Hematopoietic Stem Cell Transplantation

Background: People who have had an allogeneic hematopoietic stem cell transplant (HCT) have bone marrow or an immune system that is damaged. They get stem cells from a donor who is a relative. Researchers want to study stem cell donors and recipients to learn about the long-term effects of HCT. They want to learn how the stem cells change and how to improve their ability to fight cancer. Objective: To provide long-term follow-up care for people who underwent or will undergo HCT. To collect data, blood, and tissue samples to learn about late complications after HCT. Eligibility: Adults age 18 and older who will undergo HCT or underwent HCT and are surviving one year or more from the date of HCT. The stem cell donors for these recipients are also needed. Design: Recipients will have 1 visit each year. They will have a physical exam. They will answer questions about their medical history and health. They will receive screening and surveillance testing. They will complete brief questionnaires. Recipients will have blood tests. They may have tissue biopsies or specimens (such as tissue in their cheek or skin or bone marrow biopsy). Recipients will give their current address and phone number, and the same data for one or two other people, who can get in contact with them. After the first visit at the clinic, some recipients may see a doctor close to home to get the necessary information and send it to NIH. Donors will come to the clinic for 1 visit. They will answer questions about their medical history. Blood samples will be taken.

Cell therapy (CT), including hematopoietic stem cell transplantation (HSCT) and advanced CAR T-cell therapies, is used for the treatment of oncohematological and other diseases. HSCT is associated with treatment-related toxicities, including fatigue, muscle weakness, and reduced functional capacity due to intensive conditioning chemotherapy, immunosuppressive treatments, corticosteroids, and complications such as infections or graft-versus-host disease. Emotional symptoms, including anxiety, depression, fear, and frustration, also affect patients' recovery and ability to regain functional independence. Evidence indicates that exercise interventions improve emotional well-being, fatigue, quality of life, physical function, cardiovascular fitness, and muscle mass in patients with hematological malignancies and HSCT recipients. Virtual reality (VR) has emerged as an innovative tool in rehabilitation, supporting patient motivation, exercise guidance, and monitoring. Immersive virtual reality (IVR), through head-mounted displays and multisensory environments, enhances the sense of presence and engagement. Studies suggest that IVR-based exercise programs are feasible, improving functional abilities, quality of life, satisfaction, and adherence. Since 2017, a Therapeutic Exercise program for patients admitted for HSCT has been implemented at Álvaro Cunqueiro Hospital (Vigo) through collaboration between the Physiotherapy Unit and the Hematology Department. Before admission, patients undergo a physical assessment, receive an individualized exercise plan, education, and a therapeutic exercise guide. Based on clinical experience, the team hypothesizes that integrating IVR into therapeutic exercise may improve motivation, adherence, and emotional well-being during hospitalization.

This study aims to compare individualized anti-thymocyte globulin (ATG) dosing versus conventional fixed-dose regimens in unrelated donor peripheral blood stem cell transplantation (URD-PBSCT). This study notes that URD-HSCT is a key treatment for malignant hematologic diseases and severe bone marrow failure, with rapid expansion in China. However, this study identifies post-transplant CMV infection as a major challenge, adversely affecting survival and quality of life. This study finds that CMV infection compromises immunity and causes multi-organ complications. Given the high costs, long treatment cycles, and limited efficacy of current interventions, this study considers optimizing CMV prevention to be of greater value than expanding treatment options. This study asserts that effective prevention can reduce infection rates and improve overall survival (OS) and long-term prognosis. This study recognizes that ATG is widely used in URD-HSCT to prevent graft-versus-host disease (GVHD), but its dosage is significantly linked to CMV risk. This study indicates that inadequate ATG exposure increases GVHD risk, while excessive exposure raises viral reactivation (e.g., CMV, EBV) and may cause relapse. This study thus identifies balancing GVHD prevention and infection control as a key clinical goal. This study cites Remberger et al. (2004), who compared ATG doses (4-10 mg/kg) in 162 URD-HSCT patients, finding lower doses increased acute GVHD (aGVHD) and 10 mg/kg raised infection-related mortality, suggesting 6-8 mg/kg as a balanced range. This study also references Bacigalupo et al. (2001), who found no survival differences across doses but noted higher doses reduced severe aGVHD at the cost of increased infection. Therefore, this study concludes that optimal ATG dosing requires balancing GVHD, infection, and relapse. This study acknowledges that ATG pharmacokinetics (PK) are complex, influenced by dose, body weight, and absolute lymphocyte count (ALC). This study points out that even with fixed dosing, internal exposure (active ATG-AUC) varies greatly among individuals, indicating that fixed dosing is suboptimal and individualized strategies are needed. This study notes that Admiraal et al. developed an ALC-based individualized ATG model, improving immune reconstitution, reducing viral infections, and enhancing OS. However, this study observes that this model was designed for non-myeloablative conditioning and is not applicable to myeloablative conditioning (MAC), which is standard in China. To address this, this study states that our team initiated ATG PK studies in 2019. This study explains that under MAC, ALC is nearly eliminated, making traditional models unsuitable. By monitoring active ATG-AUC in 106 haploidentical HSCT (haplo-HSCT) patients and using machine learning, this study identified an optimal exposure window of 100-148.5 UE·day/mL. This study found that patients within this window had lower CMV/EBV reactivation without increased GVHD. This study developed a protocol adjusting doses on days -3 and -2 based on ATG concentrations measured on days -5 and -4. This study confirmed through a prospective single-arm study in haplo-HSCT that this regimen reduces CMV/EBV infection and improves disease-free survival (DFS) and OS while maintaining GVHD control. Given the consistency between URD-PBSCT and haplo-PBSCT in conditioning, GVHD prophylaxis, and CMV prevention-and that CMV infection rates in Chinese URD-PBSCT patients reach 65%-70%-this study extends the individualized ATG protocol to URD-PBSCT to validate its universality across donor sources. In summary, building on prior haploidentical transplant research, this study applies individualized ATG dosing to URD-PBSCT. This study aims to precisely regulate ATG exposure to reduce CMV infection while maintaining GVHD prophylaxis. This study seeks to improve patient survival and outcomes, laying the foundation for a population PK model and advancing HSCT toward precision medicine.

