Therapy-Related Acute Myeloid Leukemia after CAR-T Cell Therapy with Brexucabtagene Autoleucel for Mantle Cell Lymphoma.

Introduction: The introduction of CAR-T cell treatment for relapsed/refractory (r/r) mantle cell lymphoma improved survival rates of these patients. Along with its introduction in clinical routine, long-term events after CAR-T cell treatment are increasingly emerging.

Case Presentation: We report the case of a patient developing acute erythroid leukemia with biallelic inactivation occurring 26 months after CAR-T therapy with brexucabtagene autoleucel (brexu-cel) for r/r mantle cell lymphoma.

Gender-Specific Prognostic Impact of Treosulfan Levels in High-Dose Chemotherapy for Multiple Myeloma.

Introduction: The growing body of evidence around sexual and gender dimorphism in medicine, particularly in oncology, has highlighted differences in treatment response, outcomes, and side effects between males and females. Differences in drug metabolism, distribution, and elimination, influenced by factors like body composition and enzyme expression, contribute to these variations.

Methods: We retrospectively analyzed data of 112 multiple myeloma (MM) patients treated with first-line high-dose chemotherapy (HDCT) with treosulfan and melphalan (TreoMel) followed by autologous stem cell transplantation (ASCT) at a single academic center between January 2020 and August 2022.

Examining nutrition strategies to influence DNA methylation and epigenetic clocks: a systematic review of clinical trials.

Nutrition has powerful impacts on our health and longevity. One of the mechanisms by which nutrition might influence our health is by inducing epigenetic modifications, modulating the molecular mechanisms that regulate aging. Observational studies have provided evidence of a relationship between nutrition and differences in DNA methylation.

Maintaining brain health across the lifespan.

Across the lifespan, the human body and brain endure the impact of a plethora of exogenous and endogenous factors that determine the health outcome in old age. The overwhelming inter-individual variance spans between progressive frailty with loss of autonomy to largely preserved physical, cognitive, and social functions. Understanding the mechanisms underlying the diverse aging trajectories can inform future strategies to maintain a healthy body and brain.

BeEAM Conditioning including High-Dose Bendamustine before Autologous Stem Cell Transplantation Is Safe and Effective in Patients with Waldenstrom's Macroglobulinemia.

High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is an option to consolidate remission in Waldenstrom's macroglobulinemia (WM), particularly in selected younger patients with chemosensitive disease. BEAM, consisting of BCNU, etoposide, cytarabine, and melphalan, is often used as a conditioning regimen. However, problems with BCNU, including pneumotoxicity, tolerance, and availability, necessitate the search for alternatives.

Clonal Hematopoiesis after Autologous Stem Cell Transplantation Does Not Confer Adverse Prognosis in Patients with AML.

Introduction: Despite a 50% cure rate, relapse remains the main cause of death in patients with acute myeloid leukemia (AML) consolidated with autologous stem cell transplantation (ASCT) in first remission (CR1). Clonal hematopoiesis of indeterminate potential (CH) increases the risk for hematological and cardiovascular disorders and death. The impact of CH persisting after ASCT in AML patients is unclear.

Analysis of IL-6 serum levels and CAR T cell-specific digital PCR in the context of cytokine release syndrome.

Introduction: Chimeric antigen receptor T-cell (CAR-T) therapies are increasingly used to treat relapsed B-cell lymphomas and acute lymphoblastic leukemia. Considering the frequency of cytokine release syndrome and CAR-T-related encephalopathy syndrome (CRS/CRES) after CAR-T administration, strategies enabling timely prediction of impending CRS/CRES are a clinical need.

Methods: We evaluated the dynamics of serum interleukin (IL)-6 levels and CAR-T transgene copy numbers by digital droplet polymerase chain reaction in the peripheral blood of 11 consecutive patients with aggressive B-cell malignancies.

Spatial statistics of hydrography and water chemistry in a eutrophic boreal lake based on sounding and water samples.

