Blood Marrow Disorder

This NIH-sponsored study aims to characterize three biomarkers derived from 129Xe gas exchange MRI and understand how they change in response to interventions. The study focuses on markers derived from the interaction of 129Xe with pulmonary capillary red blood cells RBCs, specifically RBC transfer MRI, cardiogenic oscillations in 129Xe-RBC signal amplitude, and the 129Xe-RBC chemical shift. The study population includes healthy volunteers, patients scheduled to undergo transfusion or phlebotomy, patients with dyspnea, interstitial lung disease ILD, idiopathic pulmonary fibrosis IPF, non-specific interstitial pneumonias NSIP, chronic hypersensitivity pneumonitis cHP, sarcoid, chronic thromboembolic pulmonary hypertension CTEPH, and acute pulmonary embolism.

Researchers are evaluating the safety, side effects, best dose, and effectiveness of a combination conditioning treatment for donor stem cell transplantation in patients with high-risk acute myeloid leukemia AML, acute lymphoblastic leukemia ALL, and myelodysplastic syndrome MDS. This phase I trial studies a targeted radioimmunotherapy drug, 225Ac-DOTA-Anti-CD38 daratumumab, combined with chemotherapy drugs fludarabine and melphalan, and total marrow and lymphoid irradiation TMLI. Daratumumab targets CD38 on cancer and immune cells, potentially helping the immune system to attack cancer cells. Participants receive daratumumab intravenously followed by indium In 111-DOTA-daratumumab and actinium Ac 225-DOTA-daratumumab on day -15. Total marrow and lymphoid irradiation is given twice daily from days -8 to -5, fludarabine is given intravenously on days -4 to -2, and melphalan on day -2. On day 0, participants undergo hematopoietic cell transplantation HCT. Graft-versus-host disease GVHD prevention with sirolimus and tacrolimus starts on day -1. Throughout the study, participants undergo various scans, biopsies, and blood tests to monitor treatment effects and safety. Participants are monitored closely after transplantation with visits twice weekly for the first 100 days, then twice monthly up to six months, and monthly thereafter until immunosuppressive therapy is stopped without GVHD signs. Yearly follow-up continues for two years. Assessments include adverse events, survival rates, relapse, graft-versus-host disease incidence, infections, blood cell recovery, organ function, and drug distribution. The study aims to determine the maximum tolerated dose and evaluate overall safety and effectiveness of the treatment combination.

Myelodysplastic syndrome MDS, also called bone marrow failure, is a condition where the bone marrow produces fewer blood cells due to abnormal cell development. This study evaluates a new approach to treating MDS by using an alternating low-dose schedule of two chemotherapy drugs, 5-azacitidine 5AZA and decitabine DEC, to overcome resistance that can occur when either drug is given alone. The study is an early phase 1 pilot trial focusing on this combined treatment for myeloid malignancies including MDS and related disorders. Participants will receive 5AZA and DEC in a weekly alternating schedule 5AZA at 50 mgm on Day 1 and DEC at 5 mgm on Day 4 each week. The first 8 weeks serve as an induction phase, followed by a long-term treatment phase starting from week 9. Treatment will continue for at least 24 weeks unless the disease progresses. Those who respond to therapy may continue treatment until relapse or disease progression not responsive to dose escalation. During the trial, participants will be regularly monitored for response using criteria including complete or partial response and hematologic improvement. Safety will be assessed by tracking adverse events. The study also explores biological markers related to treatment response. Participants may remain in the study for up to 6 months after treatment to assess overall response, with some outcomes followed for up to 2 years. Careful evaluation of blood counts, disease status, and side effects will guide treatment continuation and study assessments.

The GENESIS clinical study aims to map HLA genetic variation in the Greek population and evaluate possible correlations with selected underlying diseases. It is a multicenter, prospective, non-interventional clinical study targeting 12,000 subjects over an anticipated duration of 36 months, with the goal of creating a pilot HLA map for medical research and possible clinical applications. Each subject will complete one visit at a participating site and provide demographic information, including date of birth, gender, race, ancestry, height, and weight, as well as information about smoking or vaping, alcohol consumption, arterial blood pressure, diagnosed diseases, and current treatments. Recent clinical laboratory results from up to 12 months before sample collection may also be collected when available, including blood count, metabolic, liver enzyme, and biochemical parameters. Two buccal swabs will be collected from each subject for DNA extraction and HLA genotyping analysis. Selected DNA samples will also undergo low-pass whole genome sequencing to further investigate associations between the HLA region and autoimmune diseases. After the analysis is completed, an individualized ancestry report will be securely available to study subjects if they elect to access it.

Researchers are evaluating whether a high-fiber plant-based diet HFPBD can improve quality of life for people with clonal hematopoiesis CH. This diet mainly includes plant foods such as fruits, vegetables, nuts, beans, and whole grains. The study measures quality of life using questionnaires and surveys filled out by participants. Participants will be randomly assigned to one of two groups. One group will receive high-fiber plant-based meals delivered to their homes for 12 weeks and have regular phone or video calls with a dietitian every 2 weeks for the first 12 weeks, every 4 weeks from weeks 13 to 24, and every 8 weeks from weeks 25 to 52. The other group will receive usual care with phone calls every 4 weeks for the first 12 weeks and dietitian calls at weeks 13 and 53. During the study, participants will complete quality of life surveys using the EORTC QLQ C30 questionnaire. Assessments include phone or video visits with dietitians, dietary intake monitoring, and adherence to the assigned diet. The main outcome is improvement in quality of life within the first 12 weeks. The total study duration for participants is 52 weeks, with ongoing monitoring and support throughout this time.

