28 results on '"Lisa Lassay"'
Search Results
2. Evaluation of lung function in a German single center cohort of young patients with sickle cell disease using EIT and standard techniques
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Alina Rein, Chuong Ngo, Maike van den Berg, Svenja Böll, Lisa Lassay, Udo Kontny, Norbert Wagner, Steffen Leonhardt, Klaus Tenbrock, and Eva Verjans
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sickle cell disease ,lung function ,electrical impedance tomography ,sickle cell chronic lung disease ,pediatric pulmology ,Medicine (General) ,R5-920 - Abstract
Background and objectiveSickle cell disease (SCD) is a very common autosomal recessive hemoglobinopathy leading to multiple pulmonary complications that are closely associated with mortality. The pathophysiology of chronic pulmonary involvement is not yet fully understood and no specific therapies are available.MethodsThe aim of this cross-sectional study was to characterize the lung function of children and young adolescents with SCD in a German single-center cohort and to extend conventional lung function testing by the use of a new imaging method. We performed spirometry and body plethysmography in 35 children and young adults with hemoglobin SS, SC, S/β-thalassemia as well as 50 controls. These data were compared with clinical characteristics and typical laboratory parameters of hemolysis and disease activity in SCD. To identify lung inhomogeneities, for example due to atelectasis, hyperinflation, air trapping or vascular occlusions, we used the promising new method of electrical impedance tomography (EIT) and calculated global inhomogeneity indices.ResultsLung function of patients with SCD was significantly reduced compared to that of healthy controls. When the result was found to be pathological, the most commonly observed type of breathing disorder was classified as restrictive. Laboratory parameters showed typical features of SCD including decreased levels of hemoglobin and hematocrit and elevated levels of leucocytes, platelets, lactate dehydrogenase and total bilirubin. However, there was no correlation between blood values and reduced lung function. Electrical impedance tomography (EIT) revealed no abnormalities in SCD patients compared to healthy controls. In particular, we were unable to demonstrate any regional inhomogeneities in lung ventilation.ConclusionIn our study, SCD patients showed impaired lung function, with a relevant percentage of patients suffering from restrictive breathing disorder. Signs of obstruction could not be detected. Electrical impedance tomography (EIT) measurements revealed no unevenness that would suggest air entrapment, blockage of blood vessels, excessive inflation, obstruction, or other forms of lung disease. Additionally, the reduction in lung function observed in SCD patients was not related to the disease severity or laboratory test results.
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- 2023
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3. The German National Registry of Primary Immunodeficiencies (2012–2017)
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Sabine M. El-Helou, Anika-Kerstin Biegner, Sebastian Bode, Stephan R. Ehl, Maximilian Heeg, Maria E. Maccari, Henrike Ritterbusch, Carsten Speckmann, Stephan Rusch, Raphael Scheible, Klaus Warnatz, Faranaz Atschekzei, Renata Beider, Diana Ernst, Stev Gerschmann, Alexandra Jablonka, Gudrun Mielke, Reinhold E. Schmidt, Gesine Schürmann, Georgios Sogkas, Ulrich H. Baumann, Christian Klemann, Dorothee Viemann, Horst von Bernuth, Renate Krüger, Leif G. Hanitsch, Carmen M. Scheibenbogen, Kirsten Wittke, Michael H. Albert, Anna Eichinger, Fabian Hauck, Christoph Klein, Anita Rack-Hoch, Franz M. Sollinger, Anne Avila, Michael Borte, Stephan Borte, Maria Fasshauer, Anja Hauenherm, Nils Kellner, Anna H. Müller, Anett Ülzen, Peter Bader, Shahrzad Bakhtiar, Jae-Yun Lee, Ursula Heß, Ralf Schubert, Sandra Wölke, Stefan Zielen, Sujal Ghosh, Hans-Juergen Laws, Jennifer Neubert, Prasad T. Oommen, Manfred Hönig, Ansgar Schulz, Sandra Steinmann, Klaus Schwarz, Gregor Dückers, Beate Lamers, Vanessa Langemeyer, Tim Niehues, Sonu Shai, Dagmar Graf, Carmen Müglich, Marc T. Schmalzing, Eva C. Schwaneck, Hans-Peter Tony, Johannes Dirks, Gabriele Haase, Johannes G. Liese, Henner Morbach, Dirk Foell, Antje Hellige, Helmut Wittkowski, Katja Masjosthusmann, Michael Mohr, Linda Geberzahn, Christian M. Hedrich, Christiane Müller, Angela Rösen-Wolff, Joachim Roesler, Antje Zimmermann, Uta Behrends, Nikolaus Rieber, Uwe Schauer, Rupert Handgretinger, Ursula Holzer, Jörg Henes, Lothar Kanz, Christoph Boesecke, Jürgen K. Rockstroh, Carolynne Schwarze-Zander, Jan-Christian Wasmuth, Dagmar Dilloo, Brigitte Hülsmann, Stefan Schönberger, Stefan Schreiber, Rainald Zeuner, Tobias Ankermann, Philipp von Bismarck, Hans-Iko Huppertz, Petra Kaiser-Labusch, Johann Greil, Donate Jakoby, Andreas E. Kulozik, Markus Metzler, Nora Naumann-Bartsch, Bettina Sobik, Norbert Graf, Sabine Heine, Robin Kobbe, Kai Lehmberg, Ingo Müller, Friedrich Herrmann, Gerd Horneff, Ariane Klein, Joachim Peitz, Nadine Schmidt, Stefan Bielack, Ute Groß-Wieltsch, Carl F. Classen, Jessica Klasen, Peter Deutz, Dirk Kamitz, Lisa Lassay, Klaus Tenbrock, Norbert Wagner, Benedikt Bernbeck, Bastian Brummel, Eusebia Lara-Villacanas, Esther Münstermann, Dominik T. Schneider, Nadine Tietsch, Marco Westkemper, Michael Weiß, Christof Kramm, Ingrid Kühnle, Silke Kullmann, Hermann Girschick, Christof Specker, Elisabeth Vinnemeier-Laubenthal, Henriette Haenicke, Claudia Schulz, Lothar Schweigerer, Thomas G. Müller, Martina Stiefel, Bernd H. Belohradsky, Veronika Soetedjo, Gerhard Kindle, and Bodo Grimbacher
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registry for primary immunodeficiency ,primary immunodeficiency (PID) ,German PID-NET registry ,PID prevalence ,European Society for Immunodeficiencies (ESID) ,IgG substitution therapy ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
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- 2019
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4. Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions
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Benjamin Werner, Fabian Beier, Sebastian Hummel, Stefan Balabanov, Lisa Lassay, Thorsten Orlikowsky, David Dingli, Tim H Brümmendorf, and Arne Traulsen
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telomere length distribution ,stem cell ,mathematical modelling ,hematopoiesis ,self renewal ,personalised medicine ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
We investigate the in vivo patterns of stem cell divisions in the human hematopoietic system throughout life. In particular, we analyze the shape of telomere length distributions underlying stem cell behavior within individuals. Our mathematical model shows that these distributions contain a fingerprint of the progressive telomere loss and the fraction of symmetric cell proliferations. Our predictions are tested against measured telomere length distributions in humans across all ages, collected from lymphocyte and granulocyte sorted telomere length data of 356 healthy individuals, including 47 cord blood and 28 bone marrow samples. We find an increasing stem cell pool during childhood and adolescence and an approximately maintained stem cell population in adults. Furthermore, our method is able to detect individual differences from a single tissue sample, i.e. a single snapshot. Prospectively, this allows us to compare cell proliferation between individuals and identify abnormal stem cell dynamics, which affects the risk of stem cell related diseases.
