Marie von Lilienfeld-Toal's research while affiliated with Universitätsklinikum Jena and other places
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Publications (146)
Purpose
Outcomes of multiple myeloma (MM) patients who are refractory to daratumumab are dismal and no standard of treatment exists for this patients’ population. Here, we investigate the role of pomalidomide combinations in daratumumab-refractory MM patients.
Methods
We performed a retrospective analysis of myeloma patients treated at four referr...
Alveolar macrophages belong to the first line of defense against inhaled conidia of the human-pathogenic fungus Aspergillus fumigatus. In lung alveoli, they contribute to phagocytosis and elimination of conidia. As a counterdefense, conidia have a gray-green pigment that enables them to survive in phagosomes of macrophages for some time. Previously...
The novel coronavirus SARS-CoV-2 and the associated infectious disease COVID-19 pose a significant challenge to health care systems worldwide. Cancer patients have been identified as a high-risk population for severe infections, rendering prophylaxis and treatment strategies for these patients particularly important. Rapidly evolving clinical resea...
Invasive mucormycosis (IM) is a life-threatening infection caused by the fungal order Mucorales, its diagnosis is often delayed, and mortality rates range from 40-80% due to its rapid progression. Individuals suffering from hematological malignancies, diabetes mellitus, organ transplantations, and most recently COVID-19 are particularly susceptible...
Poverty is an independent risk factor for cancer. Socioeconomically deprived groups are more likely to develop cancer, to develop it earlier in their life, show a shorter life expectancy after diagnosis, and benefit less from treatment. During the COVID-19 pandemic, these effects have intensified. Herein, we give an overview of these findings for G...
To assess morbidity and mortality of parainfluenza virus (PIV) infections in immunocompromised patients, we analysed PIV infections in a hematology and stem cell transplantation (SCT) unit over the course of three years. Isolated PIV strains were characterized by sequence analysis and nosocomial transmission was assessed including phylogenetic anal...
Introduction:
Multiple Myeloma (MM) is a plasma cell disease that affects more men than women. Although there is an obvious imbalance in incidence, knowledge on differences in biology and outcome between the sexes is surprisingly rare.
Methods:
We performed a unicentric retrospective analysis of patients with MM treated at a tertiary cancer cent...
Mycobacterial infections, both tuberculosis and nontuberculous, are more common in patients with haematological malignancies and haematopoietic stem cell transplant recipients than in the general population—although these infections remain rare. Mycobacterial infections pose both diagnostic and therapeutic challenges. The management of mycobacteria...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel virus that spread worldwide from 2019 causing the Coronavirus disease 19 (COVID-19) pandemic. SARS-CoV-2 infection is characterised by an initial viral phase followed in some patients by a severe inflammatory phase. Importantly, immunocompromised patients may have a prolonged v...
Patients with cancer generally have a higher risk of adverse outcomes from COVID-19, with higher age, male sex, poor performance status, cancer type, and uncontrolled malignant disease as the main risk factors. However, the influence of specific cancer therapies varies and raises concerns during the pandemic. In patients undergoing cancer immunothe...
Patients with cancer are at increased risk of infection due to disease-associated or therapy-induced immunosuppression. Taking into account globally increasing antimicrobial resistance rates and negative effects associated with antibiotic treatments, the effective, appropriate and guideline-conform use of anti-infectives must be promoted in this cl...
Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on react...
Extramedullary involvement (or extramedullary disease, EMD) represents an aggressive form of multiple myeloma (MM), characterized by the ability of a clone and/or subclone to thrive and grow independent of the bone marrow microenvironment. Several different definitions of EMD have been used in the published literature. We advocate that true EMD is...
Patients with cancer have a higher risk of severe coronavirus disease (COVID-19) and associated mortality than the general population. Owing to this increased risk, patients with cancer have been prioritized for COVID-19 vaccination globally, for both primary and booster vaccinations. However, given that these patients were not included in the pivo...
Alveolar macrophages are among the first cells to come into contact with inhaled fungal conidia of the human pathogenic fungus Aspergillus fumigatus. In lung alveoli, they contribute to phagocytosis and elimination of conidia. As a counter defense, conidia contain a grey-green pigment allowing them to survive in phagosomes of macrophages for some t...
Background
The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies, raising questions about the optimal care of this patient group.
Methods
This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of hemat...
Patients with cancer are at particular risk for infection but also have diminished vaccine responses, usually quantified by the level of specific antibodies. Nonetheless, vaccines are specifically recommended in this vulnerable patient group. Here, we discuss the cellular part of the vaccine response in patients with cancer. We summarize the experi...
Background: The objective of the study was to assess the current clinical practice and the attitude towards deferral of HCT/chemotherapy in patients with hematological diseases in cases of asymptomatic patients with a positive assay for SARS-CoV-2.
