275 results on '"K. Spiekermann"'
Search Results
2. P416: CLONAL HEMATOPOIESIS IS COMMON IN AML LONG-TERM SURVIVORS AND MAY ASSOCIATE WITH DIABETES AND SECONDARY NEOPLASIAS, BUT NOT OTHER HEALTH OUTCOMES
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S. M. Krauß, E. Telzerow, A. S. Moret, D. Richter, M. Rothenberg-Thurley, D. Görlich, M. C. Sauerland, W. E. Berdel, B. Wörmann, U. Krug, J. Braess, P. Heussner, W. Enard, W. Hiddemann, K. Spiekermann, U. Platzbecker, and K. H. Metzeler
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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3. P558: GERMAN AMLCG-SURVIVORSHIP STUDY – SOMATIC LONG-TERM CONSEQUENCE OF AML AND ITS THERAPY: FROM HEART TO KIDNEY.
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A. S. Moret, E. Telzerow, C. Sauerland, M. Rothenberg-Thurley, F. H. A. Mumm, J. Braess, B. Wörmann, U. Krug, W. E. Berdel, W. Hiddemann, K. Spiekermann, P. Heußner, K. Kraywinkel, D. Görlich, and K. H. Metzeler
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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4. P479: DNA METHYLATION PROFILING REFINES THE PROGNOSTIC CLASSIFICATION OF ACUTE MYELOID LEUKEMIA PATIENTS TREATED WITH INTENSIVE CHEMOTHERAPY
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S. Vosberg, A. Ohnmacht, C. Moser, A. Arneth, V. Jurinovic, K. H. Metzeler, M. C. Sauerland, D. Görlich, W. E. Berdel, J. Braess, S. Amler, U. Krug, W. Hiddemann, K. Spiekermann, C. C. Oakes, M. P. Menden, T. Herold, and P. A. Greif
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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5. P1402: ALTERATIONS OF HUMAN BONE MARROW NICHE IN CLONAL HEMATOPOIESIS AND AML
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Y. Dragieva, M. Rothenberg-Thurley, B. Ksienzyk, A. Hadzic, A. Paulus, B. Tast, M. Subklewe, K. Spiekermann, S. Theurich, K. Metzeler, M. Solovey, and F. Ziemann
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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6. Silencing of GATA3 defines a novel stem cell-like subgroup of ETP-ALL
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L. Fransecky, M. Neumann, S. Heesch, C. Schlee, J. Ortiz-Tanchez, S. Heller, M. Mossner, S. Schwartz, L. H. Mochmann, K. Isaakidis, L. Bastian, U. R. Kees, T. Herold, K. Spiekermann, N. Gökbuget, and C. D. Baldus
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GATA3 ,ETP-ALL ,PER-117 ,Decitabine ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background GATA3 is pivotal for the development of T lymphocytes. While its effects in later stages of T cell differentiation are well recognized, the role of GATA3 in the generation of early T cell precursors (ETP) has only recently been explored. As aberrant GATA3 mRNA expression has been linked to cancerogenesis, we investigated the role of GATA3 in early T cell precursor acute lymphoblastic leukemia (ETP-ALL). Methods We analyzed GATA3 mRNA expression by RT-PCR (n = 182) in adult patients with T-ALL. Of these, we identified 70 of 182 patients with ETP-ALL by immunophenotyping. DNA methylation was assessed genome wide (Illumina Infinium® HumanMethylation450 BeadChip platform) in 12 patients and GATA3-specifically by pyrosequencing in 70 patients with ETP-ALL. The mutational landscape of ETP-ALL with respect to GATA3 expression was investigated in 18 patients and validated by Sanger sequencing in 65 patients with ETP-ALL. Gene expression profiles (Affymetrix Human genome U133 Plus 2.0) of an independent cohort of adult T-ALL (n = 83) were used to identify ETP-ALL and investigate GATA3low and GATA3high expressing T-ALL patients. In addition, the ETP-ALL cell line PER-117 was investigated for cytotoxicity, apoptosis, GATA3 mRNA expression, DNA methylation, and global gene expression before and after treatment with decitabine. Results In our cohort of 70 ETP-ALL patients, 33 % (23/70) lacked GATA3 expression and were thus defined as GATA3low. DNA methylation analysis revealed a high degree of GATA3 CpG island methylation in GATA3low compared with GATA3high ETP-ALL patients (mean 46 vs. 21 %, p
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- 2016
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7. Leukämien, myelodysplastische Syndrome und myeloproliferative Neoplasien: Empfehlungen zur Diagnostik, Therapie und Nachsorge
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K. Spiekermann, K. Spiekermann and K. Spiekermann, K. Spiekermann
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- 2015
8. PF217 TARGETING FLT3 IN AML: MODULATION OF FLT3-BITE® ACTIVITY THROUGH COMBINATION WITH VARIOUS TKI
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Bettina Brauchle, Tara Arvedson, K. Spiekermann, Sascha Haubner, Christina Krupka, Christine Sastri, Dan A. Rock, M. Subklewe, L. Chi-Ming, Klaus H. Metzeler, K. Cooke, Rebecca Goldstein, M. von Bergwelt-Baildon, Priya Koppikar, Veit Buecklein, and O. Thomas
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business.industry ,Modulation ,Cancer research ,Medicine ,Hematology ,business - Published
- 2019
9. RNA and protein expression of herpesvirus entry mediator (HVEM) is associated with molecular markers, immunity-related pathways and relapse-free survival of patients with AML
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Thomas Büchner, Tobias Herold, Felix S. Lichtenegger, Marion Subklewe, Stephanie Schneider, Anna L. Weber, Bernhard Wörmann, Wolfgang E. Berdel, K. Spiekermann, Michael Krempasky, Isabell Kondla, Christina Krupka, and Wolfgang Hiddemann
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Adult ,Male ,Cancer Research ,Herpesvirus entry mediator ,NPM1 ,Immunology ,Biology ,Disease-Free Survival ,Flow cytometry ,Immunophenotyping ,Bone Marrow ,CEBPA ,Gene expression ,Biomarkers, Tumor ,medicine ,Humans ,Immunology and Allergy ,Gene ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,Middle Aged ,Flow Cytometry ,Gene Expression Regulation, Neoplastic ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Oncology ,Cancer research ,RNA ,Female ,Bone marrow ,Nucleophosmin ,Receptors, Tumor Necrosis Factor, Member 14 - Abstract
Immune checkpoint molecules are highly relevant as potential prognostic markers and therapeutic targets in malignant diseases. HVEM belongs to the TNF receptor family and provides stimulatory as well as inhibitory signals depending on the ligand. Abnormal HVEM expression has been described in various malignancies, but the role in AML is unknown. Here we report extensive data on HVEM surface protein expression analyzed by flow cytometry on bone marrow leukemic cells of 169 AML patients at diagnosis. An independent cohort of 512 AML patients was analyzed for HVEM mRNA expression in bone marrow samples by Affymetrix microarrays. Consistently for both cohorts and methods, we show that HVEM was differentially expressed and that expression levels were associated with defined genetic markers. HVEM expression was lower in cases with FLT3-ITD (p = 0.001, p < 0.001), with mutations in NPM1 (p = 0.001, p < 0.001) or with the combination of NPM1 mutation and FLT3 wild type (p = 0.049, p = 0.050), while a biallelic mutation in CEBPA correlated positively with higher HVEM expression (p = 0.015, p < 0.001). In a differential gene expression analysis, we found 13 genes including HOXA9, MEIS1 and MN1 that were closely associated with HVEM expression. Besides, four gene sets closely linked to immunity were enriched in HVEM (high) samples. Finally, high expression of HVEM was associated with a trend toward longer relapse-free survival. The results of this study provide new information on the potential significance of HVEM in AML.