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- 2015
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5. Specialized pediatric palliative care services for children dying from cancer: A repeated cohort study on the developments of symptom management and quality of care over a 10-year period
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Michaela Kuhlen, Pia Schmidt, Aram Prokop, Tim Niehues, Martin Irnich, Kumar Sinha, Carola Weber, Martina Rose, Thomas Brune, Monika Pöppelmann, Margit Baumann-Köhler, Bernhard Kremens, Dominik T. Schneider, G. Janßen, Lisa Lassay, Boris Zernikow, Prasad T. Oommen, Rita Kiener, Julia Wager, Michael M. Schündeln, Heike Thorer, Katharina Szybalski, Norbert Jorch, Joanne Wolfe, Bettina Hübner-Möhler, Alfred Längler, Michael Paulussen, and Regina Wieland
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Adult ,Male ,medicine.medical_specialty ,Medizinische Fakultät » Universitätsklinikum Essen » Zentrum für Kinder- und Jugendmedizin » Klinik für Pädiatrische Hämatologie, Onkologie und Endokrinologie ,Palliative care ,pediatrics ,Adolescent ,Medizin ,MEDLINE ,Pediatrics ,palliative medicine ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,quality of health care ,030502 gerontology ,Neoplasms ,medicine ,cancer ,Humans ,ddc:610 ,Disease management (health) ,Quality of care ,Child ,Quality of Health Care ,symptom assessment ,Terminal Care ,business.industry ,Symptom management ,Medizinische Fakultät » Universitätsklinikum Essen » Zentrum für Kinder- und Jugendmedizin » Klinik für Kinderheilkunde III ,Palliative Care ,Infant, Newborn ,Disease Management ,Infant ,Cancer ,General Medicine ,medicine.disease ,Pediatric palliative care ,Anesthesiology and Pain Medicine ,Child, Preschool ,030220 oncology & carcinogenesis ,Family medicine ,Female ,0305 other medical science ,business ,Forecasting ,Cohort study - Abstract
Background: About one quarter of children affected with cancer die. For children and their families, the end-of-life period is highly distressing. Aim: This study focused on how end-of-life care in pediatric cancer patients changed over a period of 10 years and if changes in pediatric palliative care structures were associated with quality of care. Design: Over a 10-year period, all pediatric oncology departments in one German federal state were invited to participate in a repeated cross-sectional cohort study at three time-points (2005, 2010, 2015). Departments invited parents whose children died due to cancer 5 years earlier to participate. Identical semi-structured interviews were conducted with each cohort by the Survey of Caring for Children with Cancer. In addition, departments provided information on their pediatric palliative care infrastructure. Participants: In total, 124 families participated; 73% of interviews were conducted with mothers, 18% with fathers, and 9% with both parents. Results: Parents’ perception of symptom occurrence, symptom burden, and effectiveness of symptom-related treatment remained stable over the 10-year period. Over time, the availability of pediatric palliative care ( p Conclusion: Advances in the availability of pediatric palliative care were associated with improvement in some aspects of quality of care (e.g. location of death) while other aspects, such as effectiveness of symptom management, remained unchanged. Further research is required to determine whether additional improvement in structural quality may increase the effectiveness of symptom management.
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- 2018
6. Unusual phenotypes in patients with a pathogenic germline variant in DICER1
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Julia Carlens, Christian P. Kratz, Jung Kim, Lisa Lassay, Miriam Elbracht, Kris Ann P. Schultz, Udo Kontny, Martin Zenker, Kateryna Venger, Douglas R. Stewart, Peter Deutz, Ilse Wieland, Nicolaus Schwerk, Felix Zeppernick, and Ingo Kurth
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0301 basic medicine ,Genetics ,Cancer Research ,Pleuropulmonary blastoma ,030105 genetics & heredity ,Biology ,medicine.disease ,Compound heterozygosity ,Penetrance ,Germline ,Article ,Frameshift mutation ,03 medical and health sciences ,030104 developmental biology ,Oncology ,medicine ,Embryonal rhabdomyosarcoma ,Global developmental delay ,Genetics (clinical) ,Exome sequencing - Abstract
Familial cancer (2021). doi:10.1007/s10689-021-00271-z, Published by Springer Science + Business Media B.V, Dordrecht [u.a.]
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- 2021
7. Abscessing Infection by Streptococcus mitis Mimicking Metastatic Lesions in a 5-Year-Old Girl With Nephroblastoma: A Case Report
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Jan Spillner, Lisa Lassay, Udo Kontny, Simone Schrading, Till Braunschweig, Alexander Puzik, Gerhard Steinau, and Lara Imhof
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0301 basic medicine ,medicine.medical_specialty ,Pathology ,Metastatic lesions ,medicine.drug_class ,medicine.medical_treatment ,media_common.quotation_subject ,Liver Abscess ,030106 microbiology ,Antibiotics ,Streptococcus mitis ,Wilms Tumor ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Streptococcal Infections ,Biopsy ,medicine ,Humans ,Lung Abscess ,Girl ,Neoplasm Metastasis ,Hepatic Abscesses ,media_common ,Chemotherapy ,medicine.diagnostic_test ,biology ,business.industry ,Hematology ,biology.organism_classification ,Abscess ,Nephrectomy ,Surgery ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Female ,business - Abstract
Streptococcus mitis is a common pathogen causing infections in oncological patients. However, cases of abscesses caused by Streptococcus mitis in oncological patients have not been reported so far. We report on 5-year-old child with nephroblastoma and pulmonary and hepatic metastases at diagnosis who went into complete remission undergoing chemotherapy and nephrectomy, and who developed new round lesions in liver and lungs under continuous chemotherapy suggestive of new metastases. Biopsy of the lesions revealed abscesses with detection of Streptococcus mitis. The child was successfully treated with antibiotics, finished chemotherapy per protocol and has been in complete remission for 14 months. Infectious lesions involving organs of typical metastatic dissemination can easily be misdiagnosed as metastases, especially in the absence of symptoms. Histologic proof of lesions suspicious of metastases is mandatory if it leads to a change of prognosis and therapy. Streptococcus mitis can be a causative organism of pulmonary and hepatic abscesses in oncological patients.
