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51. [Density expression of the CD20 antigen on population of tumor cells in patients with chronic B-lymphocyte lymphoproliferative diseases]

Author: V, Suková, M, Klabusay, P, Coupek, Y, Brychtová, M, Doubek, and J, Mayer
Subjects: Male, B-Lymphocytes, Lymphoma, B-Cell, Leukemia, B-Cell, Humans, Female, Lymphoma, Mantle-Cell, Middle Aged, Antigens, CD20, Flow Cytometry, Leukemia, Lymphocytic, Chronic, B-Cell, Aged
Abstract: Rituximab is being used successfully in the treatment of patients with chronic B-cell lymphoproliferative diseases. The success of treatment by rituximab is influenced, among other factors, by the antigen density on tumor cells. Therefore, the authors analyzed and compared the densities of the CD20 antigen in patients with chronic lymphoproliferative diseases.Previously untreated patients with B-chronic lymphocytic leukemia (B-CLL), mantle-cell lymphoma (MCL), and small-cell lymphocytic lymphoma (SCLL) were evaluated by flow cytometry. The control group consisted of blood donors. The CD20 density was measured on tumor cell populations in patients and on the B-lymphocytes of the control group. The density was expressed in MESE In the patients with B-CLL and SCLL, the CD20 density was low (25,300 vs. 36,100 MESF) and it was significantly lower than in donors (172,800 MESF; p0.001). The difference between B-CLL and SCLL patients was not statistically significant. The density in MCL patients (196,300 MESF) was comparable to that of donors.We did not prove statistical different density of CD20 antigen in patients with SCLL when compared with B-CLL patients. High density in MCL patients may be helpful in differential diagnosis against B-CLL and
Published: 2006

52. [Anagrelide in the treatment of essential thrombocythemia (ET) and other myeloproliferative disorders with thrombocythemia based on data from patient register in the CR]

Author: M, Penka, M, Doubek, J, Schwarz, R, Pytlík, P, Dulícek, J, Kissová, A, Hlusí, V, Vozobulová, O, Cerná, Y, Brychtová, T, Szotkowski, Z, Volková, J, Seghetová, M, Schutzová, I, Hadacová, I, Hochová, J, Voglová, O, Siroký, D, Belada, T, Lhot'anová, B, Bubeník, M, Vránová, M, Micaníková, and L, Dusek
Subjects: Thrombocytosis, Myeloproliferative Disorders, Quinazolines, Humans, Platelet Aggregation Inhibitors, Thrombocythemia, Essential
Abstract: Anagrelide hydrochloride is an effective drug used in patients with ET and other myeloproliferative disorders with thrombocythemia to selectively decrease the number of thrombocytes. Indications for use of anagrelide were described in detail in Czech medical literature. Since 2005 data concerning treatment with anagrelide in some medical clinics have been collected in patient register showing course of treatment from 2004, when the medicament obtained marketing authorization from State Institute for Drug Control to be used in the treatment of thrombocythemia in myeloproliferative disorders. Aim of patient register is to monitor medical effect of anagrelide therapy and incidence of adverse effects in patients with ET and other myeloproliferative disorders and subsequent analysis of collected data. At the moment patient register contains data from 154 patients.
Published: 2006

53. Acute myeloid leukemia treatment in patients over 60 years of age. Comparison of symptomatic, palliative, and aggressive therapy

Author: M, Doubek, I, Palasek, Y, Brychtova, I, Buchtova, and J, Mayer
Subjects: Aged, 80 and over, Male, Daunorubicin, Palliative Care, Remission Induction, Cytarabine, Hematopoietic Stem Cell Transplantation, Middle Aged, Prognosis, Survival Analysis, Hospitalization, Treatment Outcome, Leukemia, Myeloid, Acute Disease, Antineoplastic Combined Chemotherapy Protocols, Humans, Hydroxyurea, Female, Mitoxantrone, Aged, Retrospective Studies
Abstract: State-of-art of aggressive treatment of acute myeloid leukemia (AML) in patients older than 60 years is one of the least satisfactory topics of present-day hematology. This fact led us to ask the following questions: Does it make sense to administer aggressive treatment to older patients with AML? Could it be that we only complicate the rest of the life of these older patients with AML, by using aggressive treatment? Would they not benefit more from palliative or symptomatic therapy? What is the quality of life of older patients with AML like? Therefore, to try to answer these questions, we performed the next analysis. A retrospective analysis was performed including (without any selection) all consecutive patients over 60 years of age who were treated with AML in our centre from 1998 till 2003. We have analyzed data from 137 elderly patients who were diagnosed with AML (excluding acute promyelocytic leukemia). Median survival from diagnosis in the aggressive (curative) therapy group was 4 months, in palliative therapy group 2 months and in symptomatic therapy group 0.8 months. Patients receiving curative therapy spent in a hospital (in-patient stay) 70% (median) of their life after diagnosis of AML, patients receiving palliative treatment 64% (median) of their life after diagnosis, and patients receiving symptomatic treatment 100% (median), respectively. Only marginal advantage in the median overall survival is observed in the group of aggressively treated patients.
Published: 2005

54. [The POEMS syndrome: a case report]

Author: M, Doubek, A, Krivanová, Z, Adam, and I, Niedermayerová
Subjects: POEMS Syndrome, Humans, Female, Middle Aged
Abstract: The POEMS syndrome is a synopsis of different symptoms such as polyneuropathy, organomegaly, endocrine disturbances, M-protein and skin changes. POEMS syndrome has a complete and incomplete form. The leading symptoms are neuropathy and the monoclonal gammopathy. The authors report about a 55 year old lady who fell ill with this disease.
Published: 2005

55. A note on the decreased number and loss of fibrillar centres in nucleoli of apoptotic HL-60 leukaemic granulocytic precursors produced by 5-aminolaevulinic acid-based photodynamic treatment

Author: K, Smetana, D, Grebenová, I, Jirásková, M, Doubek, Y, Marinov, and Z, Hrkal
Subjects: Photosensitizing Agents, Light, Humans, Apoptosis, Cell Differentiation, HL-60 Cells, Aminolevulinic Acid, Cell Nucleolus, Granulocytes
Abstract: The nuclear and nucleolar ultrastructure was studied by means of conventional transmission electron microscopy to provide more and complementary information on nucleolar changes accompanying the apoptotic process in leukaemic granulocytic precursors (HL-60 cells) produced by PDT without previous terminal differentiation. PDT induced the apoptotic process using BL irradiation and ALA as a precursor of the photosensitizer protoporphyrin IX. PDT produced marked changes of the nucleolar ultrastructure in apoptotic cells, such as reduction of the number and loss of fibrillar centres surrounding dense fibrillar components. Such nucleolar changes are known to reflect an alteration of nucleolar biosynthetic activities, which are believed to be located at the periphery of fibrillar centres. Some electron micrographs also indicated that fibrillar centres apparently migrated out from nucleolar bodies.
Published: 2004

56. [Hereditary thrombocytopenia. Differential diagnosis of a case]

Author: M, Doubek, P, Smejkal, V, Dostálová, I, Trnavská, A, Buliková, Y, Brychtová, and J, Mayer
Subjects: Diagnosis, Differential, Adolescent, Myosin Heavy Chains, Molecular Motor Proteins, Humans, Female, Thrombocytopenia
Abstract: Hereditary thrombocytopenias are a heterogeneous group of extremely rare diseases characterized by a reduced number of blood platelets and by bleeding tendency of variable severity. Some of these diseases are exclusive to platelets, while in others the pathology extends to other cell types. Although rare, hereditary thrombocytopenias should be considered in the diagnosis. Hereditary thrombocytopenias have been classified into three groups depending on platelet volume. Hereditary thrombocytopenias with giant platelets form one of these groups. About fourteen clinical entities of inherited giant platelet disorders have been described. Bernard-Soulier syndrome, grey platelet syndrome and May-Hegglin anomaly are the most common giant platelet thrombocytopenias. May-Hegglin anomaly is condition characterized by the triad of thrombocytopenia, giant platelets, and pale-blue inclusions in leukocytes. May-Hegglin anomaly has an autosomal-dominant mode of inheritance. We described clinical and laboratory features of three adult women from one family with recently diagnosed May-Hegglin anomaly. Described cases are probably the first observed cases of May-Hegglin anomaly in the Czech lands.
Published: 2003

57. [Safety of long-term administration of conventional amphotericin B in oncology patients]

Author: M, Doubek, J, Mayer, and D, Horký
Subjects: Adult, Male, Immunocompromised Host, Antifungal Agents, Mycoses, Amphotericin B, Neoplasms, Humans, Female, Middle Aged, Kidney, Aged
Abstract: In cancer patients with persistent fever and neutropenia, amphotericin B is administered for the early treatment and prevention of the clinically occult invasive fungal infections. The major drawback of the conventional amphotericin B is its nephrotoxicity. We have previously showed that massive potassium, sodium, and magnesium supplementation, which corresponds to the amount lost in kidney during amphotericin B administration, as well as vigorous hydration, can markedly reduce nephrotoxicity of conventional amphotericin B. Clinical courses of four oncological patients treated with conventional amphotericin B suspected or proven fungal infection for a period of 24 days (two patients), 39 days, and 47 days are described. During the long-term amphotericin B administration with nephroprotective measures, no severe renal function decrease was observed in any of our patients. Massive ion supplementation corresponding to the amounts lost in kidney, as well as the vigorous hydration are effective in the prevention of the renal function decrease induced by the long-term conventional amphotericin B therapy.
Published: 2002

58. [Discovery of blood cells in the 17th century]

Author: M, Doubek
Subjects: Europe, History, 17th Century, Microscopy, Blood Cells, Animals, Humans
Abstract: Landmark works of the 17th century concerning observations of blood cells are quoted in the article. "Simple" and successively "compound" microscopes made their appearance in the late 16th century and early 17th century. In 1656, Frenchman Pierre Borel, physician-in-ordinary to the King Louis XIV, who first applied the microscope to medicine described a type of "worn" found in human blood. In 1657, Athanasius Kircher, a Jesuit priest and scientist from Germany, examined blood from plague victims, and described "worms" of plague. In 1661, 1664 and 1665, the blood cells were discerned by Marcello Malpighi. In 1678, the red blood corpuscles was described by Jan Swammerdam of Amsterdam, a Dutch naturalist and physician. The first complete account of the red cells was made by Anthony van Leeuwenhoek of Delft in the last quarter of the 17th century.
Published: 2001

59. [Activation of autologous hematopoietic stem cell transplants with interleukin-2]

Author: R, Hájek, Z, Korístek, J, Vinklárková, E, Janovská, M, Klabusay, M, Doubek, D, Dvoráková, L, Bourková, L, Dusek, J, Adler, J, Mayer, and J, Vorlícek
Subjects: Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Hematopoietic Stem Cell Transplantation, Humans, Interleukin-2, Immunotherapy, Killer Cells, Lymphokine-Activated, Multiple Myeloma, Cells, Cultured
Abstract: Recent findings of the role of the immunity in eradication of residual tumour tissue after autologous transplantation rejection leading to extensive studies on T-cell mediated specific antitumor effects or nonspecific NL-cell mediated anticancer effects. We have evaluated on the methods of adoptive cell therapy--IL-2 activation of autologous graft in the preclinical conditions. In laboratory conditions we have manipulated with autologous grafts form patients suffering with chronic myelocytic leukemia and patients suffering with multiple myeloma.Autologous graft was activated with IL-2 during 24-hours cultivation period in X-Vivo 10 medium with heparine, glutamine and Dnase. Quality of grafts after cultivation, contamination and activation of T and NK cell were evaluated. No significant differences between IL-2 activated graft and control were found. Results of autologous graft quality (CD34+, CFU-GM) were comparable with already published results. Quality of final product allowed starting of clinical experimental trials.We have proved the possibility to use IL-2 activated autologous graft in the clinical conditions. Based on our preclinical results experimental clinical trials have been initiated in patients suffering from chronic myelocytic leukemia and multiple myeloma.
Published: 2001

60. Ifosfamide- and etoposide-based chemotherapy as salvage and mobilizing regimens for poor prognosis lymphoma

Author: J, Mayer, I, Vásová, Z, Korístek, M, Navrátil, M, Klabusay, M, Doubek, J, Vorlícek, I, Cernilová, P, Vodvárka, and K, Petráková
Subjects: Adult, Male, Salvage Therapy, Adolescent, Lymphoma, Graft Survival, Hematopoietic Stem Cell Transplantation, Middle Aged, Prognosis, Hematopoietic Stem Cell Mobilization, Kinetics, Methotrexate, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Ifosfamide, Mitoxantrone, Etoposide, Mesna
Abstract: Treatment of early relapsing or resistant non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) remains problematic. High-dose chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation improves the prognosis for patients in response following standard dose regimens. We adopted the strategy of using salvage chemotherapy to debulk disease and simultaneously mobilize stem cells. We used regimens based on ifosfamide and etoposide because these drugs are not usually used as the front-line treatment. Twenty-seven patients with NHL received MINE chemotherapy (mesna and ifosfamide 1330 mg/m2 and etoposide 65 mg/m2 i.v. days 1-3, and mitoxantrone 8 mg/m2 i.v. day 1). The same schedule, but higher doses were used for PBSC stimulation (mesna, ifosfamide 1700 mg/m2, etoposide 175 mg/m2, mitoxantrone 10 mg/m2). Forty-six patients with HD received VIM chemotherapy (mesna, ifosfamide 1200 mg/m2 i.v. days 1-5, etoposide 90 mg/m2 i.v. days 1, 3, and 5, methotrexate 30 mg/m2 i.v. days 1 and 5). After both VIM and high dose MINE, chemotherapy for mobilization was followed by G-CSF administered at a dose 5-16 micrograms/kg/day depending on the clinicians judgement of the patient's pretreatment. Complete response after VIM and MINE were 39% and 38%, respectively; partial response (PR) rates were 17% and 29%, and stable disease (SD) 25% and 4%, respectively. In both groups, patients with relapsing disease had better responses than did those with primary progressive disease. Both regimens exhibited excellent mobilizing capacity. We performed 213 aphereses with a median 3 per patient starting on either day 13 as a median for VIM, or on day 12 as a median for MINE. In the majority of patients, the collection started in the time interval median +/- 1 day (n = 62, 85%). The median yields were 10.6 x 10(6) CD34+ cells/kg and 53.1 x 10(4) CFU-GM/kg for VIM, and 13.3 x 10(6) CD34+ cells/kg and 54.5 x 10(4) CFU-GM/kg for MINE. We collected at least 2.5 x 10(6) CD34+ cells/kg in all but six patients (8%), and the harvested amount of CD34+ cells was less than 1.0 x 10(6)/kg in only two patients (3%). The toxicity of VIM and MINE was minimal and chemotherapy-induced trombocytopenia did not occur with PBSC collection.
Published: 2001

61. [Who was Mr. McBean and what resulted from his death?]

Author: M, Doubek, O, Kalous, and A, Oborilová
Subjects: Humans, History, 19th Century, Multiple Myeloma
Abstract: Authors present a historical overview of multiple myeloma. The first well-known case of multiple myeloma was that of Mr. McBean described in 1846, 1847, and 1850 by John Darlympe, Henry Bence Jones, and William MacIntyre. The term multiple myeloma dates from 1873, and was introduced by von Rusitzky. In 1889, Otto Kahler published the case report about Dr. Loos, his patient with multiple myeloma. In 1895, Marschalkó described the essential characteristics of plasma cells. Authors present other interesting early cases of multiple myeloma and diagnostic advances in this disease.
Published: 2001

62. [Lymphocytosis with large granular lymphocytes: case report]

Author: Y, Brychtová, M, Doubek, J, Mayer, A, Bulíková, and M, Krahulová
Subjects: Adult, Diagnosis, Differential, Humans, Female, Lymphocytes, Lymphocytosis, Gene Rearrangement, T-Lymphocyte, Prognosis
Abstract: Lymphoproliferative disorders of large granular lymphocytes (LGL) can arise from either CD3+ T cells or CD3- natural killer cells. Polyclonal proliferation of LG lymphocytes is called LGL lymphocytosis, monoclonal proliferation of LG lymphocytes is LGL leukaemia. Prominent clinical manifestations of LGL lymphocytosis and leukaemia are bacterial infections, splenomegaly, and may be connected with rheumatic or autoimmune disorders. Hematologic findings reveal particularly lymphocytosis, and severe neutropenia. The beta chain gene of T cell receptor rearrangement analysis is necessary for distinguishing of T LGL lymphocytosis from T LGL leukaemia. The authors report a case of young woman with T cells LGL lymphroproliferative disorder, bacterial infection, reactive lymphadenopathy, and spontaneous regression of the lymphocytosis within 6 months.
Published: 2001

63. [A patient with Madelung's disease at the internal medicine department]

Author: M, Doubek and M, Tomíska
Subjects: Male, Lipomatosis, Multiple Symmetrical, Humans, Middle Aged
Abstract: Madelung disease, benign symmetrical lipomatosis, is a rare disorder of unknown etiology. It is characterized by the accumulation of fat deposits around the neck and upper body. It is often associated with glucose intolerance, liver disease, and malignant tumors of the lungs. This disease normally affects middle-aged males with a history of alcohol abuse. Surgical removal of the lipomatose mass is the treatment of choice. A case of Madelung disease in a 53-year old man with hepatopathy and respiratory failure is presented.
Published: 2000

64. [Must we be really concerned about amphotericin B toxicity in oncology patients?]

Author: J, Mayer and M, Doubek
Subjects: Antifungal Agents, Mycoses, Amphotericin B, Neoplasms, Humans, Opportunistic Infections, Kidney
Abstract: Amphotericin B treatment in oncological patients is irrepaceable due to the high frequency of mycotic infections. From data in the literature ensues that the most serious undesirable effect of amphotericin B is nephrotoxicity, manifested by a reduced glomerular filtration and impaired tubular function (in particular the development of hypokalemia, and hypomagnesaemia). Prophylaxis of nephrotoxicity is despite major efforts unsatisfactory. In the submitted work the authors tested in a major group of patients their working hypothesis based on previous observations, that prophylactic replacement of the increasing ion losses in urine during amphotericin B treatment without waiting for a decline of serum concentrations of these ions, along with adequate hydration delays or eliminates the decline of glomerular functions.During amphotericin B therapy of 25 oncological patients renal functions, Na, K and Mg urinary excretion and the serum concentrations of these ions were followed up in detail. The urinary losses were replaced. No overall prophylaxis to prevent acute toxic reactions associated with administration of the drug was used. The mean dose of amphotericin B was 0.82 mg/kg, the mean diuresis 3662 ml/24 hours. Acute toxic reactions calling for hydrocortisone administration were observed only in 6% of the patients. During treatment the urinary K and Mg losses increased significantly and had to one replaced. There was also a significant increase of the excretory fractions of K and Na. However there were no significant changes of serum ions nor a rise of creatinine. The creatinine clearance even increased slightly though insignificantly (1.384 ml/s as compared with 1.392 ml/s).Consequential hydration of patients and prophylactic replacement of urinary ion losses during amphotericin B therapy are effective in preventing ion disbalances and a decline of glomerular functions. Acute toxic reactions associated with administration of amphotericin B are infrequent.
Published: 1998

65. Current role of immunotherapy in multiple myeloma

Author: R, Hájek, Z, Adam, A, Krivanová, M, Doubek, Z, Korístek, and J, Vorlícek
Subjects: Clinical Trials as Topic, Treatment Outcome, Humans, Immunotherapy, Multiple Myeloma, Combined Modality Therapy
Abstract: Myeloablative chemotherapy improved the results of multiple myeloma treatment but the disease remains incurable. Residual disease eradication is one of the main clues for further improvement of the prognosis of myeloma patients. Interferon alpha maintenance therapy has controversial results. New methods, such as consolidation therapy, antibodies, gene therapy, interleukins, immunotoxins, dendritic cells, vaccines and induction of graft-versus-tumor effect, are tested in the phase I/II clinical trials. This article briefly reviews the new treatment modalities of immunotherapy. Progress in adoptive cellular immunotherapy and progress in induction of graft versus myeloma effect are very promising. We are still not able to transfer very good preclinical results of immunotherapy into clinical results in vivo measured by event free and long-term survivals. Combination of myeloablative therapy followed a new type of immunotherapy focusing on residual disease eradication evaluated in the setting of sensitive disease may be optimal. Such approach could improve the current controversial status of immunotherapy in MM.
Published: 1998

66. Doporučení pro diagnostiku a léčbu chronické lymfocytární leukemie (CLL) České skupiny pro chronickou lymfocytární leukemii, sekce České hematologické společnosti ČLS JEP.

