A5009736563- Mast cells and histamine
- Eosinophilic Disorders and Syndromes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Asthma and respiratory diseases
- Chronic Lymphocytic Leukemia Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Spine and Intervertebral Disc Pathology
- Autoimmune Bullous Skin Diseases
- Lymphoma Diagnosis and Treatment
- DNA Repair Mechanisms
- Veterinary Oncology Research
- Click Chemistry and Applications
- Urticaria and Related Conditions
- Anesthesia and Pain Management
- Amyotrophic Lateral Sclerosis Research
- Polyomavirus and related diseases
- Peptidase Inhibition and Analysis
- Allergic Rhinitis and Sensitization
- DNA and Nucleic Acid Chemistry
- Cervical and Thoracic Myelopathy
- Assisted Reproductive Technology and Twin Pregnancy
- Meningioma and schwannoma management
- Testicular diseases and treatments
Heidelberg University
2015-2024
University Hospital Heidelberg
2015-2024
University Medical Centre Mannheim
2015-2024
University Hospital of Basel
2012-2024
University of Basel
2024
ASM International
2019
Straumann (Switzerland)
2018
Friedrich-Alexander-Universität Erlangen-Nürnberg
2017
Klinik und Poliklinik für Nuklearmedizin
2012
Universitätsklinikum des Saarlandes
2005-2006
To develop a risk score for patients with advanced systemic mastocytosis (AdvSM) that integrates clinical and mutation characteristics. The study included 383 AdvSM from the German Registry on Disorders of Eosinophils Mast Cells (training set; n = 231) several centers in United States Europe, all within European Competence Network Mastocytosis (validation 152). A Cox multivariable model was used to select variables were predictive overall survival (OS). In analysis, following factors...
Mast cell leukemia is a rare variant of advanced systemic mastocytosis characterized by at least 20% mast cells in bone marrow smear. We evaluated clinical and molecular characteristics 28 patients with (n=20, 71%) or without an associated hematologic neoplasm. De novo was diagnosed 16 (57%) secondary evolving from other subtypes 12 (43%) patients, which 7 progressed while on cytoreductive treatment. Median infiltration 65% median serum tryptase 520 μg/L. C-findings were identified 26 (93%)...
Determining the underlying cause of persistent eosinophilia is important for effective clinical management but remains a diagnostic challenge in many cases. We identified STAT5B N642H, an established oncogenic mutation, 27/1715 (1.6%) cases referred investigation eosinophilia. Of 27 mutated cases, working diagnosis hypereosinophilic syndrome (HES; n = 7) or myeloid neoplasm with (n 20) had been made prior to detection N642H. Myeloid panel analysis median 2 additional genes (range 0–4) 4...
We report on 18 patients with myeloid neoplasms and associated tyrosine kinase (TK) fusion genes treatment the TK inhibitors (TKI) ruxolitinib (PCM1-JAK2, n = 8; BCR-JAK2, 1) imatinib, nilotinib or dasatinib (ETV6-ABL1, 9). On (median 24 months, range 2-36 months), a complete hematologic response (CHR) cytogenetic (CCR) was achieved by five of nine two patients, respectively. However, stopped in eight because primary resistance (n 3), progression 3) planned allogeneic stem cell...
Background: Inevitable recurrence after radiochemotherapy is the major problem in treatment of glioblastoma, most prevalent type adult brain malignancy. Glioblastomas are notorious for a high degree intratumor heterogeneity manifest through diversity cell types and molecular patterns. The current paradigm understanding glioblastoma that cytotoxic therapy fails to target effectively glioma stem cells. Recent advances indicate therapy-driven evolution fundamental trait associated with...
PURPOSE On the basis of data from German Registry on Disorders Eosinophils and Mast Cells, we compared efficacy midostaurin cladribine in patients with advanced systemic mastocytosis (AdvSM). PATIENTS AND METHODS Patients AdvSM (n = 139) were treated only 63, 45%), 23, 17%), or sequentially (midostaurin-cladribine, n 30, 57%; cladribine-midostaurin, 43%). Prognosis was assessed through Mutation-Adjusted Risk Score (MARS). Besides comparison between response (eg, organ dysfunction, bone...
