Acquired Aplastic Anemia

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.

Thalassemia is a common inherited blood disorder, particularly prevalent in Yunnan, China, where many patients face high treatment costs. Current treatments include blood transfusions and hematopoietic stem cell transplantation HSCT, which can cure thalassemia but involve significant risks and complications such as organ damage and graft-versus-host disease GVHD. This research explores a new approach called hypertransplantation, developed by Professor Ai Huishengs team, aiming to provide a safer, more effective, and affordable treatment without the need for pre-treatment or causing GVHD. The study will test hypertransplantation, which uses hematopoietic stem cells from haplotype-compatible healthy donors without requiring pre-treatment such as chemotherapy or radiation. This innovative method relies on immune interactions between donor and recipient to achieve stable donor cell implantation. Animal studies showed promising results with no GVHD or reproductive damage, and this clinical trial plans to enroll 3 to 5 patients aged 7 to 12 years with severe Mediterranean thalassemia who are ineligible or refuse standard HSCT or gene therapy. Participants will receive the hypertransplantation treatment and be closely monitored for donor cell implantation, blood counts, hemoglobin levels, immune function, and potential complications like infections or GVHD. The primary outcome will be the donor cell implantation rate three months after transplantation, with secondary outcomes including gene carrier status after one year. The study involves a single center and a single treatment group, with follow-up assessments to evaluate safety, efficacy, and recovery of endocrine and gastrointestinal functions over time.

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 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.

Researchers are evaluating a new combination of evidence-based interventions EBIs aimed at improving diagnostic safety and efficiency in primary care for patients with anemia and decreased glomerular filtration rate. The study is designed as a stepped wedge cluster randomized control trial to measure how these interventions affect patient safety and healthcare efficiency, while also assessing factors influencing their implementation such as acceptability, cost, and sustainability. The study compares an enhanced diagnostic team approach to usual care. The enhanced approach includes automated detection and tracking of abnormal test results, expanding the primary care team to include clinical pharmacists to guide anemia evaluation, and engaging patients through nurse navigators to increase their activation in the diagnostic process. The study involves several clinic groups that receive the intervention at different times, ranging from 12 to 24 months, with some initial control periods. Participants will have their diagnostic accuracy for causes of low hemoglobin and decreased glomerular filtration rate assessed within six months. Researchers will track time to diagnosis, appropriate test usage, treatment costs, and primary care physicians views on the interventions acceptability and feasibility. The study also monitors how well the diagnostic process steps are followed, the interventions reach among patients, and sustainability in clinics over 2.5 years. Patient activation and clinic-level facilitators and barriers are evaluated through surveys and measures during the study period.

This research aims to assess the effectiveness and safety of a new BFCA conditioning regimen in patients aged 40 to 60 years with severe aplastic anemia undergoing haploidentical hematopoietic stem cell transplantation haplo-HSCT. The study is a prospective, multicenter, single-arm observational trial focused on this specific older patient group. It evaluates important outcomes such as failure-free survival and the incidence of complications associated with the transplant procedure. The BFCA conditioning regimen being studied includes busulfan, fludarabine, cyclophosphamide, and antithymocyte globulin given in a specific schedule before transplantation. The regimen is administered over several days prior to the stem cell transplant to prepare the body. This study observes patients receiving this regimen without comparison groups as it is a single-arm design conducted across multiple hospitals. Participants will be monitored from enrollment until two years after the transplant. Researchers will assess survival rates, blood cell recovery, graft-versus-host disease occurrence, viral reactivation, regimen-related toxicity, and transplant-related mortality. Follow-up evaluations include laboratory tests and clinical assessments at defined intervals up to two years to carefully track treatment effects and safety. The total participation duration extends from before transplant through long-term post-transplant monitoring.