Author: L., Smolej, M., Špaček, P., Obrtlíková, Š., Pospíšilová, M., Jarošová, R., Urbanová, D., Lysák, M., Brejcha, J., Schwarz, and M., Doubek
Abstract: Copyright of Transfusiology & Haematology Today / Transfuze a Hematologie Dnes is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Published: 2016

67. Luminosity-independent measurements of total, elastic and inelastic cross-sections at \chem{\sqrt {s} = 7\,TeV}

Author: J. Whitmore, M. Calicchio, H. Niewiadomski, M. Macrí, P. Palazzi, C. Taylor, J. Kopal, F. Oljemark, E. Lippmaa, Francisco Garcia, G. Ruggiero, A. Scribano, J. Procházka, Milos Lokajicek, J. Kaspar, M. Lo Vetere, T. Maki, R. Lauhakangas, F. Cafagna, R. A. Intonti, E. Radermacher, R. Ferretti, L. Ropelewski, F. Nemes, V. Avati, Eraldo Oliveri, Edoardo Bossini, M. Quinto, Federico Ravotti, M. Bozzo, M. Oriunno, A. Santroni, Erik Brücken, E. Robutti, Mate Csanad, A. Fiergolski, K. Kurvinen, G. Antchev, Mario Deile, M. Doubek, V. Kundrát, J. Welti, T. Hilden, S. Minutoli, V. K. Eremin, Paolo Brogi, L. Grzanka, W. Snoeys, F. Lucas Rodríguez, Tamas Ferenc Csorgo, Fabrizio Ferro, N. Turini, N. Minafra, J. Smajek, J. Heino, V. Greco, P. Aspell, S. Giani, Giuseppe Latino, P. Wyszkowski, I. Atanassov, Corbin Covault, V. Vacek, J. Baechler, V. Berardi, T. Leszko, M. Berretti, S. Lami, E. Radicioni, K. Osterberg, M. Vitek, M. G. Catanesi, K. Eggert, A. Mercadante, J. Sziklai, Heimo Saarikko, A. Buzzo, and R. Orava
Subjects: Physics, Particle physics, Large Hadron Collider, Luminosity (scattering theory), 010308 nuclear & particles physics, Detector, Roman pot, General Physics and Astronomy, Optical theorem, Beam optics, 7. Clean energy, 01 natural sciences, Nuclear physics, 0103 physical sciences, Range (statistics), High Energy Physics::Experiment, 010306 general physics, Particle Physics - Experiment, Beam (structure)
Abstract: The TOTEM experiment at the LHC has performed the first luminosity-independent determination of the total proton-proton cross-section at $\sqrt {s} = 7\,{\mathrm { TeV}}$ . This technique is based on the optical theorem and requires simultaneous measurements of the inelastic rate – accomplished with the forward charged-particle telescopes T1 and T2 in the range 3.1
Published: 2013

68. O51 Acute myeloid leukemia in the Czech Republic and the Slovak Republic from 1996 to 2007. Prognostic and therapeutic results of 1890 patients from the ALERT registry

Author: Vladimir Koza, Tomáš Szotkowski, Jaroslava Voglová, P. Cetkovský, P. Kotouček, Kyra Michalova, Karel Indrak, Jacqueline Maaloufová, Tomas Kozak, Elena Tóthová, Marie Jarošová, L. Chudej, J. Mužík, E. Demečková, M. Doubek, J. Mayer, Ladislav Dušek, P. Žák, and L. Demetrovičová
Subjects: Czech, education.field_of_study, Acute leukemia, Pediatrics, medicine.medical_specialty, business.industry, Population, Myeloid leukemia, Hematology, language.human_language, Oncology, hemic and lymphatic diseases, Cohort, language, Medicine, Clinical registry, Slovak, business, education, neoplasms
Abstract: Project ALERT (Acute LEukemia clinical RegisTry) was initiated 11 years ago. The database is representative for the Czech population, at least in the category of curatively treated AML patients. Presented cohort consists of 1890 AML patients registered from January 1996 to February 2007.
Published: 2007

69. Doporučení pro diagnostiku a léčbu chronické lymfocytární leukemie (CLL).

Author: L., Smolej, M., Doubek, M., Špaček, R., Urbanová, P., Obrtlíková, J., Schwarz, D., Lysák, Š., Pospíšilová, M., Jarošová, S., Peková, and T., Kozák
Subjects: *CHRONIC lymphocytic leukemia, *CHRONIC diseases, *COMORBIDITY, *DECISION making
Abstract: Chronic lymphocytic leukaemia (CLL) is a disease with a remarkably heterogeneous clinical course. Because diagnosis and therapy must be tailored individually according to patient age, comorbidities and therapeutic gaols and as the understanding of CLL has been deepening at considerable speed, the Czech CLL Study Group, the working party of the Czech Haematological Society, has developed the following guidelines to facilitate the diagnostic and therapeutic decision-making process in clinical practice. These guidelines are based on a comprehensive analysis of current literature and follow the principles of evidence-based medicine. [ABSTRACT FROM AUTHOR]
Published: 2013

70. Mikroprostředí kostní dřeně a jeho role v patogenezi leukemií.

Author: E., Létalová, M., Doubek, F., Folber, J., Verner, M., Mráz, Š., Pospíšilová, and J., Mayer
Subjects: *BONE marrow, *HEMATOPOIESIS, *HEMATOPOIETIC stem cells, *CELL differentiation, *CELL proliferation
Abstract: Bone marrow microenvironment plays a key role in the process of haematopoiesis. It has a supportive function for quiescent haematopoietic stem cells located in so called „niches“. It provides appropriate conditions for haematopoietic stem cell differentiation and for the proliferation of blood elements. Under certain conditions, the bone marrow microenvironment may be colonized by circulating peripheral haematopoietic stem cells (a fact used in the process of peripheral blood stem cell transplantation). It is probable that this mechanism is also used by malignant (leukemic) cells to infiltrate the microenvironment and thus take advantage of all the supportive functions provided to divide, proliferate and more or less differentiate into the leukemic population. [ABSTRACT FROM AUTHOR]
Published: 2011

71. A note on the preparation of particulate material for an electron microscopic study

Author: L, Benesová, M, Doubek, and H, Mohelská
Subjects: Agar, Microscopy, Electron, Suspensions, Bacteriophages, Filtration
Abstract: Modifications of two rapid and satisfactory procedures of purification of minute biological particulate material for electron microscopic observations were described. These modifications eliminate the alterations of the investigated particles and the possibility of their artificial disintegration. In addition, these procedures preserve the grouping of the particles as compared with the original suspensions. The dialysis is made directly on the grids coated with the supporting formvar membrane. In the second procedure the filtration of the soluble components of the material into the agar is combined with the transfer of the particles on the membrane covered grids.
Published: 1975

72. [Experience with the use of electron microscopes Philips EM 300 and Tesla BS 500 and the comparison of their utilization properties]

Author: M, Doubek
Subjects: Czechoslovakia, Microscopy, Electron, Germany, West
Published: 1978

73. Observation of proton-tagged, central (semi)exclusive production of high-mass lepton pairs in pp collisions at 13 TeV with the CMS-TOTEM precision proton spectrometer

