, Emília, Dufour, Carlo, Duhem, Caroline, Notheis, Gundula, Papadaki, Helen A., Tamary, Hannah, Tjønnfjord, Geir E., Tucci, Fabio, Van Droogenbroeck, Jan, Vermylen, Christiane, Voglova, Jaroslava, Xicoy, Blanca, Welte, Karl, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique, Zeidler, Cornelia, Grote, Ulrike A. H., Nickel, Anna, Brand, Beate, Carlsson, Göran, Cortesão, Emília, Dufour, Carlo, Duhem, Caroline, Notheis, Gundula, Papadaki, Helen A., Tamary, Hannah, Tjønnfjord, Geir E., Tucci, Fabio, Van Droogenbroeck, Jan, Vermylen, Christiane, Voglova, Jaroslava, Xicoy, Blanca, and Welte, Karl

Abstract

Long-term granulocyte-colony stimulating factor treatment has been shown to be safe and effective in severe chronic neutropenia patients. However, data on its use during pregnancy are limited. To address this issue, we analyzed all pregnancies reported to the European branch of the Severe Chronic Neutropenia International Registry since 1994. A total of 38 pregnancies in 21 women with chronic neutropenia (16 pregnancies in 10 women with congenital, 10 in 6 women with cyclic, 12 in 5 women with idiopathic neutropenia) were reported. Granulocyte-colony stimulating factor was administered throughout pregnancy in 16 women and for at least one trimester in a further 5 women. No major differences were seen between treated and untreated women with respect to pregnancy outcome, newborn complications and infections. In addition, we evaluated the genetic transmission of known or suspected genetic defects in 16 mothers having 22 newborns as well as in 8 men fathering 15 children. As a proof of inheritance, neutropenia was passed on to the newborn in 58% from female and in 62% from male patients with ELANE mutations, but also to some newborns from parents with unknown gene mutation. Based on our results, granulocyte-colony stimulating factor therapy has been shown to be safe for mothers throughout pregnancies and for newborns without any signs of teratogenicity. With an increasing number of adult patients, genetic counseling prior to conception and supportive care of mothers during pregnancy are crucial. The acceptance of having affected children may reflect the high quality of life obtained due to this treatment. © 2014 Ferrata Storti Foundation.

Published
2014

12. “Duration of Deep Molecular Response” Has Most Impact on the Success of Cessation of Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukemia - Results from the EURO-SKI Trial

Author

Saussele, Susanne, Richter, Johan, Guilhot, Joelle, Hjorth-Hansen, Henrik, Almeida, Antonio Medina de, Janssen, Jeroen J.W.M., Mayer, Jiri, Koskenvesa, Perttu, Panayiotidis, Panayiotis, Olsson-Strömberg, Ulla, Steegmann, Juan Luis, Vestergaard, Hanne, Ehrencrona, Hans, Kairisto, Veli, Machová Poláková, Kateřina, Müller, Martin, Mustjoki, Satu, Berger, Marc G., Rousselot, Philippe, Escoffre-Barbe, Martine, Etienne, Gabriel, Dengler, Jolanta, Rigal-Huguet, Françoise, von Bubnoff, Nikolas, Klamova, Hana, Faber, Edgar, Guilhot, François, Lotfi, Kourosh, Rea, Delphine, Brümmendorf, Tim H., de Greef, Gorgine, Stenke, Leif, Nicolini, Franck Emmanuel, Legros, Laurence, Burchert, Andreas, Voglová, Jaroslava, Charbonnier, Aude, Gyan, Emmanuel, Goebeler, Maria-Elisabeth, Westerweel, Peter E., Hochhaus, Andreas, Pfirrmann, Markus, and Mahon, Francois-Xavier

Published
2017
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13. Comparison of Glucose and Lipid Metabolism Abnormality during Nilotinib, Imatinib and Dasatinib Therapy – Results of Enigma 2 Study

Author

Daniela Zackova, Voglova Jaroslava, Pavel Zak, Tomasz Sacha, Hana Klamova, Petra Belohlavkova, Edgar Faber, Jiri Mayer, Racil Zdenek, Petr Cetkovsky, and Malaskova Ludmila

Subjects
medicine.medical_specialty, Adiponectin, business.industry, C-peptide, Insulin, medicine.medical_treatment, Immunology, Cell Biology, Hematology, medicine.disease, Biochemistry, 3. Good health, Dasatinib, chemistry.chemical_compound, Endocrinology, Insulin resistance, Imatinib mesylate, chemistry, Nilotinib, Internal medicine, Diabetes mellitus, medicine, business, medicine.drug
Abstract