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- 2015
10. Persistence of pre-leukemic clones during first remission and risk of relapse in acute myeloid leukemia
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M Rothenberg-Thurley, S Amler, D Goerlich, T Köhnke, N P Konstandin, S Schneider, M C Sauerland, T Herold, M Hubmann, B Ksienzyk, E Zellmeier, S K Bohlander, M Subklewe, A Faldum, W Hiddemann, J Braess, K Spiekermann, and K H Metzeler
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Cancer Research ,Oncology ,Hematology - Abstract
Some patients with acute myeloid leukemia (AML) who are in complete remission after induction chemotherapy harbor persisting pre-leukemic clones, carrying a subset of leukemia-associated somatic mutations. There is conflicting evidence on the prognostic relevance of these clones for AML relapse. Here, we characterized paired pre-treatment and remission samples from 126 AML patients for mutations in 68 leukemia-associated genes. Fifty patients (40%) retained ⩾1 mutation during remission at a variant allele frequency of ⩾2%. Mutation persistence was most frequent in DNMT3A (65% of patients with mutations at diagnosis), SRSF2 (64%), TET2 (55%), and ASXL1 (46%), and significantly associated with older age (P0.0001) and, in multivariate analyses adjusting for age, genetic risk, and allogeneic transplantation, with inferior relapse-free survival (hazard ratio, 2.34; P=0039) and overall survival (hazard ratio, 2.14; P=036). Patients with persisting mutations had a higher cumulative incidence of relapse before, but not after allogeneic stem cell transplantation. Our work underlines the relevance of mutation persistence during first remission as a novel risk factor in AML. Persistence of pre-leukemic clones may contribute to the inferior outcome of elderly AML patients. Allogeneic transplantation abrogated the increased relapse risk associated with persisting pre-leukemic clones, suggesting that mutation persistence may guide postremission treatment.Leukemia accepted article preview online, 18 December 2017. doi:10.1038/leu.2017.350.
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- 2017
11. Genetic characteristics determine lentiviral transduction rates in patient-derived ALL cells
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W Hiddemann, R Marschalek, B. C. Heckl, Michaela Grunert, Denis M. Schewe, Michela Carlet, Binje Vick, Irmela Jeremias, and K Spiekermann
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Lentiviral transduction ,Cancer research ,In patient ,Biology - Published
- 2017
12. Leukämien, myelodysplastische Syndrome und myeloproliferative Neoplasien : Empfehlungen zur Diagnostik, Therapie und Nachsorge
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Tumorzentrum München, K. Spiekermann, Tumorzentrum München, and K. Spiekermann
- Abstract
Das neue Manual zu den Leukämien, myelodysplastischen Syndromen und myeloproliferativen Neoplasien gibt einen praxisnahen Überblick über die wesentlichen Aspekte in der Diagnostik und Behandlung. Es wurde interdisziplinär erarbeitet. Im Mittelpunkt stehen die spezifischen Kapitel zu den verschiedenen Neoplasien des Knochenmarks sowie zur aplastischen Anämie. All diesen Erkrankungen gemeinsam ist die Notwendigkeit zu einer differenzierten hämatologischen Diagnostik, welche heutzutage sehr spezialisiert ist und daher in einem eigenen einführenden Kapitel behandelt wird. Abgeschlossen wird das Manual mit einem Kapitel zur hämatopoetischen Transplantation, die sich zunehmend als Therapiemodalität für Hochrisikopatienten etabliert und weiterhin das Verfahren mit dem höchsten kurativen Potenzial bei vielen dieser Entitäten darstellt.
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- 2015
13. Age, not therapy intensity, determines outcomes of adults with acute myeloid leukemia
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R Peter Gale, Torsten Haferlach, Peter Staib, Eva Lengfelder, Rolf M. Mesters, Wolfgang E. Berdel, Aristoteles Giagounidis, Utz Krug, Ruediger Hehlmann, Th. Büchner, A. Reichle, K. Spiekermann, Hubert Serve, Leopold Balleisen, Bernhard Wörmann, Andreas Grüneisen, Dennis Görlich, M Stelljes, Jan Braess, Maria-Cristina Sauerland, Andreas Faldum, Wolfgang Hiddemann, Wolfgang Köpcke, Susanne Schnittger, Hartmut Eimermacher, Carsten Müller-Tidow, Herbert Rasche, Achim Heinecke, and Claudia Haferlach
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Treatment outcome ,Kaplan-Meier Estimate ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,Young adult ,Aged ,Aged, 80 and over ,business.industry ,Age Factors ,Myeloid leukemia ,Hematology ,Middle Aged ,Prognosis ,Intensity (physics) ,Leukemia, Myeloid, Acute ,Treatment Outcome ,030220 oncology & carcinogenesis ,Immunology ,Female ,business ,030215 immunology - Published
- 2016
14. Hämatologie 2010
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M Dreyling, M Subklewe, J Braess, and K Spiekermann
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General Medicine - Published
- 2010
15. Hämatologische Neoplasien und solide Tumoren in der Schwangerschaft
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A Wollenberg, C Spitzweg, H Popp, K Spiekermann, and B Loehrs
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Oncology ,medicine.medical_specialty ,Pregnancy ,Pathology ,business.industry ,Principal (computer security) ,MEDLINE ,Treatment options ,General Medicine ,medicine.disease ,Internal medicine ,Medicine ,business ,Melanoma diagnosis - Published
- 2009
16. The target cell of transformation is distinct from the leukemia stem cell in murine CALM/AF10 leukemia models
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Maik Dahlhoff, Stefan Krebs, Helmut Blum, Eckhard Wolf, Maja Rothenberg-Thurley, K. Spiekermann, Belay Tizazu, U Zimber-Strobl, Sebastian Vosberg, Stefan K. Bohlander, Sayantanee Dutta, A T Vetter, Alexander Graf, Tobias Herold, Klaus H. Metzeler, Martin Chopra, Marlon R. Schneider, Bianka Ksienzyk, Alexandre Krause, Leticia Quintanilla-Martinez, and Philipp A. Greif