Author: The CMS collaboration, A. M. Sirunyan, A. Tumasyan, W. Adam, F. Ambrogi, E. Asilar, T. Bergauer, J. Brandstetter, E. Brondolin, M. Dragicevic, J. Erö, A. Escalante Del Valle, M. Flechl, M. Friedl, R. Frühwirth, V. M. Ghete, J. Grossmann, J. Hrubec, M. Jeitler, A. König, N. Krammer, I. Krätschmer, D. Liko, T. Madlener, I. Mikulec, E. Pree, N. Rad, H. Rohringer, J. Schieck, R. Schöfbeck, M. Spanring, D. Spitzbart, A. Taurok, W. Waltenberger, J. Wittmann, C.-E. Wulz, M. Zarucki, V. Chekhovsky, V. Mossolov, J. Suarez Gonzalez, E. A. De Wolf, D. Di Croce, X. Janssen, J. Lauwers, M. Pieters, M. Van De Klundert, H. Van Haevermaet, P. Van Mechelen, N. Van Remortel, S. Abu Zeid, F. Blekman, J. D’Hondt, I. De Bruyn, J. De Clercq, K. Deroover, G. Flouris, D. Lontkovskyi, S. Lowette, I. Marchesini, S. Moortgat, L. Moreels, Q. Python, K. Skovpen, S. Tavernier, W. Van Doninck, P. Van Mulders, I. Van Parijs, D. Beghin, B. Bilin, H. Brun, B. Clerbaux, G. De Lentdecker, H. Delannoy, B. Dorney, G. Fasanella, L. Favart, R. Goldouzian, A. Grebenyuk, A. K. Kalsi, T. Lenzi, J. Luetic, T. Seva, E. Starling, C. Vander Velde, P. Vanlaer, D. Vannerom, R. Yonamine, T. Cornelis, D. Dobur, A. Fagot, M. Gul, I. Khvastunov, D. Poyraz, C. Roskas, D. Trocino, M. Tytgat, W. Verbeke, B. Vermassen, M. Vit, N. Zaganidis, H. Bakhshiansohi, O. Bondu, S. Brochet, G. Bruno, C. Caputo, A. Caudron, P. David, S. De Visscher, C. Delaere, M. Delcourt, B. Francois, A. Giammanco, G. Krintiras, V. Lemaitre, A. Magitteri, A. Mertens, M. Musich, K. Piotrzkowski, L. Quertenmont, A. Saggio, M. Vidal Marono, S. Wertz, J. Zobec, W. L. Aldá Júnior, F. L. Alves, G. A. Alves, L. Brito, G. Correia Silva, C. Hensel, A. Moraes, M. E. Pol, P. Rebello Teles, E. Belchior Batista Das Chagas, W. Carvalho, J. Chinellato, E. Coelho, E. M. Da Costa, G. G. Da Silveira, D. De Jesus Damiao, D. Figueiredo, S. Fonseca De Souza, H. Malbouisson, M. Medina Jaime, M. Melo De Almeida, C. Mora Herrera, L. Mundim, H. Nogima, L. J. Sanchez Rosas, A. Santoro, A. Sznajder, M. Thiel, E. J. Tonelli Manganote, F. Torres Da Silva De Araujo, A. Vilela Pereira, S. Ahuja, C. A. Bernardes, L. Calligaris, T. R. Fernandez Perez Tomei, E. M. Gregores, P. G. Mercadante, S. F. Novaes, Sandra S. Padula, D. Romero Abad, J. C. Ruiz Vargas, A. Aleksandrov, R. Hadjiiska, P. Iaydjiev, A. Marinov, M. Misheva, M. Rodozov, M. Shopova, G. Sultanov, A. Dimitrov, L. Litov, B. Pavlov, P. Petkov, W. Fang, X. Gao, L. Yuan, M. Ahmad, J. G. Bian, G. M. Chen, H. S. Chen, M. Chen, Y. Chen, C. H. Jiang, D. Leggat, H. Liao, Z. Liu, F. Romeo, S. M. Shaheen, A. Spiezia, J. Tao, C. Wang, Z. Wang, E. Yazgan, H. Zhang, J. Zhao, Y. Ban, G. Chen, J. Li, Q. Li, S. Liu, Y. Mao, S. J. Qian, D. Wang, Z. Xu, Y. Wang, C. Avila, A. Cabrera, C. A. Carrillo Montoya, L. F. Chaparro Sierra, C. Florez, C. F. González Hernández, M. A. Segura Delgado, B. Courbon, N. Godinovic, D. Lelas, I. Puljak, P. M. Ribeiro Cipriano, T. Sculac, Z. Antunovic, M. Kovac, V. Brigljevic, D. Ferencek, K. Kadija, B. Mesic, A. Starodumov, T. Susa, M. W. Ather, A. Attikis, G. Mavromanolakis, J. Mousa, C. Nicolaou, F. Ptochos, P. A. Razis, H. Rykaczewski, M. Finger, E. Carrera Jarrin, A. Ellithi Kamel, A. Mohamed, E. Salama, S. Bhowmik, R. K. Dewanjee, M. Kadastik, L. Perrini, M. Raidal, C. Veelken, P. Eerola, H. Kirschenmann, J. Pekkanen, M. Voutilainen, J. Havukainen, J. K. Heikkilä, T. Järvinen, V. Karimäki, R. Kinnunen, T. Lampén, K. Lassila-Perini, S. Laurila, S. Lehti, T. Lindén, P. Luukka, T. Mäenpää, H. Siikonen, E. Tuominen, J. Tuominiemi, T. Tuuva, M. Besancon, F. Couderc, M. Dejardin, D. Denegri, J. L. Faure, F. Ferri, S. Ganjour, S. Ghosh, A. Givernaud, P. Gras, G. Hamel de Monchenault, P. Jarry, C. Leloup, E. Locci, M. Machet, J. Malcles, G. Negro, J. Rander, A. Rosowsky, M. Ö. Sahin, M. Titov, A. Abdulsalam, C. Amendola, I. Antropov, S. Baffioni, F. Beaudette, P. Busson, L. Cadamuro, C. Charlot, R. Granier de Cassagnac, M. Jo, I. Kucher, S. Lisniak, A. Lobanov, J. Martin Blanco, M. Nguyen, C. Ochando, G. Ortona, P. Paganini, P. Pigard, R. Salerno, J. B. Sauvan, Y. Sirois, A. G. Stahl Leiton, Y. Yilmaz, A. Zabi, A. Zghiche, J.-L. Agram, J. Andrea, D. Bloch, J.-M. Brom, E. C. Chabert, C. Collard, E. Conte, X. Coubez, F. Drouhin, J.-C. Fontaine, D. Gelé, U. Goerlach, M. Jansová, P. Juillot, A.-C. Le Bihan, N. Tonon, P. Van Hove, S. Gadrat, S. Beauceron, C. Bernet, G. Boudoul, N. Chanon, R. Chierici, D. Contardo, P. Depasse, H. El Mamouni, J. Fay, L. Finco, S. Gascon, M. Gouzevitch, G. Grenier, B. Ille, F. Lagarde, I. B. Laktineh, H. Lattaud, M. Lethuillier, L. Mirabito, A. L. Pequegnot, S. Perries, A. Popov, V. Sordini, M. Vander Donckt, S. Viret, S. Zhang, T. Toriashvili, Z. Tsamalaidze, C. Autermann, L. Feld, M. K. Kiesel, K. Klein, M. Lipinski, M. Preuten, M. P. Rauch, C. Schomakers, J. Schulz, M. Teroerde, B. Wittmer, V. Zhukov, A. Albert, D. Duchardt, M. Endres, M. Erdmann, S. Erdweg, T. Esch, R. Fischer, A. Güth, T. Hebbeker, C. Heidemann, K. Hoepfner, S. Knutzen, M. Merschmeyer, A. Meyer, P. Millet, S. Mukherjee, T. Pook, M. Radziej, H. Reithler, M. Rieger, F. Scheuch, D. Teyssier, S. Thüer, G. Flügge, B. Kargoll, T. Kress, A. Künsken, T. Müller, A. Nehrkorn, A. Nowack, C. Pistone, O. Pooth, A. Stahl, M. Aldaya Martin, T. Arndt, C. Asawatangtrakuldee, K. Beernaert, O. Behnke, U. Behrens, A. Bermúdez Martínez, A. A. Bin Anuar, K. Borras, V. Botta, A. Campbell, P. Connor, C. Contreras-Campana, F. Costanza, V. Danilov, A. De Wit, C. Diez Pardos, D. Domínguez Damiani, G. Eckerlin, D. Eckstein, T. Eichhorn, E. Eren, E. Gallo, J. Garay Garcia, A. Geiser, J. M. Grados Luyando, A. Grohsjean, P. Gunnellini, M. Guthoff, A. Harb, J. Hauk, M. Hempel, H. Jung, M. Kasemann, J. Keaveney, C. Kleinwort, J. Knolle, I. Korol, D. Krücker, W. Lange, A. Lelek, T. Lenz, K. Lipka, W. Lohmann, R. Mankel, I.-A. Melzer-Pellmann, A. B. Meyer, M. Meyer, M. Missiroli, G. Mittag, J. Mnich, A. Mussgiller, D. Pitzl, A. Raspereza, M. Savitskyi, P. Saxena, R. Shevchenko, N. Stefaniuk, H. Tholen, G. P. Van Onsem, R. Walsh, Y. Wen, K. Wichmann, C. Wissing, O. Zenaiev, R. Aggleton, S. Bein, V. Blobel, M. Centis Vignali, T. Dreyer, E. Garutti, D. Gonzalez, J. Haller, A. Hinzmann, M. Hoffmann, A. Karavdina, G. Kasieczka, R. Klanner, R. Kogler, N. Kovalchuk, S. Kurz, D. Marconi, J. Multhaup, M. Niedziela, D. Nowatschin, T. Peiffer, A. Perieanu, A. Reimers, C. Scharf, P. Schleper, A. Schmidt, S. Schumann, J. Schwandt, J. Sonneveld, H. Stadie, G. Steinbrück, F. M. Stober, M. Stöver, D. Troendle, E. Usai, A. Vanhoefer, B. Vormwald, M. Akbiyik, C. Barth, M. Baselga, S. Baur, E. Butz, R. Caspart, T. Chwalek, F. Colombo, W. De Boer, A. Dierlamm, N. Faltermann, B. Freund, R. Friese, M. Giffels, M. A. Harrendorf, F. Hartmann, S. M. Heindl, U. Husemann, F. Kassel, S. Kudella, H. Mildner, M. U. Mozer, Th. Müller, M. Plagge, G. Quast, K. Rabbertz, M. Schröder, I. Shvetsov, G. Sieber, H. J. Simonis, R. Ulrich, S. Wayand, M. Weber, T. Weiler, S. Williamson, C. Wöhrmann, R. Wolf, G. Anagnostou, G. Daskalakis, T. Geralis, A. Kyriakis, D. Loukas, I. Topsis-Giotis, G. Karathanasis, S. Kesisoglou, A. Panagiotou, N. Saoulidou, E. Tziaferi, K. Kousouris, I. Papakrivopoulos, I. Evangelou, C. Foudas, P. Gianneios, P. Katsoulis, P. Kokkas, S. Mallios, N. Manthos, I. Papadopoulos, E. Paradas, J. Strologas, F. A. Triantis, D. Tsitsonis, M. Csanad, N. Filipovic, G. Pasztor, O. Surányi, G. I. Veres, G. Bencze, C. Hajdu, D. Horvath, Á. Hunyadi, F. Sikler, T. Á. Vámi, V. Veszpremi, G. Vesztergombi, N. Beni, S. Czellar, J. Karancsi, A. Makovec, J. Molnar, Z. Szillasi, M. Bartók, P. Raics, Z. L. Trocsanyi, B. Ujvari, S. Choudhury, J. R. Komaragiri, S. Bahinipati, P. Mal, K. Mandal, A. Nayak, D. K. Sahoo, S. K. Swain, S. Bansal, S. B. Beri, V. Bhatnagar, S. Chauhan, R. Chawla, N. Dhingra, R. Gupta, A. Kaur, M. Kaur, S. Kaur, R. Kumar, P. Kumari, M. Lohan, A. Mehta, S. Sharma, J. B. Singh, G. Walia, A. Bhardwaj, B. C. Choudhary, R. B. Garg, S. Keshri, A. Kumar, Ashok Kumar, S. Malhotra, M. Naimuddin, K. Ranjan, Aashaq Shah, R. Sharma, R. Bhardwaj, R. Bhattacharya, S. Bhattacharya, U. Bhawandeep, D. Bhowmik, S. Dey, S. Dutt, S. Dutta, N. Majumdar, K. Mondal, S. Mukhopadhyay, S. Nandan, A. Purohit, P. K. Rout, A. Roy, S. Roy Chowdhury, S. Sarkar, M. Sharan, B. Singh, S. Thakur, P. K. Behera, R. Chudasama, D. Dutta, V. Jha, V. Kumar, A. K. Mohanty, P. K. Netrakanti, L. M. Pant, P. Shukla, A. Topkar, T. Aziz, S. Dugad, B. Mahakud, S. Mitra, G. B. Mohanty, N. Sur, B. Sutar, S. Banerjee, S. Chatterjee, P. Das, M. Guchait, Sa. Jain, S. Kumar, M. Maity, G. Majumder, K. Mazumdar, N. Sahoo, T. Sarkar, N. Wickramage, S. Dube, V. Hegde, A. Kapoor, K. Kothekar, S. Pandey, A. Rane, S. Chenarani, E. Eskandari Tadavani, S. M. Etesami, M. Khakzad, M. Mohammadi Najafabadi, M. Naseri, S. Paktinat Mehdiabadi, F. Rezaei Hosseinabadi, B. Safarzadeh, M. Zeinali, M. Felcini, M. Grunewald, M. Abbrescia, C. Calabria, A. Colaleo, D. Creanza, L. Cristella, N. De Filippis, M. De Palma, A. Di Florio, F. Errico, L. Fiore, A. Gelmi, G. Iaselli, S. Lezki, G. Maggi, M. Maggi, B. Marangelli, G. Miniello, S. My, S. Nuzzo, A. Pompili, G. Pugliese, R. Radogna, A. Ranieri, G. Selvaggi, A. Sharma, L. Silvestris, R. Venditti, P. Verwilligen, G. Zito, G. Abbiendi, C. Battilana, D. Bonacorsi, L. Borgonovi, S. Braibant-Giacomelli, R. Campanini, P. Capiluppi, A. Castro, F. R. Cavallo, S. S. Chhibra, G. Codispoti, M. Cuffiani, G. M. Dallavalle, F. Fabbri, A. Fanfani, D. Fasanella, P. Giacomelli, C. Grandi, L. Guiducci, F. Iemmi, S. Marcellini, G. Masetti, A. Montanari, F. L. Navarria, A. Perrotta, A. M. Rossi, T. Rovelli, G. P. Siroli, N. Tosi, S. Albergo, S. Costa, A. Di Mattia, F. Giordano, R. Potenza, A. Tricomi, C. Tuve, G. Barbagli, K. Chatterjee, V. Ciulli, C. Civinini, R. D’Alessandro, E. Focardi, G. Latino, P. Lenzi, M. Meschini, S. Paoletti, L. Russo, G. Sguazzoni, D. Strom, L. Viliani, L. Benussi, S. Bianco, D. Piccolo, F. Primavera, V. Calvelli, F. Ferro, F. Ravera, E. Robutti, S. Tosi, A. Benaglia, A. Beschi, L. Brianza, F. Brivio, V. Ciriolo, M. E. Dinardo, S. Fiorendi, S. Gennai, A. Ghezzi, P. Govoni, M. Malberti, S. Malvezzi, R. A. Manzoni, D. Menasce, L. Moroni, M. Paganoni, K. Pauwels, D. Pedrini, S. Pigazzini, S. Ragazzi, T. Tabarelli de Fatis, S. Buontempo, N. Cavallo, S. Di Guida, F. Fabozzi, F. Fienga, G. Galati, A. O. M. Iorio, W. A. Khan, L. Lista, S. Meola, P. Paolucci, C. Sciacca, F. Thyssen, E. Voevodina, P. Azzi, N. Bacchetta, L. Benato, D. Bisello, A. Boletti, R. Carlin, A. Carvalho Antunes De Oliveira, P. Checchia, P. De Castro Manzano, T. Dorigo, U. Dosselli, F. Gasparini, U. Gasparini, A. Gozzelino, S. Lacaprara, M. Margoni, A. T. Meneguzzo, N. Pozzobon, P. Ronchese, R. Rossin, F. Simonetto, A. Tiko, E. Torassa, M. Zanetti, P. Zotto, G. Zumerle, A. Braghieri, A. Magnani, P. Montagna, S. P. Ratti, V. Re, M. Ressegotti, C. Riccardi, P. Salvini, I. Vai, P. Vitulo, L. Alunni Solestizi, M. Biasini, G. M. Bilei, C. Cecchi, D. Ciangottini, L. Fanò, P. Lariccia, R. Leonardi, E. Manoni, G. Mantovani, V. Mariani, M. Menichelli, A. Rossi, A. Santocchia, D. Spiga, K. Androsov, P. Azzurri, G. Bagliesi, L. Bianchini, T. Boccali, L. Borrello, R. Castaldi, M. A. Ciocci, R. Dell’Orso, G. Fedi, L. Giannini, A. Giassi, M. T. Grippo, F. Ligabue, T. Lomtadze, E. Manca, G. Mandorli, A. Messineo, F. Palla, A. Rizzi, P. Spagnolo, R. Tenchini, G. Tonelli, A. Venturi, P. G. Verdini, L. Barone, F. Cavallari, M. Cipriani, N. Daci, D. Del Re, E. Di Marco, M. Diemoz, S. Gelli, E. Longo, B. Marzocchi, P. Meridiani, G. Organtini, F. Pandolfi, R. Paramatti, F. Preiato, S. Rahatlou, C. Rovelli, F. Santanastasio, N. Amapane, R. Arcidiacono, S. Argiro, M. Arneodo, N. Bartosik, R. Bellan, C. Biino, N. Cartiglia, R. Castello, F. Cenna, M. Costa, R. Covarelli, A. Degano, N. Demaria, B. Kiani, C. Mariotti, S. Maselli, E. Migliore, V. Monaco, E. Monteil, M. Monteno, M. M. Obertino, L. Pacher, N. Pastrone, M. Pelliccioni, G. L. Pinna Angioni, A. Romero, M. Ruspa, R. Sacchi, K. Shchelina, V. Sola, A. Solano, A. Staiano, S. Belforte, M. Casarsa, F. Cossutti, G. Della Ricca, A. Zanetti, D. H. Kim, G. N. Kim, M. S. Kim, J. Lee, S. Lee, S. W. Lee, C. S. Moon, Y. D. Oh, S. Sekmen, D. C. Son, Y. C. Yang, H. Kim, D. H. Moon, G. Oh, J. A. Brochero Cifuentes, J. Goh, T. J. Kim, S. Cho, S. Choi, Y. Go, D. Gyun, S. Ha, B. Hong, Y. Jo, Y. Kim, K. Lee, K. S. Lee, J. Lim, S. K. Park, Y. Roh, J. Almond, J. Kim, J. S. Kim, H. Lee, K. Nam, S. B. Oh, B. C. Radburn-Smith, S. h. Seo, U. K. Yang, H. D. Yoo, G. B. Yu, J. H. Kim, J. S. H. Lee, I. C. Park, Y. Choi, C. Hwang, I. Yu, V. Dudenas, A. Juodagalvis, J. Vaitkus, I. Ahmed, Z. A. Ibrahim, M. A. B. Md Ali, F. Mohamad Idris, W. A. T. Wan Abdullah, M. N. Yusli, Z. Zolkapli, M. C. Duran-Osuna, H. Castilla-Valdez, E. De La Cruz-Burelo, G. Ramirez-Sanchez, I. Heredia-De La Cruz, R. I. Rabadan-Trejo, R. Lopez-Fernandez, J. Mejia Guisao, R Reyes-Almanza, A. Sanchez-Hernandez, S. Carrillo Moreno, C. Oropeza Barrera, F. Vazquez Valencia, J. Eysermans, I. Pedraza, H. A. Salazar Ibarguen, C. Uribe Estrada, A. Morelos Pineda, D. Krofcheck, P. H. Butler, A. Ahmad, Q. Hassan, H. R. Hoorani, A. Saddique, M. A. Shah, M. Shoaib, M. Waqas, H. Bialkowska, M. Bluj, B. Boimska, T. Frueboes, M. Górski, M. Kazana, K. Nawrocki, M. Szleper, P. Traczyk, P. Zalewski, K. Bunkowski, A. Byszuk, K. Doroba, A. Kalinowski, M. Konecki, J. Krolikowski, M. Misiura, M. Olszewski, A. Pyskir, M. Walczak, P. Bargassa, C. Beirão Da Cruz E Silva, A. Di Francesco, P. Faccioli, B. Galinhas, M. Gallinaro, J. Hollar, N. Leonardo, L. Lloret Iglesias, M. V. Nemallapudi, J. Seixas, G. Strong, O. Toldaiev, D. Vadruccio, J. Varela, S. Afanasiev, P. Bunin, M. Gavrilenko, I. Golutvin, I. Gorbunov, A. Kamenev, V. Karjavin, A. Lanev, A. Malakhov, V. Matveev, P. Moisenz, V. Palichik, V. Perelygin, S. Shmatov, S. Shulha, N. Skatchkov, V. Smirnov, N. Voytishin, A. Zarubin, Y. Ivanov, V. Kim, E. Kuznetsova, P. Levchenko, V. Murzin, V. Oreshkin, I. Smirnov, D. Sosnov, V. Sulimov, L. Uvarov, S. Vavilov, A. Vorobyev, Yu. Andreev, A. Dermenev, S. Gninenko, N. Golubev, A. Karneyeu, M. Kirsanov, N. Krasnikov, A. Pashenkov, D. Tlisov, A. Toropin, V. Epshteyn, V. Gavrilov, N. Lychkovskaya, V. Popov, I. Pozdnyakov, G. Safronov, A. Spiridonov, A. Stepennov, V. Stolin, M. Toms, E. Vlasov, A. Zhokin, T. Aushev, A. Bylinkin, M. Chadeeva, R. Chistov, P. Parygin, D. Philippov, S. Polikarpov, E. Tarkovskii, E. Zhemchugov, V. Andreev, M. Azarkin, I. Dremin, M. Kirakosyan, S. V. Rusakov, A. Terkulov, A. Baskakov, A. Belyaev, E. Boos, M. Dubinin, L. Dudko, A. Ershov, A. Gribushin, V. Klyukhin, O. Kodolova, I. Lokhtin, I. Miagkov, S. Obraztsov, S. Petrushanko, V. Savrin, A. Snigirev, V. Blinov, D. Shtol, Y. Skovpen, I. Azhgirey, I. Bayshev, S. Bitioukov, D. Elumakhov, A. Godizov, V. Kachanov, A. Kalinin, D. Konstantinov, P. 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Khukhunaishvili, A, Lo, K, Tan, P, Verzetti, M, Ciesielski, R, Goulianos, K, Mesropian, C, Agapitos, A, Chou, J, Gershtein, Y, Gomez Espinosa, T, Halkiadakis, E, Heindl, M, Hughes, E, Kaplan, S, Kunnawalkam Elayavalli, R, Kyriacou, S, Lath, A, Montalvo, R, Nash, K, Osherson, M, Saka, H, Salur, S, Schnetzer, S, Sheffield, D, Somalwar, S, Stone, R, Thomas, S, Thomassen, P, Walker, M, Delannoy, A, Heideman, J, Riley, G, Rose, K, Spanier, S, Thapa, K, Bouhali, O, Castaneda Hernandez, A, Celik, A, Dalchenko, M, De Mattia, M, Delgado, A, Dildick, S, Eusebi, R, Gilmore, J, Huang, T, Kamon, T, Mueller, R, Pakhotin, Y, Patel, R, Perloff, A, Pernie, L, Rathjens, D, Safonov, A, Tatarinov, A, Akchurin, N, Damgov, J, De Guio, F, Dudero, P, Faulkner, J, Gurpinar, E, Kunori, S, Lamichhane, K, Mengke, T, Muthumuni, S, Peltola, T, Undleeb, S, Volobouev, I, Greene, S, Gurrola, A, Janjam, R, Johns, W, Maguire, C, Melo, A, Ni, H, Padeken, K, Ruiz Alvarez, J, Sheldon, P, Tuo, S, Velkovska, J, Xu, Q, Arenton, M, Barria, P, Cox, B, Hirosky, R, Joyce, M, Ledovskoy, A, Li, H, Neu, C, Sinthuprasith, T, Wolfe, E, Xia, F, Harr, R, Karchin, P, Poudyal, N, Sturdy, J, Thapa, P, Zaleski, S, Brodski, M, Buchanan, J, Caillol, C, Carlsmith, D, Dasu, S, Dodd, L, Duric, S, Gomber, B, Grothe, M, Herndon, M, Herve, A, Hussain, U, Klabbers, P, Lanaro, A, Levine, A, Long, K, Loveless, R, Rekovic, V, Ruggles, T, Savin, A, Smith, N, Smith, W, Woods, N, Antchev, G, Aspell, P, Atanassov, I, Avati, V, Baechler, J, Baldenegro Barrera, C, Berardi, V, Berretti, M, Bossini, E, Bottigli, U, Bozzo, M, Cafagna, F, Catanesi, M, Csorgo, T, Deile, M, De Leonardis, F, D'Orazio, A, Doubek, M, Druzhkin, D, Eggert, K, Eremin, V, Fiergolski, A, Garcia, F, Georgiev, V, Giani, S, Grzanka, L, Hammerbauer, J, Heino, J, Isidori, T, Ivanchenko, V, Janda, M, Karev, A, Kaspar, J, Kopal, J, Kundrat, V, Lami, S, Lauhakangas, R, Linhart, R, Lindsey, C, Lokajicek, M, Losurdo, L, Lo Vetere, M, Lucas Rodriguez, F, Macri, M, Malawski, M, Minafra, N, Minutoli, S, Naaranoja, T, Nemes, F, Niewiadomski, H, Novak, T, Oliveri, E, Oljemark, F, Oriunno, M, Osterberg, K, Palazzi, P, Passaro, V, Peroutka, Z, Prochazka, J, Quinto, M, Radermacher, E, Radicioni, E, Ravotti, F, Ruggiero, G, Saarikko, H, Scribano, A, Siroky, J, Smajek, J, Snoeys, W, Stefanovitch, R, Sziklai, J, Taylor, C, Tcherniaev, E, Turini, N, Vacek, V, Welti, J, Williams, J, Wyszkowski, P, Zich, J, Zielinski, K, Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire Leprince-Ringuet (LLR), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Centre de Calcul de l'IN2P3 (CC-IN2P3), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut de Physique Nucléaire de Lyon (IPNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), CMS, TOTEM, Sirunyan, A.M., Tumasyan, A., Adam, W., Ambrogi, F., Asilar, E., Bergauer, T., Brandstetter, J., Brondolin, E., Dragicevic, M., Erö, J., Escalante Del Valle, A., Flechl, M., Friedl, M., Frühwirth, R., Ghete, V.M., Grossmann, J., Hrubec, J., Jeitler, M., König, A., Krammer, N., Krätschmer, I., Liko, D., Madlener, T., Mikulec, I., Pree, E., Rad, N., Rohringer, H., Schieck, J., Schöfbeck, R., Spanring, M., Spitzbart, D., Taurok, A., Waltenberger, W., Wittmann, J., Wulz, C.-E., Zarucki, M., Chekhovsky, V., Mossolov, V., Suarez Gonzalez, J., De Wolf, E.A., Di Croce, D., Janssen, X., Lauwers, J., Pieters, M., Van De Klundert, M., Van Haevermaet, H., Van Mechelen, P., Van Remortel, N., Abu Zeid, S., Blekman, F., D’Hondt, J., De Bruyn, I., De Clercq, J., Deroover, K., Flouris, G., Lontkovskyi, D., Lowette, S., Marchesini, I., Moortgat, S., Moreels, L., Python, Q., Skovpen, K., Tavernier, S., Van Doninck, W., Van Mulders, P., Van Parijs, I., Beghin, D., Bilin, B., Brun, H., Clerbaux, B., De Lentdecker, G., Delannoy, H., Dorney, B., Fasanella, G., Favart, L., Goldouzian, R., Grebenyuk, A., Kalsi, A.K., Lenzi, T., Luetic, J., Seva, T., Starling, E., Vander Velde, C., Vanlaer, P., Vannerom, D., Yonamine, R., Cornelis, T., Dobur, D., Fagot, A., Gul, M., Khvastunov, I., Poyraz, D., Roskas, C., Trocino, D., Tytgat, M., Verbeke, W., Vermassen, B., Vit, M., Zaganidis, N., Bakhshiansohi, H., Bondu, O., Brochet, S., Bruno, G., Caputo, C., Caudron, A., David, P., De Visscher, S., Delaere, C., Delcourt, M., Francois, B., Giammanco, A., Krintiras, G., Lemaitre, V., Magitteri, A., Mertens, A., Musich, M., Piotrzkowski, K., Quertenmont, L., Saggio, A., Vidal Marono, M., Wertz, S., Zobec, J., Aldá Júnior, W.L., Alves, F.L., Alves, G.A., Brito, L., Correia Silva, G., Hensel, C., Moraes, A., Pol, M.E., Rebello Teles, P., Belchior Batista Das Chagas, E., Carvalho, W., Chinellato, J., Coelho, E., Da Costa, E.M., Da Silveira, G.G., De Jesus Damiao, D., Figueiredo, D., Fonseca De Souza, S., Malbouisson, H., Medina Jaime, M., Melo De Almeida, M., Mora Herrera, C., Mundim, L., Nogima, H., Sanchez Rosas, L.J., Santoro, A., Sznajder, A., Thiel, M., Tonelli Manganote, E.J., Torres Da Silva De Araujo, F., Vilela Pereira, A., Ahuja, S., Bernardes, C.A., Calligaris, L., Fernandez Perez Tomei, T.R., Gregores, E.M., Mercadante, P.G., Novaes, S.F., Padula, Sandra S., Romero Abad, D., Ruiz Vargas, J.C., Aleksandrov, A., Hadjiiska, R., Iaydjiev, P., Marinov, A., Misheva, M., Rodozov, M., Shopova, M., Sultanov, G., Dimitrov, A., Litov, L., Pavlov, B., Petkov, P., Fang, W., Gao, X., Yuan, L., Ahmad, M., Bian, J.G., Chen, G.M., Chen, H.S., Chen, M., Chen, Y., Jiang, C.H., Leggat, D., Liao, H., Liu, Z., Romeo, F., Shaheen, S.M., Spiezia, A., Tao, J., Wang, C., Wang, Z., Yazgan, E., Zhang, H., Zhao, J., Ban, Y., Chen, G., Li, J., Li, Q., Liu, S., Mao, Y., Qian, S.J., Wang, D., Xu, Z., Wang, Y., Avila, C., Cabrera, A., Carrillo Montoya, C.A., Chaparro Sierra, L.F., Florez, C., González Hernández, C.F., Segura Delgado, M.A., Courbon, B., Godinovic, N., Lelas, D., Puljak, I., Ribeiro Cipriano, P.M., Sculac, T., Antunovic, Z., Kovac, M., Brigljevic, V., Ferencek, D., Kadija, K., Mesic, B., Starodumov, A., Susa, T., Ather, M.W., Attikis, A., Mavromanolakis, G., Mousa, J., Nicolaou, C., Ptochos, F., Razis, P.A., Rykaczewski, H., Finger, M., Carrera Jarrin, E., Ellithi Kamel, A., Mohamed, A., Salama, E., Bhowmik, S., Dewanjee, R.K., Kadastik, M., Perrini, L., Raidal, M., Veelken, C., Eerola, P., Kirschenmann, H., Pekkanen, J., Voutilainen, M., Havukainen, J., Heikkilä, J.K., Järvinen, T., Karimäki, V., Kinnunen, R., Lampén, T., Lassila-Perini, K., Laurila, S., Lehti, S., Lindén, T., Luukka, P., Mäenpää, T., Siikonen, H., Tuominen, E., Tuominiemi, J., Tuuva, T., Besancon, M., Couderc, F., Dejardin, M., Denegri, D., Faure, J.L., Ferri, F., Ganjour, S., Ghosh, S., Givernaud, A., Gras, P., Hamel de Monchenault, G., Jarry, P., Leloup, C., Locci, E., Machet, M., Malcles, J., Negro, G., Rander, J., Rosowsky, A., Sahin, M.Ã ., Titov, M., Abdulsalam, A., Amendola, C., Antropov, I., Baffioni, S., Beaudette, F., Busson, P., Cadamuro, L., Charlot, C., Granier de Cassagnac, R., Jo, M., Kucher, I., Lisniak, S., Lobanov, A., Martin Blanco, J., Nguyen, M., Ochando, C., Ortona, G., Paganini, P., Pigard, P., Salerno, R., Sauvan, J.B., Sirois, Y., Stahl Leiton, A.G., Yilmaz, Y., Zabi, A., Zghiche, A., Agram, J.-L., Andrea, J., Bloch, D., Brom, J.-M., Chabert, E.C., Collard, C., Conte, E., Coubez, X., Drouhin, F., Fontaine, J.-C., Gelé, D., Goerlach, U., Jansová, M., Juillot, P., Le Bihan, A.-C., Tonon, N., Van Hove, P., Gadrat, S., Beauceron, S., Bernet, C., Boudoul, G., Chanon, N., Chierici, R., Contardo, D., Depasse, P., El Mamouni, H., Fay, J., Finco, L., Gascon, S., Gouzevitch, M., Grenier, G., Ille, B., Lagarde, F., Laktineh, I.B., Lattaud, H., Lethuillier, M., Mirabito, L., Pequegnot, A.L., Perries, S., Popov, A., Sordini, V., Vander Donckt, M., Viret, S., Zhang, S., Toriashvili, T., Tsamalaidze, Z., Autermann, C., Feld, L., Kiesel, M.K., Klein, K., Lipinski, M., Preuten, M., Rauch, M.P., Schomakers, C., Schulz, J., Teroerde, M., Wittmer, B., Zhukov, V., Albert, A., Duchardt, D., Endres, M., Erdmann, M., Erdweg, S., Esch, T., Fischer, R., Güth, A., Hebbeker, T., Heidemann, C., Hoepfner, K., Knutzen, S., Merschmeyer, M., Meyer, A., Millet, P., Mukherjee, S., Pook, T., Radziej, M., Reithler, H., Rieger, M., Scheuch, F., Teyssier, D., Thüer, S., Flügge, G., Kargoll, B., Kress, T., Künsken, A., Müller, T., Nehrkorn, A., Nowack, A., Pistone, C., Pooth, O., Stahl, A., Aldaya Martin, M., Arndt, T., Asawatangtrakuldee, C., Beernaert, K., Behnke, O., Behrens, U., Bermúdez Martínez, A., Bin Anuar, A.A., Borras, K., Botta, V., Campbell, A., Connor, P., Contreras-Campana, C., Costanza, F., Danilov, V., De Wit, A., Diez Pardos, C., Domínguez Damiani, D., Eckerlin, G., Eckstein, D., Eichhorn, T., Eren, E., Gallo, E., Garay Garcia, J., Geiser, A., Grados Luyando, J.M., Grohsjean, A., Gunnellini, P., Guthoff, M., Harb, A., Hauk, J., Hempel, M., Jung, H., Kasemann, M., Keaveney, J., Kleinwort, C., Knolle, J., Korol, I., Krücker, D., Lange, W., Lelek, A., Lenz, T., Lipka, K., Lohmann, W., Mankel, R., Melzer-Pellmann, I.-A., Meyer, A.B., Meyer, M., Missiroli, M., Mittag, G., Mnich, J., Mussgiller, A., Pitzl, D., Raspereza, A., Savitskyi, M., Saxena, P., Shevchenko, R., Stefaniuk, N., Tholen, H., Van Onsem, G.P., Walsh, R., Wen, Y., Wichmann, K., Wissing, C., Zenaiev, O., Aggleton, R., Bein, S., Blobel, V., Centis Vignali, M., Dreyer, T., Garutti, E., Gonzalez, D., Haller, J., Hinzmann, A., Hoffmann, M., Karavdina, A., Kasieczka, G., Klanner, R., Kogler, R., Kovalchuk, N., Kurz, S., Marconi, D., Multhaup, J., Niedziela, M., Nowatschin, D., Peiffer, T., Perieanu, A., Reimers, A., Scharf, C., Schleper, P., Schmidt, A., Schumann, S., Schwandt, J., Sonneveld, J., Stadie, H., Steinbrück, G., Stober, F.M., Stöver, M., Troendle, D., Usai, E., Vanhoefer, A., Vormwald, B., Akbiyik, M., Barth, C., Baselga, M., Baur, S., Butz, E., Caspart, R., Chwalek, T., Colombo, F., De Boer, W., Dierlamm, A., Faltermann, N., Freund, B., Friese, R., Giffels, M., Harrendorf, M.A., Hartmann, F., Heindl, S.M., Husemann, U., Kassel, F., Kudella, S., Mildner, H., Mozer, M.U., Müller, Th., Plagge, M., Quast, G., Rabbertz, K., Schröder, M., Shvetsov, I., Sieber, G., Simonis, H.J., Ulrich, R., Wayand, S., Weber, M., Weiler, T., Williamson, S., Wöhrmann, C., Wolf, R., Anagnostou, G., Daskalakis, G., Geralis, T., Kyriakis, A., Loukas, D., Topsis-Giotis, I., Karathanasis, G., Kesisoglou, S., Panagiotou, A., Saoulidou, N., Tziaferi, E., Kousouris, K., Papakrivopoulos, I., Evangelou, I., Foudas, C., Gianneios, P., Katsoulis, P., Kokkas, P., Mallios, S., Manthos, N., Papadopoulos, I., Paradas, E., Strologas, J., Triantis, F.A., Tsitsonis, D., Csanad, M., Filipovic, N., Pasztor, G., Surányi, O., Veres, G.I., Bencze, G., Hajdu, C., Horvath, D., Hunyadi, Ã ., Sikler, F., Vámi, T.Ã ., Veszpremi, V., Vesztergombi, G., Beni, N., Czellar, S., Karancsi, J., Makovec, A., Molnar, J., Szillasi, Z., Bartók, M., Raics, P., Trocsanyi, Z.L., Ujvari, B., Choudhury, S., Komaragiri, J.R., Bahinipati, S., Mal, P., Mandal, K., Nayak, A., Sahoo, D.K., Swain, S.K., Bansal, S., Beri, S.B., Bhatnagar, V., Chauhan, S., Chawla, R., Dhingra, N., Gupta, R., Kaur, A., Kaur, M., Kaur, S., Kumar, R., Kumari, P., Lohan, M., Mehta, A., Sharma, S., Singh, J.B., Walia, G., Bhardwaj, A., Choudhary, B.C., Garg, R.B., Keshri, S., Kumar, A., Kumar, Ashok, Malhotra, S., Naimuddin, M., Ranjan, K., Shah, Aashaq, Sharma, R., Bhardwaj, R., Bhattacharya, R., Bhattacharya, S., Bhawandeep, U., Bhowmik, D., Dey, S., Dutt, S., Dutta, S., Majumdar, N., Mondal, K., Mukhopadhyay, S., Nandan, S., Purohit, A., Rout, P.K., Roy, A., Roy Chowdhury, S., Sarkar, S., Sharan, M., Singh, B., Thakur, S., Behera, P.K., Chudasama, R., Dutta, D., Jha, V., Kumar, V., Mohanty, A.K., Netrakanti, P.K., Pant, L.M., Shukla, P., Topkar, A., Aziz, T., Dugad, S., Mahakud, B., Mitra, S., Mohanty, G.B., Sur, N., Sutar, B., Banerjee, S., Chatterjee, S., Das, P., Guchait, M., Jain, Sa., Kumar, S., Maity, M., Majumder, G., Mazumdar, K., Sahoo, N., Sarkar, T., Wickramage, N., Dube, S., Hegde, V., Kapoor, A., Kothekar, K., Pandey, S., Rane, A., Chenarani, S., Eskandari Tadavani, E., Etesami, S.M., Khakzad, M., Mohammadi Najafabadi, M., Naseri, M., Paktinat Mehdiabadi, S., Rezaei Hosseinabadi, F., Safarzadeh, B., Zeinali, M., Felcini, M., Grunewald, M., Abbrescia, M., Calabria, C., Colaleo, A., Creanza, D., Cristella, L., De Filippis, N., De Palma, M., Di Florio, A., Errico, F., Fiore, L., Gelmi, A., Iaselli, G., Lezki, S., Maggi, G., Maggi, M., Marangelli, B., Miniello, G., My, S., Nuzzo, S., Pompili, A., Pugliese, G., Radogna, R., Ranieri, A., Selvaggi, G., Sharma, A., Silvestris, L., Venditti, R., Verwilligen, P., Zito, G., Abbiendi, G., Battilana, C., Bonacorsi, D., Borgonovi, L., Braibant-Giacomelli, S., Campanini, R., Capiluppi, P., Castro, A., Cavallo, F.R., Chhibra, S.S., Codispoti, G., Cuffiani, M., Dallavalle, G.M., Fabbri, F., Fanfani, A., Fasanella, D., Giacomelli, P., Grandi, C., Guiducci, L., Iemmi, F., Marcellini, S., Masetti, G., Montanari, A., Navarria, F.L., Perrotta, A., Rossi, A.M., Rovelli, T., Siroli, G.P., Tosi, N., Albergo, S., Costa, S., Di Mattia, A., Giordano, F., Potenza, R., Tricomi, A., Tuve, C., Barbagli, G., Chatterjee, K., Ciulli, V., Civinini, C., D’Alessandro, R., Focardi, E., Latino, G., Lenzi, P., Meschini, M., Paoletti, S., Russo, L., Sguazzoni, G., Strom, D., Viliani, L., Benussi, L., Bianco, S., Piccolo, D., Primavera, F., Calvelli, V., Ferro, F., Ravera, F., Robutti, E., Tosi, S., Benaglia, A., Beschi, A., Brianza, L., Brivio, F., Ciriolo, V., Dinardo, M.E., Fiorendi, S., Gennai, S., Ghezzi, A., Govoni, P., Malberti, M., Malvezzi, S., Manzoni, R.A., Menasce, D., Moroni, L., Paganoni, M., Pauwels, K., Pedrini, D., Pigazzini, S., Ragazzi, S., Tabarelli de Fatis, T., Buontempo, S., Cavallo, N., Di Guida, S., Fabozzi, F., Fienga, F., Galati, G., Iorio, A.O.M., Khan, W.A., Lista, L., Meola, S., Paolucci, P., Sciacca, C., Thyssen, F., Voevodina, E., Azzi, P., Bacchetta, N., Benato, L., Bisello, D., Boletti, A., Carlin, R., Carvalho Antunes De Oliveira, A., Checchia, P., De Castro Manzano, P., Dorigo, T., Dosselli, U., Gasparini, F., Gasparini, U., Gozzelino, A., Lacaprara, S., Margoni, M., Meneguzzo, A.T., Pozzobon, N., Ronchese, P., Rossin, R., Simonetto, F., Tiko, A., Torassa, E., Zanetti, M., Zotto, P., Zumerle, G., Braghieri, A., Magnani, A., Montagna, P., Ratti, S.P., Re, V., Ressegotti, M., Riccardi, C., Salvini, P., Vai, I., Vitulo, P., Alunni Solestizi, L., Biasini, M., Bilei, G.M., Cecchi, C., Ciangottini, D., Fanò, L., Lariccia, P., Leonardi, R., Manoni, E., Mantovani, G., Mariani, V., Menichelli, M., Rossi, A., Santocchia, A., Spiga, D., Androsov, K., Azzurri, P., Bagliesi, G., Bianchini, L., Boccali, T., Borrello, L., Castaldi, R., Ciocci, M.A., Dell’Orso, R., Fedi, G., Giannini, L., Giassi, A., Grippo, M.T., Ligabue, F., Lomtadze, T., Manca, E., Mandorli, G., Messineo, A., Palla, F., Rizzi, A., Spagnolo, P., Tenchini, R., Tonelli, G., Venturi, A., Verdini, P.G., Barone, L., Cavallari, F., Cipriani, M., Daci, N., Del Re, D., Di Marco, E., Diemoz, M., Gelli, S., Longo, E., Marzocchi, B., Meridiani, P., Organtini, G., Pandolfi, F., Paramatti, R., Preiato, F., Rahatlou, S., Rovelli, C., Santanastasio, F., Amapane, 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I., Dudenas, V., Juodagalvis, A., Vaitkus, J., Ahmed, I., Ibrahim, Z.A., Md Ali, M.A.B., Mohamad Idris, F., Wan Abdullah, W.A.T., Yusli, M.N., Zolkapli, Z., Duran-Osuna, M.C., Castilla-Valdez, H., De La Cruz-Burelo, E., Ramirez-Sanchez, G., Heredia-De La Cruz, I., Rabadan-Trejo, R.I., Lopez-Fernandez, R., Mejia Guisao, J., Reyes-Almanza, R., Sanchez-Hernandez, A., Carrillo Moreno, S., Oropeza Barrera, C., Vazquez Valencia, F., Eysermans, J., Pedraza, I., Salazar Ibarguen, H.A., Uribe Estrada, C., Morelos Pineda, A., Krofcheck, D., Butler, P.H., Ahmad, A., Hassan, Q., Hoorani, H.R., Saddique, A., Shah, M.A., Shoaib, M., Waqas, M., Bialkowska, H., Bluj, M., Boimska, B., Frueboes, T., Górski, M., Kazana, M., Nawrocki, K., Szleper, M., Traczyk, P., Zalewski, P., Bunkowski, K., Byszuk, A., Doroba, K., Kalinowski, A., Konecki, M., Krolikowski, J., Misiura, M., Olszewski, M., Pyskir, A., Walczak, M., Bargassa, P., Beirão Da Cruz E Silva, C., Di Francesco, A., Faccioli, P., Galinhas, B., 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V., Azarkin, M., Dremin, I., Kirakosyan, M., Rusakov, S.V., Terkulov, A., Baskakov, A., Belyaev, A., Boos, E., Dubinin, M., Dudko, L., Ershov, A., Gribushin, A., Klyukhin, V., Kodolova, O., Lokhtin, I., Miagkov, I., Obraztsov, S., Petrushanko, S., Savrin, V., Snigirev, A., Blinov, V., Shtol, D., Skovpen, Y., Azhgirey, I., Bayshev, I., Bitioukov, S., Elumakhov, D., Godizov, A., Kachanov, V., Kalinin, A., Konstantinov, D., Mandrik, P., Petrov, V., Ryutin, R., Sobol, A., Troshin, S., Tyurin, N., Uzunian, A., Volkov, A., Babaev, A., Adzic, P., Cirkovic, P., Devetak, D., Dordevic, M., Milosevic, J., Alcaraz Maestre, J., Álvarez Fernández, A., Bachiller, I., Barrio Luna, M., Cerrada, M., Colino, N., De La Cruz, B., Delgado Peris, A., Fernandez Bedoya, C., Fernández Ramos, J.P., Flix, J., Fouz, M.C., Gonzalez Lopez, O., Goy Lopez, S., Hernandez, J.M., Josa, M.I., Moran, D., Pérez-Calero Yzquierdo, A., Puerta Pelayo, J., Redondo, I., Romero, L., Soares, M.S., Triossi, A., Albajar, C., de Trocóniz, J.F., Cuevas, J., Erice, C., Fernandez Menendez, J., Folgueras, S., Gonzalez Caballero, I., González Fernández, J.R., Palencia Cortezon, E., Sanchez Cruz, S., Vischia, P., Vizan Garcia, J.M., Cabrillo, I.J., Calderon, A., Chazin Quero, B., Duarte Campderros, J., Fernandez, M., Fernández Manteca, P.J., García Alonso, A., Garcia-Ferrero, J., Gomez, G., Lopez Virto, A., Marco, J., Martinez Rivero, C., Martinez Ruiz del Arbol, P., Matorras, F., Piedra Gomez, J., Prieels, C., Rodrigo, T., Ruiz-Jimeno, A., Scodellaro, L., Trevisani, N., Vila, I., Vilar Cortabitarte, R., Abbaneo, D., Akgun, B., Auffray, E., Baillon, P., Ball, A.H., Barney, D., Bendavid, J., Bianco, M., Bocci, A., Botta, C., Camporesi, T., Cepeda, M., Cerminara, G., Chapon, E., d’Enterria, D., Dabrowski, A., Daponte, V., David, A., De Gruttola, M., De Roeck, A., Deelen, N., Dobson, M., du Pree, T., Dünser, M., Dupont, N., Elliott-Peisert, A., Everaerts, P., Fallavollita, F., Franzoni, G., Fulcher, J., Funk, W., Gigi, 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Hangal, D.A., Hofman, D.J., Jung, K., Kamin, J., Sandoval Gonzalez, I.D., Tonjes, M.B., Varelas, N., Wang, H., Wu, Z., Zhang, J., Bilki, B., Clarida, W., Dilsiz, K., Durgut, S., Gandrajula, R.P., Haytmyradov, M., Khristenko, V., Merlo, J.-P., Mermerkaya, H., Mestvirishvili, A., Moeller, A., Nachtman, J., Ogul, H., Onel, Y., Ozok, F., Penzo, A., Snyder, C., Tiras, E., Wetzel, J., Yi, K., Blumenfeld, B., Cocoros, A., Eminizer, N., Fehling, D., Feng, L., Gritsan, A.V., Hung, W.T., Maksimovic, P., Roskes, J., Sarica, U., Swartz, M., Xiao, M., You, C., Al-bataineh, A., Baringer, P., Bean, A., Boren, S., Bowen, J., Castle, J., Forthomme, L., Khalil, S., Kropivnitskaya, A., Majumder, D., Mcbrayer, W., Murray, M., Rogan, C., Royon, C., Sanders, S., Schmitz, E., Tapia Takaki, J.D., Wang, Q., Ivanov, A., Kaadze, K., Maravin, Y., Modak, A., Mohammadi, A., Saini, L.K., Skhirtladze, N., Rebassoo, F., Wright, D., Baden, A., Baron, O., Belloni, A., Eno, S.C., Feng, Y., Ferraioli, C., Hadley, N.J., Jabeen, S., Jeng, G.Y., Kellogg, R.G., Kunkle, J., Mignerey, A.C., Ricci-Tam, F., Shin, Y.H., Skuja, A., Tonwar, S.C., Abercrombie, D., Allen, B., Azzolini, V., Barbieri, R., Baty, A., Bauer, G., Bi, R., Brandt, S., Busza, W., Cali, I.A., D’Alfonso, M., Demiragli, Z., Gomez Ceballos, G., Goncharov, M., Harris, P., Hsu, D., Hu, M., Iiyama, Y., Innocenti, G.M., Klute, M., Kovalskyi, D., Lee, Y.-J., Levin, A., Luckey, P.D., Maier, B., Marini, A.C., Mcginn, C., Mironov, C., Narayanan, S., Niu, X., Paus, C., Roland, C., Roland, G., Stephans, G.S.F., Sumorok, K., Tatar, K., Velicanu, D., Wang, T.W., Wyslouch, B., Zhaozhong, S., Benvenuti, A.C., Chatterjee, R.M., Evans, A., Hansen, P., Kalafut, S., Kubota, Y., Lesko, Z., Mans, J., Nourbakhsh, S., Ruckstuhl, N., Rusack, R., Turkewitz, J., Wadud, M.A., Acosta, J.G., Oliveros, S., Avdeeva, E., Bloom, K., Claes, D.R., Fangmeier, C., Golf, F., Gonzalez Suarez, R., Kamalieddin, R., Kravchenko, I., Monroy, J., Siado, J.E., Snow, G.R., Stieger, B., Godshalk, A., Harrington, C., Iashvili, I., Nguyen, D., Parker, A., Rappoccio, S., Roozbahani, B., Alverson, G., Barberis, E., Freer, C., Hortiangtham, A., Massironi, A., Morse, D.M., Orimoto, T., Teixeira De Lima, R., Wamorkar, T., Wang, B., Wisecarver, A., Wood, D., Charaf, O., Hahn, K.A., Mucia, N., Odell, N., Schmitt, M.H., Sung, K., Trovato, M., Velasco, M., Bucci, R., Dev, N., Hildreth, M., Hurtado Anampa, K., Jessop, C., Karmgard, D.J., Kellams, N., Lannon, K., Li, W., Loukas, N., Marinelli, N., Meng, F., Mueller, C., Musienko, Y., Planer, M., Reinsvold, A., Ruchti, R., Siddireddy, P., Smith, G., Taroni, S., Wayne, M., Wightman, A., Wolf, M., Woodard, A., Alimena, J., Antonelli, L., Bylsma, B., Durkin, L.S., Flowers, S., Francis, B., Hart, A., Hill, C., Ji, W., Ling, T.Y., Luo, W., Winer, B.L., Wulsin, H.W., Cooperstein, S., Driga, O., Elmer, P., Hardenbrook, J., Hebda, P., Higginbotham, S., Kalogeropoulos, A., Lange, D., Luo, J., Marlow, D., Mei, K., Ojalvo, I., Olsen, J., Palmer, C., Piroué, P., Salfeld-Nebgen, J., Stickland, D., Tully, C., Norberg, S., Barker, A., Barnes, V.E., Das, S., Gutay, L., Jones, M., Jung, A.W., Khatiwada, A., Miller, D.H., Neumeister, N., Peng, C.C., Qiu, H., Schulte, J.F., Sun, J., Wang, F., Xiao, R., Xie, W., Cheng, T., Dolen, J., Parashar, N., Chen, Z., Ecklund, K.M., Freed, S., Geurts, F.J.M., Guilbaud, M., Kilpatrick, M., Michlin, B., Padley, B.P., Roberts, J., Rorie, J., Shi, W., Tu, Z., Zabel, J., Zhang, A., Bodek, A., de Barbaro, P., Demina, R., Duh, Y.T., Ferbel, T., Galanti, M., Garcia-Bellido, A., Han, J., Hindrichs, O., Khukhunaishvili, A., Lo, K.H., Tan, P., Verzetti, M., Ciesielski, R., Goulianos, K., Mesropian, C., Agapitos, A., Chou, J.P., Gershtein, Y., Gómez Espinosa, T.A., Halkiadakis, E., Heindl, M., Hughes, E., Kaplan, S., Kunnawalkam Elayavalli, R., Kyriacou, S., Lath, A., Montalvo, R., Nash, K., Osherson, M., Saka, H., Salur, S., Schnetzer, S., Sheffield, D., Somalwar, S., Stone, R., Thomas, S., Thomassen, P., Walker, M., Delannoy, A.G., Heideman, J., Riley, G., Rose, K., Spanier, S., Thapa, K., Bouhali, O., Castaneda Hernandez, A., Celik, A., Dalchenko, M., De Mattia, M., Delgado, A., Dildick, S., Eusebi, R., Gilmore, J., Huang, T., Kamon, T., Mueller, R., Pakhotin, Y., Patel, R., Perloff, A., Perniè, L., Rathjens, D., Safonov, A., Tatarinov, A., Akchurin, N., Damgov, J., De Guio, F., Dudero, P.R., Faulkner, J., Gurpinar, E., Kunori, S., Lamichhane, K., Mengke, T., Muthumuni, S., Peltola, T., Undleeb, S., Volobouev, I., Greene, S., Gurrola, A., Janjam, R., Johns, W., Maguire, C., Melo, A., Ni, H., Padeken, K., Ruiz Alvarez, J.D., Sheldon, P., Tuo, S., Velkovska, J., Xu, Q., Arenton, M.W., Barria, P., Cox, B., Hirosky, R., Joyce, M., Ledovskoy, A., Li, H., Neu, C., Sinthuprasith, T., Wolfe, E., Xia, F., Harr, R., Karchin, P.E., Poudyal, N., Sturdy, J., Thapa, P., Zaleski, S., Brodski, M., Buchanan, J., Caillol, C., Carlsmith, D., Dasu, S., Dodd, L., Duric, S., Gomber, B., Grothe, M., Herndon, M., Hervé, A., Hussain, U., Klabbers, P., Lanaro, A., Levine, A., Long, K., Loveless, R., Rekovic, V., Ruggles, T., Savin, A., Smith, N., Smith, W.H., Woods, N., Antchev, G., Aspell, P., Atanassov, I., Avati, V., Baechler, J., Baldenegro Barrera, C., Berardi, V., Berretti, M., Bossini, E., Bottigli, U., Bozzo, M., Cafagna, F.S., Catanesi, M.G., Csanád, M., Csörgő, T., Deile, M., De Leonardis, F., D’Orazio, A., Doubek, M., Druzhkin, D., Eggert, K., Eremin, V., Fiergolski, A., Garcia, F., Georgiev, V., Giani, S., Grzanka, L., Hammerbauer, J., Heino, J., Isidori, T., Ivanchenko, V., Janda, M., Karev, A., Kašpar, J., Kopal, J., Kundrát, V., Lami, S., Lauhakangas, R., Linhart, R., Lindsey, C., Lokajíček, M.V., Losurdo, L., Lo Vetere, M., Lucas Rodríguez, F., Macrí, M., Malawski, M., Minafra, N., Minutoli, S., Naaranoja, T., Nemes, F., Niewiadomski, H., Novák, T., Oliveri, E., Oljemark, F., Oriunno, M., Österberg, K., Palazzi, P., Passaro, V., Peroutka, Z., Procházka, J., Quinto, M., Radermacher, E., Radicioni, E., Ravotti, F., Ruggiero, G., Saarikko, H., Scribano, A., Siroky, J., Smajek, J., Snoeys, W., Stefanovitch, R., Sziklai, J., Taylor, C., Tcherniaev, E., Turini, N., Vacek, V., Welti, J., Williams, J., Wyszkowski, P., Zich, J., Zielinski, K., Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches sur les lois Fondamentales de l'Univers ( IRFU ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Laboratoire Leprince-Ringuet ( LLR ), Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pluridisciplinaire Hubert Curien ( IPHC ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Haute-Alsace (UHA) Mulhouse - Colmar ( Université de Haute-Alsace (UHA) ), Centre de Calcul de l'IN2P3 ( CC-IN2P3 ), Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Physique Nucléaire de Lyon ( IPNL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), CMS Collaboration, and TOTEM Collaboration
Subjects: electron, two-photon [exchange], lepton, 13000 GeV-cms, Forward physics, Hadron-Hadron scattering (experiments), Photon, production, proton-proton scattering, LHC, DETECTORS, Physics, Particles & Fields, High Energy Physics - Experiment, electron: pair production, High Energy Physics - Experiment (hep-ex), spectrometer [p], [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], pair production [lepton], scattering [p p], Nuclear Experiment, (muon+ muon-) [mass spectrum], 02 Physical Sciences, p: spectrometer, Physics, scale: electroweak interaction, Settore FIS/01 - Fisica Sperimentale, electroweak interaction [scale], Nuclear & Particles Physics, (electron positron) [mass spectrum], muon: pair production, CERN LHC Coll, kinematics, Photon production, Physical Sciences, colliding beams [p p], mass spectrum: (lepton+ lepton-), Particle Physics - Experiment, p p: scattering, Nuclear and High Energy Physics, lepton: pair production, FOS: Physical sciences, [ PHYS.HEXP ] Physics [physics]/High Energy Physics - Experiment [hep-ex], 5/3, muon, mass spectrum: (electron positron), lcsh:Nuclear and particle physics. Atomic energy. Radioactivity, ddc:530, pair production [electron], pair production [muon], Forward physics, Hadron-Hadron scattering (experiments), Photon production, proton-proton scattering, (lepton+ lepton-) [mass spectrum], Forward physic, 01 Mathematical Sciences, exchange: two-photon, Science & Technology, hep-ex, background, exclusive production, mass spectrum: (muon+ muon-), lcsh:QC770-798, High Energy Physics::Experiment, p p: colliding beams, experimental results
Abstract: The process pp$\to\ell^+\ell^-$p$^{(*)}$, with $\ell^+\ell^-$ a muon or an electron pair produced at midrapidity with mass larger than 110 GeV, has been observed for the first time at the LHC in pp collisions at $\sqrt{s} =$ 13 TeV. One of the two scattered protons is measured in the CMS-TOTEM precision proton spectrometer (CT-PPS), which operated for the first time in 2016. The second proton either remains intact or is excited and then dissociates into a low-mass state p$^{*}$, which is undetected. The measurement is based on an integrated luminosity of 9.4 fb$^{-1}$ collected during standard, high-luminosity LHC operation. A total of 12 $\mu^+\mu^-$ and 8 e$^+$e$^-$ pairs with $m(\ell^{+}\ell^{-}) >$ 110 GeV, and matching forward proton kinematics, are observed, with expected backgrounds of 1.49 $\pm$ 0.07 (stat) $\pm$ 0.53 (syst) and 2.36 $\pm$ 0.09 (stat) $\pm$ 0.47 (syst), respectively. This corresponds to an excess of more than five standard deviations over the expected background. The present result constitutes the first observation of proton-tagged $\gamma\gamma$ collisions at the electroweak scale. This measurement also demonstrates that CT-PPS performs according to the design specifications., Comment: Replaced with published version. All figures and tables can be found at http://cms-results.web.cern.ch/cms-results/public-results/publications/PPS-17-001 (CMS Public Pages)
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74. LHC optics measurement with proton tracks detected by the Roman pots of the TOTEM experiment.