Researchers are evaluating IM-1021, an antibody-drug conjugate, in a Phase 1 study involving participants with advanced B-cell lymphomas and solid tumors. This first-in-human, open-label study aims to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of IM-1021. The study includes a dose escalation phase to find safe and tolerable doses and an expansion phase to further evaluate these doses in specific cancer types. The study has two parts Part A focuses on escalating doses of IM-1021 given intravenously to determine safety and recommended dosing schedules, including the possibility of alternative dosing. Part B involves expanding participant groups to further test safety and early effectiveness of IM-1021 at doses chosen from Part A. Participants receive the study drug intravenously on an intermittent basis throughout these phases. Participants will undergo multiple assessments including monitoring for treatment-related adverse events, pharmacokinetic blood tests, and evaluations of anti-tumor effects from week 6 until disease progression or study discontinuation. Safety and tolerability will be tracked from the first dose until about 37 days after the last dose. The study duration spans from screening, treatment, and follow-up with data collection continuing up to the study end in 2029.

Researchers are studying whether allogeneic hematopoietic stem cell transplantation HSCT can be successfully performed in adults aged 18 to 75 with VEXAS Syndrome, a condition involving severe inflammatory and blood-related problems that are often resistant to standard treatments. This disease causes systemic inflammation and bone marrow failure, leading to serious health issues and increased mortality. The study aims to see if HSCT can reverse the disease symptoms and achieve sustained donor cell engraftment. Participants receive different reduced intensity conditioning regimens depending on their donor match status before undergoing HSCT. Those with an 88 HLA matched donor receive fludarabine and busulfan, while those with a 78 matched or haploidentical donor receive fludarabine, cyclophosphamide, total body irradiation, and busulfan. After transplant, all participants receive drugs to prevent graft-versus-host disease GVHD, including cyclophosphamide, mycophenolate mofetil, and tacrolimus. These treatments are given according to a detailed schedule around the transplant day. Participants undergo extensive screening including physical exams, blood and urine tests, imaging scans, and specialist evaluations. After transplant, they stay in or near the hospital for at least 100 days with weekly visits, followed by study visits at 30, 60, 100, 180, 210, 240, 300, and 360 days post-transplant, then yearly visits for two years and annual phone contacts thereafter. Researchers monitor disease reversal, donor cell engraftment, safety, GVHD incidence, survival, and other outcomes over several years.

Pregnant women with aplastic anemia AA, a rare blood disorder causing bone marrow failure and low blood counts, face serious risks including heavy bleeding, infections, and complications for their babies like preterm birth and restricted growth. This research aims to develop and validate a tool to predict adverse pregnancy outcomes in women with AA, helping guide early clinical decisions and improve health for mothers and infants. The study combines retrospective and prospective data collection across multiple centers to address the current lack of comprehensive data in this area. The study involves observing pregnant women diagnosed with AA either before or during their pregnancy. Researchers will gather baseline information and diagnostic data, then follow participants regularly through questionnaires, phone calls, video consultations, online platforms, and in-person visits. They will record treatments, other health conditions, and pregnancy outcomes, aiming to build a prediction model for adverse outcomes. Participants will be monitored from their first hospital visit during pregnancy until 42 days after delivery. Data collected includes clinical assessments and neonatal Apgar scores shortly after birth. The study will provide detailed information on the health and risks for mothers and babies affected by AA during pregnancy, helping improve care strategies. The total participation duration varies depending on the timing of enrollment and delivery.

Researchers are evaluating a reduced-intensity treatment regimen including cyclophosphamide, pentostatin, and anti-thymocyte globulin before a CD4 T-cell depleted haploidentical hematopoietic cell transplant haploHCT for patients with severe aplastic anemia that is refractory or recurrent. This phase I trial aims to assess the safety and feasibility of this approach, including the ability to prepare the required cell product and reduce risks such as graft versus host disease. Participants receive cyclophosphamide both orally and intravenously, pentostatin intravenously, and anti-thymocyte globulin intravenously before undergoing the CD4 T-cell depleted haploHCT. The study includes procedures like bone marrow aspirate and biopsy, along with blood sample collection at screening and follow-up. The regimen is designed to prepare the patients body for the transplant by making room for healthy cells and modulating the immune response. During the study, participants will be monitored for adverse events, blood cell recovery, infections, graft versus host disease, survival rates, and donor cell engraftment over periods extending up to three years. Assessments include lab tests, bone marrow evaluations, and questionnaires. Researchers will also study immune cell profiles and bone marrow environment changes for up to two years after transplant to better understand treatment effects and long-term outcomes.