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- 2018
8. Diagnosis and Treatment of Nasopharyngeal Carcinoma in Children and Adolescents - Recommendations of the GPOH-NPC Study Group
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G. Staatz, Lisa Lassay, Christian P. Kratz, Uta Behrends, Tobias Feuchtinger, C. Schmitt, Beate Timmermann, F. M. Mottaghy, Hans Christiansen, Peter Vorwerk, Bernd Granzen, M. Bührlen, Udo Kontny, Rolf Mertens, Henri Jacques Delecluse, S. Franzen, H. A. Wolff, S. Wilop, Guenther Gademann, Ivo Leuschner, Michael J. Eble, RS: FHML non-thematic output, RS: GROW - School for Oncology and Reproduction, Kindergeneeskunde, MUMC+: MA Medische Staf Kindergeneeskunde (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Beeldvorming
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Oncology ,medicine.medical_specialty ,Epstein-Barr Virus Infections ,Adolescent ,medicine.medical_treatment ,Nasopharyngeal neoplasm ,Medizin ,chemotherapy ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Maintenance therapy ,children ,Internal medicine ,Nasopharynx ,otorhinolaryngologic diseases ,medicine ,Biomarkers, Tumor ,Humans ,adolescents ,Prospective cohort study ,Child ,Lymph node ,Survival rate ,Neoplasm Staging ,therapy ,business.industry ,nasopharyngeal ,Nasopharyngeal Neoplasms ,interferon ,medicine.disease ,Primary tumor ,Combined Modality Therapy ,Magnetic Resonance Imaging ,Surgery ,Radiation therapy ,Survival Rate ,medicine.anatomical_structure ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,Pediatrics, Perinatology and Child Health ,DNA, Viral ,Lymph Nodes ,business ,030215 immunology - Abstract
Nasopharyngeal carcinoma (NPC) is a rare malignant tumor arising from epithelial cells of the nasopharynx. Its incidence is highest in Southeast Asia. Age distribution of NPC is bimodal, with one peak in young adolescents and another in patients 55-59 years of age. EBV appears to be the primary etiologic agent in the pathogenesis, environmental factors such as nitrosamines and genetic factors are contributory. NPC is most commonly diagnosed in locally advanced stages, with lymph node metastases occurring in up to 90 % of patients. About 5-10 % of patients present with distant metastases. Diagnosis of NPC is made histologically, supported by an abnormal anti-EBV-VCA IgA titer and elevated plasma EBV-DNA load. Superior results in children and adolescents with advanced locoregional NPC, with overall and event-free survival rates >90 %, have been achieved by neoadjuvant chemotherapy with 5-fluoruracil and cisplatin, followed by synchronous radiochemotherapy and subsequent maintenance therapy with interferon-beta as demonstrated by the 2 prospective studies GPOH-NPC-91 and -2003. Response to therapy can be assessed by PET-imaging and in patients with complete remission after neoadjuvant chemotherapy, the radiation dose to the primary tumor can be safely reduced from 59.4 to 54.4 Gy. Since the majority of long term sequalae such as xerostomia, skin and tissue fibrosis are caused by high radiation dosages, radiotherapy modalities such as intensity-modulated radiotherapy should be used to efficiently spare non-tumorous tissue. For patients with metastatic disease and relapse, survival chances are low. New treatment strategies, such as the application of EBV-specific T-lymphocytes should be considered for these patients.
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- 2016
9. Primary central nervous system primitive neuroectodermal tumors (CNS-PNETs) of the spinal cord in children: four cases from the German HIT database with a critical review of the literature
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Daniela Sperl, Stefan Rutkowski, Martin Benesch, Torsten Pietsch, Lisa Lassay, André O. von Bueren, Rolf-Dieter Kortmann, Monika Warmuth-Metz, Katja von Hoff, Irene Schmid, and Rudolf Ferrari
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Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Spinal Cord Neoplasm ,Brain tumor ,computer.software_genre ,Autologous stem-cell transplantation ,Germany ,medicine ,Humans ,Neuroectodermal Tumors, Primitive ,Spinal Cord Neoplasms ,Database ,Brain Neoplasms ,business.industry ,Brain ,Infant ,Induction chemotherapy ,Spinal cord ,medicine.disease ,Magnetic Resonance Imaging ,Primary tumor ,Surgery ,Radiation therapy ,medicine.anatomical_structure ,Spinal Cord ,Neurology ,Oncology ,Head start ,Female ,Neurology (clinical) ,business ,computer - Abstract
Approximately 30-50% of patients with intracranial primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) develop spinal metastases. In contrast, primary spinal CNS-PNETs are extremely uncommon. The database and study records of the German/Austrian brain tumor trials HIT 91, HIT SKK 92, and HIT 2000 were retrospectively reviewed to describe clinical features, treatment modalities, and outcome of children with primary CNS-PNETs of the spinal cord who were registered as observational patients. Out of 1,248 patients with medulloblastomas or CNS-PNETs registered in the HIT database four patients (female, n = 3) with primary CNS-PNETs of the spinal cord were identified. Age at diagnosis was 10, 16, 23, and 174 months. Location of primary tumors was medulla oblongata-T3, C2-T1, T10-L2, T7-T10. Two patients had metastatic disease at diagnosis. Complete and incomplete resection was performed in one patient each, whereas two patients underwent a biopsy only. Two patients received chemotherapy only, in accordance with the HIT 91 trial (sandwich chemotherapy arm). They developed disease progression and died six months after diagnosis. One patient was given chemotherapy in accordance with the HIT 2000 trial followed by craniospinal radiotherapy and four courses of maintenance chemotherapy. The patient is in complete remission almost four years after diagnosis. The fourth patient developed disease progression while receiving induction chemotherapy. Hence, chemotherapy was switched to a modified Head Start protocol. After three cycles he underwent double autologous stem cell transplantation and craniospinal irradiation. Forty months after diagnosis the patient is alive and well, but surveillance MRIs still show nodular enhancing lesions in the area of the primary tumor and intracranial meningeal enhancement. Primary CNS-PNETs of the spinal cord probably require multimodal treatment including radiotherapy to achieve sustained tumor control.
