Cytopenia

To look at the safety and effectiveness of emapalumab for the treatment of prolonged severe cytopenia in participants with LBCL who receive CART.

This research is being done to find out more about the potential risks and benefits of early treatment in participants with high risk Clonal Cytopenia of Unknown Significance (CCUS). This study will give eligible CCUS participants the option of either being observed or taking an oral drug as treatment. The names of the study drug involved in this study is: -Decitabine/cedazuridine (DEC/CED) (a nucleoside metabolic inhibitor and cytidine deaminase inhibitor).

This observational, multi-center study aims to collect data in order to develop a novel, minimally invasive diagnostic tool for MDS based on peripheral blood profiling of circulating hematopoietic stem and progenitor cells (cHSPCs) using single-cell RNA sequencing and DNA sequencing.

This clinical trial tests next generation sequencing (NGS) for the detection of precursor features of pre-myeloid cancers and bone marrow failure syndromes. NGS is a procedure that looks at relevant cancer associated genes and what they do. Finding genetic markers for pre-malignant conditions may help identify patients who are at risk of pre-myeloid cancers and bone marrow failure syndromes and lead to earlier intervention.

The main aim of this study is to learn how safe elritercept is and how well adults with anemia associated with lower-risk MDS tolerate treatment with different doses of elritercept. Other aims are to learn how safe elritercept is by looking at how many participants have MDS that worsens during the study and learn about the effects of elritercept on anemia linked to MDS. The study will also look to learn how elritercept affects the production of healthy RBCs.

The purpose of this study is to find out whether upfront emapalumab treatment can help in sAA (Aplastic Anemia) treatment planning and increase the effectiveness of standard treatment options. Funding Source- FDA OOPD

Somatic mutations as seen in myeloid malignancies can also be detected in healthy, elderly individuals (clonal hematopoiesis of indeterminate potential, CHIP), in patients with unex-plained cytopenia, that do not fulfill the criteria for myeloid malignancy (clonal cytopenia of un-determined significance, CCUS) It has been shown that these conditions predispose to hema-tological cancer. For patients with CCUS, it has been reported that in a 5-year period up to 50-90 % of the patients will progress to myelodysplastic syndrome (MDS) or acute myeloid leu-kemia (AML), both devastating diseases with poor outcomes, especially for the elderly popula-tion. There is currently no treatment available for patients with CCUS besides supporting agents. Since the somatic mutations can be detected up to 10 years before a diagnosis of MDS, it opens the potential for early intervention. Physical inactivity is associated with multiple solid cancers, and it has been suggested that exercise can prevent for example certain colon- or breast cancers. Studies in mice have shown that exercise can reduce tumor size and incidence of solid cancers, and different mechanisms have been suggested including increased immune cell infiltration, reduced systemic inflamma-tion, and metabolic changes. The mechanisms of disease progression of pre-leukemia and MDS are complex and probably multifactorial, but recent studies suggest that components such as natural killer cells, adipocytes, and inflammatory substances in the bone marrow mi-croenvironment play a crucial role; factors that exercise may modulate. In addition, recent stud-ies have shown that increased bone marrow adipose tissue (BMAT) may create a microenvi-ronment that supports the expansion of leukemic cells and thus may facilitate disease progres-sion, and earlier studies among healthy, younger individuals have shown that exercise can reduce the amount of BMAT significantly. Therefore, the investigators hypothesize that exercise may prevent or delay the progression from pre-leukemia to leukemia by altering the microenvironment in the bone marrow. The purpose with this clinical, pilot trial where patients with the preleukemic condition CCUS or early stage of leukemia (i.e., lower-risk MDS) will undergo an individualized exercise interven-tion, is to investigate: 1. whether an exercise intervention and the trial set-up, are feasible and safe in this cohort, 2. potential mechanisms in leukemogenesis affected by exercise in controlling dis-ease progression, 3. and the effect hereof on quality of life and activities of daily living. The above will inform the decision-making on designing a larger randomized, controlled trial.

This is a phase II pilot study designed to assess the safety and efficacy of danazol for treatment of cytopenias in patients with CPC A/B cirrhosis. Subjects with or without telomere mutations and/or shortened telomeres will be treated with danazol 600 mg per day by mouth for a duration of 24 months. The goal will be to treat a total of 10 patients.

This is a single-arm pilot study of the feasibility and safety of metformin in patients with clonal cytopenia of undetermined significance (CCUS) or lower-risk myelodysplastic neoplasms (LR-MDS).