[Graphic][1] Background: Recently we have published results of pilot study on CML patients demonstrating fast development of hyperinsulinaemia, peripheral insulin resistance, hypoadiponectinaemia and hypercholesterolemia during nilotinib therapy. Aims: To analyze results from follow up multicenter study “ENIGMA 2” with the aim to confirm or to exclude results from the pilot study, as well as to analyze whether these abnormalities are detected in control groups of patients treated with other TKIs - imatinib and dasatinib. Methods: Patients received intensive laboratory workup before the start of TKI and after 3 month of therapy. This included fasting insulin, glucose, adiponectin and lipid serum concentration, HbA1c and oral glucose tolerance test. Patients with TKI treatment interruption for >2 weeks and/or dose reduction for > 25% were excluded. Results: Between 2/2011-6/2014 in 5 centers 37 CML patients initiated therapy with nilotinib, 18 with imatinib and 8 with dasatinib. After 3 months patients treated with nilotinib developed significant hypersinulinaemia and hyperglycaemia as result of fast development of peripheral insulin resistance. This was proved by significant increase in HOMA-2 index during 3 months of nilotinib therapy (mean – 1.4 vs. 1.8; p = 0.0023). Moreover, we have proved significant decrease of adiponectin (major insulin sensitizer) concentration as well as significant increase in total and LDL cholesterol concentration after 3 month of nilotinib treatment. Details are presented in Table. Contrary – none of these abnormalities were detected in the control group of patients treated with imatinib and dasatinib, including any change in insulin resistance measured by HOMA-2 index (means – 0.9 vs. 1.3; p = 0.1046 and 1.1 vs. 1.1; p = 0.9255). Moreover, administration of imatinib (and probably also dasatinib, however only limited data are available at this moment) leads to increase of adiponectin concentration, which serves as major insulin sensitizer in peripheral tissues. Conclusions: Our study proved fast development of peripheral insulin resistance already during the first 3 months of nilotinib therapy as underlying cause of glucose and secondary also lipid metabolism impairment during this treatment. Moreover, this was not proved for patients treated with imatinib and dasatinb and significant increase in adiponectin concentration during imatinib (and probably dasatinib) therapy could at least partly explain observed amelioration of diabetes 2 during its administration described in some studies Supported by the CELL – the Czech Leukemia Study Group – for life | NILOTINIB THERAPY (n=37) | |:--------------------------------------:| ---------------- | | | Start | Month 3 | p | | mean (range) | mean (range) | | Fasting glucose [mmol/l] | 5.3 (4.5-6.7) | 5.7 (4.6-8.2)

Published
2014
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14. Chronic Myeloid Leukemia Patients in Prolonged Remission following Interferon-alpha Monotherapy Have Distinct Cytokine and Oligoclonal Lymphocyte Profile

Author

University of Helsinki, Medicum, University of Helsinki, Dep. of Bacteriology and Immunology (Haartman Institute) (-2009), University of Helsinki, Clinicum, Kreutzman, Anna, Rohon, Peter, Faber, Edgar, Indrak, Karel, Juvonen, Vesa, Kairisto, Veli, Voglova, Jaroslava, Sinisalo, Marjatta, Flochova, Emilia, Vakkila, Jukka, Arstila, Petteri, Porkka, Kimmo, Mustjoki, Satu, University of Helsinki, Medicum, University of Helsinki, Dep. of Bacteriology and Immunology (Haartman Institute) (-2009), University of Helsinki, Clinicum, Kreutzman, Anna, Rohon, Peter, Faber, Edgar, Indrak, Karel, Juvonen, Vesa, Kairisto, Veli, Voglova, Jaroslava, Sinisalo, Marjatta, Flochova, Emilia, Vakkila, Jukka, Arstila, Petteri, Porkka, Kimmo, and Mustjoki, Satu

Published
2011

15. Early PK-Analysis Predicts Molecular Response In Patients With Early Chronic Phase Chronic Myelogenous Leukemia (CML-CP) Treated With Frontline Nilotinib

Author

Wolf, Dominik, primary, Skavland, Jorn, additional, Seger, Christoph, additional, Sopper, Sieghart, additional, Jedrzejczak, Wiktor-Wieslaw, additional, Sertic, Dubravka, additional, Voglova, Jaroslava, additional, Mustjoki, Satu, additional, Stenke, Leif, additional, Ferrant, Augustin, additional, Greil, Richard, additional, Lang, Alois, additional, Thaler, Josef, additional, Linkesch, Werner, additional, Duletić-Načinović, Antica, additional, Hellmann, Andrzej, additional, Mihaylov, Georgi G., additional, Gedde-Dahl, Tobias, additional, Hjorth-Hansen, Henrik, additional, Majeed, Waleed, additional, Stentoft, Jesper, additional, Verhoef, Gregor, additional, Van Droogenbroeck, Jan, additional, Mark, Ute, additional, Haenig, Jens, additional, Jurjonas, Nidas, additional, Giles, Frank, additional, Hochhaus, Andreas, additional, Porkka, Kimmo, additional, Ossenkoppele, Gert J., additional, and Gjertsen, Bjorn T., additional

Published
2013
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16. Interferon Alpha Treated Patients with Chronic Myeloid Leukemia (CML) In Prolonged Complete Remission Have Increased Numbers of NK-Cells and Clonal Gamma-Delta T-Cells, and a Distinct Plasma Cytokine Profile.