Background: Blood cancers (such as leukemias or lymphomas) often do not respond to standard treatments. A transplant of blood stem cells from a healthy donor can help people with these cancers. Sometimes these transplants cause serious side effects, including a common immunologic problem called graft-versus-host disease. A drug called cyclophosphamide given early after the transplant (post-transplantation cyclophosphamide, PTCy) can reduce these complications. But sometimes this drug has its own negative effects. Furthermore, studies in mice suggest that an intermediate, rather than very high, dose of this drug may best protect against graft-versus-host disease. Objective: To find out if a lower dose of PTCy is more helpful for people who undergo blood stem cell transplants. Eligibility: People aged 18 and older who have a blood cancer and are eligible for a transplant of blood stem cells from another person. Healthy donors are also needed but must be related to the individual needing the transplant. Design: Participants will undergo screening. Transplant recipients will have imaging scans and tests of their heart and lung function. They will be assessed for the status of their cancer, including bone marrow taken from their pelvis and possibly also scans and/or fluid drawn from the spine depending on the disease type. Donors will be screened for general health. They will give several tubes of blood. They will give an oral swab and saliva and stool samples for research. Recipients will be in the hospital at least 4 to 6 weeks. They will have a temporary catheter inserted into a vein in the chest or neck. Medications will be given and blood will be drawn through the catheter. The transplanted stem cells will be given through the catheter. Participants will receive medications both before and after the transplant. Participants will return to the clinic at least once a week for 3 months after leaving the hospital. Follow-up visits will continue periodically for 5 years.

Background: For adolescent and young adults (AYAs) with certain life-threatening illnesses, hematopoietic stem cell transplant (HSCT) provides the best chance for cure and survival. HSCT is a life-saving therapy, but this treatment also comes with significant risks. Given these risks, it is imperative that patients and their families have the opportunity to share their values, priorities, and goals through advance care planning (ACP) to ensure that the care they receive through the transplant process remains patient-centered. Despite the benefits of ACP discussions, many barriers, including provider discomfort, may prevent these conversations with AYAs. Objective: To see if AYAs who undergo HSCT and their caregivers benefit from discussing ACP topics. Eligibility: People aged 18 to 39 years enrolled in an NIH study with a planned HSCT. One caregiver aged 18 years or older will also be invited to participate. Design: Participants will complete a 20-minute questionnaire. They will be asked about the priorities they have related to their care and their prior experiences with ACP. Participants will have 3 conversations with a study team member over 4 to 9 weeks. Each talk will last 45 to 60 minutes. First, participants will talk about their upcoming transplant and their expectations. They will also be asked about their fears and worries and will discuss what is most important to them in terms of support, comfort, their values, and their goals. Next, they will learn about Voicing My CHOiCES . This guide gives people a place to say what kind of care they want to receive during their treatment and includes a place to document how they would want to be cared for if they can no longer make decisions on their own. Participants will be guided as they fill in a few pages from this guide. The third conversation will review the first talks. Participants may ask questions and review any topic. They will complete follow-up questionnaires and be provided with a summary of their care priorities revealed in the discussions. They will be asked about their experience participating in this study, and their comfort with ACP discussions. They will be asked what they think of the meaningfulness, timing, and cultural sensitivity of these talks....