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- 2010
10. Safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with recurrent or refractory brain tumors: a multi-institutional retrospective study
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Stefan Rutkowski, Lisa Lassay, Nele Siegler, C Sommer, Martin Benesch, Gabriele Kropshofer, Gudrun Fleischhack, Christian Urban, Hermann L. Müller, and Katja von Hoff
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Compassionate Use Trials ,Male ,Antimetabolites, Antineoplastic ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Salvage therapy ,Phases of clinical research ,Gastroenterology ,Young Adult ,Lethargy ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Child ,Injections, Spinal ,Dexamethasone ,Retrospective Studies ,Salvage Therapy ,Pharmacology ,Medulloblastoma ,Brain Neoplasms ,business.industry ,Cytarabine ,Infant ,medicine.disease ,Surgery ,Oncology ,Drug Resistance, Neoplasm ,Child, Preschool ,Delayed-Action Preparations ,Concomitant ,Liposomes ,Atypical teratoid rhabdoid tumor ,Female ,business ,medicine.drug - Abstract
This retrospective study aimed to evaluate the safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with refractory or recurrent brain tumors. Nineteen heavily pretreated patients (males, n = 14; females, n = 5; median age at diagnosis 8.5 years; range, 1.4-22 years) were given intrathecal liposomal cytarabine on a compassionate use basis for recurrent refractory medulloblastoma (n = 12), mixed germ cell tumor (n = 2), central nervous system primitive neuroectodermal tumors of the pons (n = 1), anaplastic ependymoma (n = 1), anaplastic oligodendroglioma (n = 1), atypical teratoid rhabdoid tumor (n = 1), or rhabdoid papillary meningioma (n = 1). Eighteen patients received concomitant systemic radiochemotherapy. A total of 88 intrathecal injections of liposomal cytarabine (dose range, 20-50 mg) were administered with concomitant dexamethasone prophylaxis. The median number of doses per patient was four (range, 1-10). Duration of treatment ranged from (1/2) to 10 months. Eleven patients (57.9%) did not show any side effects, whereas eight patients (42.1%) developed side effects related to either chemical arachnoiditis (n = 4) or neurological progression (n = 2). Less typical treatment-related symptoms (e.g. lethargy, ataxia, and slurred speech) were observed in two patients. Treatment with intrathecal liposomal cytarabine was discontinued twice because of side effects. In conclusion, although intrathecal liposomal cytarabine was generally well tolerated, it should be used cautiously and only with dexamethasone prophylaxis in extensively pretreated patients with recurrent brain tumors. Proof of efficacy requires a prospective single-agent phase II study.
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- 2009
11. Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions
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Tim H. Brümmendorf, Arne Traulsen, Sebastian Hummel, Lisa Lassay, David Dingli, Thorsten Orlikowsky, Benjamin Werner, Stefan Balabanov, Fabian Beier, University of Zurich, and Werner, B
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2400 General Immunology and Microbiology ,Lymphocytes ,Prospective Studies ,Biology (General) ,Child ,Aged, 80 and over ,General Neuroscience ,personalised medicine ,2800 General Neuroscience ,General Medicine ,Middle Aged ,Telomere ,Healthy Volunteers ,Cell biology ,Haematopoiesis ,medicine.anatomical_structure ,Child, Preschool ,Cord blood ,Medicine ,Stem cell ,Research Article ,Computational and Systems Biology ,Human ,Adult ,Adolescent ,QH301-705.5 ,Science ,Cytological Techniques ,Stem cell theory of aging ,610 Medicine & health ,Biology ,telomere length distribution ,General Biochemistry, Genetics and Molecular Biology ,Young Adult ,stem cells ,1300 General Biochemistry, Genetics and Molecular Biology ,medicine ,Humans ,mathematical modelling ,Progenitor cell ,Aged ,Cell Proliferation ,General Immunology and Microbiology ,Infant, Newborn ,Infant ,Models, Theoretical ,Hematopoietic Stem Cells ,hematopoiesis ,stem cell ,self renewal ,Developmental Biology and Stem Cells ,10032 Clinic for Oncology and Hematology ,Immunology ,Bone marrow ,Developmental biology ,Granulocytes - Abstract
We investigate the in vivo patterns of stem cell divisions in the human hematopoietic system throughout life. In particular, we analyze the shape of telomere length distributions underlying stem cell behavior within individuals. Our mathematical model shows that these distributions contain a fingerprint of the progressive telomere loss and the fraction of symmetric cell proliferations. Our predictions are tested against measured telomere length distributions in humans across all ages, collected from lymphocyte and granulocyte sorted telomere length data of 356 healthy individuals, including 47 cord blood and 28 bone marrow samples. We find an increasing stem cell pool during childhood and adolescence and an approximately maintained stem cell population in adults. Furthermore, our method is able to detect individual differences from a single tissue sample, i.e. a single snapshot. Prospectively, this allows us to compare cell proliferation between individuals and identify abnormal stem cell dynamics, which affects the risk of stem cell related diseases. DOI: http://dx.doi.org/10.7554/eLife.08687.001, eLife digest Human cells die off regularly due to normal wear and tear, aging or injury. To replace these cells, humans maintain pockets of tissue specific stem cells that can develop into one of several different types of specialized cell. For example, stem cells in the bone marrow can develop into red blood cells, white blood cells or any of the other blood cell types. Unavoidably, over the course of a lifetime stem cells accumulate mutations that may cause them to become cancerous. Researchers have learned a lot about stem cells by studying them under laboratory conditions. However, these studies cannot answer all the questions we have about human stem cells. As a result, human studies are needed; but frequently taking samples of stem cells from humans to assess them is impossible for numerous reasons, most importantly it is invasive and potentially harmful. Instead, researchers are looking for indirect ways to measure how stem cells grow. Each time a cell divides, the protective ends of a chromosome – known as telomeres – get shorter. Now, Werner, Beier et al. have developed a mathematical model to assess human stem cell growth based on the length of the cells’ telomeres. This model can gauge the growth patterns of the stem cell populations in an individual based on a sample taken from a single tissue. Werner, Beier et al. tested the model using telomere measurements from blood and bone marrow samples taken from 356 healthy people of different ages. The results suggest that the stem cell population that gives rise to blood cells (the hematopoietic stem cells) increases in size during childhood and adolescence, but levels off during adulthood. The model also revealed that patterns of stem cell growth vary among individuals. Further studies of telomere length differences may help scientists identify the abnormal (stem cell-like) growth patterns associated with diseases like cancer. DOI: http://dx.doi.org/10.7554/eLife.08687.002
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- 2015
12. Author response: Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions
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Sebastian Hummel, Thorsten Orlikowsky, Lisa Lassay, Tim H. Brümmendorf, Arne Traulsen, Benjamin Werner, Stefan Balabanov, Fabian Beier, and David Dingli
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Haematopoiesis ,In vivo ,Dynamics (mechanics) ,Biology ,Stem cell ,Telomere ,Cell biology - Published
- 2015
13. Treatment of nasopharyngeal carcinoma in children and adolescents
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G. Heimann, Peter Bucsky, Claudia Weiss, Manfred Hundgen M.D., Lisa Lassay, Clemens F. Hess, Günther Gademann, Rolf Mertens, Gunter Stetter, and Bernd Granzen
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Combination therapy ,medicine.medical_treatment ,Gastroenterology ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Mucositis ,Humans ,Child ,Neoplasm Staging ,Chemotherapy ,Cardiotoxicity ,business.industry ,Cancer ,Nasopharyngeal Neoplasms ,Radiotherapy Dosage ,Interferon-beta ,medicine.disease ,Combined Modality Therapy ,3. Good health ,Surgery ,Radiation therapy ,Oncology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Female ,Methotrexate ,business ,medicine.drug - Abstract
BACKGROUND Preliminary results of combined neoadjuvant chemotherapy, radiotherapy, and postradiation interferon beta (IFN-β) in children and adolescents with nasopharyngeal carcinoma, especially in high-risk patients, have been promising. METHODS From 1992 to 2003, 59 patients (58 high-risk patients and 1 low-risk patient, median age 13 yrs; range, 8–25 yrs) were treated in the GPOH-NPC-91 study. The Stage II patient received irradiation as initial therapy. Fifty-eight patients received preradiation chemotherapy with methotrexate, cisplatin, and 5-fluorouracil. The cumulative radiation dose to primary sites was 59.4 Gy, a total dose of 45 Gy was delivered to the neck area. After irradiation, all patients were treated with 105 U recombinant IFN-β/kg body weight 3 times a week for 6 months. RESULTS After combination therapy, complete response was accomplished in 58 patients. In one patient, there was tumor progression during chemotherapy. In 3 patients, distant metastases were observed 14, 15, and 18 months after diagnosis, respectively. One patient had a local relapse 12 months after diagnosis. Fifty-four patients are still in first remission with a median follow-up of 48 months (range, 10–110 mos). Chemotherapy-related toxicity was mucositis Grade II, III, or IV in all patients and acute cardiotoxicity in 2 (3.5%) of the patients. Nephrotoxicity Grade I–II occurred in 8.8% of patients. CONCLUSIONS The combination of initial chemotherapy, radiotherapy, and IFN-β results in an excellent outcome. These results strongly support the development of a future treatment strategy along this line. Cancer 2005. © 2005 American Cancer Society.
