Antineoplastic therapy affects the in vitro phenotype and functionality of healthy human bone marrow-derived mesenchymal stromal cells.

While antineoplastic therapies aim to specifically target cancer cells, they may also exert adverse effects on healthy tissues, like healthy hematopoietic stem and progenitor cells (HSPC), leading to hematotoxicity as a common side effect. Mesenchymal stromal cells (MSC) are a major component of the bone marrow (BM) microenvironment, regulating normal hematopoiesis, while their susceptibility to anticancer therapies and contribution to therapy-related hematotoxicity remains largely unexplored. To address this, we investigated the effects of etoposide, temozolomide, 5-azacitidine, and venetoclax on healthy BM-derived MSC functionality.

Overlapping Stromal Alterations in Myeloid and Lymphoid Neoplasms.

Myeloid and lymphoid neoplasms share the characteristics of potential bone marrow infiltration as a primary or secondary effect, which readily leads to hematopoietic insufficiency. The mechanisms by which clonal malignant cells inhibit normal hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) have not been unraveled so far. Given the pivotal role of mesenchymal stromal cells (MSCs) in the regulation of hematopoiesis in the BM niche it is assumed that MSCs also play a relevant role in the pathogenesis of hematological neoplasms.

Stromal alterations in patients with monoclonal gammopathy of undetermined significance, smoldering myeloma, and multiple myeloma.

The hallmark of multiple myeloma (MM) is a clonal plasma cell infiltration in the bone marrow accompanied by myelosuppression and osteolysis. Premalignant stages such as monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic stages such as smoldering myeloma (SMM) can progress to MM. Mesenchymal stromal cells (MSCs) are an integral component of the bone marrow microenvironment and play an important role in osteoblast differentiation and hematopoietic support.

Allogeneic hematopoietic stem cell transplantation and pre-transplant strategies in patients with NPM1-mutated acute myeloid leukemia: a single center experience.

Patients with acute myeloid leukemia (AML) and nucleophosmin 1 gene mutations (NPM1) show a favorable prognosis with chemotherapy (CT) in the absence of negative prognostic genetic abnormalities. Between 2008 and 2021 64 patients with NPM1AML received alloHSCT because of additional adverse prognostic factors (1st line), inadequate response to or relapse during or after CT (2nd line). To expand the evidence in alloTX in NPM1 AML, clinical and molecular data were retrospectively analyzed with respect to pre-transplant strategies and outcome.

The mycotoxin viriditoxin induces leukemia- and lymphoma-specific apoptosis by targeting mitochondrial metabolism.

Inhibition of the mitochondrial metabolism offers a promising therapeutic approach for the treatment of cancer. Here, we identify the mycotoxin viriditoxin (VDT), derived from the endophytic fungus Cladosporium cladosporioides, as an interesting candidate for leukemia and lymphoma treatment. VDT displayed a high cytotoxic potential and rapid kinetics of caspase activation in Jurkat leukemia and Ramos lymphoma cells in contrast to solid tumor cells that were affected to a much lesser extent.

Bone marrow stroma cells promote induction of a chemoresistant and prognostic unfavorable S100A8/A9high AML cell subset.

The bone marrow (BM) stroma represents a protective niche for acute myeloid leukemia (AML) cells. However, the complex underlying mechanisms remain to be fully elucidated. We found 2 small, intracellular, calcium-sensing molecules, S100A8 and S100A9, among the top genes being upregulated in primary AML blasts upon stromal contact.

Acute myeloid leukemia-induced functional inhibition of healthy CD34+ hematopoietic stem and progenitor cells.

Acute myeloid leukemia (AML) is characterized by an expansion of leukemic cells and a simultaneous reduction of normal hematopoietic precursors in the bone marrow (BM) resulting in hematopoietic insufficiency, but the underlying mechanisms are poorly understood in humans. Assuming that leukemic cells functionally inhibit healthy CD34+ hematopoietic stem and progenitor cells (HSPC) via humoral factors, we exposed healthy BM-derived CD34+ HSPC to cell-free supernatants derived from AML cell lines as well as from 24 newly diagnosed AML patients. Exposure to AML-derived supernatants significantly inhibited proliferation, cell cycling, colony formation, and differentiation of healthy CD34+ HSPC.

Prognostic impact of peripheral blood WT1-mRNA expression in patients with MDS.

Few reports suggested a prognostic impact of Wilms'Tumor-1 (WT1)-mRNA overexpression in MDS, but translation into clinical routine was hampered by limited patients numbers, differing sample sources, non-standardized methods/cut-offs. To evaluate whether WT1-mRNA expression yields additional prognostic information, we measured peripheral blood (PB) WT1-mRNA expression in 94 MDS using a standardized assay offering a validated cut-off to discriminate between normal and WT1-mRNA overexpression. Overall, 54 patients (57%) showed WT1-mRNA overexpression, while 40 patients (43%) had normal WT1-mRNA expression.