Myeloproliferative neoplasms with eosinophilia are commonly characterized by a normal karyotype and remain poorly defined at the molecular level. We therefore investigated 426 samples from patients hypereosinophilia of unknown significance initially referred for screening FIP1L1-PDGFRA (FP) fusion gene also KIT D816V JAK2 V617F mutations. Overall, 86 (20%) tested positive: FP+ in 55 (12%), D816V+ 14 (3%), V617F+ 17 (4%) patients, respectively. To gain better insight into clinical...
The clinical behavior of systemic mastocytosis (SM) is strongly associated with activating mutations in KIT (D816V >80% cases), the severity phenotype influenced by additional somatic mutations, for example, SRSF2, ASXL1, or RUNX1. Complex molecular profiles are frequently presence an hematologic neoplasm (AHN) and unfavorable outcome. However, little known about incidence prognostic impact cytogenetic aberrations. We analyzed characteristics 109 patients (KIT D816V+, n = 102, 94%) indolent...
In a registry-based analysis of 135 patients with "myeloid/lymphoid neoplasms eosinophilia and tyrosine kinase gene fusions" (MLN-TK; FIP1L1::PDGFRA, n = 78; PDGFRB, diverse fusions, 26; FGFR1, diverse, 9; JAK2, 11; ETV6::ABL1, 11), we sought to evaluate the disease-defining characteristics. 81/135 (60%) evaluable patients, hypereosinophilia (>1.5 × 109/l) was observed in 40/44 (91%) FIP1L1::PDGFRA 7/7 (100%) ETV6::ABL1 positive but only 13/30 (43%) JAK2 fusion genes while 9/30 (30%) had no...
Abstract In 70 patients with KIT D816V positive systemic mastocytosis (SM) including 36 advanced SM (AdvSM), we correlated the extent of reported mucosal mast cell ([m]MC) infiltration upper and/or lower gastrointestinal tract (UGIT, n = 63; LGIT, 64; both, 57) symptoms and markers MC burden/subtype. GI were by all (mean 2.1 number symptoms). A strong mMC was identified in 24 17/63, 27%; 19/64, 30%). Concurrent involvement UGIT LGIT (n 12) female gender (75%) a higher symptom burden 2.7) but...
Advanced systemic mastocytosis (advSM) is characterized by the presence of an acquired KIT D816V mutation in >90% patients. In majority patients, not only detected mast cells but also other hematopoietic lineages. We sought to investigate effects KIT-inhibitors midostaurin and avapritinib on single-cell-derived myeloid progenitor using granulocyte-macrophage colony-forming-units patients with positive advSM. Colonies obtained prior treatment were incubated vitro (n = 10) or 11) showed a...
Abstract FIP1L1-PDGFRA–positive myeloid/lymphoid neoplasms with eosinophilia (MLN-eo) are exquisitely sensitive to imatinib. Almost all patients achieve a complete molecular remission (CMR) by nested reverse transcription polymerase chain reaction, which can be maintained low-dose imatinib (eg, 3 × 100 mg/wk). Because safely stopped in substantial proportion of BCR-ABL1–positive CML, we sought analyze the clinical and follow-up 12 MLN-eo chronic phase who discontinued after achievement CMR....
DNA damage and alterations in the response (DDR) are critical sources of genetic instability that might be involved BCR-ABL1 kinase-mediated blastic transformation chronic myeloid leukemia (CML). Here, increased is detected by γH2AX foci analysis peripheral blood mononuclear cells (PBMCs) de novo untreated phase (CP)-CML patients (n = 5; 2.5 per PBMC ± 0.5) blast (BP)-CML 3; 4.4 0.7) as well CP-CML with loss major molecular (MMR) 1.8 0.4) when compared to healthy donors 8; 1.0 0.1) deep or...
Abstract Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management chronic myeloid leukemia (CML) patients. From 2016 to 2021 European Treatment and Outcome Study CML (EUTOS) explored use secondary, lyophilized cell-based reference panels traceable World Health Organization primary material standardize validate local laboratory tests. Panels were used assign conversion factors (CFs) International Scale assess ability laboratories deep molecular response (DMR). The...
KIT D816 mutations (KIT D816mut) are strongly associated with systemic mastocytosis (SM) but also detectable in acute myeloid leukemia (AML), where they represent an adverse prognostic factor combination core binding (CBF) fusion genes. Here, we evaluated the clinical and molecular features of D816mut/CBF-negative (CBFneg) AML, a previously uncharacterized combination. All D816mut/CBFneg cases (n = 40) had histologically proven SM AML (SM-AML). Molecular analyses revealed at least one...