- Published
- 2005
14. Femurkopfnekrose als Komplikation der ALL-Therapie bei Kindern und Jugendlichen
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Lisa Lassay, H. R. Casser, T. Peschgens, Rolf Mertens, G. Heimann, and B. Granzen
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Gynecology ,medicine.medical_specialty ,business.industry ,Pediatrics, Perinatology and Child Health ,medicine ,Surgery ,business - Abstract
Mit Hilfe moderner Therapieverfahren, v. a. der kombinierten zytostatischen Therapie, konnte die Prognose der Erkrankung im Laufe der letzten Jahrzehnte erheblich verbessert werden. Die rezidivfreie Uberlebensrate nach 5 Jahren liegt in Deutschland derzeit bei 70–75% [16]. In Anbetracht dieser ausgezeichneten Prognose gewinnt die Frage nach der Lebensqualitat nach uberstandener Erkrankung an Bedeutung. Die Autoren mochten anhand der hier dargestellten Kasuistiken auf eine mogliche Folge der ALL-Therapie hinweisen, und zwar auf die im padiatrischen Krankengut v.a. bei jugendlichen Patienten zu beobachtende Huftkopfnekrose, deren Auftreten nicht selten mit einer dauerhaften Behinderung des betroffenen Patienten einhergeht.
- Published
- 1999
15. Partielle Milzembolisation bei Kindern mit Hypersplenismus unterschiedlicher Genese
- Author
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G. Heimann, B. Granzen, R. W. Günther, T. Wenzl, S. Müller-Weihrich, Lisa Lassay, Rolf Mertens, and G. Alzen
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,Pediatrics, Perinatology and Child Health ,medicine ,Surgery ,business - Abstract
Fragestellung: Die Splenektomie stellt lebenslang ein erhohtes Risiko dar, an einer Postsplenektomiesepsis zu erkranken. Das Risiko bis zu 10% ist bei Patienten, die im Alter von weniger als 5 Jahren splenektomiert wurden, besonders hoch. Als Alternative zu den chirurgischen Verfahren Splenektomie und Hemisplenektomie bei Patienten mit Hypersplenismus wird die partielle Milzembolisation vorgestellt. Methode: Bei 4 Kleinkindern im Alter von 13–84 Monaten (Median 43 Monate) mit Hyperspleniesyndrom unterschiedlicher Genese wurde eine selektive Milzembolisation erfolgreich durchgefuhrt. Die partielle Embolisation erfolgte durch eine Verabreichung von 150–250 µm grosen Ivalonpartikeln nach selektiver Katheterisierung der Milzarterienaste 2. Ordnung, wodurch ein peripherer Verschlus einzelner Milzsegmente gelang. Schmerzkrisen und infektiologische Komplikationen konnten in der Postembolisationsphase durch eine konsequente analgetische Behandlung mit einer mehrtagigen Morphindauertropfinfusion und Antibiotikagaben (Tobramycin und Ampicillin) vermieden werden. Bei einem Patienten traten unmittelbar nach der Embolisation eine kurzzeitige Ileussymptomatik und eine Fieberepisode auf. Alle Patienten konnten nach 5–10 Tagen entlassen werden. Ergebnisse: Wenige Tage nach der Embolisation stiegen Hamoglobin, Leukozyten und Thrombozyten bei allen Patienten an. Weitere Erythrozyten- bzw. Thrombozytentransfusionen waren nicht mehr erforderlich. Ein Patient mit unklarem Dysmorphiesyndrom, Gedeihstorung, nicht klassifizierbaren Immundefekt, Karnitinmangel und Verdacht auf eine Lymphohistiozytose wies in der Nachbeobachtungszeit stabile Blutwerte (Leukozyten >5×103/µl und Hamoglobin >10 g/dl) auf. Der Patient starb 26 Monate nach der Embolisation an einer therapierefraktaren Pneumonie und Sepsis mit Verbrauchskoagulopathie bei einer seit 8 Monaten bekannten Atelektase der rechten Lunge. Die ubrigen 3 Patienten befinden sich in einem guten Allgemeinzustand mit einer mittleren Beobachtungszeit von 32 Monaten. Schwere Infektionen wurden nicht mehr beobachtet. Ein erneutes Hyperspleniesyndrom wurde bisher bei keinem Patienten beobachtet. Schlusfolgerung: Eine partielle Milzembolisation stellt beim dauerhaft transfusionspflichtigen Hyperspleniesyndrom im Kindesalter eine risikoarme, unter konsequenter Analgesie wenig schmerzhafte Alternative zur Hemi- bzw. Splenektomie dar.