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0301 basic medicine ,Cancer Research ,Myeloid ,Oncogene Proteins, Fusion ,Biology ,03 medical and health sciences ,Mice ,hemic and lymphatic diseases ,medicine ,Animals ,Exome ,Progenitor cell ,Acute leukemia ,B-Lymphocytes ,ABL ,Leukemia, Experimental ,Myeloid leukemia ,Hematology ,Sequence Analysis, DNA ,medicine.disease ,Leukemia ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,Oncology ,Mutation ,Cancer research ,Neoplastic Stem Cells ,Stem cell ,Genetic Engineering - Abstract
The CALM/AF10 fusion gene is found in various hematological malignancies including acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia and malignant lymphoma. We have previously identified the leukemia stem cell (LSC) in a CALM/AF10-driven murine bone marrow transplant AML model as B220+ lymphoid cells with B-cell characteristics. To identify the target cell for leukemic transformation or 'cell of origin of leukemia' (COL) in non-disturbed steady-state hematopoiesis, we inserted the CALM/AF10 fusion gene preceded by a loxP-flanked transcriptional stop cassette into the Rosa26 locus. Vav-Cre-induced panhematopoietic expression of the CALM/AF10 fusion gene led to acute leukemia with a median latency of 12 months. Mice expressing CALM/AF10 in the B-lymphoid compartment using Mb1-Cre or CD19-Cre inducer lines did not develop leukemia. Leukemias had a predominantly myeloid phenotype but showed coexpression of the B-cell marker B220, and had clonal B-cell receptor rearrangements. Using whole-exome sequencing, we identified an average of two to three additional mutations per leukemia, including activating mutations in known oncogenes such as FLT3 and PTPN11. Our results show that the COL for CALM/AF10 leukemia is a stem or early progenitor cell and not a cell of B-cell lineage with a phenotype similar to that of the LSC in CALM/AF10+ leukemia.
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- 2015
17. Risikoadaptierte Therapie der akuten myeloischen Leukämie
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W. Hiddemann, K. Spiekermann, J. Braess, M. Feuring-Buske, C. Buske, and T. Büchner
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Internal Medicine - Published
- 2006
18. Molekulare Zielstrukturen in der Onkologie
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K. Spiekermann and Wolfgang Hiddemann
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Gynecology ,medicine.medical_specialty ,business.industry ,Internal Medicine ,medicine ,business - Abstract
Die Aufklarung der molekularen Pathogenese maligner Erkrankungen hat in den letzten Jahren deutliche Fortschritte erfahren. Insbesondere wurden molekulare und zellulare Zielstrukturen identifiziert, die als Angriffspunkte fur therapeutische Interventionen („targeted therapies“) dienen konnen. Hierzu gehoren Komponenten von zellularen Signalketten, wie z.B. Proteintyrosinkinasen (PTK), die durch Mutationen, Translokationen oder Uberexpression aktiviert werden. Kleinmolekulare PTK-Inhibitoren, die als kompetitive ATP-Antagonisten fungieren, haben bei der CML, gastrointestinalen Stromatumoren sowie Bronchialkarzinomen bereits eine eindruckliche klinische Aktivitat gezeigt. Eine weitere Gruppe von zellularen Zielstrukturen stellen tumorselektive Oberflachenproteine dar, die Angriffspunkte fur monoklonale Antikorper darstellen. Dieses Therapiekonzept hat vor allem in der Lymphomtherapie breiten Einsatz gefunden. Die Identifizierung von molekularen Zielstrukturen, die kritisch fur den malignen Phanotyp sind, fuhrt in eine neue Ara integrierter molekularer Diagnostik und Therapie in der Onkologie.
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- 2005
19. Constitutive activation of STAT transcription factors in acute myelogenous leukemia
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S. Biethahn, Frauke Alves, Sabine Wilde, Wolfgang Hiddemann, and K. Spiekermann
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0303 health sciences ,biology ,Tyrosine phosphorylation ,Hematology ,General Medicine ,medicine.disease ,03 medical and health sciences ,chemistry.chemical_compound ,Leukemia ,0302 clinical medicine ,chemistry ,hemic and lymphatic diseases ,medicine ,biology.protein ,Cancer research ,STAT1 ,Signal transduction ,Janus kinase ,STAT3 ,Transcription factor ,Tyrosine kinase ,030304 developmental biology ,030215 immunology - Abstract
Hematopoietic growth factors (HGF) are essential for proliferation and differentiation of hematopoietic precursors and activate a distinct set of JAK-STAT (Janus kinases-signal transducers and activators of transcription) proteins. Previous results from our group have shown a strong expression of JAK-STAT proteins in primary acute myelogenous leukemia (AML) blasts and AML cell lines. Here, we asked whether a constitutive activation of the JAK-STAT pathway might be involved in the pathogenesis of AML. We could demonstrate a constitutive activation of STAT1, 3 and 5 by immunoprecipitation of the tyrosine phosphorylated proteins in different human AML cell lines. Three patterns of STAT activation were found: (I) activation of only STAT1, (II) activation of STAT1 in combination with STAT3, and (III) activation of STAT1, 3 and 5. Furthermore, STAT1 and 3 formed stable heterodimers only in cell lines with constitutive STAT3 activation. In all cell lines analyzed, tyrosine phosphorylation of the four known Janus kinases could not be detected, although JAK1 was stably associated with STAT3. To further analyze whether a constitutive activation of tyrosine kinases might contribute to the autonomous growth of AML blasts, inhibitor studies were performed. The tyrphostin AG490, an inhibitor of the JAK-STAT pathway, but not A1, an inactive tyrphostin induced a time- and dose-dependent growth arrest without overt morphological signs of differentiation in AML cell lines. Our results show that STAT transcription factors are constitutively activated in human AML cell lines and might contribute to the autonomous proliferation of AML blasts. Inhibition of this pathway might be of interest for the establishment of more specific antileukemic strategies.