Author: Collaboration, The TOTEM, G Antchev, P Aspell, I Atanassov, V Avati, J Baechler, V Berardi, M Berretti, E Bossini, U Bottigli, M Bozzo, E Brücken, A Buzzo, F S Cafagna, M G Catanesi, C Covault, M Csanád, T Csörgö, M Deile, and M Doubek
Subjects: OPTICAL measurements, LARGE Hadron Collider, BEAM optics, PROTONS, TELESCOPES, MAGNETIC fields, LATTICE theory, EXPERIMENTS
Abstract: Precise knowledge of the beam optics at the LHC is crucial to fulfill the physics goals of the TOTEM experiment, where the kinematics of the scattered protons is reconstructed with near-beam telescopes—so-called Roman pots (RP). Before being detected, the protons’ trajectories are influenced by the magnetic fields of the accelerator lattice. Thus precise understanding of the proton transport is of key importance for the experiment. A novel method of optics evaluation is proposed which exploits kinematical distributions of elastically scattered protons observed in the RPs. Theoretical predictions, as well as Monte Carlo studies, show that the residual uncertainty of the optics estimation method is smaller than . [ABSTRACT FROM AUTHOR]
Published: 2014
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75. LHC optics measurement with proton tracks detected by the Roman pots of the TOTEM experiment