- Published
- 1998
16. Nasopharyngeal carcinoma in childhood and adolescence
- Author
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Bernd Granzen, Clemens F. Hess, Rolf Mertens, Günther Gademann, Lisa Lassay, and Gerhard Heimann
- Subjects
Oncology ,Cancer Research ,Cardiotoxicity ,medicine.medical_specialty ,Chemotherapy ,medicine.drug_class ,Cumulative dose ,business.industry ,medicine.medical_treatment ,Cancer ,medicine.disease ,Antimetabolite ,3. Good health ,Surgery ,Radiation therapy ,Nasopharyngeal carcinoma ,Internal medicine ,medicine ,Carcinoma ,business - Abstract
BACKGROUND The increasing use of chemotherapy has improved the prognosis of patients with nasopharyngeal carcinoma (NPC), and the authors demonstrated the beneficial effect of adjuvant interferon (IFN)-β in a previous pilot study of children with advanced stage NPC. The current multi-institutional, cooperative GPOH (Gesellschaft fur Padiatrische Onkologie und Hamatologie) study NPC-91 was begun in 1992 to determine the efficacy of preradiation chemotherapy, radiotherapy, and adjuvant IFN-β in the treatment of advanced stage NPC. METHODS Of a total of 22 patients, 21 had American Joint Committee on Cancer Stage III or IV disease, and 1 had Stage II disease. The median age was 12 years (range, 8-16 years). Twenty of 22 received 3 courses of preradiation chemotherapy consisting of methotrexate 120 mg/m2 on Day 1, cisplatin 100 mg/m2 on Day 1, and 5-fluorouracil 1000 mg/m2 for five days as well as 6 doses of leucovorin 25 mg/m2 every six hours beginning on Day 2. The Stage II patient received no chemotherapy, and chemotherapy was terminated for another during the first course. All patients had radiation therapy, stratified by stage. The cumulative dose to the primary sites was 59.4 gray (Gy), with single doses of 1.8 Gy. A total of 45 Gy was delivered to the neck area. Finally, all patients were treated with recombinant IFN-β (105 U per kg of body weight) 3 times a week for 6 months. RESULTS The response rate was 91%. These patients stayed in first remission during a median follow-up of 32 months. With the exception of one reversible cardiotoxicity, moderate chemotherapy-related toxicity was observed. CONCLUSIONS In this study, patients with advanced stage NPC had a good prognosis with treatment consisting of neoadjuvant cisplatin and 5-fluorouracil, radiotherapy, and adjuvant IFN-β. It is particularly noteworthy that distant metastases did not develop. Cancer 1997; 80:951-9. © 1997 American Cancer Society.
- Published
- 1997
17. SCE-Rate und Lymphozytendifferenzierung bei Kindern mit akuter lymphatischer Leukämie sowie SCE-Raten von Leukämiepatienten in Langzeitremission
- Author
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Rolf Mertens, Lisa Lassay, F Rubbert, G Heimann, and A Büssing
- Subjects
medicine.medical_specialty ,Chemotherapy ,Cyclophosphamide ,business.industry ,DNA repair ,medicine.medical_treatment ,Lymphocyte ,Sister chromatid exchange ,medicine.disease ,Gastroenterology ,medicine.anatomical_structure ,In vivo ,Acute lymphocytic leukemia ,Internal medicine ,Pediatrics, Perinatology and Child Health ,Immunology ,Second Malignancy ,Medicine ,business ,medicine.drug - Abstract
Sister chromatid exchanges (SCE) and lymphocyte subsets of children with acute lymphoblastic leukemia (ALL) were investigated in children with ALL during chemotherapy and at least 5 years after chemotherapy. The treatment of the new admitted patients followed protocol ALL-BFM-90. Children with ALL at the time of diagnosis showed statistically significant higher SCE frequencies (4.9 +/- 0.77) than healthy controls (3.6 +/- 0.93; p = 0.002). The in vivo effects of cyclophosphamide (CP) resulted in a dramatic increase of the SCE frequency (20.5 +/- 3.76). This increased SCE level of lymphocytes might reflect an instability of DNA or a deficiency of DNA repair capacity. However, immediately one week after the administration of CP, the SCE rate decreased. This decline of SCE frequency correlates with a severe reduction of the absolute numbers of T lymphocytes. The observed reduction of SCE frequency may be due to a depletion of T lymphocytes, or a repair of DNA. The patients in long term remission ( > 5 years) have had the therapy according BFM-83 (9 pat.) and modified 'Pinkel-regime' (2 pat.). No difference was found between the SCE-rate of the patients in remission and of the age-dependent control group. These results might correlate with the low risk for future development of relaps or second malignancy.
- Published
- 1996
18. Multimodal treatment, including interferon beta, of nasopharyngeal carcinoma in children and young adults: preliminary results from the prospective, multicenter study NPC-2003-GPOH/DCOG
- Author
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Peter Deutz, Peter Vorwerk, Bernd Granzen, Christian M. Zwaan, Miriam Tamm, Guenther Gademann, Lisa Lassay, Foppe Oldenburger, Gundula Staatz, Martina Buehrlen, Hans Christiansen, and Rolf Mertens
- Subjects
Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Disease-Free Survival ,Drug Administration Schedule ,Folinic acid ,Young Adult ,Internal medicine ,Germany ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Mucositis ,Humans ,Prospective Studies ,Prospective cohort study ,Child ,Survival rate ,Neoplasm Staging ,Nasopharyngeal Carcinoma ,business.industry ,Carcinoma ,Remission Induction ,Nasopharyngeal Neoplasms ,Chemoradiotherapy, Adjuvant ,Interferon-beta ,medicine.disease ,Magnetic Resonance Imaging ,Neoadjuvant Therapy ,Surgery ,Radiation therapy ,Treatment Outcome ,Nasopharyngeal carcinoma ,Concomitant ,Positron-Emission Tomography ,Female ,Dose Fractionation, Radiation ,Fluorouracil ,Cisplatin ,Neoplasm Recurrence, Local ,business ,Chemoradiotherapy ,medicine.drug - Abstract
BACKGROUND: The authors report preliminary results from a prospective multicenter study (Nasopharyngeal Carcinoma [NPC] 2003 German Society of Pediatric Oncology and Hematology/German Children's Oncology Group [NPC-2003-GPOH/DCOG]). METHODS: From 2003 to 2010, 45 patients (ages 8-20 years), including 1 patient with stage II NPC and 44 patients with stage III/IV NPC, were recruited to the study. The patient with stage II disease received radiotherapy (59.4 grays [Gy]). The patients with stage III/IV disease received 3 courses of neoadjuvant chemotherapy with cisplatin, 5-fluorouracil, and folinic acid. The cumulative irradiation dose was 54 Gy in 5 patients, who achieved complete remission after neoadjuvant chemotherapy, and 59.4 Gy in the remaining 40 patients. All patients received concomitant cisplatin during the first week and last week of irradiation. After irradiation, all patients received interferon beta for 6 months. Tumor response was evaluated by magnetic resonance imaging studies and positron emission tomography scans. RESULTS: After the completion of treatment, 43 of 45 patients were in complete remission. In 2 patients, only a partial response was achieved, followed by distant metastases (1 patient) or local progression and distant metastases (1 patient), 6 months and 10 months after diagnosis, respectively. Another patient developed a solitary pelvic bone metastasis 21 months after diagnosis. After a median follow-up of 30 months (range, 6-95 months), the event-free survival rate was 92.4%, and the overall survival was 97.1%. Acute toxicity consisted mainly of leucopenia, mucositis, and nausea; and late toxicity consisted of hearing loss and hypothyroidism. CONCLUSIONS: Combined therapy with neoadjuvant chemotherapy, radiochemotherapy, and interferon beta was well tolerated and resulted in a very good outcome that was superior to the outcomes of published results from all other pediatric NPC study groups. Cancer 2012. © 2012 American Cancer Society.