Secretome analysis of human bone marrow derived mesenchymal stromal cells.

As an essential cellular component of the bone marrow (BM) microenvironment mesenchymal stromal cells (MSC) play a pivotal role for the physiological regulation of hematopoiesis, in particular through the secretion of cytokines and chemokines. Mass spectrometry (MS) facilitates the identification and quantification of a large amount of secreted proteins (secretome), but can be hampered by the false-positive identification of contaminating proteins released from dead cells or derived from cell medium. To reduce the likelihood of contaminations we applied an approach combining secretome and proteome analysis to characterize the physiological secretome of BM derived human MSC.

Perceived posttraumatic growth and depreciation after spinal cord injury: Actual or illusory?

Objective: This study examined whether retrospective reports of posttraumatic growth (PTG) and depreciation (PTD) of individuals recently diagnosed with a spinal cord injury (SCI) coincide with prospectively measured changes in the conceptually close domains of general self-efficacy (SE) and purpose in life (PIL). The study also tested whether PTG/D and changes in SE and PIL independently predict psychological adjustment to the injury (depressive symptoms, anxiety, life satisfaction).

Method: Adopting a longitudinal design, a sample of 206 newly injured patients admitted to one of the four Swiss SCI rehabilitation centers was analyzed.

Coping and posttraumatic growth: A longitudinal comparison of two alternative views.

Purpose: In the current study, we aimed to examine two possible explanations for why higher levels of posttraumatic growth (PTG) were repeatedly found to be predicted by both approach- and avoidance-oriented coping, focusing on individuals recently diagnosed with a spinal cord injury (SCI). First, negative changes (posttraumatic depreciation, PTD) may moderate the association between PTG and the two types of coping, indicating that PTG reflects avoidance of PTD for some individuals, but a constructive view on posttraumatic life changes for others. Second, it may be that a flexible use of different types of coping strategies (coping flexibility) enables the experience of PTG.

Transforming growth factor β1-mediated functional inhibition of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia.

Mesenchymal stromal cells are involved in the pathogenesis of myelodysplastic syndromes and acute myeloid leukemia, but the underlying mechanisms are incompletely understood. To further characterize the pathological phenotype we performed RNA sequencing of mesenchymal stromal cells from patients with myelodysplastic syndromes and acute myeloid leukemia and found a specific molecular signature of genes commonly deregulated in these disorders. Pathway analysis showed a strong enrichment of genes related to osteogenesis, senescence, inflammation and inhibitory cytokines, thereby reflecting the structural and functional deficits of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia on a molecular level.

Wilms' Tumor 1 Gene Expression Using a Standardized European LeukemiaNet-Certified Assay Compared to Other Methods for Detection of Minimal Residual Disease in Myelodysplastic Syndrome and Acute Myelogenous Leukemia after Allogeneic Blood Stem Cell Transplantation.

Overexpression of the Wilms' tumor 1 (WT1) gene is informative in many patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS) and is measurable in peripheral blood (PB). Despite these advantages, WT1 has not broadly been established as a marker for minimal residual disease (MRD) monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to limited patient numbers, differing sample sources, and nonstandardized in-house methods. To estimate the value of WT1 as an MRD marker, we serially quantified PB WT1 expression using a standardized European LeukemiaNet-certified assay in 59 patients with AML and MDS after allo-HSCT.

Representing and organizing information to describe the lived experience of health from a personal factors perspective in the light of the International Classification of Functioning, Disability and Health (ICF): a discussion paper.

Purpose: To discuss the representation and organization of information describing persons' lived experience of health from a personal factors perspective in the light of the International Classification of Functioning, Disability and Health, using spinal cord injury as a case in point for disability.

Methods: The scientific literature was reviewed, discussion rounds conducted, and qualitative secondary analyses of data carried out using an iterative inductive-deductive approach.

Results: Conceptual considerations are explicated that distinguish the personal factors perspective from other components of the International Classification of Functioning, Disability and Health.

Treatment of relapsed AML and MDS after allogeneic stem cell transplantation with decitabine and DLI-a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group.

In contrast to the evidence regarding azacitidine (Aza), there is limited knowledge about the combination of decitabine (DAC) and donor lymphocyte infusions as salvage therapy for relapse after allogeneic stem cell transplantation (allo-SCT) so far. We retrospectively analyzed data of 36 patients with hematological (n = 35) or molecular relapse (n = 1) of acute myeloid leukemia (AML, n = 29) or myelodysplastic syndrome (MDS, n = 7) collected from 6 German transplant centers. Patients were treated with a median of 2 cycles DAC (range, 1 to 11).