- Published
- 2001
20. Hämatologie 2009
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M Dreyling, K Spiekermann, and W Hiddemann
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General Medicine - Published
- 2009
21. 89-year-old woman with hemorrhagic diathesis
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T, Seiler, P, Goehring, and K, Spiekermann
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Aged, 80 and over ,Factor VIII ,Plasma Exchange ,Humans ,Female ,Partial Thromboplastin Time ,Hemophilia A ,Hemorrhagic Disorders ,Immunosuppressive Agents - Published
- 2009
22. High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG
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E, Lengfelder, C, Haferlach, S, Saussele, T, Haferlach, B, Schultheis, S, Schnittger, W-D, Ludwig, P, Staib, C, Aul, A, Grüneisen, W, Kern, A, Reichle, H, Serve, W E, Berdel, J, Braess, K, Spiekermann, B, Wörmann, M-C, Sauerland, A, Heinecke, W, Hiddemann, R, Hehlmann, T, Büchner, and W, Zschille
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Acute promyelocytic leukemia ,Adult ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Tretinoin ,Gastroenterology ,Young Adult ,Maintenance therapy ,Leukemia, Promyelocytic, Acute ,Internal medicine ,Germany ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cumulative incidence ,Longitudinal Studies ,Lymphocyte Count ,Survival analysis ,Chemotherapy ,business.industry ,Remission Induction ,Cytarabine ,Induction chemotherapy ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,Surgery ,Leukemia ,Treatment Outcome ,Oncology ,business ,medicine.drug - Abstract
The objective of this study for newly diagnosed acute promyelocytic leukemia (APL) was to evaluate the efficacy of an intensified double induction chemotherapy including high dose ara-C (HD) and all-trans retinoic acid (ATRA) followed by consolidation and 3 years maintenance therapy. In contrast to APL studies stratifying therapy according to pretreatment white blood cell (WBC) count or =10 x 10(9)/l (low/intermediate and high risk according to the Sanz score), our patients received uniform therapy. From 1994 to 2005, 142 patients (age, 16-60 years) were enrolled. In the low/intermediate (n=105) vs high (n=37) WBC group, the rates of complete remission were 95.2 vs 83.8%, of induction death were 4.8 vs 16.2% (P=0.05) and of molecular remission were 87.5 vs 91.3% (P=1). Long-term overall survival was 84.4 vs 73.0% (P=0.12), event free survival was 78.3 vs 67.3% (P=0.11), relapse free survival was 82.1 vs 80.0% (P=0.83) and the cumulative incidence of relapse was 7.4 vs 11.4% (P=0.46). No relapse or death occurred after 4.7 years. ATRA and intensified chemotherapy including HD ara-C followed by prolonged maintenance therapy reduced the relapse risk in high risk patients. Pretreatment WBC count > or =10 x 10(9)/l count was no relevant prognostic factor for relapse.
- Published
- 2009
23. [Severe microcytic anemia with megaloblastic changes in the bone marrow. A hematological paradoxon?]
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R, Reibke, A, Hausmann, J, Cnossen, W, Hiddemann, K, Spiekermann, and J, Braess
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Adult ,Diagnosis, Differential ,Male ,Anemia, Pernicious ,beta-Thalassemia ,Humans ,Vitamin B 12 Deficiency - Abstract
We discuss the case of a 32 year-old male with severe microcytic anemia (hemoglobin 2,9 g/dl) and megaloblastic changes in the bone marrow. The patient reported of substantial dietary weight loss. The family history was positive for beta-thalassemia. Previous blood work showed iron deficiency with mild anemia. Further work-up verified beta-thalassemia minor and revealed severely decreased vitamin B12 levels with positive anti intrinsic-factor antibodies, pathognomonic for autoimmune pernicious anemia. The paradoxon therefore dissolved as a pernicious anemia with megaloblastic changes with microcytic erythrocytes due to beta-thalassemia.
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- 2009
24. [Modern leukemia diagnosis in adults]
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B, Heilmeier, K, Spiekermann, S, Bohlander, C, Buske, M, Feuring-Buske, S, Schneider, W, Hiddemann, and J, Braess
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Adult ,Leukemia ,Neoplasm, Residual ,Histocytochemistry ,Cytogenetic Analysis ,Cytological Techniques ,Humans ,Prognosis ,Polymerase Chain Reaction ,In Situ Hybridization, Fluorescence ,Immunophenotyping ,Oligonucleotide Array Sequence Analysis - Abstract
Identification of numerous criteria important in the pathogenesis, biology, prognosis and treatment of the different types of leukemia necessitates a broad spectrum of diagnostic methods for the initial diagnosis and in the further course of the disease. In addition to cytomorphology with cytochemistry, which is been path-breaking for the application of further diagnostic methods, cytogenetics has become an obligatory diagnostic tool. Immunophenotyping and, even more relevant, molecular genetics plays an important role. Other diagnostic techniques are widely developed. The diagnostic procedures are described, with a focus on their mode of operation as well as their clinical significance. Because of their high clinical relevance and growing complexity, the diagnosis of leukemias should be performed in specialized laboratories.
- Published
- 2009
25. [Hematologic neoplasias and solid tumors in pregnancy. Part 2: Specific treatment]
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H, Popp, K, Spiekermann, A, Wollenberg, C, Spitzweg, and B, Loehrs
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Ovarian Neoplasms ,Leukemia ,Uterine Cervical Neoplasms ,Breast Neoplasms ,Prognosis ,Hodgkin Disease ,Pregnancy ,Hematologic Neoplasms ,Humans ,Female ,Thyroid Neoplasms ,Colorectal Neoplasms ,Melanoma ,Pregnancy Complications, Neoplastic - Published
- 2009
26. [Hematologic neoplasias and solid tumors in pregnancy. Part 1: diagnosis and principal treatment options]
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H, Popp, K, Spiekermann, A, Wollenberg, C, Spitzweg, and B, Loehrs
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Adult ,Ovarian Neoplasms ,Leukemia ,Skin Neoplasms ,Pregnancy Complications, Hematologic ,Uterine Cervical Neoplasms ,Breast Neoplasms ,Prognosis ,Hodgkin Disease ,Pregnancy ,Risk Factors ,Hematologic Neoplasms ,Humans ,Female ,Thyroid Neoplasms ,Colorectal Neoplasms ,Melanoma ,Pregnancy Complications, Neoplastic ,Maternal Age - Published
- 2009
27. [When pregnant women become ill]
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K, Spiekermann and W, Siegenthaler
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Pregnancy Complications ,Pregnancy ,Humans ,Female - Published
- 2008
28. [Nonsymptomatic leukocytosis]
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D, Sauter, K, Spiekermann, M, Feuring-Buske, and J, Braess
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Diagnosis, Differential ,Inflammation ,Leukocyte Count ,Leukocytosis ,Humans ,Family Practice ,Infections - Abstract
Leukocytosis is a condition often met with in the clinical and ambulatory setting. Although it is usually caused by an increase in the numbers of neutrophilic granulocytes, an increase in other leukocytes populations may also account for leukocytosis. Etiologically, both primary pathological conditions affecting the white blood cells, such as various forms of leukemia and lymphomas, and also rare genetic disorders must be considered. Decidedly more common, however, are reactive changes caused by infections, cigarette smoking, chronic inflammation, necrotic tissue or certain drugs. Although moderate leukocytosis in the absence of a clinical correlate and/or an apparent trigger, requires no diagnostic clarification, it should be kept under observation. If the etiology is uncertain, or a treatment-requiring disorder is suspected, the differential blood count is at the focus of the further diagnostic work-up. Depending upon the findings, this is supplemented by additional laboratory parameters, bone marrow examination, microbiological investigations and imaging procedures. Leukostasis resulting from vasoocclusion in the presence of very high numbers of leukocytes represents an emergency situation, and is an indication for leukapheresis.