Author

Kreutzman, Anna, primary, Rohon, Peter, additional, Faber, Edgar, additional, Indrak, Karel, additional, Juvonen, Vesa, additional, Kairisto, Veli, additional, Voglova, Jaroslava, additional, Sinisalo, Marjatta, additional, Flochova, Emilia, additional, Arstila, Petteri, additional, Porkka, Kimmo, additional, and Mustjoki, Satu, additional

Published
2010
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17. The Outcome of Unselected Patients with Chronic Myeloid Leukemia (CML) In Chronic Phase (CP) Treated with Imatinib In the First Line and the Prognostic Value of ELN Defined Responses – Population Based Analysis of 458 Patients Treated Between 2003–2009.

Author

Klamova, Hana, primary, Zackova, Daniela, additional, Faber, Edgar, additional, Steinerova, Katerina, additional, Karas, Michal, additional, Demeckova, Eva, additional, Voglova, Jaroslava, additional, Demitrovicova, Ludmila, additional, Tothova, Elena, additional, Chudej, Juraj, additional, Markuljak, Imrich, additional, Kozak, Tomas, additional, Cmunt, Eduard, additional, Jarosova, Marie, additional, Machova-Polakova, Katerina, additional, Michalova, Kyra, additional, Dusek, Ladislav, additional, Muzik, Jan, additional, Mistrik, Martin, additional, Mayer, Jiri, additional, Trneny, Marek, additional, and Indrak, Karel, additional

Published
2010
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19. Successful Treatment with Imatinib Mesylate Significantly Decreases Plasma Levels of Vascular Endothelial Growth Factor (VEGF) and Soluble Endoglin (sCD105) but Not Basic Fibroblast Growth Factor (bFGF) or Angiopoietin-2 (Ang-2) in Patients with Chronic Myeloid Leukemia (CML) in Chronic Phase

Author

Smolej, Lukas, primary, Andrys, Ctirad, primary, Voglova, Jaroslava, primary, Belohlavkova, Petra, primary, Rabasova, Jana, primary, Beranek, Martin, primary, and Maly, Jaroslav, primary

Published
2008
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20. Outcome and management of pregnancies in severe chronic neutropenia patients by the European Branch of the Severe Chronic Neutropenia International Registry.

Author

Zeidler C, Grote UA, Nickel A, Brand B, Carlsson G, Cortesão E, Dufour C, Duhem C, Notheis G, Papadaki HA, Tamary H, Tjønnfjord GE, Tucci F, Van Droogenbroeck J, Vermylen C, Voglova J, Xicoy B, and Welte K

Subjects
Adult, Cohort Studies, Disease Management, Europe epidemiology, Female, Humans, Infant, Newborn, Male, Neutropenia epidemiology, Pregnancy, Pregnancy Complications, Hematologic epidemiology, Pregnancy Outcome epidemiology, Treatment Outcome, Young Adult, Neutropenia diagnosis, Neutropenia therapy, Pregnancy Complications, Hematologic diagnosis, Pregnancy Complications, Hematologic therapy, Registries
Abstract

Long-term granulocyte-colony stimulating factor treatment has been shown to be safe and effective in severe chronic neutropenia patients. However, data on its use during pregnancy are limited. To address this issue, we analyzed all pregnancies reported to the European branch of the Severe Chronic Neutropenia International Registry since 1994. A total of 38 pregnancies in 21 women with chronic neutropenia (16 pregnancies in 10 women with congenital, 10 in 6 women with cyclic, 12 in 5 women with idiopathic neutropenia) were reported. Granulocyte-colony stimulating factor was administered throughout pregnancy in 16 women and for at least one trimester in a further 5 women. No major differences were seen between treated and untreated women with respect to pregnancy outcome, newborn complications and infections. In addition, we evaluated the genetic transmission of known or suspected genetic defects in 16 mothers having 22 newborns as well as in 8 men fathering 15 children. As a proof of inheritance, neutropenia was passed on to the newborn in 58% from female and in 62% from male patients with ELANE mutations, but also to some newborns from parents with unknown gene mutation. Based on our results, granulocyte-colony stimulating factor therapy has been shown to be safe for mothers throughout pregnancies and for newborns without any signs of teratogenicity. With an increasing number of adult patients, genetic counseling prior to conception and supportive care of mothers during pregnancy are crucial. The acceptance of having affected children may reflect the high quality of life obtained due to this treatment., (Copyright© Ferrata Storti Foundation.)

Published
2014
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