The purpose of this study is to evaluate the efficacy and safety of a personalized strategy for discontinuing Letermovir (a drug used to prevent Cytomegalovirus \[CMV\] infection) based on the recovery of the patient's own immune system. Cytomegalovirus (CMV) is a common and serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Currently, Letermovir is typically given as a standard prevention for about 100 days post-transplant. However, some patients may recover their CMV-specific immunity earlier, while others may need longer protection. In this study, researchers will use a dynamic monitoring technology (QuantiFERON-CMV) to detect the level of CMV-specific T-cells in patients. Participants will be randomly assigned to either the experimental group or the control group: Experimental Group: Letermovir discontinuation will be guided by T-cell recovery. If the test shows that the patient's CMV-specific T-cells have recovered, Letermovir may be stopped earlier than the standard 100 days. Control Group: Patients will receive the standard Letermovir prophylaxis for approximately 100 days, regardless of T-cell status. The study aims to determine if this immune-guided strategy can effectively prevent CMV infection while potentially reducing the duration of medication and associated costs, without increasing the risk of CMV disease.

This is a single-center, prospective, randomized, dose-escalation Phase II clinical study. A total of 46 patients with newly diagnosed depression following allogeneic hematopoietic stem cell transplantation (allo-HSCT) will be enrolled. Participants will be randomly assigned to receive different doses of Xiaochaihu Granules in addition to standard post-transplant care for 100 days. The primary objective is to evaluate the efficacy of Xiaochaihu Granules in improving depressive symptoms. Secondary objectives include assessment of safety and clinical outcomes such as event-free survival (EFS), graft-versus-host disease (GVHD), infections, and other transplantation-related complications.

Background: Allogeneic hematopoietic stem cell transplant involves taking blood stem cells from a donor and giving them to a recipient. The transplants are used to treat certain diseases and cancers. Researchers want to see if the transplant can treat VEXAS Syndrome. Objective: To see if stem cell transplants can be successfully performed in people with VEXAS and even improve the disease. Eligibility: People ages 18-75 who have VEXAS Syndrome that has caused significant health problems and standard treatment either has not worked or is not available. Design: Participants will be screened with: Physical exam Medical review Blood and urine tests Heart and lung function tests Bone marrow biopsy Participants will have a chest x-ray. They will have an imaging scan of the head, chest, abdomen, pelvis, and sinus. They will have a bone density scan. They will have a dental exam and eye exam. They will meet with specialists. They will repeat some screening tests. Participants will be admitted to the NIH hospital. They have a central venous catheter put into a vein in the chest or neck. They will receive drugs to prepare their bone marrow for the transplant. They may have total body irradiation. They will receive the donor stem cells through the catheter. They will get other drugs to prevent complications and infections. After discharge, they must stay in the DC area for 3 months for weekly study visits. Participants will have study visits 30, 60, 100, 180, 210, 240, 300, and 360 days later. After that, they will have yearly visits for 2 years and then be contacted yearly by phone....

This is a feasibility study to implement a Survivorship Care (SC) Plan for patients with hematologic cancer undergoing hematopoietic stem cell transplantation (HSCT). The study evaluates if the intervention is feasible within the Italian national health system, focusing on retention rates, quality of life, unmet needs and caregiver burden

The main purpose of this study is to determine if a tailored peer support intervention (STEPP-Care) is feasible among caregivers of patients undergoing hematopoietic stem cell transplantation (HSCT).

The goal of this prospective, cohort study is to learn about smell, taste and trigeminal dysfunction in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). The research team hypothesizes that treatment with allo-HSCT will induce: * Distortion of taste and smell and trigeminal functions like cooling, tingling, and burning sensations. * Reduced saliva production leading to oral dryness and dental caries. * Changes in the connectivity of the taste-, smell- and pain-cortical brain regions.