Author: The TOTEM Collaboration, G Antchev, P Aspell, I Atanassov, V Avati, J Baechler, V Berardi, M Berretti, E Bossini, U Bottigli, M Bozzo, E Brücken, A Buzzo, F S Cafagna, M G Catanesi, C Covault, M Csanád, T Csörgö, M Deile, M Doubek, K Eggert, V Eremin, F Ferro, A Fiergolski, F Garcia, V Georgiev, S Giani, L Grzanka, J Hammerbauer, J Heino, T Hilden, A Karev, J Kašpar, J Kopal, V Kundrát, S Lami, G Latino, R Lauhakangas, T Leszko, E Lippmaa, J Lippmaa, M V Lokajíček, L Losurdo, M Lo Vetere, F Lucas Rodríguez, M Macrí, T Mäki, A Mercadante, N Minafra, S Minutoli, F Nemes, H Niewiadomski, E Oliveri, F Oljemark, R Orava, M Oriunno, K Österberg, P Palazzi, Z Peroutka, J Procházka, M Quinto, E Radermacher, E Radicioni, F Ravotti, E Robutti, L Ropelewski, G Ruggiero, H Saarikko, A Scribano, J Smajek, W Snoeys, J Sziklai, C Taylor, N Turini, V Vacek, J Welti, J Whitmore, P Wyszkowski, and K Zielinski
Subjects: elastic scattering, LHC proton transport, Roman pot, optics reconstruction, TOTEM experiment, 29.27.Eg, Science, Physics, QC1-999
Abstract: Precise knowledge of the beam optics at the LHC is crucial to fulfill the physics goals of the TOTEM experiment, where the kinematics of the scattered protons is reconstructed with near-beam telescopes—so-called Roman pots (RP). Before being detected, the protons’ trajectories are influenced by the magnetic fields of the accelerator lattice. Thus precise understanding of the proton transport is of key importance for the experiment. A novel method of optics evaluation is proposed which exploits kinematical distributions of elastically scattered protons observed in the RPs. Theoretical predictions, as well as Monte Carlo studies, show that the residual uncertainty of the optics estimation method is smaller than $2.5$ .
Published: 2014
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76. Inotuzumab Ozogamicin and Low-Intensity Chemotherapy in Older Patients With Newly Diagnosed CD22 + Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia.

Author: Chevallier P, Leguay T, Delord M, Salek C, Kim R, Huguet F, Hicheri Y, Wartiovaara-Kautto U, Raffoux E, Cluzeau T, Balsat M, Roth-Guepin G, Tavernier E, Lepretre S, Bilger K, Bergugnat H, Berceanu A, Alexis M, Doubek M, Brissot E, Hunault-Berger M, Lebon D, Turlure P, Chantepie S, Belhabri A, Wickenhauser S, Bastie JN, Cacheux V, Himberlin C, Banos A, Gardin C, Bonnet S, Plantier I, Pica GM, Escoffre-Barbe M, Boissel N, Dombret H, Clappier E, and Rousselot P
Abstract: Purpose: The use of inotuzumab ozogamicin (InO), a conjugated anti-CD22 monoclonal antibody, is becoming a promising frontline treatment for older patients with ALL., Patients and Methods: EWALL-INO is an open-label prospective multicenter phase II trial (ClinicalTrials.gov identifier: NCT03249870). Patients age 55 years and older with newly diagnosed CD22 + Philadelphia chromosome-negative (Ph-) B-cell precursor (BCP) ALL were eligible. After a prephase, a first induction consisting of vincristine, dexamethasone, and three injections of InO (0.8 mg/m 2 day 1, 0.5 mg/m 2 day 8/day 15) was followed by a second induction combining cyclophosphamide, dexamethasone, and two injections of InO (0.5 mg/m 2 day 1/day 8). Responders received up to six cycles of chemotherapy consolidation and 18-month chemotherapy maintenance. Allotransplant was allowed after three consolidations. The primary end point was 1-year overall survival (OS)., Results: Between December 2017 and March 2022, 131 patients (median age 68 years) were included. Three patients died during induction 1 (n = 130), two from multiple organ failure and one from hemorrhage, and none during induction 2 (n = 120). After induction 2, 90% of the patients achieved complete remission (CR) or CR with incomplete platelet recovery (CRp) and 80% had measurable residual disease (MRD2) <10 -4 . Among responders (n = 119), 47 relapsed and 14 died in CR/CRp. One-year OS, relapse-free survival (RFS), and cumulative incidence of relapse (CIR) rates were 73.2%, 66%, and 25%, respectively. High-risk cytogenetics and lower CD22 expression (<70%) were associated with worse OS, while both high-risk cytogenetics and MRD2 ≥10 -4 were associated with lower RFS and higher CIR. The 10 allotransplanted patients had very favorable outcomes (90% 2-year OS/RFS and no relapse). Only one nonfatal sinusoidal obstructive syndrome was documented during the study., Conclusion: Our results support InO's use in first-line regimens for older patients with CD22 + Ph- BCP-ALL.
Published: 2024
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77. Unveiling the dynamics and molecular landscape of a rare chronic lymphocytic leukemia subpopulation driving refractoriness: insights from single-cell RNA sequencing.

Author: Kurucova T, Reblova K, Janovska P, Porc JP, Navrkalova V, Pavlova S, Malcikova J, Plevova K, Tichy B, Doubek M, Bryja V, Kotaskova J, and Pospisilova S
Subjects: Humans, Drug Resistance, Neoplasm genetics, Sequence Analysis, RNA, Male, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Single-Cell Analysis methods
Abstract: Early identification of resistant cancer cells is currently a major challenge, as their expansion leads to refractoriness. To capture the dynamics of these cells, we made a comprehensive analysis of disease progression and treatment response in a chronic lymphocytic leukemia (CLL) patient using a combination of single-cell and bulk genomic methods. At diagnosis, the patient presented with unfavorable genetic markers, including notch receptor 1 (NOTCH1) mutation and loss(11q). The initial and subsequent treatment lines did not lead to a durable response and the patient developed refractory disease. Refractory CLL cells featured substantial dysregulation in B-cell phenotypic markers such as human leukocyte antigen (HLA) genes, immunoglobulin (IG) genes, CD19 molecule (CD19), membrane spanning 4-domains A1 (MS4A1; previously known as CD20), CD79a molecule (CD79A) and paired box 5 (PAX5), indicating B-cell de-differentiation and disease transformation. We described the clonal evolution and characterized in detail two cell populations that emerged during the refractory disease phase, differing in the presence of high genomic complexity. In addition, we successfully tracked the cells with high genomic complexity back to the time before treatment, where they formed a rare subpopulation. We have confirmed that single-cell RNA sequencing enables the characterization of refractory cells and the monitoring of their development over time., (© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Published: 2024
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78. Therapeutic strategies and treatment sequencing in patients with chronic lymphocytic leukemia: An international study of ERIC, the European Research Initiative on CLL.