Methods: In August 2021 we performed a survey among EBMT centers regarding their attitude towards def...
Fungal eye infections can lead to loss of vision and blindness. The disease is most prevalent in the tropics, although case numbers in moderate climates are increasing as well. This study aimed to determine the dominating filamentous fungi causing eye infections in Germany and their antifungal susceptibility profiles in order to improve treatment,...
Purpose:
Fungal keratitis (FK) is a serious ophthalmic disease with a potentially devastating outcome that seems to be increasing in recent years. The use of contact lenses (CLs) was evaluated as a risk factor for FK to determine possible differences in course and outcome.
Methods:
Data from 173 cases reported in the German FK registry until Aug...
Zusammenfassung
Patient*innen mit Krebserkrankungen haben ein erhöhtes Risiko, schwere Verläufe einer COVID-19-Erkrankung zu erleiden. Spezifische Schutzmaßnahmen inkl. der COVID-19-Impfungen sind daher hier von besonderer Bedeutung. Eine durch Therapie und Grunderkrankung oftmals bedingte Abwehrschwäche kann jedoch eine Herausforderung für Impfstr...
Hematologic and oncologic patients with chemo- or immunotherapy-related immunosuppression are at substantial risk for bacterial infections and Pneumocystis jirovecii pneumonia (PcP). As bacterial resistances are increasing worldwide and new research reshapes our understanding of the interactions between the human host and bacterial commensals, admi...
The worldwide spread of SARS-CoV-2 and the associated infectious disease COVID-19 has posed a unique challenge to medical staff, patients and their families. Cancer patients, particularly those with haematologic malignancies, have been identified to be at high risk to develop severe COVID-19.
Since publication of our previous guideline on evidence-...
Activation of mucosal-associated invariant T cells (MAIT cells) by certain bacteria, viruses, and yeast is well studied, but the activation potential of filamentous moulds from the order Mucorales is not known. Here, we show a rapid response of human MAIT cells against the Mucorales species Mucor circinelloides, Rhizopus arrhizus, and Rhizopus micr...
Autologous stem cell transplantation (ASCT) conditioned with melphalan 200 mg/m² (Mel200) is standard of care for young multiple myeloma (MM) patients. Lower doses of melphalan (MelRed) have been used to reduce toxicity, although data regarding their efficacy are not concordant. We retrospectively evaluated 313 MM patients receiving ASCT at Jena Un...
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Since its first detection in China in late 2019 the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated infectious disease COVID-19 continue to have a major impact on global healthcare and clinical practice. Cancer patients, in particular those with haematological malignancies, seem to be at an increased risk for a...
Background
Community‐acquired respiratory viruses (CARV) cause upper and lower respiratory tract infections (URTI/LRTI) and may be life‐threatening for recipients of an allogeneic stem cell transplantation (allo‐SCT).
Methods
In a prospective study encompassing 4 winter‐seasons we collected throat gargles (TG) at random time points from allo‐SCT r...
Since early 2020, the SARS-CoV-2 pandemic has a massive impact on health care systems worldwide. Patients with malignant diseases are assumed to be at increased risk for a worse outcome of SARS-CoV-2 infection, and therefore, guidance regarding prevention and management of the infection as well as safe administration of cancer-therapy is required....
Invasive fungal infections caused by the mold Aspergillus fumigatus are a growing concern in the clinic due to the increasing use of immunosuppressive therapies and increasing antifungal drug resistance. These infections result in high rates of mortality, as treatment and diagnostic options remain limited. In healthy individuals, neutrophilic granu...
Background
Invasive fungal diseases remain a major cause of morbidity and mortality in cancer patients undergoing intensive cytotoxic therapy. The choice of the most appropriate antifungal treatment (AFT) depends on the fungal species suspected or identified, the patient’s risk factors (e.g. length and depth of granulocytopenia) and the expected si...
Purpose
The German Maintenance Study (GERMAIN) was designed to evaluate the impact of lenalidomide maintenance after induction therapy with bortezomib, melphalan and prednisolone (VMP) in transplant-ineligible newly diagnosed multiple myeloma (MM) patients.
Methods
Due to poor accrual and high dropout rate, only 85 patients (planned 286) entered t...
Purpose:
Outcome for relapsed acute myeloid leukemia (AML) is poor. Cladribine has activity in AML and an enhancing effect on other cytostatic drugs thus may help overcome resistance. Here, we present the final analysis of our phase II trial evaluating safety and efficacy of cladribine, cytarabine and idarubicin (CAI) in relapsed AML.
Methods:
P...
MAIT cells can recognize and respond to several pathogens in a distinct manner. However, many studies are focused on activation by bacteria and by viruses, while reports about molds and MAIT cells are rare. Here, we describe a method to investigate MAIT cell interaction with filamentous fungi from Aspergillus and Mucorales species. This includes pr...