This study aims to see if a single intravenous infusion of a cell therapy called Amimestrocel injection can help prevent severe mouth sores (oral mucositis) in patients receiving a stem cell transplant. Patients getting a stem cell transplant often receive strong chemotherapy (with radiation and/or a drug called melphalan) that can cause painful mouth and gut sores, making eating difficult and increasing infection risk. Amimestrocel injection is made from human umbilical cord cells that may help reduce inflammation and promote healing. About 22 adult patients scheduled for this type of transplant at one hospital in China will receive the infusion 1-2 days before their stem cell transplant. Researchers will closely check for mouth sores, pain, and side effects for the first 28 days, and continue safety monitoring for 100 days. The main goal is to see if the treatment lowers the rate of severe (Grade 3-4) mouth sores. The study will also track pain levels, need for pain medication, diarrhea, time for blood counts to recover, and overall safety.

Infections are a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplant (HSCT). The purpose of this study is to evaluate if metagenomic next-generation sequencing (mNGS) can detect microbial signatures in people undergoing HSCT, and if microbial identification can be correlated with clinical features of infection (e.g., fever). Participants undergoing HSCT as part of other studies at the NIH Clinical Center (CC) will provide blood before the transplant and through 6 months after. Total nucleic acid will be extracted from plasma and subjected to mNGS. The primary objective of this study is to investigate if by using plasma and an mNGS approach, we can detect bacterial, fungal, protozoan, or viral DNA/RNA over time, in immunocompromised patients undergoing transplantation. Secondary objectives are to: (1) To correlate microbial identification with episodes of fever or clinical suspicion of infection; and to (2) correlate change in microbial signatures in patients with suspected immune reconstitution inflammatory syndrome. The study is conducted at the NIH Clinical Center. Participants, aged 3 years and older, on other research studies at the NIH CC who are undergoing HSCT are invited to take part of this study. Expected participation is up to six months.

Allogeneic haematopoietic stem cell transplantation (AHSCT) is a therapeutic resource for many haemopathies. The number of HSCTs has risen sharply in recent years due to the use of attenuated conditioning, which has increased the risk of non-haematological complications. Pulmonary pathologies are a frequent cause of complications following HSCA, both infectious and non-infectious(1,3,4). Among these, late non-infectious pulmonary complications (LNIPC), all taken together, occur in 25% of post-HSCA cases(1). These NIPCs, the most common of which is bronchiolitis obliterans, significantly alter the prognosis(4,5). The pathophysiology of CPTNI is poorly understood, but it seems that the occurrence of a viral respiratory infection (pre- or post-ACSH) may be a potential trigger for the onset of CPTNI(1). These viral infections can become "chronic", given that viral clearance is impaired by the underlying immunodepression, and can thus cause chronic inflammation leading to the fibrosing and irreversible process of obliterative bronchiolitis(6). Given the prognostic importance of this type of CPTNI, it seems essential to gain a better understanding of its pathophysiology, which may involve a number of mechanisms: cellular expression of the graft and its evolution, disruption of the host response (innate immunity) following viral infection, influence of the microbiome and alteration of epithelial repair(1,3,5). Interest in the digestive and respiratory microbiome has been growing in recent years(7-9). The literature is gradually being enriched with data on the links between infection, the microbiome and chronic respiratory pathology and, in the post-HSCA context, a potential link between the enteric microbiome and Chronic Graft Versus Host Disease (cGVHD). A pilot study comparing respiratory microbiomes using sequencing and metatranscriptomic analysis on 20 respiratory samples (nasopharyngeal swab and bronchoalveolar lavage pairs) taken under the conditions of the proposed study showed that the technique was highly feasible and highly sensitive. The aim of this study is therefore to use meta-genomics to investigate the respiratory virome/microbiome in a population of patients who have undergone HSCA: eukaryotic and prokaryotic viruses, bacterial expression and the expression (meta-transcriptomics) of graft-derived cell lines and their possible association with the occurrence of post-HSCA respiratory complications (infectious and non-infectious). No study has assessed the link between the composition of the respiratory virome/microbiome and the occurrence of respiratory events (infectious and CPTNI post ACSH), but also more broadly the link with the composition of the microbiome in the broad sense (respiratory virome, respiratory and digestive microbiota). The aim of this study is to establish a respiratory viral and bacterial map as a possible biomarker of the occurrence of respiratory events (infectious and CPTNI), thus enabling more personalised monitoring of patients at risk of CPTNI and management of immunosuppressive treatment of patients at risk of an infectious episode, with risk assessment based on the composition of the respiratory virome. The interest of this study is that it is multidisciplinary and transdisciplinary, studying the respiratory pathologies and infections of haematology patients and combining clinical and fundamental research, with expected spin-offs for direct patient care (personalised monitoring and management of immunosuppressive treatments).