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- 2007
29. [Risk-adapted therapy of acute myeloid leukemia]
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W, Hiddemann, K, Spiekermann, J, Braess, M, Feuring-Buske, C, Buske, and T, Büchner
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Leukemia, Myeloid, Acute ,Risk Factors ,Practice Guidelines as Topic ,Humans ,Antineoplastic Agents ,Practice Patterns, Physicians' ,Risk Assessment - Abstract
Genetic and molecular techniques have provided increasing insights into the biology of acute myeloid leukemia (AML). These investigations showed that AML is not a homogeneous disease but a heterogeneous group of biologically different subentities. These subentities are currently primarily defined by cytogenetics and molecular markers. They differ substantially in response to therapy and long-term outcome and hence allow different risk groups of patients to be defined. These will guide therapeutic decisions in future therapeutic strategies and may ultimately lead to an individualized treatment concept.
- Published
- 2006
30. [Molecular target structures in oncology]
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K, Spiekermann and W, Hiddemann
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Drug Delivery Systems ,Neoplasms ,Animals ,Antibodies, Monoclonal ,Humans ,Immunotherapy ,Medical Oncology ,Molecular Biology - Abstract
Substantial progress has been made in recent years in understanding the molecular pathogenesis of malignant disorders, especially in identification of molecular targets for therapeutic interventions ("targeted therapies"). An important group of therapeutical targets are signaling cascades, e.g. protein tyrosine kinases (PTK) that are activated by mutations, translocations or overexpression. Small molecule inhibitors that compete with ATP and inhibit kinase activity have produced clinical impressive responses in chronic myeloid leukemia, gastrointestinal stroma tumors and non-small cell lung cancer. Another group of cellular targets is represented by tumor-selective cell surface proteins that can serve as target structures for antibodies. Therapeutical concepts using monoclonal antibodies have substantially improved response rates in patients with malignant lymphomas and are currently evaluated in other types of cancer. The definition of molecular target structures critical for the malignant phenotype is driving a new era of integrated diagnostics and therapeutics in the field of oncology.
- Published
- 2005
31. [Mutations of the gene coding for the receptor tyrosine kinase FLT3 in acute myeloid leukemia. Significance as the disease-specific molecular marker for diagnosis, prognosis and innovative therapy approaches]
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K, Spiekermann, W, Hiddemann, and S, Schnittger
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Gene Expression Regulation, Neoplastic ,Leukemia, Myeloid, Acute ,fms-Like Tyrosine Kinase 3 ,Proto-Oncogene Proteins ,Mutation ,Biomarkers, Tumor ,Humans ,Receptor Protein-Tyrosine Kinases ,Enzyme Inhibitors ,Hematopoiesis - Published
- 2005
32. Establishment of Inducible Expression Systems to Study the Role of STAT-Transcription Factors in AML
- Author
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T. Schroeder, K. Spiekermann, W. Hiddemann, R. Balling, S. Franzrahe, and U. Just
- Subjects
Myeloid ,U937 cell ,biology ,Oncogene ,medicine.medical_treatment ,Myeloid leukemia ,medicine.anatomical_structure ,Cytokine ,hemic and lymphatic diseases ,biology.protein ,medicine ,Cancer research ,STAT3 ,Receptor ,neoplasms ,STAT5 - Abstract
Acute myeloid leukemia (AML) is characterized by a clonal, malignant expansion of myeloid precursor cells. These cells are characterized by a block of differentiation. AML- blasts express cytokine receptors to which myeloid growth factors are binding and thus activate the JAK/STAT-signalling-pathway. In a subset of human cancers, including AML, and transformed cell lines STAT-proteins are persistently activated. Furthermore, STAT3 has transforming potential in epithelial cells in vitro and STAT5 is also involved in cellular transformation by the BCR-ABL oncogene. Recently it has been shown that STAT3 and STAT5 are also activated by transforming tyrosine-kinases in acute leukemias (TEL- JAK2, FLT3-ITD, TEL-ABL). The aim of this project is to further elucidate the functional role of STATs in AML.
- Published
- 2003
33. Constitutive activation of STAT transcription factors in acute myelogenous leukemia
- Author
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K, Spiekermann, S, Biethahn, S, Wilde, W, Hiddemann, and F, Alves
- Subjects
STAT3 Transcription Factor ,Transcription, Genetic ,HL-60 Cells ,Granulocyte Colony-Stimulating Factor ,STAT5 Transcription Factor ,Tumor Cells, Cultured ,Humans ,Enzyme Inhibitors ,Phosphorylation ,TYK2 Kinase ,Gene Expression Regulation, Leukemic ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Granulocyte-Macrophage Colony-Stimulating Factor ,Proteins ,Janus Kinase 1 ,U937 Cells ,Protein-Tyrosine Kinases ,Tyrphostins ,Milk Proteins ,Neoplasm Proteins ,DNA-Binding Proteins ,Enzyme Activation ,Alternative Splicing ,STAT1 Transcription Factor ,Leukemia, Myeloid ,Acute Disease ,Trans-Activators ,Interleukin-3 ,K562 Cells ,Dimerization ,Protein Processing, Post-Translational ,Cell Division ,Signal Transduction - Abstract
Hematopoietic growth factors (HGF) are essential for proliferation and differentiation of hematopoietic precursors and activate a distinct set of JAK-STAT (Janus kinases-signal transducers and activators of transcription) proteins. Previous results from our group have shown a strong expression of JAK-STAT proteins in primary acute myelogenous leukemia (AML) blasts and AML cell lines. Here, we asked whether a constitutive activation of the JAK-STAT pathway might be involved in the pathogenesis of AML. We could demonstrate a constitutive activation of STAT1, 3 and 5 by immunoprecipitation of the tyrosine phosphorylated proteins in different human AML cell lines. Three patterns of STAT activation were found: (I) activation of only STAT1, (II) activation of STAT1 in combination with STAT3, and (III) activation of STAT1, 3 and 5. Furthermore, STAT1 and 3 formed stable heterodimers only in cell lines with constitutive STAT3 activation. In all cell lines analyzed, tyrosine phosphorylation of the four known Janus kinases could not be detected, although JAK1 was stably associated with STAT3. To further analyze whether a constitutive activation of tyrosine kinases might contribute to the autonomous growth of AML blasts, inhibitor studies were performed. The tyrphostin AG490, an inhibitor of the JAK-STAT pathway, but not A1, an inactive tyrphostin induced a time- and dose-dependent growth arrest without overt morphological signs of differentiation in AML cell lines. Our results show that STAT transcription factors are constitutively activated in human AML cell lines and might contribute to the autonomous proliferation of AML blasts. Inhibition of this pathway might be of interest for the establishment of more specific antileukemic strategies.