Recurrence of cytomegalovirus reactivation remains a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Monitoring cytomegalovirus-specific cellular immunity using a standardized assay might improve the risk stratification of patients. A prospective multicenter study was conducted in 175 intermediat...
Introduction The kidney is an important target organ in plasma cell dyscrasias, subjected to various mechanisms of injury such as tubular obstruction, hypercalcemia, and pre-existing disease. Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) is of concern as treatment-related toxicity (for instance infections and mucosit...
Polymorphonuclear granulocytes (PMNs) are indispensable for controlling life-threatening fungal infections. In addition to various effector mechanisms, PMNs also produce extracellular vesicles (EVs). Their contribution to antifungal defense has remained unexplored. We reveal that the clinically important human pathogenic fungus Aspergillus fumigatu...
Background:
The incidence of invasive fungal infection is approximately 6 cases per 100 000 persons per year. It is estimated that only half of such infections are detected during the patient's lifetime, making this one of the more common overlooked causes of death in intensive-care patients. The low detection rate is due in part to the complexity...
Objectives:
We assessed the efficacy and safety of an oral antimicrobial regimen for short- and long-term intestinal eradication of ESBL-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EC/KP) in immunocompromised patients.
Methods:
We performed a randomized (2:1), double-blind multicentre Phase II study in four haematology-oncology de...
Increasing evidence suggests that impaired cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) is a major cause of uncontrolled CMV reactivations and associated complications in hematopoietic stem cell transplantation (HSCT). No reliable test exists to predict patients at risk of primary and/or recurrent CMV reactivations following HSCT...
Infections represent a major cause of morbidity and mortality in multiple myeloma and are linked to both therapy- and disease-related factors. Although it has been suggested that the rate of infections increased since the introduction of novel agents, controversies still exist. To better assess the risk factors associated with infections in the era...
Introduction
MEL at the dose of 200 mg/m2 (MEL200) is considered the standard conditioning regimen before ASCT in MM patients (pts). Lower doses of 140 mg/m2 (MEL140) or 100 mg/m2 (MEL100) are used when toxicity is a concern. Whether these lower doses are equally effective is still a matter of debate and available data are conflicting.
Aims and Met...
Introduction
Based on improvement of overall survival (OS), lenalidomide (R) maintenance after up-front autologous stem cell transplantation has recently been approved for multiple myeloma (MM) patients (pts). Conversely, in transplant non-eligible (TNE) pts R maintenance after R-based induction improved progression free survival (PFS) but had no i...
Background
Impaired cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) is a major cause of uncontrolled CMV reactivation and associated complications in both solid-organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). Reliably assessing CMV-CMI is desirable to individually adjust antiviral and immunosuppressiv...
Systemic infections with the opportunistic mold Aspergillus fumigatus are a great threat to immunocompromised patients such as transplant recipients. Immunological research on A. fumigatus involves the measurement of phagocytosis of fungal conidia (spores) by human phagocytes. Here, we present a fast and flexible way to analyze phagocytosis by flow...
Invasive fungal diseases (IFD) are a primary cause of morbidity and mortality in patients with haematological malignancies. These infections are mostly life‐threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However,...
Mucosal associated invariant T cells (MAIT) are innate‐like T cells (TC) which are known to be activated by several bacteria and viruses. However, activation of MAIT cells by moulds such as the opportunistic human pathogen Aspergillus is not well described. Stimulation of human PBMC with A. fumigatus, A. flavus or A. terreus conidia revealed that i...
Infections remain a threat for patients with haematological malignancies. In accordance with the European Hematology Association roadmap we provide a concise overview regarding the most relevant current challenges in infectious diseases for haematologists. These include bacterial infections and the need for antibiotic stewardship as well as infecti...
Immunocompromised patients are at high risk of invasive fungal infections (IFI), in particular those with haematological malignancies undergoing remission-induction chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) and recipients of allogeneic haematopoietic stem cell transplants (HSCT). Despite the development of new...
Background:
Piperacillin (PIP) in combination with tazobactam is commonly used for anti-infective treatment in cancer patients. PIP exerts a time-dependent killing. Thus, the maintenance of plasma concentrations above a pre-defined target concentration for a pre-defined time may be relevant for optimal efficacy. It is assumed that PIP-plasma conce...
Fusarium
keratitis is a destructive eye infection that is difficult to treat and results in poor outcome. In tropical and subtropical areas, the infection is relatively common and associated with trauma or chronic eye diseases. However, in recent years, an increased incidence has been reported in temperate climate regions. At the German National Re...
To assess the scope of infection control measures for multidrug-resistant bacteria in high-risk settings, a survey among university hospitals was conducted. Fourteen professionals from 8 sites participated. Reported policies varied largely with respect to the types of wards conducting screening, sample types used for screening and implementation of...