- Published
- 2011
19. Kombinierte Behandlung des Nasopharynxkarzinoms bei Kindern und Jugendlichen - Konzept einer Studie
- Author
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G Heimann, Rolf Mertens, and Lisa Lassay
- Subjects
Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Incidence (epidemiology) ,Disease ,Radiation therapy ,El Niño ,Internal medicine ,Pediatrics, Perinatology and Child Health ,Immunology ,Adjuvant therapy ,Etiology ,Medicine ,business ,Survival rate - Abstract
Nasopharyngeal carcinomas (NPCs) are malignant tumors which exhibit a wide disparity in their age, racial, and geographic incidence. In parts of Africa NPCs account for 10% to 20% of childhood malignancies. In USA and Europe, the NCP is an uncommon tumor (0.2% of all malignancies) and amounts to only 1% to 2% of childhood malignancies. Etiology and pathogenesis are closely related to an infection with Epstein-Barr Virus (EBV) and the EBV genome was detected in tumor tissues. Children with NPC differ from their adult counterparts in having a closer association with Epstein-Barr-Virus-Infections. The classical lymphoepithelial carcinomas (Cologne type II-type III) have been found in young patients. Clinically, the disease is aggressive, characterised by frequent metastases in bone and lung. These carcinomas are associated with significantly elevated anti-EBV-titers. The prognosis of children with advanced NPC is poor with a 5-year survival rate between 20-30%. Radiotherapy is the treatment of choice in NPC which has provided an improvement in local tumor control in recent years. Human fibroblast interferon is an active agent in recurrent NPC. Seven children have been treated with IFN-beta, (6 with human und 1 with recombinant IFN-beta) as an adjuvant therapy in doses of 10(5) U/kg body weight three times a week for half a year. All patients received radiotherapy to primary site and had advanced stages (III-IV) at presentation. The patients' age ranged from 14-19 years at diagnosis. Six are still in CR (RFS are 10, 8, 8, 7, 6 and 1.5 years) and one patient relapsed after 18 months.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1993
20. Hämophagozytische Lymphohistiozytose (HLH): Intensivmedizinischer Notfall bei Säuglingen und Kleinkindern
- Author
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Lisa Lassay, Mark Schoberer, Thorsten Orlikowsky, Konrad Heimann, and Norbert Wagner
- Subjects
Pediatrics, Perinatology and Child Health - Published
- 2010
21. Poor outcome for children and adolescents with progressive disease or relapse of lymphoblastic lymphoma: a report from the berlin-frankfurt-muenster group
- Author
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Birgit Burkhardt, Lisa Lassay, Max Lakomek, Eva Landmann, Arend von Stackelberg, Alfred Reiter, Peter Lang, Roswitha Dickerhoff, and Günter Henze
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Pediatrics ,Adolescent ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,Young Adult ,Recurrence ,hemic and lymphatic diseases ,Germany ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Multicenter Studies as Topic ,Transplantation, Homologous ,Young adult ,Child ,Chemotherapy ,Analysis of Variance ,business.industry ,Lymphoblastic lymphoma ,Cancer ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Prognosis ,Surgery ,Lymphoma ,Transplantation ,Treatment Outcome ,Oncology ,El Niño ,Disease Progression ,Female ,business ,Progressive disease ,Switzerland ,Stem Cell Transplantation - Abstract
Purpose Little is known about the outcome of pediatric patients with lymphoblastic lymphoma (LBL) who suffer from progressive disease or relapse. Patients and Methods We analyzed the pattern of LBL relapses after current non-Hodgkin's lymphoma Berlin-Frankfurt-Muenster (BFM) frontline therapy between April 1990 and March 2003. Relapse therapy was according to acute lymphoblastic leukemia (ALL) –Relapse-BFM protocols or ALL-BFM protocols for high-risk patients. Results Twenty-eight (11%) of 251 registered patients with precursor T-cell LBL (T-LBL) and six (8%) of 73 patients with precursor B-cell LBL (pB-LBL) suffered from relapse. Of the 28 patients with T-LBL, one died from infection during relapse chemotherapy, 18 failed to achieve stable remission and died from disease progression, and nine reached allogeneic stem-cell transplantation (SCT). Two of these nine patients who underwent SCT died from transplantation-associated toxicity, three died from disease progression, and four are still alive. These four patients are in second remission of their lymphoma for 48, 68, 125, and 131 months, respectively, after allogeneic SCT. One of the four patients developed colon adenocarcinoma 47 months after SCT. Of the six patients with pB-LBL who experienced relapse, one patient died as a result of toxicity of relapse chemotherapy, two died from disease progression after chemotherapy, and three received allogeneic SCT. Of these, two died from subsequent disease progression, and one is still alive 57 months after allogeneic SCT. Conclusion Using modern conventional therapy in the frontline treatment of LBL, 10% of patients suffer from progressive disease or relapse. Because of the extremely poor reinduction success, the salvage rate for these patients is poor, with only a 14% (SE = 6%) overall survival. Long-term survival was only achieved in those few patients who were able to undergo an allogeneic SCT.
- Published
- 2009
22. Saving the red baby: successful allogeneic cord blood transplantation in Omenn syndrome
- Author
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Lisa Lassay, Tim Niehues, Stefan Wüller, Hagen Ott, Dagmar Dilloo, Oliver Feyen, H.F. Merk, Arndt Borkhardt, Hans-Jürgen Laws, Stefan Schönberger, Jens M. Baron, Sonja Gudowius, and Mosaad Megahed
- Subjects
Transplantation Conditioning ,medicine.medical_treatment ,Immunology ,Cord Blood Stem Cell Transplantation ,Hematopoietic stem cell transplantation ,Umbilical cord ,Leukocyte Count ,Immunology and Allergy ,Medicine ,Humans ,Transplantation, Homologous ,Severe combined immunodeficiency ,business.industry ,Infant ,medicine.disease ,Flow Cytometry ,Omenn syndrome ,Transplantation ,medicine.anatomical_structure ,Cord blood ,Female ,Severe Combined Immunodeficiency ,business ,Dermatitis, Exfoliative - Abstract
Haematopoietic stem cell transplantation is the treatment of choice for severe primary immunodeficiencies, but only has moderate prognosis in Omenn syndrome as it is complicated by highly activated Omenn T-cells resulting in delayed T-cell engraftment and a high rate of graft failure. A 6 1/2 months old patient with a previously unknown compound heterozygous defect within the RAG1 gene (R474C; R975W) underwent 8/10 HLA-matched cord blood transplantation after myeloablative conditioning. Immune reconstitution was impressive with T-, B- and NK-cells reaching the median of age-dependent reference values within twelve, four and two months respectively. With a continuous decrease of activated Omenn T-cells there was a steady increase of naive, probably thymus-derived T-cells. Polyclonal B-cell activation and hypergammaglobulinaemia disappeared with B-cell engraftment. This case emphasizes that, despite their naive status and HLA-barriers, cord blood T-cells were apparently able to achieve T-effector function resulting in the elimination of all activated Omenn T-cells.