- Published
- 2001
34. 89-jährige Patientin mit hämorrhagischer Diathese
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T Seiler, K Spiekermann, and P Goehring
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,Hemorrhagic diathesis ,medicine ,General Medicine ,business - Abstract
Bei der 89-jahrigen, sonst stets gesunden Patientin war es plotzlich ohne adaquates Trauma zu dem in Abb. 1 gezeigten Befund gekommen. B-Symptomatik oder wesentliche Blutbildveranderungen bestanden nicht. Eine verstarkte Blutungsneigung ist aus der Vorgeschichte nicht bekannt. Der Quick-Wert betrug 110%, die aktivierte partielle Thromboplastinzeit (aPTT) 73 s und die Fibrinogenkonzentration 218mg/dl. EIN PLASMATAUSCHVERSUCH ERBRACHTE EINEN WEITEREN AUFFaLLIGEN BEFUND.ERLAUBT DIE BEFUNDKONSTELLATION EINE DIAGNOSE? WENN JA, WELCHE?SIND DIFFERENZIALDIAGNOSEN MoGLICH? WENN JA, WELCHE?Auflosung
- Published
- 2009
35. Functional features of neutrophils induced by G-CSF and GM-CSF treatment: differential effects and clinical implications
- Author
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Andreas Emmendoerffer, K Spiekermann, Karl Welte, Elsner J, and Joachim Roesler
- Subjects
Cancer Research ,Neutropenia ,Neutrophils ,medicine.medical_treatment ,Inflammation ,Biology ,Neutrophil Activation ,03 medical and health sciences ,0302 clinical medicine ,Phagocytosis ,In vivo ,Granulocyte Colony-Stimulating Factor ,medicine ,Cell Adhesion ,Humans ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,Leukopenia ,Chemotaxis ,Granulocyte-Macrophage Colony-Stimulating Factor ,Hematology ,medicine.disease ,Sweet Syndrome ,3. Good health ,Granulocyte colony-stimulating factor ,Haematopoiesis ,Cytokine ,Oncology ,Immunology ,Vasculitis, Leukocytoclastic, Cutaneous ,medicine.symptom ,030215 immunology - Abstract
G-CSF and GM-CSF are hematopoietic growth factors required for proliferation and differentiation of hematopoietic precursors. G-CSF is now widely used to overcome neutropenias of various origins. Beside the absolute number, the functional capacity of neutrophils at sites of inflammation is of major importance in host defense. This review summarizes major functional and phenotypical features of neutrophils induced by G-CSF treatment in patients with acquired and congenital neutropenias. Furthermore, we focus on the differential effect of G-CSF and GM-CSF on neutrophil function in vitro and in vivo. Some of the altered abilities of cytokine-induced neutrophils are important to understand side-effects of G-CSF therapy.
- Published
- 1997
36. Molekulare Zielstrukturen in der Inneren Medizin
- Author
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Wolfgang Hiddemann and K. Spiekermann
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,General surgery ,Internal Medicine ,medicine ,Hepatology ,business - Published
- 2005
37. Evaluation of flow cytometric methods for diagnosis of chronic granulomatous disease variants under routine laboratory conditions
- Author
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K. Spiekermann, Andreas Emmendörffer, M. Nakamura, Joachim Roesler, G. Rothe, M L Lohmann-Matthes, and Publica
- Subjects
Adult ,Male ,X Chromosome ,Phagocyte ,Genetic Linkage ,Neutrophils ,Phagocytosis ,Biophysics ,chronic granulomatous disease ,cytochrome b-558 ,medicine.disease_cause ,Granulomatous Disease, Chronic ,Sensitivity and Specificity ,Pathology and Forensic Medicine ,Flow cytometry ,law.invention ,immunology ,Endocrinology ,Chronic granulomatous disease ,law ,medicine ,Humans ,Child ,Escherichia coli ,Chemiluminescence ,Peroxidase ,Myeloperoxidase deficiency ,medicine.diagnostic_test ,business.industry ,Genetic Carrier Screening ,Genetic Variation ,Cell Biology ,Hematology ,medicine.disease ,Flow Cytometry ,chemiluminescence ,Staining ,medicine.anatomical_structure ,cytochrome c ,Evaluation Studies as Topic ,Immunology ,Mutation ,phagocytes ,Female ,business - Abstract
Neutrophils from 50 pediatric patients with normal phagocyte functions, from 150 healthy adults, from 10 chronic granulomatous disease (CGD)-patients (4 CGD+), and from 18 X-linked carriers for CGD have been tested for their production of H2O2 using staining with dihydrorhodamine 123 and subsequent flow cytometry. Additionally, neutrophils from three patients with myeloperoxidase deficiency were assessed. Cells were activated to produce H2O2 by the phorbol ester phorbol-myristate-acetate (PMA) and by phagocytosis of Escherichia coli bacteria. To evaluate the sensitivity of the method, H2O2-production by neutrophils which was inhibited by different concentrations of diphenyljodonium (DPI) was measured. The results were compared to those from other methods (NBT-testing, cytochrome c-reduction, and especially chemiluminescence). Normal values and ranges of scatter profile were evaluated in terms of peak channel fluorescence: 97%700, x = 840 +/- 59 (S.D.), 97%890, for pediatric patients. Normal quantitative values also resulted from small blood samples of infants (1 year, n = 6, x = 830 +/- 52). For CGD+ (n = 4) the results were clearly far below the normal range. In indicating decreased production of reactive oxygen intermediates the method was at least as sensitive as lucigenin enhanced chemiluminescence. Cytochrome b558-expression of neutrophils from patients and healthy controls was established by flow cytometry following staining with the monoclonal antibody 7D5. The normal range was 97%485, 97%680, peak channel fluorescence. We conclude that flow cytometric routine diagnostics of CGD can easily enhance the reliability of recognition and the yield of information about this disease compared to conventional methods.
