A5053767571- Hematopoietic Stem Cell Transplantation
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- Mesenchymal stem cell research
- MicroRNA in disease regulation
- Extracellular vesicles in disease
- Acute Lymphoblastic Leukemia research
- Chronic Myeloid Leukemia Treatments
- CAR-T cell therapy research
- Inflammasome and immune disorders
- Chronic Lymphocytic Leukemia Research
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Biosimilars and Bioanalytical Methods
- Autoimmune and Inflammatory Disorders Research
- RNA Interference and Gene Delivery
- Neonatal Respiratory Health Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Nietzsche, Schopenhauer, and Hegel
- Reproductive System and Pregnancy
- Renal Transplantation Outcomes and Treatments
- Clinical Nutrition and Gastroenterology
Essen University Hospital
2011-2024
University of Duisburg-Essen
2012-2024
DRK-Blutspendedienst Baden-Württemberg - Hessen
2024
German Cancer Research Center
2017
University Hospital Heidelberg
2017
Heidelberg University
2002-2017
West Cancer Center
2011
Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types participate in physiological pathophysiological processes. EVs mediate intercellular communication cell‐derived extracellular signalling organelles that transmit specific information from their of origin to target cells. As a result these properties, defined may serve novel tools for various therapeutic approaches, including (a) anti‐tumour therapy, (b) pathogen vaccination, (c)...
Background We report a prospective multicenter phase II study of haploidentical hematopoietic stem cell transplantation using CD3/CD19-depleted grafts after reduced intensity conditioning with fludarabine, thiotepa, melphalan and OKT-3.Design Methods Sixty-one adults median age 46 years (range 19-65 years) have been enrolled. Diagnoses were acute myeloid leukemia (n=38), lymphoblastic (n=8), non-Hodgkin's lymphoma (n=6), myeloma (n=4), chronic (n=3), lymphatic (n=1) myelodysplastic syndrome...
Extracellular vesicles (EVs) harvested from conditioned media of human mesenchymal stromal cells (MSCs) suppress acute inflammation in various disease models and promote regeneration damaged tissues. After successful treatment a patient with steroid-refractory graft-versus-host (GVHD) using EVs prepared bone marrow-derived MSCs, this study focused on improving the MSC-EV production for clinical application.
We previously reported that the "Endothelial Activation and Stress Index" (EASIX; ((creatinine×lactate dehydrogenase)÷thrombocytes)) measured before start of conditioning predicts mortality after allogeneic hematopoietic stem cell transplantation (alloSCT) when used as continuous score. For broad clinical implementation, a prospectively validated EASIX-pre cut-off is needed defines high-risk cohort easy to use. In current study, we first performed retrospective analysis in n=2022 alloSCT...
Abstract Treatment of relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains a great challenge. Aiming to evaluate the combination venetoclax and hypomethylating agents (HMAClax) for treatment myeloid malignancies alloHSCT, we retrospectively collected data from 32 patients treated at 11 German centers. Venetoclax was applied with azacitidine ( n = 13) or decitabine 19); received DLI in addition. HMAClax first salvage therapy 8 patients. The median number cycles...
Allogeneic stem cell transplantation (alloSCT) of homozygous CCR5 Δ32 cells once resulted in the cure human immunodeficiency virus (HIV) infection. We have recently reported a viral breakthrough similar setting. Here, we demonstrate that rapid rebound after alloSCT was related to highly replicative CXCR4-tropic HIV variant, which could already be detected before alloSCT.
Summary The success of haematopoietic stem cell ( HSC ) transplantation largely depends on numbers transplanted s, which reside in the CD 34 + populations bone marrow BM ), peripheral blood cells PBSC and umbilical cord UCB ). More specifically s 38 low/− subpopulation, cannot be objectively discriminated from mature progenitors. Thus, better marker combinations for quantification more primitive progenitor transplants are required. Recently, by combining 133 we could clearly distinguish...
Treatment with extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have been suggested as novel therapeutic option in acute inflammation-associated disorders due to their immune-modulatory capacities. As we previously observed differences the cytokine profile of independent MSC-EV preparations, functional preparations be considered. To evaluate capabilities specific reliable assays are required characterize functionality prior administration a patient. this end,...
