Graft-Versus-Host Disease (GVHD)

This is a longitudinal natural history study to evaluate and study the immunologic changes to the ocular surface in cancer patients. Two groups of subjects will be recruited for the study: 1) Pre-bone marrow transplant cancer patients. They will be evaluated every 3 months for 2 years.2) Normal control patients. They will be evaluated every 6 months for the duration of the study. During each study visit, in addition to standard of care exams, certain biological specimens ( ocular surface wash, mucocellular material, corneal filaments, or impression cytology of conjunctiva, blood, or serum) will be collected.

Imaging will consist of administration of maximum 50 µg IV PentixaFor, labelled with 150 ±15 MBq of 68Ga, as bolus injection 60 ±15 minutes prior PET/CT

The most clinically meaningful way to discover new targets of T cells in autoimmune diseases is to study the tissues of patients with active autoimmune disease mediated organ inflammation. These tissues contain both cytotoxic and helper T cells that are driving their disease, and these T cells are being guided by TCRs that recognize tissue-specific targets. By collecting tissue when a patient has active inflammation, it is possible to determine which T cells are activated and undergoing clonal expansion in the patient's diseased organ. TScan has developed a genome-wide, high-throughput technology to determine the natural, physiological target of any TCR (Kula, 2019). The goal of this study is to isolate T cells from inflamed tissues and matched blood samples and/or matched normal tissues (for patients with inflammatory bowel diseases). T cell clones that are expanded in diseased tissues relative to blood or normal tissues will be selected and the targets of their TCRs will be defined using TScan's genome-wide, high-throughput target ID technology. The goal of this study is to discover a collection of peptide targets, along with their associated TCRs to be developed as new tolerogenic therapies for patients with autoimmune diseases.

The goal of this clinical study is to evaluate the safety and efficacy of GT729 universal cell injection in the treatment of refractory or relapsed chronic graft-versus-host disease (cGVHD).

A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-CD19 CAR NK cells (KN5501) in patients with relapsed/refractory B-cell related autoimmune diseases.15 patients are planned to be enrolled in the dose-escalation trial (6×10\^9 cells, 9×10\^9 cells). The primary objective of the study is to evaluation of the safety and feasibility of KN5501 for the treatment of relapsed/refractory B-cell related autoimmune diseases. The secondary objective is to evaluate the effectiveness of KN5501 for the treatment of relapsed/refractory B-cell related autoimmune diseases. The exploratory objective is to evaluate expansion, persistence and ability to deplete CD19 positive B cells of KN5501 in patients with relapsed/refractory B-cell related autoimmune diseases.