Author: Chatzikonstantinou T, Scarfò L, Minga E, Karakatsoulis G, Chamou D, Kotaskova J, Iacoboni G, Demosthenous C, Albi E, Alcoceba M, Al-Shemari S, Aurran-Schleinitz T, Bacchiarri F, Chatzileontiadou S, Collado R, Davis Z, de Deus Santos MD, Dimou M, Dmitrieva E, Donaldson D, Dos Santos G, Dreta B, Efstathopoulou M, El-Ashwah S, Enrico A, Frygier A, Galimberti S, Galitzia A, Gimeno E, Guarente V, Guieze R, Harrop S, Hatzimichael E, Herishanu Y, Hernández-Rivas JÁ, Jaksic O, Kalicińska E, Laribi K, Karakus V, Kater AP, Kho B, Kislova M, Konstantinou Ε, Koren-Michowitz M, Kotsianidis I, Kubova Z, Labrador J, Lad D, Laurenti L, Longval T, Lopez-Garcia A, Marquet J, Maslejova S, Mayor-Bastida C, Mihaljevic B, Milosevic I, Miras F, Moia R, Morawska M, Nath UK, Navarro-Bailón A, Olivieri J, Panovska-Stavridis I, Papaioannou M, Pierie C, Puiggros A, Reda G, Rigolin GM, Ruchlemer R, Schipani M, Schiwitza A, Shen Y, Shokralla T, Simkovic M, Smirnova S, Soliman DSA, Stilgenbauer S, Tadmor T, Tomic K, Tse E, Vassilakopoulos T, Visentin A, Vitale C, Vrachiolias G, Vukovic V, Walewska R, Xu Z, Yagci M, Yañez L, Yassin M, Zuchnicka J, Oscier D, Gozzetti A, Panagiotidis P, Bosch F, Sportoletti P, Espinet B, Pangalis GA, Popov VM, Mulligan S, Angelopoulou M, Demirkan F, Papajík T, Biderman B, Murru R, Coscia M, Tam C, Cuneo A, Gaidano G, Claus R, Stavroyianni N, Trentin L, Antic D, Smolej L, Kalashnikova OB, Catherwood M, Spacek M, Pospisilova S, Doubek M, Nikitin E, Chatzidimitriou A, Ghia P, and Stamatopoulos K
Abstract: Competing Interests: Thomas Chatzikonstantinou received honoraria from AbbVie. Lydia Scarfò received honoraria from AbbVie, AstraZeneca, BeiGene, Lilly, Janssen, Octapharma. Gloria Iacoboni received honoraria and travel support from Novartis, Kite/Gilead, Bristol‐Myers Squibb, Abbvie, Autolus, Miltenyi, and AstraZeneca. Rosa Collado received support for attending meetings from Janssen‐Cilag and S.A. Sara Galimberti received honoraria support for attending meetings from AbbVie, AstraZeneca, Jazz, Novartis, and Incyte, honoraria from Roche, Celgene, Pfizer, and Janssen, and support for attending meetings from Jazz, AstraZeneca, and Roche. Romain Guieze received honoraria, consulting fees, and support for attending meetings from AbbVie, Beigene, Roche, Janssen, and AstraZeneca. Eleftheria Hatzimichael received honoraria from AbbVie, Janssen‐Cilag, AstraZeneca, and Roche. Yair Herishanu received honoraria from Janssen, AbbVie, Roche, AstraZeneca, Medion, and Lilly. José‐Ángel Hernández‐Rivas received honoraria as a consultant from Janssen, AbbVie, AstraZeneca, Lilly, and BeiGene and support for attending meetings from Janssen, AbbVie, AstraZeneca, and BeiGene. Ozren Jaksic received honoraria from Johnson and Johnson, AstraZeneca, and Lilly, honoraria from Johnson and Johnson, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Johnson and Johnson, and AbbVie. Kamel Laribi received consulting fees from AbbVie, AstraZeneca, Janssen, Beigene, Takeda, and Novartis. Maya Koren‐Michowitz received honoraria from Novartis, Pfizer, and Gad Medical LTD. and support for attending meetings from Novartis. Arnon P. Kater received advisory board fees and research money from Janssen, AbbVie, BMS, AstraZeneca, and Roche/Genentech, and support for attending meetings from Janssen and AbbVie. Ioannis Kotsianidis received honoraria and consulting fees from AbbVie and Janssen. Ivana Milosevic received honoraria from AbbVie, Roche, Sandoz, AstraZeneca, and Janssen, and support for attending meetings from AbbVie, Roche, and Takeda. Almudena Navarro‐Bailón received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, Takeda, Janssen, and Beigene. Jacopo Olivieri received honoraria from AbbVie, AstraZeneca, and Janssen. Gianluigi Reda received consulting fees from AbbVie, AstraZeneca, Janssen, and Beigene, and is currently employed by AstraZeneca. Gian M. Rigolin received honoraria for participation in speaker's bureau from AbbVie, Astra Zeneca, Beigene, and Janssen, and support for attending meetings from Janssen. Mattia Schipani received honoraria and support for attending meetings from AstraZeneca, AbbVie, and Janssen‐Cilag and owns shares of stock in AbbVie, AstraZeneca, Merck, Eli Lilly, Sanofi, Johnson and Johnson, Pfizer, Gilead, and GSK. Tereza Shokralla and Stephan Stilgenbauer reports research funding from, consultancy or advisory role for, honoraria from, speakers' bureau participation for, and travel support from AbbVie, Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Celgene, Gilead, GlaxoSmithKline, Hoffmann‐La Roche, Incyte, Infinity, Janssen, Novartis, and Sunesis. Eric Tse received support for attending meetings from Takeda. Theodoros Vassilakopoulos received honoraria from Takeda, Roche, Genesis Pharma, Merck, Novartis, Gilead, Sandoz, AstraZeneca, Integris, and Servier, and support for attending meetings from Takeda, Roche, Genesis Pharma, Merck, Pfizer, and Winmedica. Candida Vitale received honoraria from AbbVie, consulting fees from AstraZeneca, and support for attending meetings from AstraZeneca, Takeda, and Janssen. Renata Walewska received honoraria from AbbVie, AstraZeneca, and Beigene, support for attending meetings from Janssen, AbbVie, and AstraZeneca, and advisory board fees from AbbVie, AstraZeneca, Janssen, Beigene, and SecuraBio. Lucrecia Yañez received honoraria from AbbVie, AstraZeneca, Novartis, Gilead, Janssen, Jazz, MSD, and Pfizer, support for attending meetings from AbbVie, AstraZeneca, Gilead, Janssen, and Pfizer, and advisory board fees from AbbVie, AstraZeneca, Jazz, Janssen, Beigene, and Celgene. Francesc Bosch received consulting fees, honoraria, and payment for expert testimony from AbbVie, Genentech, Novartis, Takeda, Janssen, Roche, Mundipharma, Celgene/BMS, AstraZeneca, Lilly, Beigene, Gilead and TG Therapeutics, Advantage Allogene, Lava Therapeutics, and Enterome. Stephen Mulligan received advisory board fees from AbbVie, AstraZeneca, Janssen, Roche, and BeiGene. Maria Angelopoulou received consulting fees from AbbVie, Takeda, Janssen, Roche, Genesis, Gilead, and Amgen and honoraria from AbbVie, Takeda, Roche, Genesis, Gilead, and Novartis. Fatih Demirkan received support for attending meetings from Janssen and AbbVie. Tomas Papajík received honoraria and advisory board fees from AbbVie, Janssen‐Cilag, and AstraZeneca, and support for attending meetings from AstraZeneca. Marta Coscia received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, and Janssen. Constantine Tam received honoraria from AbbVie, Beigene, Janssen, and LOXO. Antonio Cuneo received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, Beigene, Janssen, and Lilly. Gianluca Gaidano received honoraria from Abbvie, AstraZeneca, BeiGene, Hikma, Incyte, Janssen, and Lilly. Niki Stavroyianni received honoraria from Janssen, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Janssen and AstraZeneca. Lukas Smolej received consulting fees, honoraria, and support for attending meetings from AbbVie, AstraZeneca, and Janssen and advisory board fees from AbbVie and AstraZeneca. Martin Spacek received honoraria and consulting and advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, and Janssen. Michael Doubek received research support and honoraria from AbbVie, AstraZeneca, and Janssen. Eugene Nikitin received honoraria from AbbVie. Kostas Stamatopoulos received research support from AbbVie, AstraZeneca, Janssen, Novartis, and Roche; honoraria from AbbVie, AstraZeneca, Bristol Myers Squibb, Lilly, and Janssen. Paolo Ghia received research support from AbbVie, AstraZeneca, BMS, Janssen and honoraria from AbbVie, AstraZeneca, BeiGene, BMS, Galapagos, Genmab, Janssen, Loxo Oncology @Lilly, MSD, Roche, and is an Editor of HemaSphere. Georgios Karakatsoulis, Eva Minga, Dimitra Chamou, Jana Kotaskova, Christos Demosthenous, Elisa Albi, Miguel Alcoceba, Salem Al‐Shemari, Thérèse Aurran‐Schleinitz, Francesca Bacchiarri, Sofia Chatzileontiadou, Zadie Davis, Marcos Daniel de Deus Santos, Maria Dimou, Elena Dmitrieva, David Donaldson, Gimena Dos Santos, Barbara Dreta, Maria Efstathopoulou, Shaimaa El‐Ashwah, Alicia Enrico, Andrzej Frygier, Andrea Galitzia, Eva Gimeno, Valerio Guarente, Sean Harrop, Elżbieta Kalicińska, Volkan Karakus, Bonnie Kho, Maria Kislova, Εliana Konstantinou, Zuzana Kubova, Jorge Labrador, Deepesh Lad, Luca Laurenti, Thomas Longval, Alberto Lopez‐Garcia, Juan Marquet, Stanislava Maslejova, Carlota Mayor‐Bastida, Biljana Mihaljevic, Fatima Miras, Riccardo Moia, Marta Morawska, Uttam K. Nath, Irina Panovska‐Stavridis, Maria Papaioannou, Cheyenne Pierie, Anna Puiggros, Rosa Ruchlemer, Annett Schiwitza, Yandong Shen, Tereza Shokralla, Martin Simkovic, Svetlana Smirnova, Dina S. A. Soliman, Tamar Tadmor, Kristina Tomic, Andrea Visentin, George Vrachiolias, Vojin Vukovic, Zhenshu Xu, Munci Yagci, Mohamed Yassin, Jana Zuchnicka, David Oscier, Alessandro Gozzetti, Panagiotis Panagiotidis, Blanca Espinet, Paolo Sportoletti, Gerassimos A. Pangalis, Viola M. Popov, Bella Biderman, Roberta Murru, Rainer Claus, Livio Trentin, Darko Antic, Olga B. Kalashnikova, Mark Catherwood, Sarka Pospisilova, and Anastasia Chatzidimitriou have no conflict of interest to disclose.
Published: 2024
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79. Prevalence of hypersensitivity reactions in various forms of mastocytosis: A pilot study of 2485 adult patients with mastocytosis collected in the ECNM registry.

Author: Niedoszytko M, Gorska A, Brockow K, Bonadonna P, Lange M, Kluin-Nelemans H, Oude-Elberink H, Sabato V, Shoumariyeh K, von Bubnoff D, Müller S, Illerhaus A, Doubek M, Angelova-Fischer I, Hermine O, Arock M, Elena C, Malcovati L, Yavuz AS, Schug TD, Fortina AB, Judit V, Gotlib J, Panse J, Vucinic V, Reiter A, Schwaab J, Triggiani M, Mattsson M, Breynaert C, Romantowski J, Zanotti R, Olivieri E, Zink A, van de Ven A, Stefan A, Barete S, Caroppo F, Perkins C, Kennedy V, Christen D, Jawhar M, Luebke J, Parente R, Levedahl K, Hadzijusufovic E, Hartmann K, Nedoszytko B, Sperr WR, and Valent P
Subjects: Humans, Adult, Middle Aged, Male, Female, Aged, Prevalence, Young Adult, Adolescent, Aged, 80 and over, Pilot Projects, Risk Factors, Hypersensitivity epidemiology, Hypersensitivity diagnosis, Registries, Mastocytosis epidemiology, Mastocytosis diagnosis, Mastocytosis complications
Abstract: Background: Hypersensitivity reactions (HR) are common in mastocytosis. However, little is known about triggers and risk factors. The registry of the European Competence Network on Mastocytosis (ECNM) enables reliable studies in a larger cohort of mastocytosis patients. We assessed prevalence, triggers and risk factors of HR in adults with mastocytosis in the ECNM registry., Methods: Data were collected in 27 ECNM centers. We analyzed potential triggers (Hymenoptera venoms, food, drug, inhalant and others) and risk factors at diagnosis and during follow-up. The study group consisted of 2485 adults with mastocytosis, 1379 women (55.5%) and 1106 men (44.5%). Median age was 48.2 years (range 18-91 years)., Results: Nine hundred and forty eight patients (38.1%) reported one or more HR`. Most common triggers were Hymenoptera venoms in cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM), whereas in advanced SM (advSM), most common elicitors were drugs, including nonsteroidal anti-inflammatory agents and penicillin. In multivariate analyses, tryptase level < 90 ng/mL, <15% infiltration by mast cells in bone marrow biopsy-sections, and diagnosis of ISM were identified as independent risk factors for HR. For drug-induced HR, prominent risk factors were advSM and high tryptase levels. New reactions were observed in 4.8% of all patients during 4 years follow-up., Conclusions: HR are mainly triggered by Hymenoptera venoms in patients with CM and ISM and by drugs in patients with advSM. Tryptase levels <90 ng/mL, mast cell bone marrow infiltration <15%, and WHO category ISM are predictors of HR. New HR occur in 4.8% of all patients within 4 years., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Published: 2024
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80. A novel thrombocytopenia-4-causing CYCS gene variant decreases caspase activity: Three-generation study.

Author: Štika J, Pešová M, Kozubík KS, Skalníková M, Dostálová L, Loja T, Radová L, Palušová V, Réblová K, Vrzalová Z, Blaháková I, Trizuljak J, Uldrijan S, Blatný J, Šmída M, Pospíšilová Š, and Doubek M
Abstract: The CYCS gene is highly evolutionarily conserved, with only a few pathogenic variants that cause thrombocytopenia-4 (THC4). Here, we report a novel CYCS variant NM_018947.6: c.59C>T [NP_061820.1:p.(Thr20Ile)] segregating with thrombocytopenia in three generations of a Czech family. The phenotype of the patients corresponds to THC4 with platelets of normal size and morphology and dominant inheritance. Intriguingly, a gradual decline in platelet counts was observed across generations. CRISPR/Cas9-mediated gene editing was used to introduce the new CYCS gene variant into a megakaryoblast cell line (MEG-01). Subsequently, the adhesion, shape, size, ploidy, viability, mitochondrial respiration, cytochrome c protein (CYCS) expression, cell surface antigen expression and caspase activity were analysed in cells carrying the studied variant. Interestingly, the variant decreases the expression of CYCS while increasing mitochondrial respiration and the expression of CD9 cell surface antigen. Surprisingly, the variant abates caspase activation, contrasting with previously known effects of other CYCS variants. Some reports indicate that caspases may be involved in thrombopoiesis; thus, the observed dysregulation of caspase activity might contribute to thrombocytopenia. The findings significantly enhance our understanding of the molecular mechanisms underlying inherited thrombocytopenia and may have implications for diagnosis, prognosis and future targeted therapies., (© 2024 Masaryk University. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
Published: 2024
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81. Overall survival of patients with CLL treated with ibrutinib in the first line compared to second-line ibrutinib after chemotherapy/chemoimmunotherapy.

Author: Robak T, Doubek M, Ferrant E, Diels J, Andersone L, Wilbertz S, Healy NC, Neumayr L, and van Sanden S
Subjects: Humans, Female, Aged, Male, Middle Aged, Immunotherapy methods, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Survival Rate, Adenine analogs & derivatives, Adenine therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Piperidines therapeutic use, Piperidines administration & dosage, Pyrimidines therapeutic use, Pyrimidines administration & dosage, Pyrazoles therapeutic use, Pyrazoles administration & dosage
Abstract: Objective: To evaluate the overall survival (OS) of patients with chronic lymphocytic leukemia (CLL) receiving either ibrutinib monotherapy as a first-line (1L) treatment or chemotherapy/chemoimmunotherapy-based (CT/CIT) regimens in 1L followed by ibrutinib in the second line (1L CT/CIT-2L ibrutinib) after disease progression by emulating a randomized trial comparing both treatment sequences., Methods: Patient-level data from the RESONATE-2 trial (NCT01722487) and real-world PHEDRA databases were analyzed. Three scenarios were considered using the following data sources: (1) RESONATE-2, (2) combined RESONATE-2/PHEDRA, (3) combined RESONATE-2/PHEDRA for 1L ibrutinib and PHEDRA for 1L CT/CIT-2L ibrutinib. Propensity score-based weights and inverse probability of censoring weighting were used to adjust for baseline (Scenarios 2 and 3) and time-dependent confounding (all scenarios), and to address potential biases. A weighted Cox proportional hazards model was used to estimate the OS hazard ratio (HR) and 95% confidence interval (CI) for 1L ibrutinib versus 1L CT/CIT-2L ibrutinib., Results: Results from Scenario 1 showed a significantly lower risk of death with 1L ibrutinib compared with 1L chlorambucil followed by 2L ibrutinib (HR 0.35 [95% CI 0.20-0.62]). Results from Scenarios 2 and 3 demonstrated a reduced risk of death with 1L ibrutinib compared with 1L CT/CIT-2L ibrutinib (HR 0.35 [0.21-0.61] and 0.64 [0.39-1.04], respectively)., Conclusion: The analyses consistently showed a reduced risk of death when ibrutinib was used as a 1L treatment in CLL compared with delaying its use until 2L after CT/CIT regimens, which suggests that initiating ibrutinib in 1L is advantageous for improving survival outcomes.
Published: 2024
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82. Stromal cells engineered to express T cell factors induce robust CLL cell proliferation in vitro and in PDX co-transplantations allowing the identification of RAF inhibitors as anti-proliferative drugs.

Author: Hoferkova E, Seda V, Kadakova S, Verner J, Loja T, Matulova K, Skuhrova Francova H, Ondrouskova E, Filip D, Blavet N, Boudny M, Mladonicka Pavlasova G, Vecera J, Ondrisova L, Pavelkova P, Hlavac K, Kostalova L, Michaelou A, Pospisilova S, Dorazilova J, Chochola V, Jaros J, Doubek M, Jarosova M, Hampl A, Vojtova L, Kren L, Mayer J, and Mraz M
Subjects: Humans, Animals, Mice, T-Lymphocytes immunology, T-Lymphocytes metabolism, Xenograft Model Antitumor Assays, Interleukins genetics, Interleukins metabolism, Protein Kinase Inhibitors pharmacology, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Cell Proliferation, Coculture Techniques, Stromal Cells metabolism, Stromal Cells pathology, CD40 Ligand metabolism, CD40 Ligand genetics
Abstract: Several in vitro models have been developed to mimic chronic lymphocytic leukemia (CLL) proliferation in immune niches; however, they typically do not induce robust proliferation. We prepared a novel model based on mimicking T-cell signals in vitro and in patient-derived xenografts (PDXs). Six supportive cell lines were prepared by engineering HS5 stromal cells with stable expression of human CD40L, IL4, IL21, and their combinations. Co-culture with HS5 expressing CD40L and IL4 in combination led to mild CLL cell proliferation (median 7% at day 7), while the HS5 expressing CD40L, IL4, and IL21 led to unprecedented proliferation rate (median 44%). The co-cultures mimicked the gene expression fingerprint of lymph node CLL cells (MYC, NFκB, and E2F signatures) and revealed novel vulnerabilities in CLL-T-cell-induced proliferation. Drug testing in co-cultures revealed for the first time that pan-RAF inhibitors fully block CLL proliferation. The co-culture model can be downscaled to five microliter volume for large drug screening purposes or upscaled to CLL PDXs by HS5-CD40L-IL4 ± IL21 co-transplantation. Co-transplanting NSG mice with purified CLL cells and HS5-CD40L-IL4 or HS5-CD40L-IL4-IL21 cells on collagen-based scaffold led to 47% or 82% engraftment efficacy, respectively, with ~20% of PDXs being clonally related to CLL, potentially overcoming the need to co-transplant autologous T-cells in PDXs., (© 2024. The Author(s).)
Published: 2024
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83. Impact of thrombocytopenia-associated c.-118C>T and c.-140C>G ANKRD26 5'UTR variants in three-generational pedigree.