The main objectives of this study were :(1) to comprehensively and systematically evaluate the nutritional status of patients after hematopoietic stem cell transplantation. (2) to explore the effect of nutritional factors on the prognosis of patients treated by hematopoietic stem cell transplantation.

This study was a prospective, multicenter, randomized controlled clinical study planned to recruit 266 hematological patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were randomly divided into two groups according to gender, type of transplantation, and type of primary disease. The control group was treated conventionally, and the experimental group increased moxibustion of Zhongji, Guanyuan and Qihai for 30 min qd starting on the first day after HSCT was performed until the 14th day after transplantation. Urine routine tests were performed at the time of admission, +1d, and +14d, and urine BK virus, JC virus, and adenovirus were tested at four time points, namely, +1d, +14 days, onset of hematuria symptoms, and remission of HC, respectively; routine urine tests were performed once every 7 days for all patients within 100days. For patients with Hemorrhagic cystitis (HC), daily severity grading, pain scoring, cystitis symptom scoring, use of antispasmodic and analgesic medications, and major TCM evidence were recorded with the aim of evaluating the efficacy of moxibustion in the prevention of HC in this patient population.

The overall goal of this study is to assess the efficacy of the care.coach Avatar™ in improving anxiety and quality of life for patients undergoing outpatient transplant. After care.coach Avatar™ content and scheduling ("digital intervention" or "program") has been optimized for outpatient allogeneic hematopoietic stem cell transplantation (HCT), a randomized controlled trial (RCT) will be conducted of the digital versus usual supportive care program for outpatient HCT recipients. Potential improvements in anxiety and quality of life will be evaluated, with the intent of increasing comfortability with outpatient transplant and expanding the population of eligible patients willing to receive their transplants in an outpatient setting.

This study employs a prospective, randomized, double-blind, placebo-controlled design. It aims to compare the efficacy of etamsylate versus placebo in preventing bleeding complications in patients with thrombocytopenia following hematopoietic stem cell transplantation.

To develop and measure the effects of a culturally sensitive yoga program for inpatients

AMBU-VAX is a prospective, single-center observational study designed to develop and implement an organizational model for delivering recommended vaccinations within a hospital setting. The study targets adult and elderly patients with chronic diseases or immunocompromising conditions who are eligible for vaccination according to national immunization guidelines. Vaccination is actively proposed during outpatient visits, hospital admissions, or at discharge and, when accepted, administered within the hospital or coordinated with local public health vaccination services. The study aims to evaluate the feasibility, uptake, and completion of hospital-based vaccination pathways and to support integration between hospital and territorial prevention services for vulnerable populations.

The purpose of this pilot study is to investigate the safety and preliminarily assess efficacy of early intervention with zoledronate in high risk pediatric hematopoietic stem cell transplantation (HSCT) patients to prevent the development of bone disease and fractures and reduce potential pain and suffering.

The investigators hypothesize that graft rejection after hematopoietic stem cell transplant (HSCT) is primarily driven by interferon gamma, and prophylactic interferon gamma inhibition in high-risk patients will prevent graft rejection. Additionally, knowledge of emapalumab PK/PD and in vitro mechanistic effects of emapalumab in this novel setting will guide optimization of dosing regimens and treatment approaches in future studies.

This is a prospective, multicenter observational study for recipients of hematopoietic stem cell transplantation. Patients who underwent hematopoietic stem cell transplantation at the participating centers will be entrolled in the study. The clinical characteristics, laboratory profiles, management measures, and clinical outcomes such as post-transplant cardiovascular events will be prospectively collected.

This is a feasibility study of a Work Support (WorkS) intervention designed to ameliorate employment challenges for people preparing to return to work after allogeneic stem cell transplantation. The aim of this study is to evaluate "proof of concept" by: 1. examining the feasibility and acceptability of the WorkS intervention and the study procedures, and 2. exploring the preliminary effects of WorkS for improving patient-reported return-to-work self-efficacy, work status, quality of life, and financial toxicity.

As part of postremission consolidative therapy, the decision to proceed with hematopoietic stem cell transplantation is a recommendable regimen in ALL therapy. However, The recurrence rate is high after transplantation. Minimal Residual Disease (MRD) is an important factor affecting the effect of HSCT. The hematologic recurrence rate of MRD-positive patients with adult ALL is high. MRD- is associated with better prognosis. Therefore, maintaining MRD- after transplantation is necessary for long-term survival. The purpose of this study is to explore the efficacy and safety of Inotuzumab Ozogamicin in the treatment of minimal residual disease recurrence after HSCT of ALL patients.