Active clinical trials for "Bone Marrow Failure Disorders"

This is a single arm pilot study using TCR alpha/beta+ T cell-depleted peripheral blood stem cells (PBSC) from closely matched unrelated donors or partially matched/haploidentical related donors for hematopoietic stem cell transplant (HSCT) in patients with acquired and inherited bone marrow failure (BMF) syndromes.

This study is designed to estimate the efficacy and toxicity of familial HLA mismatched bone marrow transplants in patients with non-malignant disease who are less than 21 years of age and could benefit from the procedure.

The goal of this protocol is to expand access for patients who lack a fully HLA (Human leukocyte antigen) matched sibling donor and who are candidates for allogeneic hematopoietic stem cell transplant (HSCT). These patients have a serious or immediately life-threatening disease for which HSCT is indicated. These patients are not eligible for other Children's Hospital of Philadelphia IRB approved protocols that utilize CliniMACs technology for T depletion.

This is a single-arm study to investigate 1-year treatment related mortality (TRM) in patients with life threatening non-malignant and malignant hematologic disorders who do not have a matched related donor for allogeneic transplantation.

This is a Phase II study of allogeneic hematopoietic stem cell transplant (HCT) using a myeloablative preparative regimen (of either total body irradiation (TBI); or, fludarabine/busulfan for patients unable to receive further radiation). followed by a post-transplant graft-versus-host disease (GVHD) prophylaxis regimen of post-transplant cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF).

This is a pilot study to determine whether fludarabine-based reduced intensity conditioning (RIC) regimens facilitate successful donor engraftment of patients with acquired aplastic anemia (AA) and Inherited bone marrow failure (iBMF) syndromes undergoing Matched related donor bone marrow transplant (MRD-BMT).

Bone marrow failure disease(BMFD) is a kind of bone marrow due to congenital or acquired hematopoietic stem cells (hemopoietic stem cell, HSC) function damage. Allogenic hemopoietic stem cell transplantation (Allo-HSCT) might be the most possible treatment to cure the disease.However, 5-26% of patients have been reported to have delayed platelet engraftment (DPE), which is defined as persistent severe thrombocytopenia (<20 × 109/L) for >35 days after transplantation . To date, no standard treatment and prevention has been recommended for DPE. In patients with DPE, the amount of transfusion, the increased risk of infection, and the prolonged average hospital stay were independent risk factors affecting the prognosis of allo-HSCT patients. Due to continuous and progressive failure in the bone marrow hematopoiesis, thrombocytopenia post HSCT is more common in BMFD patients and often achieves low response to conventional therapy, such as platelet transfusion. Therefore, it is of great significance to effectively promote hematopoietic reconstruction to improve the prognosis of transplant patients.

Background: Moderate aplastic anemia is a blood disease which may require frequent blood and platelet transfusions. Sometimes patients with this disease can be treated with immunosuppressive drugs. Not all patients respond and not all patients are suitable for this treatment. Thrombopoietin (TPO) is a protein made by the body. The bone marrow needs TPO to produce platelets. TPO may also be able to stimulate bone marrow stem cells to produce red cells and white cells. However, TPO cannot be given by mouth. This has led researchers to develop the drug eltrombopag, which acts in the same way and can be given by mouth. Eltrombopag has been shown to safely increase platelet numbers in healthy volunteers and in patients with other chronic blood diseases, including severe aplastic anemia. Researchers are interested in looking at whether eltrombopag can be given to people with moderate aplastic anemia and significantly low blood cell counts. Objectives: - To evaluate the safety and effectiveness of eltrombopag in people with moderate aplastic anemia or patients with bone marrow failure and unilineage cytopenia who need treatment for significantly low blood cell counts. Eligibility: - People at least 2 years of age who have moderate aplastic anemia or bone marrow failure and unilineage cytopenia,and significantly low blood cell counts. Design: Patients will be screened with a physical examination, medical history, blood tests, a bone marrow biopsy, and an eye exam. Patients will receive eltrombopag by mouth once a day. Patients will have weekly blood tests to monitor the effectiveness of the treatment and adjust the dose in response to possible side effects. Patients may continue to take eltrombopag if their platelet count or hemoglobin increases, their requirement for platelet or blood transfusion decreases after 16 to 20 weeks of treatment, and there have been no serious side effects. Access to the drug will continue until the study is closed. Patients will be asked to return for a follow-up visit 6 months after the last dose of medication.

This is an open label, prospective Pilot interventional study will investigate the safety and efficacy of Romiplostim, thrombopoietin (TPO) mimetic, in children (ages: 0 to 21 years) with broad scope of bone marrow failure disorders including acquired and inherited conditions as a first line of therapy along with standard of care.

This study is a prospective, single center phase II clinical trial in which patients with Severe Aplastic Anemia (SAA) ) will receive a haploidentical transplantation. The purpose of this study is to learn more about newer methods of transplanting blood forming cells donated by a family member that is not fully matched to the patient. This includes studying the effects of the chemotherapy, radiation, the transplanted cell product and additional white blood cell (lymphocyte) infusions on the patient's body, disease and overall survival. The primary objective is to assess the rate of engraftment at 30 days and overall survival (OS) and event free survival (EFS) at 1 year post-hematopoietic cell transplantation (HCT). Primary Objectives To estimate the rate of engraftment at 30 days after TCR αβ+ T-cell-depleted graft infusion in patients receiving a single dose of post graft infusion cyclophosphamide. To estimate the overall survival and event free survival at 1-year post transplantation. Secondary Objectives To calculate the incidence of acute and chronic GVHD after HCT. To calculate the rate of secondary graft rejection at 1-year post transplantation To calculate the cumulative incidence of viral reactivation (CMV, EBV and adenovirus). To describe the immune reconstitution after TCR αβ+ T-cell-depleted graft infusion at 1 month, 3 months, 6 months, 9 months, and 1 year. Exploratory Objectives To longitudinally assess the phenotype and epigenetic profile of T-cells in SAA patients receiving HCT for SAA. To assess the phenotype and epigenetic profile of T-cells in DLI administered to SAA patients post HCT. To longitudinally assess CD8 T cell differentiation status in SAA patients using an epigenetic atlas of human CD8 T cell differentiation. To examine the effector functions and proliferative capacity of CD8 T cells isolated from SAA patients before and after DLI. Quantify donor derived Treg cells at different time points in patients received HCT. Determine Treg activation status at different stages after HCT. Are specific features of the DLI product associated with particular immune repertoire profiles post-transplant? How does the diversity and functional profile of the DLI product alter the response to pathogens in the recipient? Do baseline features of the recipient's innate and adaptive immune cells correlate with post-transplant immune repertoires and response profiles?