- Published
- 2008
23. Seltene Tumoren
- Author
-
Rolf Mertens and Lisa Lassay
- Published
- 2005
24. Direct right atrial insertion of a Hickman catheter in an 11-year-old girl
- Author
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Lisa Lassay, Jaime F. Vazquez-Jimenez, Heike Schnoering, and Sabine M. Detering
- Subjects
Short Bowel Syndrome ,Pulmonary and Respiratory Medicine ,Catheterization, Central Venous ,Parenteral Nutrition ,medicine.medical_specialty ,Intercostal veins ,medicine.medical_treatment ,Femoral vein ,Risk Assessment ,Inferior vena cava ,Catheters, Indwelling ,medicine ,Humans ,Heart Atria ,cardiovascular diseases ,Atrium (heart) ,Child ,business.industry ,medicine.disease ,Thrombosis ,Surgery ,Catheter ,medicine.anatomical_structure ,Thoracotomy ,medicine.vein ,cardiovascular system ,Female ,Cardiology and Cardiovascular Medicine ,business ,Subclavian vein ,Central venous catheter ,Follow-Up Studies - Abstract
Central venous lines are of particular importance in seriously ill children that require parenteral nutrition, chemotherapy, or other medications. The jugular or subclavian veins are ordinarily used for primary access. Alternatives include the femoral veins, the intercostal veins, and transhepatic approaches. If the use of these standard sites of placement is made impossible, due, for example, to chronic thrombosis, an alternative approach has to be found. The following report presents the case of an 11-year-old girl with short-bowel syndrome and a desperate need for parenteral nutrition. Over the course of her treatment, she developed chronic thrombosis of the jugular, subclavian, and femoral veins, as well as thrombosis of the inferior vena cava. As an alternative route for central venous access, we describe a successful direct placement of a tunnelled catheter into the right atrium via a right anterolateral thoracotomy.
- Published
- 2011
25. Successful Topical Treatment of Sorafenib-Induced Hand-Foot Skin Reaction in a Child with Hepatocellular Carcinoma
- Author
-
Bernhardt Sachs, Matthias Hütten, Lisa Lassay, Peter Deutz, Roland Mertens, Jens Malte Baron, Hans-Friedrich Merk, and Hagen Ott
- Subjects
Male ,Niacinamide ,Sorafenib ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Adolescent ,Pyridines ,Antineoplastic Agents ,Topical treatment ,Hand Dermatoses ,Dermatology ,medicine ,Humans ,Protein Kinase Inhibitors ,Foot Dermatoses ,Adult patients ,Kinase ,business.industry ,Phenylurea Compounds ,Benzenesulfonates ,Liver Neoplasms ,Cancer ,medicine.disease ,Surgery ,Skin reaction ,Orally active ,Hepatocellular carcinoma ,Pediatrics, Perinatology and Child Health ,business ,medicine.drug - Abstract
Orally active kinase inhibitors such as Sorafenib are known to elicit cutaneous side effects in the majority of adult patients, whereas specific cutaneous complications of this agent have not been described in children so far. We here present the first pediatric case of Sorafenib-induced hand-foot-skin reaction and its successful topical therapy facilitating continuation of kinase inhibitor treatment.
- Published
- 2009
26. Phakomatosis pigmentovascularis Typ II a (Phakomatosis cesioflammea)
- Author
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Hagen Ott, J. M. Baron, Lisa Lassay, H.F. Merk, Matthias C. Hütten, and Mosaad Megahed
- Subjects
medicine.medical_specialty ,Phakomatosis pigmentovascularis ,Phakomatosis cesioflammea ,business.industry ,medicine ,Dermatology ,medicine.disease ,business - Published
- 2006
27. Poor Outcome for Children and Adolescents with Progressive Disease or Relapse of Lymphoblastic Lymphoma - a Report of the BFM Group
- Author
-
Arend von Stackelberg, A. Reiter, Guenter Henze, Roswitha Dickerhoff, Peter Lang, Lisa Lassay, Birgit Burkhardt, Eva Landmann, and Max Lakomek
- Subjects
Chemotherapy ,High-grade lymphoma ,medicine.medical_specialty ,Pediatrics ,business.industry ,medicine.medical_treatment ,Immunology ,Lymphoblastic lymphoma ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Lymphoma ,Surgery ,Transplantation ,Progressive Neoplastic Disease ,hemic and lymphatic diseases ,medicine ,Colon adenocarcinoma ,business ,Progressive disease - Abstract
Background/Objectives: Little is known about the outcome of pediatric patients with lymphoblastic lymphoma (LBL) who suffer form progressive disease or relapse. Patients and Methods: We analyzed the pattern of LBL-relapses after current NHL-BFM-frontline therapy between 4/90 and 3/03. Relapse therapy was according to ALL-Relapse-BFM protocols or ALL-BFM protocols for high-risk patients. Results: 28 of 251 registered T-LBL-patients (11%) and six of 73 pB-LBL-patients (8%) suffered from relapse. Of the 28 T-LBL-patients, one died from infection during relapse-chemotherapy, 18 failed to achieve stable remission and died from disease-progression, and nine reached allogeneic stemcell transplantation (SCT). Two of these nine SCT patients died from transplantation-associated toxicity, three died from disease-progression and four are still alive. The patients are in 2nd remission of their lymphoma for 48, 68, 125 and 131 months respectively after allogeneic SCT. One of the four patients developed colon adenocarcinoma 47 months after SCT. Of the six relapsed pB-LBL patients one died due to toxicity of relapse-chemotherapy, two died from disease-progression after chemotherapy and three received allogeneic SCT. Of these, two died from subsequent disease-progression while one patient is still alive 57 months after allogeneic SCT. Conclusions: Outcome of LBL-patients with relapse during or after current intensive 1st line therapy is poor. More than 50% of these patients failed to achieve remission to intensive 2nd line chemotherapy. Consolidation by allogeneic SCT may offer a cure for those who reach second remission.
- Published
- 2008
28. Treatment of nasopharyngeal carcinoma in children and adolescentsThese participating institutions recruited patients into the study and are listed in alphabetical order. The number of patients recruited appears after each researcher's name. Departments of Pediatric Hematology and Oncology 1 and Departments of Radio‐oncology 2, University of Aachen (Mertens R. 1, Eble, M. 2); University of Berlin (Henze G.1, Wurm D. 2); University of Bonn (Bode U. 1, Schüller M. H.2); University of Bremen (Spaar J. 1, Habermalz M. 2); Children's Hospital Datteln, St.Vincenz‐Hospital (Andler W. 1, Langrock J. 2); University of Dusseldorf (Gobel U. 1, Schmitt G. 2); University of Essen (Havers W. 1, Streffer Ch. 2); University of Erfurt (Weinmann G.1, Glaser F.H.2); University of Freiburg (Niemeyer C. 1, Frommhold H. 2); University of Gottingen (Lakomek M. 1, Hess C. F. 2); University of Giessen (Reiter A. 1, Lieven von, H. 2); Children's Hospital Gummersbach (Gerein V. 1, Adamietz, I. 2); University o
- Author
-
Rolf Mertens, Bernd Granzen, Lisa Lassay, Peter Bucsky, Manfred Hundgen, Gunter Stetter, Gerhard Heimann, Claudia Weiss, Clemens F. Hess, and Gunther Gademann
- Published
- 2005
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