Thalassemia (thalassemia, referred to as "ground poverty"), the incidence rate of birth defects in the third place, is a major public health problem worldwide. Yunnan is located in the subtropical region, adjacent to Southeast Asia, and is one of the high incidence areas of hemoglobinopathy in China. Its carrier rates of abnormal hemoglobinopathy and thalassemia are high, with obvious uniqueness and diversity. The detection rate of thalassemia carriers in the province is about 10.71%, while Dehong Prefecture, Xishuangbanna Prefecture, and Wenshan Prefecture are even higher at over 20.1%. Based on this, it is estimated that the number of patients with moderate to severe thalassemia in Yunnan is about 97000. The common treatments for patients with thalassemia include blood transfusion and hematopoietic stem cell transplantation. The cost of hematopoietic stem cell transplantation for each patient with thalassemia is approximately 250000 to 300000 yuan. The economic burden of blood transfusion treatment for children with thalassemia is greater and increases with age. A 1-year-old child with thalassemia requires approximately 20000 milliliters of blood per year, with an annual treatment cost of about 100000 yuan; To ensure the patient's survival at the age of 40, a total of approximately 4 million RMB is required. Such high treatment costs are difficult for ordinary families to afford. Hematopoietic stem cell transplantation (HSCT) is the only definitive treatment for thalassemia, and the development of clinical and basic research on gene therapy has led to a success rate of around 70%. HSCT and gene therapy both require pre-treatment with radiation, chemotherapy, and immunosuppression. The complications of HSCT include multi organ dysfunction caused by pre-treatment drugs, poor stem cell implantation, acute and chronic GVHD, some special complications (such as capillary leak syndrome (CLS), sinusoidal occlusion syndrome (SOS), interstitial pneumonia, thrombotic microvascular disease (TMA), post transplant lymphoproliferative disease (PTLD), hemorrhagic cystitis, central nervous system complications, etc.), which seriously affect the prognosis and quality of life of patients and cause varying degrees of damage to the reproductive development of children. HSCT supplier screening is also an urgent issue that needs to be addressed. The 5-year survival rate of MSD donor transplantation is 95-97%, but the sibling matching rate is 25%; The 5-year survival rate of MUD plants is 90-95%. Our province is a multi-ethnic mixed population, and the HLA polymorphism is significantly different from other Han ethnic populations. The success rate of non blood related matching is very low; The 5-year survival rate of haplotype donor transplantation is 80-87%, and the incidence of complications is significantly increased. Long term blood transfusion, high bone marrow load hematopoiesis, and irregular iron removal treatment are common among patients with thalassemia in China. The incidence of liver iron abnormalities is 89%, and the incidence increases with age. Long term anemia leading to heart damage, liver iron deposition, and other factors significantly reduces the success rate and long-term productivity of HSCT in critically ill thalassemia patients aged ≥ 7 years compared to patients aged\<7 years, and most patients over 19 years old miss the opportunity for HSCT. Our province has long been in a backward state of economic and social development. Due to non-standard treatment of thalassemia and a shortage of MUD donors, there are many severe thalassemia patients who do not have the conditions for transplantation. Therefore, finding safer, more effective, and low-cost treatment strategies for severe thalassemia patients without transplantation conditions is a key challenge for the prevention and treatment of thalassemia in our province and even in the whole country and the world. As is well known, Professor Ai Huisheng's team was the first to carry out non myeloablative transplantation (NST) in Asia and China in the late 1990s, and led the Chinese Non myeloablative Transplantation Collaboration Group. Afterwards, in 2011, they independently conducted micro transplantation and organized and led the International Micro Transplantation Interest Research Group internationally. Micro transplantation is simple, effective, and very safe, with almost no GVHD; Micro transplantation has received widespread support and replication applications both domestically and internationally. On this basis, Professor Ai's team has gone through more than ten years of research and exploration, and has innovatively proposed and developed new theories and models for super transplantation. Hypertransplantation does not require any pre-treatment of the recipient, nor does it use any cytotoxic drugs, radiotherapy, chemotherapy, or immunosuppressants. Through mutual immune reactions between the donor and recipient, a completely stable donor implantation (FDC) is ultimately formed. The results of animal experiments showed that even without any GVHD prevention, successful transplant recipients did not develop GVHD. At present, Professor Ai's team has conducted pioneering research on super transplantation, including animal experiments using C57BL/6 male mice as donor mice and CB6F1 β 654 female mice as transplant recipients; Experimental study on super transplantation of H2 haploidentical leukemia mice and thalassemia recipients. Especially in the super transplantation treatment of mice with thalassemia, all mice were not subjected to any GVHD pretreatment or GVHD prevention. However, all mice were able to form stable complete donor implants, and the thalassemia gene was reduced to an extremely low level close to zero; Hemoglobin, red blood cell count, white blood cell count, and platelet count all returned to normal levels in mice; Significant recovery of peripheral blood lymphocytes and thymus, and completion of immune reconstruction; Moreover, no acute or chronic GVHD was observed in the mice. In addition, the reproductive gland structure of female mice in the super transplantation group was intact after transplantation, and they were able to conceive, give birth, and breastfeed offspring normally. The good results of super transplantation in animal experiments of thalassemia are a major breakthrough in the treatment of thalassemia, and also lay a very good foundation for our upcoming clinical research on super transplantation of thalassemia. Our center is the earliest unit in our province to carry out HSCT treatment for hematological diseases. The HSCT technology level is leading in the province, and we have solid clinical application conditions and foundations. We are willing to accept and adopt the new concept and treatment of super transplantation from Professor Ai Huisheng's team. Under Professor Ai's guidance and assistance, we will conduct clinical research on super transplantation for the treatment of severe thalassemia, verify its "safety and effectiveness", cure patients, and promote the continuous development of science, creating a safe and effective new treatment model for severe thalassemia without pre-treatment, reproductive damage, and post transplant complications.

This is an open, multi-center clinical study designed to evaluate the efficacy and safety of TQ05105 Tablets in patients with chronic graft-versus-host disease

This is a prospective observational study. The investigators plan to utilize this model as a tool for early classification and interrogate ANS function of transplant recipients.