Mesenchymal stromal cells in myeloid malignancies.

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal myeloid disorders characterized by hematopoietic insufficiency. As MDS and AML are considered to originate from genetic and molecular defects of hematopoietic stem and progenitor cells (HSPC), the main focus of research in this field has focused on the characterization of these cells. Recently, the contribution of BM microenvironment to the pathogenesis of myeloid malignancies, in particular MDS and AML has gained more interest.

Posttraumatic growth and adjustment to spinal cord injury: Moderated by posttraumatic depreciation?

Objective: Findings on the relationship of posttraumatic growth (PTG) with adjustment to potentially traumatic events are inconsistent, whereupon posttraumatic depreciation (PTD) has been suggested as a possible moderator. The objective of this study is to investigate the associations between PTG and PTD on one side and life satisfaction and indicators of mental and physical health on the other side in individuals with spinal cord injury (SCI). The primary study aim is to test whether PTD moderates the relationships of PTG and different adjustment indicators.

Describing functioning and health after spinal cord injury in the light of psychological-personal factors.

Objective: To describe and explore functioning and health of persons with spinal cord injury from the perspective of psychological-personal factors in the light of the International Classification of Functioning, Disability and Health (ICF) framework.

Methods: Data from 511 participants regarding feelings, thoughts and beliefs, motives, and patterns of experience and behaviour were analysed. Measurement instruments included the Mental Health Index-5, Positive and Negative Affect Schedule, Hospital Anxiety and Depression Scale, Appraisal of Life Events Scale, 5 items from the World Health Organization Quality of Life Scale, Purpose in Life Test-Short Form, General Self-Efficacy Scale, Big Five Inventory-21, Social Skills Inventory-SF, Brief COPE.

Rasch analysis of measurement instruments capturing psychological personal factors in persons with spinal cord injury.

Objective: To evaluate the metric properties of distinct measures of psychological personal factors comprising feelings, beliefs, motives, and patterns of experience and behaviour assessed in the Swiss Spinal Cord Injury Cohort Study (SwiSCI), using Rasch methodology.

Methods: SwiSCI Pathway 2 is a community-based, nationwide, cross-sectional survey for persons with spinal cord injury (SCI) (n = 511). The Rasch partial credit model was used for each subscale of the Positive Affect Negative Affect Scale (PANAS), Appraisal of Life Events Scale (ALE), Purpose in Life test - Short Form (PIL-SF), and the Big Five Inventory-K (BFI-K).

Functional inhibition of mesenchymal stromal cells in acute myeloid leukemia.

Hematopoietic insufficiency is the hallmark of acute myeloid leukemia (AML) and predisposes patients to life-threatening complications such as bleeding and infections. Addressing the contribution of mesenchymal stromal cells (MSC) to AML-induced hematopoietic failure we show that MSC from AML patients (n=64) exhibit significant growth deficiency and impaired osteogenic differentiation capacity. This was molecularly reflected by a specific methylation signature affecting pathways involved in cell differentiation, proliferation and skeletal development.

Perceived needs and experiences with healthcare services of women with spinal cord injury during pregnancy and childbirth - a qualitative content analysis of focus groups and individual interviews.

Background: Women after a spinal cord injury (SCI), who decide to get pregnant and to become mothers, have special health care service needs. This study aims to identify the perceived service needs of woman with SCI during pregnancy and childbirth in Switzerland and to reconstruct their experiences of healthcare service utilization based on their accounts.

Methods: A qualitative content analysis based on focus groups and individual interviews was conducted.

Depression in spinal cord injury: assessing the role of psychological resources.

Purpose: To test the spinal cord injury adjustment model (SCIAM) and to examine how psychological resources may influence depressive symptoms in persons with spinal cord injury (SCI). We expect that (a) higher general self-efficacy (GSE) and higher purpose in life (PIL) are associated with lower levels of depressive symptoms, and that (b) the effect of GSE and PIL on depressive symptoms is mediated by appraisals and coping strategies, as proposed by the SCIAM.

Method: A nationwide cross-sectional survey (the Swiss Spinal Cord Injury Cohort Study) was conducted with individuals with SCI living in the Swiss community (N = 516).

Personal factors in systemic sclerosis and their coverage by patient-reported outcome measures. A multicentre European qualitative study and literature review.

Background: Systemic sclerosis (SSc) is an autoimmune disease where thickening of the skin can lead to reduced body function and limitations in activities. Severe forms can also affect and seriously damage inner organs. Patient-centred rehabilitation emphasises considerations of patients' background, experience and behavior which highlights the need to know if patient-reported outcome measures (PROMs) include such personal factors.