Natural killer (NK) cells play a central role in the innate immune system. In allogeneic stem cell transplantation (alloSCT), alloreactive NK derived by graft are discussed to mediate elimination of leukemic and dendritic patient thereby reduce risk for relapses graft-versus-host reactions. The alloreactivity is determined various receptors including activating CD94/NKG2C inhibitory CD94/NKG2A receptors, which both recognize non-classical human leukocyte antigen E (HLA-E). Here we analyze...
Abstract Patients with hematological malignancies who survive the first year after allogeneic stem cell transplantation (allo-SCT) without relapse have a substantial risk of nonrelapse mortality (NRM) and missing predictive markers. The Endothelial Activation Stress Index (EASIX) predicts endothelial complications NRM early allo-SCT. We hypothesized that EASIX assessed 1 allo-SCT in survivors were disease free may predict late NRM. Survivors relapse-free at retrospectively studied 2...
Purpose Vitamin D (VitD) deficiency is common in patients with hematologic malignancies undergoing allogeneic transplantation (alloSCT), but its prognostic relevance unclear. Patients and Methods The impact of pretransplant VitD status on overall survival, relapse mortality, nonrelapse mortality was investigated retrospectively a cohort 492 alloSCT at our center from 2002 to 2013. defined as serum level 25-hydroxyvitamin D3 < 20 ng/mL (equivalent 50 nM) before assessed using accredited...
Impaired gastric emptying is common in critically ill patients. Intestinal dysmotility, a major cause of feed intolerance, may foster infectious complications due to mucosal barrier disruption. However, little known about gut-directed immune activation, intestinal function and its association with impaired patients at ICU admission.We conducted prospective observational study two tertiary care medical ICUs. Fifty consecutive needing invasive mechanical ventilation were recruited within 24 h...
Considering the unsatisfactory results of salvage therapies for patients with relapsed/refractory acute myeloid leukaemia (R/R-AML), their value before allogeneic haematopoietic stem cell transplantation (HSCT) remains questionable. However, direct HSCT following established conditioning regimens applied in R/R-AML during active disease has been equally disappointing. In this retrospective observational study, high-dose melphalan, as part a sequential preparative regimen, followed by total...
Abstract Immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is slow and patients carry a high prolonged risk of opportunistic infections. We hypothesized that the adoptive transfer donor B cells can foster HSCT immuno-reconstitution. Here, we report, to our knowledge, results first-in-human phase 1/2a study aimed evaluate feasibility safety adoptively transferred test their activity upon recall vaccination. Good manufactoring practice (GMP) B-cell...
Background Selective inhibition of the BCR-ABL tyrosine kinase by RNA interference has been demonstrated in leukemic cells. We, therefore, evaluated specific small interfering silencing BCR-ABL-positive cell lines, including those resistant to imatinib and particularly with T315I mutation.Design Methods The factor-independent 32Dp210 oligoclonal lines human imatinib-resistant cells from patients disorders were investigated. effects or combination nilotinib compared ABL inhibitors...
Posttransplant lymphoproliferative disease (PTLD) is a life-threatening complication after allogeneic hematopoietic stem cell (HSCT) or solid organ transplantation. The majority of PTLD are associated with the Epstein-Barr virus (EBV). may involve several organs like liver, lungs, kidney, spleen, and small intestine. central nervous system (CNS) involvement only has been reported in very few cases so far.We here describe 2 who 7 12 months HSCT developed EBV CNS lymphomas only. efficacy...
Abstract Extracellular vesicles (EVs) harvested from cell culture supernatants of human mesenchymal stromal cells (MSCs) suppress acute inflammation in preclinical models various diseases. Furthermore, they promote regeneration damaged tissues. Following successful clinical treatment a steroid-refractory Graft-versus-Host-Disease (GvHD) patient with EVs prepared conditioned media bone marrow (BM)-derived MSCs, we aim to improve MSC-EV production and quality control towards application....
Interleukin-18 (IL-18) is involved in endothelial activation and dysfunction, the pathogenesis severity of acute graft-versus-host disease (aGVHD). Its relevance for patient outcome after allogeneic stem cell transplantation (alloSCT) has not yet been comprehensively addressed. Pre-transplant serum levels free IL-18 were retrospectively assessed a cohort 589 patients (training cohort). Results validated 688 allografted different centre. The primary endpoint was overall survival (OS)....