- Published
- 1994
38. Independent opinions?
- Author
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F.K., Dietrich, primary and K., Spiekermann, additional
- Published
- 2010
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39. Epistemic democracy with defensible premises
- Author
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F.K., Dietrich, primary and K., Spiekermann, additional
- Published
- 2010
- Full Text
- View/download PDF
40. Cyclosporine metabolite pattern in blood from patients with acute GVHD after BMT
- Author
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U, Christians, K, Spiekermann, A, Bader, R, Schottmann, A, Linck, K, Wonigeit, K F, Sewing, and H, Link
- Subjects
Adult ,Male ,Time Factors ,Adolescent ,Liver ,Acute Disease ,Cyclosporine ,Graft vs Host Disease ,Humans ,Female ,Child ,Bone Marrow Transplantation - Abstract
The cyclosporine (CYA) metabolite patterns in blood were evaluated in patients with liver dysfunction after allogeneic BMT. Fifty-five BMT patients were included in the study until discharge from hospital. Blood trough levels of CYA and 12 of its metabolites were quantified using HPLC. The patients were assigned to three groups: group I (no acute GVHD, n = 23), group II (acute GVHD of the skin and good liver function, overall acute GVHD: grade I: n = 18, grade II: n = 2) and group III (acute GVHD and liver dysfunction, overall acute GVHD: grade II: n = 2, grade III/IV: n = 8). Analysis of the trough blood concentrations of CYA and its metabolites revealed higher concentrations of metabolite AM19 in group III than in the other groups without reaching statistical significance. During acute GVHD of the liver, the metabolites AM19 (p0.01), AM1c9 (p0.05) and AM1A (p0.05) were significantly elevated compared with patients with normal liver function while CYA and all other metabolites did not differ. The CYA metabolite pattern in patients with acute GVHD and liver involvement was identical with that of liver graft patients during acute graft rejection, while the metabolite patterns of the patients without acute GVHD paralleled that of kidney grafted patients with normal liver function. Acute GVHD of the liver leads to an impaired elimination of CYA with increased blood concentrations of single CYA metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1993
41. F13 AML: How to characterize and treat elderly patients non fit for standard treatment
- Author
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K. Spiekermann
- Subjects
medicine.medical_specialty ,Oncology ,business.industry ,Internal medicine ,Standard treatment ,medicine ,Hematology ,business - Published
- 2009
42. Wenn Schwangere krank werden
- Author
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W Siegenthaler and K Spiekermann
- Subjects
medicine.medical_specialty ,Text mining ,business.industry ,Family medicine ,medicine ,General Medicine ,business - Published
- 2008
43. [Recurrent hemolysis and iron overload of unclear origin].
- Author
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Distelmaier L, Gebhard C, Holzäpfel A, von Bergwelt-Baildon M, Theurich S, Cario H, and Spiekermann K
- Abstract
The case of a 33-year-old male with recurrent icterus and hemolysis since childhood that was long mistaken for Gilbert disease is presented. Subsequently, the patient also developed splenomegaly and gallstones together with iron overload. Genetic testing revealed the diagnosis of hereditary xerocytosis, which is an erythrocyte membrane disorder causing recurrent hemolysis. Xerocytosis is often challenging to diagnose and the frequency of the condition might be underestimated as there are often no typical findings in the microscopic differential blood count, and Eosin-5-maleimide dye (EMA) test, which is used to diagnose other erythrocyte membrane disorders, is normal. In cases of splenomegaly, iron overload and recurrent hemolysis, or in the case of a clinical diagnosis of Gilbert disease together with one of the above-mentioned symptoms, further investigations and possibly also genetic testing should be considered., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
44. Evolution of T-cell fitness through AML progression: enhanced bispecific T-cell engager-mediated function of bone marrow T cells at remission compared to initial diagnosis and relapse.
- Author
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Kazerani M, Marcinek A, Philipp N, Brauchle B, Taylor JJ, Moreno HD, Terrasi A, Tast B, Rohrbacher L, Wang Y, Warm M, Emhardt AJ, Magno G, Spiekermann K, Herold T, Straub T, Theurich S, Schotta G, Kischel R, Bücklein VL, and Subklewe M
- Subjects
- Humans, Remission Induction, Antibodies, Bispecific therapeutic use, Neoplasm Recurrence, Local pathology, Male, Female, Recurrence, Bone Marrow Cells pathology, Bone Marrow Cells immunology, Middle Aged, T-Lymphocytes immunology, Leukemia, Myeloid, Acute pathology, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute therapy, Disease Progression
- Published
- 2024
- Full Text
- View/download PDF
45. Identifying long-term survivors and those at higher or lower risk of relapse among patients with cytogenetically normal acute myeloid leukemia using a high-dimensional mixture cure model.
- Author
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Archer KJ, Fu H, Mrózek K, Nicolet D, Mims AS, Uy GL, Stock W, Byrd JC, Hiddemann W, Braess J, Spiekermann K, Metzeler KH, Herold T, and Eisfeld AK
- Subjects
- Humans, Middle Aged, Adult, Male, Female, Cancer Survivors, Recurrence, Young Adult, Prognosis, Survivors, Leukemia, Myeloid, Acute genetics
- Abstract
Patients with cytogenetically normal acute myeloid leukemia (CN-AML) may harbor prognostically relevant gene mutations and thus be categorized into one of the three 2022 European LeukemiaNet (ELN) genetic-risk groups. Nevertheless, there remains heterogeneity with respect to relapse-free survival (RFS) within these genetic-risk groups. Our training set included 306 adults on Alliance for Clinical Trials in Oncology studies with de novo CN-AML aged < 60 years who achieved a complete remission and for whom centrally reviewed cytogenetics, RNA-sequencing, and gene mutation data from diagnostic samples were available (Alliance trial A152010). To overcome deficiencies of the Cox proportional hazards model when long-term survivors are present, we developed a penalized semi-parametric mixture cure model (MCM) to predict RFS where RNA-sequencing data comprised the predictor space. To validate model performance, we employed an independent test set from the German Acute Myeloid Leukemia Cooperative Group (AMLCG) consisting of 40 de novo CN-AML patients aged < 60 years who achieved a complete remission and had RNA-sequencing of their pre-treatment sample. For the training set, there was a significant non-zero cure fraction (p = 0.019) with 28.5% of patients estimated to be cured. Our MCM included 112 genes associated with cure, or long-term RFS, and 87 genes associated with latency, or shorter-term time-to-relapse. The area under the curve and C-statistic were respectively, 0.947 and 0.783 for our training set and 0.837 and 0.718 for our test set. We identified a novel, prognostically relevant molecular signature in CN-AML, which allows identification of patient subgroups independent of 2022 ELN genetic-risk groups.Trial registration Data from companion studies CALGB 8461, 9665 and 20202 (trials registered at www.clinicaltrials.gov as, respectively, NCT00048958, NCT00899223, and NCT00900224) were obtained from Alliance for Clinical Trials in Oncology under data sharing study A152010. Data from the AMLCG 2008 trial was registered at www.clinicaltrials.gov as NCT01382147., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