Introduction
In the last decade, the availability of new drugs for the treatment of Multiple Myeloma (MM) significantly improved patients’ outcomes. But also raised attention towards a new spectrum of adverse events. Recently, four novel agents with different mechanisms of action (carfilzomib, elotuzumab, daratumumab and panobinostat) have been app...
Background:
Community acquired viruses (CRVs) may cause severe disease in cancer patients. Thus, efforts should be made to diagnose CRV rapidly and manage CRV infections accordingly.
Methods:
A panel of 18 clinicians from the Infectious Diseases Working Party of the German Society for Haematology and Medical Oncology have convened to assess the...
Key Clinical Message
Positive galactomannan tests in patients who underwent chemotherapy without any clinical signs of a fungal infection should lead the clinician to consideration of a false‐positive test result. Oral nutritional supplements may be a cause, especially in the case of concomitant disturbance of the gastrointestinal mucosal barrier b...
The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts con...
The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts con...
Infections and subsequent septicemia are major complications in neutropenic patients with hematological malignancies. Here, we identify biomarker candidates for the early detection of an infectious origin, and monitoring of febrile neutropenia (FN).
Proteome, metabolome, and conventional biomarkers from 20 patients with febrile neutropenia without...
Reactivation of viral infections is common in patients with solid tumour or haematological malignancy. Incidence and severity depend on the extent of cellular immunosuppression. Antiviral prophylaxis may be effective to prevent viral reactivation. In 2006, the Infectious Diseases Working Party of German Society for Hematology and Medical Oncology (...
Severe infectious complications reflect a continuing problem in patients with acute myeloid leukemia (AML). Based on data from a randomized clinical trial demonstrating a reduction of proven and probable invasive fungal disease (IFD), posaconazole has been approved for prophylaxis of fungal infections in AML patients during induction chemotherapy....
Recent meta-analyses showed that antibiotic prophylaxis in patients with neutropenia after chemotherapy reduced the incidence of fever and mortality rate. Fluoroquinolones appear to be most effective and well tolerated. Thus, in April 2008, we changed our antibiotic prophylaxis regimen from cotrimoxazole/colistin (COT/COL) to the fluoroquinolone ci...
Background: We recently showed that the combination of ATRA and arsenic trioxide (ATO) is at least not inferior and possibly superior to standard ATRA and chemotherapy (CHT) in the front-line management of low/intermediate risk APL (Italian-German APL 0406 trial; Lo-Coco et al., NEJM 2013). We report herein on the extended and final series of 276 p...
Background:
Bloodstream infections (BSIs) caused by enterobacteria remain a leading cause of mortality in patients with chemotherapy-induced neutropenia. The rate and type of colonization and infection with ESBL-producing Enterobacteriaceae (ESBL-E) and their mode of transmission in German cancer centres is largely unknown.
Methods:
We performed...
![Table 1 Categories of evidence used in this guideline [88]](profile/Michael-Kiehl/publication/262937684/figure/tbl1/AS:614162484957206@1523439155519/Categories-of-evidence-used-in-this-guideline-88_Q320.jpg)
Sepsis is a major cause of mortality during the neutropenic phase after intensive cytotoxic therapies for malignancies. Improved management of sepsis during neutropenia may reduce the mortality of cancer therapies. Clinical guidelines on sepsis treatment have been published by others. However, optimal management may differ between neutropenic and n...
Lenalidomide activates the immune system, but the exact immunomodulatory mechanisms of lenalidomide in vivo are poorly defined. In an observational study we assessed the impact of lenalidomide on different populations of immune cells in multiple myeloma patients. Lenalidomide therapy was associated with increased amounts of a CD8+ T cell subset, ph...
Background
All-trans retinoic acid (ATRA) with chemotherapy is the standard of care for acute promyelocytic leukemia (APL), resulting in cure rates exceeding 80%. Pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity.
Methods
We conducted a phase 3, multicenter trial compari...
In this study, we evaluated the frequency and prognostic impact of DNMT3A mutations (DNMT3A(mut)) in 1770 younger adult patients with acute myeloid leukemia (AML) in the context of other genetic alterations and the European LeukemiaNet (ELN) classification. DNMT3A(mut) were found in 20.9% of AMLs and were associated with older age (P < .0001), high...
Management of patients suffering from metastatic malignant melanoma and brain metastasis remains challenging in routine clinical practice. The inhibitory anti-CTLA-4 antibody ipilimumab has recently been approved as second-line therapeutic option for melanoma patients. Increasing evidence suggests distinct therapeutic activity on central nervous sy...
6
Background
Simultaneous ATRA and chemotherapy (CHT) is the current gold standard for newly diagnosed APL resulting in ∼80% cure rates, while arsenic trioxide (ATO) is the treatment of choice for relapsed patients. ATO in variable combinations including ± ATRA ± CHT has also been tested as front-line therapy yielding encouraging results in severa...