Author: Trizuljak J, Likavcová P, Staňo Kozubík K, Vrzalová Z, Hynšt J, Deissová T, Štika J, Radová L, Prudková M, Vaculová J, Blaháková I, Smejkal P, Kamelander J, Pospíšilová Š, and Doubek M
Subjects: Humans, Female, Male, Adult, Middle Aged, Genetic Predisposition to Disease, Intercellular Signaling Peptides and Proteins, Thrombocytopenia genetics, 5' Untranslated Regions, Pedigree
Abstract: Inherited thrombocytopenias (ITs) encompass a group of rare disorders characterized by diminished platelet count. Recent advancements have unveiled various forms of IT, with inherited thrombocytopenia 2 (THC2) emerging as a prevalent subtype associated with germline variants in the critical 5' untranslated region of the ANKRD26 gene. This region is crucial in regulating the gene expression of ANKRD26 , particularly in megakaryocytes. THC2 is an autosomal dominant disorder presenting as mild-to-moderate thrombocytopenia with minimal symptoms, with an increased risk of myeloproliferative malignancies. In our study of a family with suspected IT, three affected individuals harbored the c.-118C>T ANKRD26 variant, while four healthy members carried the c.-140C>G ANKRD26 variant. We performed a functional analysis by studying platelet-specific ANKRD26 gene expression levels using quantitative real-time polymerase-chain reaction. Functional analysis of the c.-118C>T variant showed a significant increase in ANKRD26 expression in affected individuals, supporting its pathogenicity. On the contrary, carriers of the c.-140C>G variant exhibited normal platelet counts and no significant elevation in the ANKRD26 expression, indicating the likely benign nature of this variant. Our findings provide evidence confirming the pathogenicity of the c.-118C>T ANKRD26 variant in THC2 and suggest the likely benign nature of the c.-140C>G variant.
Published: 2024
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84. Serum chemistry profiling and prognostication in systemic mastocytosis: a registry-based study of the ECNM and GREM.

Author: Lübke J, Schmid A, Christen D, Oude Elberink HNG, Span LFR, Niedoszytko M, Gorska A, Lange M, Gleixner KV, Hadzijusufovic E, Stefan A, Angelova-Fischer I, Zanotti R, Bonifacio M, Bonadonna P, Shoumariyeh K, von Bubnoff N, Müller S, Perkins C, Elena C, Malcovati L, Hagglund H, Mattsson M, Parente R, Varkonyi J, Fortina AB, Caroppo F, Brockow K, Zink A, Breynaert C, Leven T, Yavuz AS, Doubek M, Sabato V, Schug T, Hartmann K, Triggiani M, Gotlib J, Hermine O, Arock M, Kluin-Nelemans HC, Panse J, Sperr WR, Valent P, Reiter A, and Schwaab J
Subjects: Humans, Prognosis, Male, Female, Middle Aged, Adult, Aged, Biomarkers blood, Tryptases blood, Mastocytosis, Systemic diagnosis, Mastocytosis, Systemic blood, Registries
Abstract: Abstract: Certain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most specific serum parameter. For differentiation between indolent and advanced SM (AdvSM), the following serum parameters were most relevant: tryptase, alkaline phosphatase, β2-microglobulin, lactate dehydrogenase (LDH), albumin, vitamin B12, and C-reactive protein (P < .001). With regard to subvariants of AdvSM, an elevated LDH of ≥260 U/L was associated with multilineage expansion (leukocytosis, r = 0.37, P < .001; monocytosis, r = 0.26, P < .001) and the presence of an associated myeloid neoplasm (P < .001), whereas tryptase levels were highest in mast cell leukemia (MCL) vs non-MCL (308μg/L vs 146μg/L, P = .003). Based on multivariable analysis, the hazard-risk weighted assignment of 1 point to LDH (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.0; P = .018) and 1.5 points each to β2-microglobulin (HR, 2.7; 95% CI, 1.4-5.4; P = .004) and albumin (HR, 3.3; 95% CI, 1.7-6.5; P = .001) delineated a highly predictive 3-tier risk classification system (0 points, 8.1 years vs 1 point, 2.5 years; ≥1.5 points, 1.7 years; P < .001). Moreover, serum chemistry parameters enabled further stratification of patients classified as having an International Prognostic Scoring System for Mastocytosis-AdvSM1/2 risk score (P = .027). In conclusion, serum chemistry profiling is a crucial tool in the clinical practice supporting diagnosis and prognostication of SM and its subvariants., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Published: 2024
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85. Management of ALL in adults: 2024 ELN recommendations from a European expert panel.

Author: Gökbuget N, Boissel N, Chiaretti S, Dombret H, Doubek M, Fielding A, Foà R, Giebel S, Hoelzer D, Hunault M, Marks DI, Martinelli G, Ottmann O, Rijneveld A, Rousselot P, Ribera J, and Bassan R
Subjects: Humans, Adult, Europe, Disease Management, Neoplasm, Residual diagnosis, Neoplasm, Residual therapy, Prognosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis
Abstract: Abstract: Experts from the European Leukemia Net (ELN) working group for adult acute lymphoblastic leukemia have identified an unmet need for guidance regarding management of adult acute lymphoblastic leukemia (ALL) from diagnosis to aftercare. The group has previously summarized their recommendations regarding diagnostic approaches, prognostic factors, and assessment of ALL. The current recommendation summarizes clinical management. It covers treatment approaches, including the use of new immunotherapies, application of minimal residual disease for treatment decisions, management of specific subgroups, and challenging treatment situations as well as late effects and supportive care. The recommendation provides guidance for physicians caring for adult patients with ALL which has to be complemented by regional expertise preferably provided by national academic study groups., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
Published: 2024
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86. Diagnosis, prognostic factors, and assessment of ALL in adults: 2024 ELN recommendations from a European expert panel.

Author: Gökbuget N, Boissel N, Chiaretti S, Dombret H, Doubek M, Fielding A, Foà R, Giebel S, Hoelzer D, Hunault M, Marks DI, Martinelli G, Ottmann O, Rijneveld A, Rousselot P, Ribera J, and Bassan R
Subjects: Humans, Prognosis, Adult, Europe, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
Abstract: Abstract: Working groups of the European LeukemiaNet have published several important consensus guidelines. Acute lymphoblastic leukemia (ALL) has many different clinical and biological subgroups and the knowledge on disease biology and therapeutic options is increasing exponentially. The European Working Group for Adult ALL has therefore summarized the current state of the art and provided comprehensive consensus recommendations for diagnostic approaches, biologic and clinical characterization, prognostic factors, and risk stratification as well as definitions of endpoints and outcomes. Aspects of treatment, management of subgroups and specific situations, aftercare, and supportive care are covered in a separate publication. The present recommendation intends to provide guidance for the initial management of adult patients with ALL and to define principles as a basis for future collaborative research., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
Published: 2024
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87. Real-world data on diagnostics, treatment and outcomes of patients with hairy cell leukemia: The HCL-CLLEAR study.

Author: Panovská A, Žák P, Jurková T, Arpáš T, Brychtová Y, Vašíková A, Hrabčáková V, Prchlíková A, Filipová M, and Doubek M
Subjects: Humans, Male, Female, Aged, Middle Aged, Retrospective Studies, Adult, Aged, 80 and over, Treatment Outcome, Cladribine therapeutic use, Cladribine administration & dosage, Follow-Up Studies, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Proto-Oncogene Proteins B-raf genetics, Leukemia, Hairy Cell diagnosis, Leukemia, Hairy Cell drug therapy, Leukemia, Hairy Cell pathology, Leukemia, Hairy Cell mortality, Leukemia, Hairy Cell therapy
Abstract: Hairy cell leukemia (HCL) and HCL-like disorders have to be distinguished because of their different biology and treatment response. Thus, we conducted a retrospective study on patients with HCL and hairy cell leukemia variant (HCLv) to assess diagnostic algorithms and treatment outcomes in a real-world setting. We analyzed 225 HCL and 26 HCLv patients with median follow-up of 67.9 months (HCL) and 20.1 months (HCLv). Median age at diagnosis was 56.2 (HCL) and 69.5 years (HCLv), male predominance was observed in both groups (76.0% vs. 73.1%). Diagnostics was mostly based on morphological evidence of hairy cells in the peripheral blood and bone marrow. At diagnosis, BRAF V600E mutation was detected in 94.7% of examined HCL patients and in no HCLv patient. Front-line treatment was indicated in 205 (91.1%) HCL and 18 (69.2%) HCLv patients. The majority of HCL patients were administered a cladribine-based regimen (91.2%). Overall response rate (ORR) was higher in cladribine-treated patients compared to those given other treatments (97.7% vs. 81.3%), the same applied with achieving Complete remission (CR) (91.2% vs. 62.5%). HCLv treatment was heterogeneous, but cladribine remained the most frequent option (44.4%) with ORR 81.3% and CR rates 43.8%. Second-line treatment was indicated in 52 HCL and 8 HCLv patients, 25.4% and 44.4% of those treated in first-line. In the whole HCL group, median time to next treatment (TTNT) was not reached and 10-year TTNT was estimated at 74.1%. HCLv patients who underwent first-line treatment had a median TTNT of 56 months. The median overall survival (OS) in HCL patients was not reached compared to HCLv with a median OS of 9.5 years. These data confirm an excellent prognosis for HCL patients treated with cladribine-based therapy. On the contrary, HCLv with its aggressive behavior represents a group of patients in whom novel treatment approaches are needed., (© 2024 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)
Published: 2024
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88. Additional booster doses in patients with chronic lymphocytic leukemia induce humoral and cellular immune responses to SARS-CoV-2 similar to natural infection regardless ongoing treatments: A study by ERIC, the European Research Initiative on CLL.

Author: Campanella A, Capasso A, Heltai S, Taccetti C, Albi E, Herishanu Y, Haggenburg S, Chatzikonstantinou T, Doubek M, Kättström M, Giannopoulos K, Simkovic M, Moreno C, Massaia M, Bumbea H, Alshemmari S, Ranghetti P, Perotta E, Martini F, Sant'Antonio E, Colia M, Combi C, Levi S, Kater AP, Hazenberg M, Nijhof IS, Hofsink Q, Demosthenous C, Kotaskova J, Zaleska J, Vrbacky F, Raya AM, Bisogno D, Tripoli IE, Popov VM, Roman V, Stavroyianni N, Karypidou M, Scarano E, Locatelli M, Frenquelli M, Scarfò L, Stamatopoulos K, and Ghia P
Subjects: Humans, SARS-CoV-2, COVID-19 Vaccines, Antibodies, Interleukin-2 Receptor alpha Subunit, Immunity, Cellular, Antibodies, Viral, Vaccination, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, COVID-19
Abstract: Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments., (© 2024 Wiley Periodicals LLC.)
Published: 2024
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89. Monoclonal gammopathy of clinical signifi cance with osteosclerotic lesions - a case report and a literature review.

Author: Adam Z, Řehák Z, Keřkovský M, Povýšil C, Ezer E, Buliková A, Pour L, Doubek M, Stavařová Y, Zdražilová Dubská L, Szutyany P, Ševčíková S, and Král Z
Subjects: Humans, Middle Aged, Female, Positron Emission Tomography Computed Tomography, Paraproteinemias complications, Paraproteinemias pathology, Osteosclerosis diagnostic imaging, Osteosclerosis etiology, Osteosclerosis pathology, Multiple Myeloma complications, Multiple Myeloma pathology, Multiple Myeloma diagnostic imaging
Abstract: Introduction: Multiple myeloma is a common plasma cell neoplasia usually accompanied by the formation of osteolytic foci, whereas osteosclerotic myeloma is a very rare form of plasma cell dyscrasia. When osteosclerotic myeloma is detected, osteosclerotic foci are usually part of the POEMS syndrome. Osteosclerotic myeloma without other manifestations of the POEMS syndrome is an unusual finding., Case Description: In a 46-year-old woman, osteosclerotic changes of the temporoparietal region caused soft tissue induration over this lesion, which initiated further investigation. Imaging studies subsequently showed multiple osteosclerotic foci in the skull. Examination of blood proteins revealed 8 g/L of IgG-lambda monoclonal immunoglobulin, subclass IgG1. In search of the cause of the osteosclerotic changes, FDG-PET/CT was performed, which revealed no FDG accumulation, i.e., no other tumor (breast or stomach cancer). Low-dose CT showed irregular bone structure, but not significant osteolytic or osteosclerotic foci. To map the extent of osteosclerotic changes, NaF-PET/CT imagination followed, which revealed multiple spots with high fluoride accumulation. A parietal bone biopsy showed osteosclerosis with minor clonal plasma cell infiltration. Trepanobioptic bone marrow sampling revealed an infiltration of bone marrow with atypical plasma cells in 8%. Flow-cytometric examination of bone marrow showed 0,37% of plasma cells, however predominantly (91%) clonal with lambda expression. MRI of the brain identified asymptomatic meningeal thickening. There was no evidence of POEMS syndrome in the patient; thus, we concluded the diagnosis as monoclonal gammopathy of clinical significance with osteosclerosis which was previously termed osteosclerotic multiple myeloma., Conclusion: Monoclonal gammopathy of clinical significance (MGCS) with osteosclerotic skeletal changes, documented on CT and multiple foci with intensive osteoneogenesis, documented on NaF-PET/CT without evidence of POEMS syndrome, is an extremely rare form of plasma cell dyscrasia. This publication documents the unique clinical manifestations of IgG-lambda type plasma cell proliferation without signs of POEMS syndrome and the role of NaF-PET/CT imaging. Classification of this disease as MGSC with osteosclerotic manifestations is more consistent with the indolent nature of the disease with a significantly better prognosis, compared with multiple myeloma.
Published: 2024
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90. Integrative NGS testing reveals clonal dynamics of adverse genomic defects contributing to a natural progression in treatment-naïve CLL patients.

Author: Navrkalova V, Plevova K, Radova L, Porc J, Pal K, Malcikova J, Pavlova S, Doubek M, Panovska A, Kotaskova J, and Pospisilova S
Subjects: Humans, Prognosis, Mutation, Genomics, High-Throughput Nucleotide Sequencing, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
Abstract: Large-scale next-generation sequencing (NGS) studies revealed extensive genetic heterogeneity, driving a highly variable clinical course of chronic lymphocytic leukaemia (CLL). The evolution of subclonal populations contributes to diverse therapy responses and disease refractoriness. Besides, the dynamics and impact of subpopulations before therapy initiation are not well understood. We examined changes in genomic defects in serial samples of 100 untreated CLL patients, spanning from indolent to aggressive disease. A comprehensive NGS panel LYNX, which provides targeted mutational analysis and genome-wide chromosomal defect assessment, was employed. We observed dynamic changes in the composition and/or proportion of genomic aberrations in most patients (62%). Clonal evolution of gene variants prevailed over the chromosomal alterations. Unsupervised clustering based on aberration dynamics revealed four groups of patients with different clinical behaviour. An adverse cluster was associated with fast progression and early therapy need, characterized by the expansion of TP53 defects, ATM mutations, and 18p- alongside dynamic SF3B1 mutations. Our results show that clonal evolution is active even without therapy pressure and that repeated genetic testing can be clinically relevant during long-term patient monitoring. Moreover, integrative NGS testing contributes to the consolidated evaluation of results and accurate assessment of individual patient prognosis., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
Published: 2024
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91. Real-world evaluation of UK high hyperdiploidy profile using a large cohort of patients provided by HARMONY data platform.

Author: Enshaei A, Martinez Elicegui J, Anguiano E, Gibson J, Lawal S, Ampatzidou M, Doubek M, Fielding AK, La Sala E, Middleton E, Rijneveld AW, Turki AT, Zimmermann M, Vora A, and Moorman AV
Subjects: Humans, United Kingdom, Aneuploidy, Chromosome Aberrations
Published: 2023
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92. The evolving landscape of COVID-19 and post-COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL.

Author: Visentin A, Chatzikonstantinou T, Scarfò L, Kapetanakis A, Demosthenous C, Karakatsoulis G, Minga E, Chamou D, Allsup D, Cabrero AA, Andres M, Antic D, Baile M, Baliakas P, Besikli-Dimou S, Bron D, Chatzileontiadou S, Cordoba R, Correa JG, Cuéllar-García C, De Paoli L, De Paolis MR, Delgado J, Dimou M, Donaldson D, Catherwood M, Doubek M, Efstathopoulou M, Eichhorst B, Elashwah S, Enrico A, Espinet B, Farina L, Ferrari A, Foglietta M, Frederiksen H, Fürstenau M, García-Marco JA, García-Serra R, Collado R, Gentile M, Gimeno E, Glenthøj A, da Silva MG, Hakobyan YK, Herishanu Y, Hernández-Rivas JÁ, Herold T, Innocenti I, Itchaki G, Jaksic O, Janssens A, Kalashnikova ОB, Kalicińska E, Kater AP, Kersting S, Labrador J, Lad D, Laurenti L, Levin MD, Lista E, Lopez-Garcia A, Malerba L, Marasca R, Marchetti M, Marquet J, Mattsson M, Mauro FR, Morawska M, Motta M, Munir T, Murru R, Niemann CU, Rodrigues RN, Olivieri J, Orsucci L, Papaioannou M, Pavlovsky MA, Piskunova I, Popov VM, Quaglia FM, Quaresmini G, Qvist K, Rigolin GM, Ruchlemer R, Šimkovič M, Špaček M, Sportoletti P, Stanca O, Tadmor T, Capasso A, Del Poeta G, Gutwein O, Karlsson LK, Milosevic I, Mirás F, Reda G, Saghumyan G, Shrestha A, Te Raa D, Tonino SH, Van Der Spek E, van Gelder M, van Kampen R, Wasik-Szczepanek E, Wróbel T, Segundo LYS, Yassin M, Pocali B, Vandenberghe E, Iyengar S, Varettoni M, Vitale C, Coscia M, Rambaldi A, Montserrat E, Cuneo A, Stavroyianni N, Trentin L, Stamatopoulos K, and Ghia P
Subjects: Humans, SARS-CoV-2, Post-Acute COVID-19 Syndrome, Retrospective Studies, COVID-19, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
Abstract: In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
Published: 2023
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93. Why Should Physicians Care About What Law Says About Turfing and Dumping Patients?

Author: Doubek M and Schweikart SJ
Subjects: Humans, Physician-Patient Relations, Patients, Criminal Law, Physicians
Abstract: When a physician refers a patient for a nonclinical reason, that patient has been "turfed." There are numerous reasons why turfing is clinically, legally, and ethically problematic; a main one is that the practice is physician centered and does not serve or center the best interests of patients. Legally, turfing patients is distinct from dumping patients: there are no civil or criminal laws regulating turfing, unlike dumping. Clinically and ethically, however, both turfing and dumping are poor practice, express poor character, and damage patient-physician and interprofessional relationships. This manuscript canvasses clinical, legal, and ethical dimensions of turfing and dumping that deserve investigation., (Copyright 2023 American Medical Association. All Rights Reserved.)
Published: 2023
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94. Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY.