46. Friday Leukemia-a Structural Phenomenon.
- Author
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Rausch C, Arnreich C, Rothenberg-Thurley M, Dufour A, Schneider S, Gittinger H, Bücklein V, Subklewe M, Sauerland C, Görlich D, Krug U, Berdel WE, Wörmann BJ, Hiddemann W, Braess J, von Bergwelt-Baildon M, Spiekermann K, Metzeler KH, and Herold T
- Subjects
- Humans, Risk Factors, Leukemia
- Published
- 2024
- Full Text
- View/download PDF
47. Prognostic impact of CEBPA mutational subgroups in adult AML.
- Author
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Georgi JA, Stasik S, Kramer M, Meggendorfer M, Röllig C, Haferlach T, Valk P, Linch D, Herold T, Duployez N, Taube F, Middeke JM, Platzbecker U, Serve H, Baldus CD, Muller-Tidow C, Haferlach C, Koch S, Berdel WE, Woermann BJ, Krug U, Braess J, Hiddemann W, Spiekermann K, Boertjes EL, Hills RK, Burnett A, Ehninger G, Metzeler K, Rothenberg-Thurley M, Dufour A, Dombret H, Pautas C, Preudhomme C, Fenwarth L, Bornhäuser M, Gale R, and Thiede C
- Subjects
- Adult, Humans, CCAAT-Enhancer-Binding Proteins genetics, Frameshift Mutation, Mutation, Prognosis, Leukemia, Myeloid, Acute
- Abstract
Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state. Using pooled primary data analysis on 1010 CEBPA-mutant adult AML patients, a comparison was performed taking into account the type of mutation (bZIP: either typical in-frame insertion/deletion (InDel) mutations (bZIP
InDel ), frameshift InDel or nonsense mutations inducing translational stop (bZIPSTOP ) or single base-pair missense alterations (bZIPms ), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs. double mutant (dmCEBPA)). Only bZIPInDel patients had significantly higher rates of complete remission and longer relapse free and overall survival (OS) compared with all other CEBPA-mutant subgroups. Moreover, co-mutations in bZIPInDel patients (e.g. GATA2, FLT3, WT1 as well as ELN2022 adverse risk aberrations) had no independent impact on OS, whereas in non-bZIPInDel patients, grouping according to ELN2022 recommendations added significant prognostic information. In conclusion, these results demonstrate bZIPInDel mutations to be the major independent determinant of outcome in CEBPA-mutant AML, thereby refining current classifications according to WHO (including all dmCEBPA and smCEBPA bZIP) as well as ELN2022 and ICC recommendations (including CEBPA bZIPms )., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
48. Sex-associated differences in frequencies and prognostic impact of recurrent genetic alterations in adult acute myeloid leukemia (Alliance, AMLCG).
- Author
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Ozga M, Nicolet D, Mrózek K, Yilmaz AS, Kohlschmidt J, Larkin KT, Blachly JS, Oakes CC, Buss J, Walker CJ, Orwick S, Jurinovic V, Rothenberg-Thurley M, Dufour A, Schneider S, Sauerland MC, Görlich D, Krug U, Berdel WE, Woermann BJ, Hiddemann W, Braess J, Subklewe M, Spiekermann K, Carroll AJ, Blum WG, Powell BL, Kolitz JE, Moore JO, Mayer RJ, Larson RA, Uy GL, Stock W, Metzeler KH, Grimes HL, Byrd JC, Salomonis N, Herold T, Mims AS, and Eisfeld AK
- Subjects
- Adult, Humans, Male, Female, Prognosis, Nucleophosmin, Mutation, fms-Like Tyrosine Kinase 3 genetics, Sex Characteristics, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute drug therapy
- Abstract
Clinical outcome of patients with acute myeloid leukemia (AML) is associated with demographic and genetic features. Although the associations of acquired genetic alterations with patients' sex have been recently analyzed, their impact on outcome of female and male patients has not yet been comprehensively assessed. We performed mutational profiling, cytogenetic and outcome analyses in 1726 adults with AML (749 female and 977 male) treated on frontline Alliance for Clinical Trials in Oncology protocols. A validation cohort comprised 465 women and 489 men treated on frontline protocols of the German AML Cooperative Group. Compared with men, women more often had normal karyotype, FLT3-ITD, DNMT3A, NPM1 and WT1 mutations and less often complex karyotype, ASXL1, SRSF2, U2AF1, RUNX1, or KIT mutations. More women were in the 2022 European LeukemiaNet intermediate-risk group and more men in adverse-risk group. We found sex differences in co-occurring mutation patterns and prognostic impact of select genetic alterations. The mutation-associated splicing events and gene-expression profiles also differed between sexes. In patients aged <60 years, SF3B1 mutations were male-specific adverse outcome prognosticators. We conclude that sex differences in AML-associated genetic alterations and mutation-specific differential splicing events highlight the importance of patients' sex in analyses of AML biology and prognostication., (© 2023. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
49. Secondary-type mutations do not impact outcome in NPM1-mutated acute myeloid leukemia - implications for the European LeukemiaNet risk classification.
- Author
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Eckardt JN, Bill M, Rausch C, Metzeler K, Spiekermann K, Stasik S, Sauer T, Scholl S, Hochhaus A, Crysandt M, Brümmendorf TH, Krug U, Wörmann B, Hiddemann W, Görlich D, Sauerland C, Steffen B, Einsele H, Neubauer A, Burchert A, Schäfer-Eckart K, Berdel WE, Schliemann C, Krause SW, Hänel M, Hanoun M, Kaufmann M, Fransecky L, Braess J, Ruhnke L, Schetelig J, Middeke JM, Serve H, Baldus CD, Platzbecker U, Müller-Tidow C, Bornhäuser M, Herold T, Thiede C, and Röllig C
- Subjects
- Humans, Mutation, Nuclear Proteins genetics, Prognosis, Leukemia, Myeloid, Acute genetics
- Published
- 2023
- Full Text
- View/download PDF
50. [Artificial Intelligence for computer-aided leukemia diagnostics].
- Author
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Matek C, Marr C, von Bergwelt-Baildon M, and Spiekermann K
- Subjects
- Humans, Algorithms, Diagnosis, Computer-Assisted, Computers, Artificial Intelligence, Leukemia diagnosis
- Abstract
The manual examination of blood and bone marrow specimens for leukemia patients is time-consuming and limited by intra- and inter-observer variance. The development of AI algorithms for leukemia diagnostics requires high-quality sample digitization and reliable annotation of large datasets. Deep learning-based algorithms using these datasets attain human-level performance for some well-defined, clinically relevant questions such as the blast character of cells. Methods such as multiple - instance - learning allow predicting diagnoses from a collection of leukocytes, but are more data-intensive. Using "explainable AI" methods can make the prediction process more transparent and allow users to verify the algorithm's predictions. Stability and robustness analyses are necessary for routine application of these algorithms, and regulatory institutions are developing standards for this purpose. Integrated diagnostics, which link different diagnostic modalities, offer the promise of even greater accuracy but require more extensive and diverse datasets., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
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