Spatial variability, an essential characteristic of lake ecosystems, has often been neglected in field research and monitoring. In this study, we apply spatial statistical methods for the key physics and chemistry variables and chlorophyll a over eight sampling dates in two consecutive years in a large (area 103 km) eutrophic boreal lake in southern Finland. In the four summer sampling dates, the water body was vertically and horizontally heterogenic except with color and DOC, in the two winter ice-covered dates DO was vertically stratified, while in the two autumn dates, no significant spatial differences in any of the measured variables were found.

Regulation of fetal hemoglobin expression during hematopoietic stem cell development and its importance in bone metabolism and osteoporosis.

We have shown that an altered tissue redox environment in mice lacking either murine beta Hemoglobin major (HgbβKO) or minor (HgbβKO) regulates inflammation. The REDOX environment in marrow stem cell niches also control differentiation pathways. We investigated osteoclastogenesis (OC)/osteoblastogenesis (OB), in bone cultures derived from untreated or FSLE-treated WT, HgbβKO or HgbβKO mice.

Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.

Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice. To investigate the role of fetal hemoglobin we derived mice with homzygous deletions for either of the two major βchains, HgbβKO or HgbβKO. Hgbβ is the most prominent fetal Hgbβ chain, with Hgbβ more prominent in adult mice.

An altered REDOX environment, assisted by over-expression of fetal hemoglobins, protects from inflammatory colitis and reduces inflammatory cytokine expression.

C5BL/6 female mice receiving dextran sodium sulfate in their drinking water develop an acute inflammatory colitis within 7d, with weight loss, histopathologic signs of inflammation, and colonic expression of inflammatory cytokines. In previous studies we have reported that increased inflammatory cytokine expression in aged mice can be attenuated by oral gavage of a crude fetal extract containing glutathione (GSH), MPLA and fetal hemoglobin, or more specifically by injection of a combination of these purified reagents. We speculated that this combination led to an altered tissue redox environment in which the immune response developed, thus regulating inflammation.

Consolidation with autologous stem cell transplantation in first remission is safe and effective in AML patients above 65 years.

The outcome of AML patients ≥65 years remains disappointing. Current post-induction strategies for elderly AML patients fit for intensive treatment involve additional cycles of chemotherapy or allogeneic transplantation. Consolidation with autologous transplantation (ASCT) is poorly studied in these patients.

Increased fibrinogen levels at diagnosis are associated with adverse outcome in patients with acute myeloid leukemia.

Increased plasma fibrinogen levels are associated with shortened overall survival (OS) in some solid tumor types. In contrast, the prognostic significance of varying fibrinogen levels in acute myeloid leukemia (AML) at diagnosis is unknown. In this study, we assessed the prognostic significance of fibrinogen levels in AML patients.

Enhancing actions of peptides derived from the γ-chain of fetal human hemoglobin on the immunostimulant activities of monophosphoryl lipid A.

Hemoglobin and its structures have been described since the 1990s to enhance a variety of biological activities of endotoxins (LPS) in a dose-dependent manner. To investigate the interaction processes in more detail, the system was extended by studying the interactions of newly designed peptides from the γ-chain of human hemoglobin with the adjuvant monophosphoryl lipid A (MPLA), a partial structure of lipid A lacking its 1-phosphate. It was found that some selected Hbg peptides, in particular two synthetic substructures designated Hbg32 and Hbg35, considerably increased the bioactivity of MPLA, which alone was only a weak activator of immune cells.

A festschrift for Roland L. Weinsier: nutrition scientist, educator, and clinician.

Roland L. Weinsier, M.D.

[Contraindications to weight reduction].

It is relatively well accepted that weight gain, even within the range of normal weight, is detrimental for health. The claimed long-term benefit of intentional weight loss is mainly based on a few observational trials, confounding intentional and non-intentional weight loss. The few data on obesity-related diseases prevented by intentional weight reduction have not been replicated.

Junctions between subsynaptic folds and rough sarcoplasmic reticulum of muscle fibres.

Serial sections through motor end plate regions of mouse muscle fibres demonstrated junctions between the subsynaptic folds and the rough sarcoplasmic reticulum of the sole plate nuclei. The shape of these structures resembles that of the well-known peripheral couplings, diads and triads of muscle fibres. However, the location of the new junctions between the surface membrane and the sole plate nuclei at a large distance from myofibrils, indicates a different function.