Author: Chatzikonstantinou T, Scarfò L, Karakatsoulis G, Minga E, Chamou D, Iacoboni G, Kotaskova J, Demosthenous C, Smolej L, Mulligan S, Alcoceba M, Al-Shemari S, Aurran-Schleinitz T, Bacchiarri F, Bellido M, Bijou F, Calleja A, Medina A, Khan MA, Cassin R, Chatzileontiadou S, Collado R, Christian A, Davis Z, Dimou M, Donaldson D, Santos GD, Dreta B, Efstathopoulou M, El-Ashwah S, Enrico A, Fresa A, Galimberti S, Galitzia A, García-Serra R, Gimeno E, González-Gascón-Y-Marín I, Gozzetti A, Guarente V, Guieze R, Gogia A, Gupta R, Harrop S, Hatzimichael E, Herishanu Y, Hernández-Rivas JÁ, Inchiappa L, Jaksic O, Janssen S, Kalicińska E, Laribi K, Karakus V, Kater AP, Kho B, Kislova M, Konstantinou E, Koren-Michowitz M, Kotsianidis I, Kreitman RJ, Labrador J, Lad D, Levin MD, Levy I, Longval T, Lopez-Garcia A, Marquet J, Martin-Rodríguez L, Maynadié M, Maslejova S, Mayor-Bastida C, Mihaljevic B, Milosevic I, Miras F, Moia R, Morawska M, Murru R, Nath UK, Navarro-Bailón A, Oliveira AC, Olivieri J, Oscier D, Panovska-Stavridis I, Papaioannou M, Papajík T, Kubova Z, Phumphukhieo P, Pierie C, Puiggros A, Rani L, Reda G, Rigolin GM, Ruchlemer R, Daniel de Deus Santos M, Schipani M, Schiwitza A, Shen Y, Simkovic M, Smirnova S, Abdelrahman Soliman DS, Spacek M, Tadmor T, Tomic K, Tse E, Vassilakopoulos T, Visentin A, Vitale C, von Tresckow J, Vrachiolias G, Vukovic V, Walewska R, Wasik-Szczepanek E, Xu Z, Yagci M, Yañez L, Yassin M, Zuchnicka J, Angelopoulou M, Antic D, Biderman B, Catherwood M, Claus R, Coscia M, Cuneo A, Demirkan F, Espinet B, Gaidano G, Kalashnikova OB, Laurenti L, Nikitin E, Pangalis GA, Panagiotidis P, Popov VM, Pospisilova S, Sportoletti P, Stavroyianni N, Tam C, Trentin L, Chatzidimitriou A, Bosch F, Doubek M, Ghia P, and Stamatopoulos K
Abstract: Background: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work., Methods: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022., Findings: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79-4.91; p < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49-2.11; p < 0.001/OR = 1.89; 95% CI = 1.6-2.24; p < 0.001).CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36-2.41; p < 0.001/OR = 2.11; 95% CI = 1.12-3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08-0.33; p < 0.001).Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001)., Interpretation: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS., Funding: AbbVie, and EU/EFPIAInnovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026., Competing Interests: TC received honoraria from AbbVie. LS received consulting fees from AbbVie, BeiGene, AstraZeneca, Lilly, and Janssen, honoraria from Janssen and Octapharma, support for attending meetings from BeiGene and Janssen and advisory board fees from Merck. SMu received advisory board fees from AbbVie, AstraZeneca, Janssen, Roche and BeiGene. JAHR received honoraria as a consultant from Janssen, AbbVie, AstraZeneca, Lilly, and BeiGene and support for attending meetings from Janssen, AbbVie, AstraZeneca, and BeiGene. LI received honoraria from AbbVie, Roche, and Janssen-Cilag. APK received advisory board fees and research money from Janssen, AbbVie, BMS, AstraZeneca, Roche/Genentech, support for attending meetings from Janssen and AbbVie. M-DL received travel expenses from Janssen and AbbVie. GMR received honoraria for participation to speaker's bureau from AbbVie, Astra Zeneca, Beigene, and Janssen, and support for attending meetings from Janssen. JVT received consulting fees from AbbVie, AstraZeneca, BeiGene, and Janssen, honoraria for scientific talks from AbbVie, AstraZeneca, BeiGene, Janssen, Lilly, and Roche, travel support from AbbVie, AstraZeneca, BeiGene, Janssen, Roche, and Lilly, and advisory boards fees for AbbVie, Amgen, AstraZeneca, BeiGene. GI received honoraria from Novartis, BMS, Sandoz, AstraZeneca, Janssen, Kite/Gilead, and Miltenyi, support for attending meetings from Kite/Gilead, AstraZeneca, and AbbVie and advisory board fees from Kite/Gilead, Novartis, BMS, and Autolus. FBi received support for attending meetings from AbbVie. RCo received support for attending meetings from Janssen-Cilag and S.A. SG received honoraria support for attending meetings from AbbVie, AstraZeneca, Jazz, Novartis, and Incyte, honoraria from Roche, Celgene, Pfizer, and Janssen, and support for attending meetings from Jazz, AstraZeneca, and Roche. RGS received support for attending meetings from AbbVie and S.L.U. RG received honoraria, consulting fees, and support for attending meetings from AbbVie, Beigene, Roche, Janssen, AstraZeneca. YH received honoraria from Janssen, AbbVie, Roche, AstraZeneca, Medion, and Lilly. OJ received honoraria from Johnson and Johnson, AstraZeneca, and Lilly, honoraria from Johnson and Johnson, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Johnson and Johnson, and AbbVie. LK received consulting fees from AbbVie, AstraZeneca, Janssen, Beigene, Takeda, and Novartis. MKM received honoraria from Novartis, Pfizer, and Gad Medical LTD and support for attending meetings from Novartis. IKo received honoraria and consulting fees from AbbVie and Janssen. IM received honoraria from AbbVie, Roche, Sandoz, AstraZeneca, and Janssen, and support for attending meetings from AbbVie, Roche, and Takeda. ANB received honoraria, advisory board fees and support for attending meetings from AbbVie, AstraZeneca, Takeda, Janssen, and Beigene. JO received honoraria from AbbVie, AstraZeneca, and Janssen. GR received consulting fees from AbbVie, AstraZeneca, Janssen, and Beigene, and is currently employed by AstraZeneca. TP received honoraria and advisory board fees from AbbVie, Janssen-Cilag, and AstraZeneca and support for attending meeting from AstraZeneca. MS received honoraria and support for attending meeting from AstraZeneca, AbbVie, and Janssen-Cilag and owns shares of stock in AbbVie, AstraZeneca, Merck, Eli Lilly, Sanofi, Johnson and Johnson, Pfizer, Gilead, and GSK. MSp received honoraria and consulting and advisory board fees, and support for attending meeting from AbbVie, AstraZeneca, and Janssen. ET received support for attending meetings from Takeda. TV received honoraria from Takeda, Roche, Genesis Pharma, Merck, Novartis, Gilead, Sandoz, AstraZeneca, Integris, and Servier and support for attending meetings from Takeda, Roche, Genesis Pharma, Merck, Pfizer, and Winmedica. CV received honoraria from AbbVie, consulting fees from AstraZeneca and support for attending meeting from AstraZeneca, Takeda, and Janssen. RW received honoraria from AbbVie, AstraZeneca, and Beigene, support for attending meetings from Janssen, AbbVie, and AstraZeneca and advisory board fees from AbbVie, AstraZeneca, Janssen, Beigene, and SecuraBio. EWS received honoraria from AbbVie, Roche, and Janssen-Cilag and support for attending meetings from AbbVie. LY received honoraria from AbbVie, AstraZeneca, Novartis, Gilead, Janssen, Jazz, MSD, and Pfizer, support for attending meetings from AbbVie, AstraZeneca, Gilead, Janssen, and Pfizer, and advisory board fees from AbbVie, AstraZeneca, Jazz, Janssen, Beigene, and Celgene. MAn received consulting fees from AbbVie, Takeda, Janssen, Roche, Genesis, Gilead, and Amgen and honoraria from AbbVie, Takeda, Roche, Genesis, Gilead, and Novartis. MC received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, and Janssen. ACu received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, Beigene, Janssen, and Lilly. FD support for attending meetings from Janssen and AbbVie. GG received honoraria, and advisory board fees from AbbVie, AstraZeneca, Beigene, Janssen and advisory board fees from Lilly. EN received honoraria from AbbVie. LSm received consulting fees, honoraria and support for attending meetings from AbbVie, AstraZeneca, and Janssen and advisory board fees from AbbVie and AstraZeneca. NS received honoraria from Janssen, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Janssen and AstraZeneca. CT received honoraria from AbbVie, Beigene, Janssen, and LOXO. FB received consulting fees, honoraria and payment for expert testimony from AbbVie, Genentech, Novartis, Takeda, Janssen, Roche, Mundipharma, Celgene/BMS, AstraZeneca, Lilly, Beigene, Gilead and TG Therapeutics, Advantage Allogene, Lava Therapeutics, and Enterome. MDo received honoraria and advisory board fees from AbbVie, AstraZeneca and Janssen, advisory board fees from Swixx, and support for attending meetings from Janssen. PG received honoraria and consulting fees from AbbVie, AstraZeneca, BMS, Janssen, Lilly/Loxo Oncology, MSD, and Roche; grant support from AbbVie, AstraZeneca, BMS, Janssen. KS received honoraria from Janssen, AbbVie, Lilly and AstraZeneca, consulting fees and support for attending meetings from Janssen and AstraZeneca. GK, EM, DC, JK, CD, MA, SA, TAS, FBa, MB, ACa, AM, AKM, RC, SC, ACh, ZD, MDi, DD, GDS, BD, ME, SEA, AE, AF, AG, EG, IGGM, AGo, AjG, RGu, SH, EH, SJ, EKa, VK, BK, MK, EK, RJK, JL, DL, IL, TL, ALG, JM, LMR, MMa, SM, CMB, BM, FM, RM, MMo, RMu, UKN, ACO, DO, IPS, MP, ZK, PP, CP, AP, LR, RR, MDDS, AS, YS, MSi, SS, DSAS, TT, KT, AV, GV, VV, ZX, MYa, MY, JZ, DA, BB, MCa, RCl, BE, OBK, LL, GP, PPa, VMP, SP, PS, LT, AC, have no conflict of interest to disclose., (© 2023 Published by Elsevier Ltd.)
Published: 2023
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95. Pedestrian Safety in Frontal Tram Collision, Part 2: Laminated Glass as a Crucial Part of the Absorption and Deformation Zone-Its Impact Test and Analysis.

Author: Jezdik R, Sebik M, Kubovy P, Marsik F, Lopot F, Hajkova B, Hylmarova D, Havlicek M, Stocek O, Doubek M, Tikkanen T, Svoboda M, and Jelen K
Abstract: As was shown in the previous part of the study, windshields are an important part of the passive safety means of modern low-floor trams with an extraordinary effect on pedestrian safety in a pedestrian-tram collisions. Therefore, maximum attention must be paid to the definition of tram windshield characteristics. This article describes a windshield crash test, from which data are obtained to verify the feasibility of the applied computational approaches. A developed analytical model is utilised for a simple description of the energy balance during collision with an illustrative definition of the important parameters of laminated glass as well as their clear physical interpretations. The finite element analysis (FEA) performed in Ansys software using two versions of material definition, namely a simpler (*MAT_ELASTIC with nonlocal failure criterion) and a more complex (*MAT_GLASS with brittle stress-state-dependent failure) material model, which are presented as suitable for obtaining a detailed description of the shattering process of laminated glass, which can also be used effectively in windshield engineering.
Published: 2023
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96. Pedestrian Safety in Frontal Tram Collision, Part 1: Historical Overview and Experimental-Data-Based Biomechanical Study of Head Clashing in Frontal and Side Impacts.

Author: Lopot F, Tomsovsky L, Marsik F, Masek J, Kubovy P, Jezdik R, Sorfova M, Hajkova B, Hylmarova D, Havlicek M, Stocek O, Doubek M, Tikkanen T, Svoboda M, and Jelen K
Subjects: Humans, Accidents, Traffic, Motor Vehicles, Walking, Craniocerebral Trauma, Pedestrians, Wounds and Injuries
Abstract: This article represents the first paper in a two-part series dealing with safety during tram-pedestrian collisions. This research is dedicated to the safety of trams for pedestrians during collisions and is motivated by the increased number of lethal cases. The first part of this paper includes an overview of tram face development from the earliest designs to the current ones in use and, at the same time, provides a synopsis and explanation of the technical context, including a link to current and forthcoming legislation. The historical design development can be characterised by three steps, from an almost vertical front face, to leaned and pointed shapes, to the current inclined low-edged windshield without a protruding coupler. However, since most major manufacturers now export their products worldwide and customisation is only of a technically insignificant nature, our conclusions are generalisable (supported by the example of Berlin). The most advantageous shape of the tram's front, minimising the effects on pedestrians in all collision phases, has evolved rather spontaneously and was unprompted, and it is now being built into the European Commission regulations. The goal of the second part of this paper is to conduct a series of tram-pedestrian collisions with a focus on the frontal and side impacts using a crash test dummy (anthropomorphic test device-ATD). Four tram types approaching the collision at four different impact speeds (5 km/h, 10 km/h, 15 km/h, and 20 km/h) were used. The primary outcome variable was the resultant head acceleration. The risk and severity of possible head injuries were assessed using the head injury criterion ( HIC 15 ) and its linkage to the injury level on the Abbreviated Injury Scale (AIS). The results showed increasing head impacts with an increasing speed for all tram types and collision scenarios. Higher values of head acceleration were reached during the frontal impact (17-124 g) compared to the side one (2-84 g). The HIC 15 values did not exceed the value of 300 for any experimental setting, and the probability of AIS4+ injuries did not exceed 10%. The outcomes of tram-pedestrian collisions can be influenced by the ATD's position and orientation, the impact speed and front-end design of trams, and the site of initial contact.
Published: 2023
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97. Extensive, 3.8 Mb-Sized Deletion of 22q12 in a Patient with Bilateral Schwannoma, Intellectual Disability, Sensorineural Hearing Loss, and Epilepsy.

Author: Trizuljak J, Duben J, Blaháková I, Vrzalová Z, Kozubík KS, Štika J, Radová L, Bergerová V, Mejstříková S, Hořínová V, Jančálek R, Pospíšilová Š, and Doubek M
Abstract: Introduction: In contrast with the well-known and described deletion of the 22q11 chromosome region responsible for DiGeorge syndrome, 22q12 deletions are much rarer. Only a few dozen cases have been reported so far. This region contains genes responsible for cell cycle control, chromatin modification, transmembrane signaling, cell adhesion, and neural development, as well as several cancer predisposition genes., Case Presentation: We present a patient with cleft palate, sensorineural hearing loss, vestibular dysfunction, epilepsy, mild to moderate intellectual disability, divergent strabism, pes equinovarus, platyspondylia, and bilateral schwannoma. Using Microarray-based Comparative Genomic Hybridization (aCGH), we identified the de novo 3.8 Mb interstitial deletion at 22q12.1→22q12.3. We confirmed deletion of the critical NF2 region by MLPA analysis., Discussion: Large 22q12 deletion in the proband encases the critical NF2 region, responsible for development of bilateral schwannoma. We compared the phenotype of the patient with previously reported cases. Interestingly, our patient developed cleft palate even without deletion of the MN1 gene, deemed responsible in previous studies. We also strongly suspect the DEPDC5 gene deletion to be responsible for seizures, consistent with previously reported cases., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
Published: 2023
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98. Treatment of adult patients with acute lymphoblastic leukemia in the Czech Republic in the period 2007-2020.

Author: Šálek C, Hrabovský Š, Folber F, Horáček JM, Kořístek Z, Szotkowski T, Pecherková P, Froňková E, Doubek M, and Leukemická Skupina-Pro Život Cell Č
Subjects: Young Adult, Humans, Adult, Retrospective Studies, Prospective Studies, Czech Republic epidemiology, Disease-Free Survival, Neoplasm, Residual diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Hematopoietic Stem Cell Transplantation
Abstract: Background: Pediatric-inspired protocols with prospective monitoring of minimal residual disease (MRD) are considered the standard of intensive treatment for adults with acute lymphoblastic leukemia (ALL). They have been used in the Czech Republic since 2007., Patients and Methods: Two hundred and ninety-seven patients aged 18-65 years were treated at five hematology centers between 2007-2020 according to the GMALL 07/2003 protocol. This is a retrospective analysis of their treatment outcomes., Results: In the Ph-negative cohort, 189 (93.1%) patients achieved complete remission, 5 (2.4%) patients were refractory, and early mortality was 3.0%. Seventy (34.5%) patients experienced relapse in a median of 10.6 months. Overall survival (OS) at 3 and 5 years was 63.5% and 55.9%, disease-free survival (DFS) at 3 and 5 years was 54.5% and 49.7%, respectively. Young adults under 35 years of age (P = 0.015), patients without initial CNS infiltration (P = 0.016), with MRD negativity before consolidation treatment (P < 0.001), transplanted in the 1st complete remission (P < 0.001), and subjects treated after 2012 (P = 0.05) had significantly better overall survival. In a multivariate analysis, MRD at week 11 was the only independent factor affecting OS (HR 3.06; P = 0.006). For DFS, baseline CNS infiltration (HR 2.08; P = 0.038) and MRD at week 11 (HR 2.15; P = 0.020) were significant. In the Ph-positive cohort, 84 (89.4%) patients achieved complete remission, 1 (1.0%) patient was refractory, early mortality was 4.3%. Twenty-six (27.7%) patients relapsed in a median of 8.6 months. Survival at 3 and 5 years was 57.2% and 52.4% for OS and 50.2% and 44.9% for DFS, respectively. Transplanted patients and patients diagnosed after 2012 had statistically better overall survival (P < 0.001)., Conclusion: The introduction of pediatric-inspired protocols with treatment intensification according to MRD levels resulted in a significant improvement in the survival outcomes of adult patients with ALL.
Published: 2023
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99. Idelalisib plus rituximab versus ibrutinib in the treatment of relapsed/refractory chronic lymphocytic leukaemia: A real-world analysis from the Chronic Lymphocytic Leukemia Patients Registry (CLLEAR).

Author: Špaček M, Smolej L, Šimkovič M, Nekvindová L, Křístková Z, Brychtová Y, Panovská A, Mašlejová S, Bezděková L, Écsiová D, Vodárek P, Zuchnická J, Mihályová J, Urbanová R, Turcsányi P, Lysák D, Novák J, Brejcha M, Líkařová T, Vodička P, Baranová J, Trněný M, and Doubek M
Subjects: Humans, Aged, Rituximab, Retrospective Studies, Recurrence, Registries, Leukemia, Lymphocytic, Chronic, B-Cell
Abstract: Idelalisib (idela), a phosphatidylinositol 3-kinase inhibitor, and ibrutinib, a Bruton tyrosine kinase inhibitor, were the first oral targeted agents approved for relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL). However, no randomised trials of idelalisib plus rituximab (R-idela) versus ibrutinib have been conducted. Therefore, we performed a real-world retrospective analysis of patients with R/R CLL treated with R-idela (n = 171) or ibrutinib (n = 244). The median age was 70 versus 69 years, with a median of two previous lines. There was a trend towards higher tumour protein p53 (TP53) aberrations and complex karyotype in the R-idela group (53% vs. 44%, p = 0.093; 57% vs. 46%, p = 0.083). The median progression-free survival (PFS) was significantly longer with ibrutinib (40.5 vs. 22.0 months; p < 0.001); similarly to overall survival (OS; median 54.4 vs. 37.7 months, p = 0.04). In multivariate analysis, only PFS but not OS remained significantly different between the two agents. The most common reasons for treatment discontinuation included toxicity (R-idela, 39.8%; ibrutinib, 22.5%) and CLL progression (27.5% vs. 11.1%). In conclusion, our data show significantly better efficacy and tolerability of ibrutinib over R-idela in patients with R/R CLL treated in routine practice. The R-idela regimen may still be considered a reasonable option in highly selected patients without a suitable treatment alternative., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)
Published: 2023
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100. Germline variant of CTC1 gene in a patient with pulmonary fibrosis and myelodysplastic syndrome.

Author: Doubková M, Vrzalová Z, Štefániková M, Červinek L, Kozubík KS, Blaháková I, Pospíšilová Š, and Doubek M
Abstract: Introduction: Telomeropathies are associated with a wide range of diseases and less common combinations of various pulmonary and extrapulmonary disorders., Case Presentation: In proband with high-risk myelodysplastic syndrome and interstitial pulmonary fibrosis, whole exome sequencing revealed a germline heterozygous variant of CTC1 gene (c.1360delG). This "frameshift" variant results in a premature stop codon and is classified as likely pathogenic/pathogenic. So far, this gene variant has been described in a heterozygous state in adult patients with hematological diseases such as idiopathic aplastic anemia or paroxysmal nocturnal hemoglobinuria, but also in interstitial pulmonary fibrosis. Described CTC1 gene variant affects telomere length and leads to telomeropathies., Conclusions: In our case report, we describe a rare case of coincidence of pulmonary fibrosis and hematological malignancy caused by a germline gene mutation in CTC1 . Lung diseases and hematologic malignancies associated with short telomeres do not respond well to standard treatment., (©Copyright: the Author(s).)
Published: 2023
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