This research is an international multicenter retrospective observational study focusing on patients with Essential Thrombocythemia ET who are positive for the JAK2V617F mutation. It aims to understand the progression from ET to Polycythemia Vera PV and compare clinical outcomes between those who progressed and those who did not, using criteria defined by the International consensus classification of myeloid neoplasms and acute leukemias from 2022. The study consists of two parts a nested case-control study and a comparative retrospective cohort study. The first part compares ET patients who progressed to PV with matched ET patients who did not progress, based on diagnosis year, age at diagnosis, and disease duration. The second part compares patients diagnosed with de novo PV without prior ET to the ET-to-PV cases, again matched by diagnosis year, age, and disease duration. All patients included in the study were diagnosed by the end of 2020 to allow at least 5 years of follow-up. Participants will have their medical histories reviewed retrospectively to analyze clinical data up to the baseline and at the time of progression. Researchers will assess phenotypic changes and clinical outcomes between groups, with no new treatments or interventions administered. The study is observational and aims to gather information from existing records to better understand disease evolution over time.

This research aims to monitor participants who previously received TSC-100 or TSC-101 T-cell receptor engineered T-cell TCR-T therapies in the TSCAN-001 study. The goal is to assess the long-term safety and efficacy of these investigational treatments over a 15-year period following their administration, focusing on people treated for conditions such as AML, ALL, and MDS. Participants will not receive any new study drug during this long-term follow-up study. Instead, they will be observed after completing the initial TSCAN-001 trial, while continuing any other cancer treatments as necessary. Monitoring will include a period lasting 15 years from the date of their original TCR-T cell therapy. During the study, participants will be evaluated for treatment-emergent adverse events to assess safety and tolerability. Researchers will also monitor overall survival, relapse-free survival, and progression-free survival over the 15 years. This observational study involves regular assessments to track long-term outcomes without administering additional investigational treatments.

This research follows patients with Hemoglobinopathy and Sickle Cell Disease who previously received BEAM-101, a gene-edited cell treatment, in an earlier study. The trial is a long-term observational follow-up to monitor safety and health outcomes over an extended period. It aims to gather important information about the long-term effects and risks after receiving BEAM-101 treatment. Participants in this study have received a single dose of BEAM-101 by intravenous infusion after a conditioning treatment with busulfan. This follow-up study will track their health for 13 years, adding up to 15 years from the initial treatment. Study visits will happen annually for the first 5 years, then every 3 years until year 11, with a final visit at year 15. Additionally, virtual or phone check-ins will occur every 6 months for the first 5 years, then annually thereafter. During the study, participants will undergo regular safety and efficacy assessments to monitor their health, including how well they remain free of severe sickle cell crises and their blood hemoglobin levels. Researchers will review long-term safety data and mortality over the 13 years. The study includes blood tests and other evaluations at scheduled visits and check-ins. Participation will last up to 15 years, with ongoing monitoring to understand the lasting impact of BEAM-101 treatment.

Researchers are investigating how cancer affects the health and well-being of both patients and their families throughout the cancer journey. This study focuses on family health, needs, perceived support, quality of life, self-efficacy, depression, stress, and resilience among patients with breast, prostate, colorectal cancer, or lymphoma and their caregivers. The goal is to identify families who are particularly burdened or vulnerable and understand the factors contributing to their vulnerability. Participants include 240 patients and their appointed adult caregivers recruited from six Danish hospital departments. The study uses a mixed-methods approach, combining a longitudinal survey and family interviews. Patients and caregivers complete questionnaires at baseline, 3, 6, 12, and 18 months, assessing various aspects such as family health, support, quality of life, self-efficacy, depression, distress, and resilience. A subset of families participates in interviews at 3 and 12 months to explore their experiences and needs more deeply. During the study, participants will fill out validated questionnaires including the Family Health Scale, ICE Family Perceived Support Questionnaires, EQ-5D-5L, General Self-Efficacy Scale, Patient Health Questionnaire-9, Distress Thermometer, and Connor-Davidson Resilience Scale. The interviews will be conducted in person, at home, or online, lasting about one hour. Researchers will analyze the data to better understand family dynamics and identify vulnerable families, monitoring family health outcomes over a one-year period.

Researchers are studying the use of unlicensed cryopreserved cord blood units CBUs for transplantation in both children and adults with blood cancers and other related disorders. This observational study involves patients with hematologic malignancies and various inherited and acquired disorders affecting the blood and immune system. The main goal is to monitor how well neutrophil recovery occurs after transplantation using these unlicensed CBUs in multiple institutions. Participants receive unlicensed cryopreserved CBUs as part of their transplant treatment. The study includes patients of any age receiving these CBUs for approved indications. The protocol focuses on the access and distribution of these unlicensed units rather than a specific treatment intervention. The study gathers data from recipients who receive these CBUs, tracking outcomes after transplantation. Participants are monitored for neutrophil recovery at 60 and 100 days after transplant, defined by a neutrophil count of at least 500mm3. Researchers also collect information on infection transmission, infusion reactions, survival rates at one year, and incidence of acute and chronic graft versus host disease. Platelet recovery is also evaluated. Safety and efficacy outcomes are followed over time to better understand the effects of unlicensed CBUs in this patient population.