The original CliniMACS® device (CD34 Reagent System) employs a reagent consisting of an antibody that specifically binds to blood cells that express the CD34+ surface marker (hematopoietic stem cells or blood stem cells). The CD34 antibody is conjugated to an iron-containing particle that is only nanometers in size and safe for infusion. The enrichment of CD34+ cells is accomplished by passing the antibody/magnetically-labeled cell suspension through a magnetic separation column, which is provided as part of a single-use disposable tubing set. Magnetically-labeled CD34+ target cells are retained within the separation column, while the unlabeled cells flow through. Recovery of CD34+ cells is achieved by removing the magnetic field and eluting the targeted CD34+ stem cells into a collection bag. On January 24, 2014, the FDA approved the CliniMACS CD34 Reagent System as a Humanitarian Use Device for the prevention of graft-versus-host disease (GVHD) in patients with acute myeloid leukemia (AML) in first complete remission undergoing allogeneic HCT from a matched related donor. Humanitarian Use Device (HUD) is a device that is intended to benefit patients by treating or diagnosing a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year. The CliniMACS® CD34 Reagent System is now indicated for processing hematopoietic progenitor cells collected by apheresis (PBSC) from an allogeneic, Human Leukocyte Antigen (HLA)-identical matched sibling donor (MSD) to obtain a CD34+ cell-enriched population for hematopoietic reconstitution following a myeloablative preparative regimen without the need for additional GVHD prophylaxis in patients with AML in first morphologic complete remission (CR1). The approval as an HUD, however, asserts that there was sufficient information for the FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury. Furthermore, the clinical data supported the premise of a "probable benefit"; in that the risk to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment.19 The CliniMACS CD34 Reagent System was shown to meet these requirements. Uses of the CliniMACS CD34 Reagent System beyond MSD PBSC HCT for AML in CR1 are currently not FDA approved and therefore considered research, even though CD34-selection is widely considered to be a standard-of-care option for haploidentical HCT. In Europe, the European Medicines Agency (EMA) has made the CliniMACs System components available as Conformité Européene (CE) marked medical devices, and "any clinical application of the target cells is exclusively within the responsibility of the user of a CliniMACS System." The CD34-selection system has been widely used in haploidentical HCTs, with the first patient treated at University of California, San Francisco (UCSF) in 2002. Since then, CD34-selection has facilitated over 70 HCTs at UCSF on 2 successive protocols (#01151 and #10082). However, the removal of almost all cells beyond those which are CD34+ leads to minimal passive transfer of immunity. It is therefore complicated by a slow recovery of immunity, with high rates of life-threatening viral infections, and an appreciable degree of transplant-related mortality (TRM). Beginning in 2014, a new approach to ex vivo processing of stem cells was developed with a goal of mainly replacing the older CD34-selection technology. This technique utilizes negative depletion of the cells thought to be most responsible for the development of aGVHD, the alpha-beta T-cell Receptor positive T-cells. All trials of alpha-beta T-cell depleted have included simultaneous depletion of CD19+ B cells from the donor graft. All references to "alpha-beta T-cell depletion" herein implies simultaneous Cluster of Differentiation antigen (CD)19+ depletion as well.

This is an open-label (identity of assigned study drug will be known) study designed to collect long-term safety and efficacy data and provide ibrutinib access to participants in completed ibrutinib studies. PCI-32765 (Ibrutinib) is a first-in-class, potent, orally-administered, covalently-binding small molecule inhibitor of bruton's tyrosine kinase. "PCI-32765" and "ibrutinib" refer to the same molecule; hereafter, "ibrutinib" will be used. Participants will continue with the current ibrutinib dosing regimen established in the parent ibrutinib study until the investigator determines that the participant is no longer benefitting from treatment (ie, disease progression or unacceptable toxicity has occurred), the participant withdraws consent, alternative access to ibrutinib is available and feasible (example, participant assistance program or commercial source of ibrutinib), or for other reasons as defined in the protocol, or until the end of the study, whichever occurs earlier. Safety will be monitored throughout the study and summarized. Efficacy may be analyzed in combination with the data collected in the parent protocol. There is no formal hypothesis testing planned for this long-term extension study. Participants for whom alternative access to ibrutinib is not available and feasible can receive treatment with single-agent ibrutinib until end of study, which is defined as the time when all participants still receiving study treatment have transitioned to commercial or alternative access to ibrutinib, have stopped receiving ibrutinib treatment, or upon a decision by the sponsor to terminate the study, whichever occurs earlier.