View clinical trials related to Bone Marrow Failure Disorders.
Filter by: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.
The objective of this study is to evaluate the efficacy of using a reduced-intensity condition (RIC) regimen with umbilical cord blood transplant (UCBT), double cord UCBT, matched unrelated donor (MUD) bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) in patients with non-malignant disorders that are amenable to treatment with hematopoietic stem cell transplant (HSCT). After transplant, subjects will be followed for late effects and for ongoing graft success.
Background: - Stem cell transplants from related donors (allogenic stem cell transplants) can be used to treat individuals with certain kinds of severe blood diseases or cancers, such as severe anemia. Allogenic stem cell transplants encourage the growth of new bone marrow to replace that of the recipient. Because stem cell transplants can have serious complications, researchers are interested in developing new approaches to stem cell transplants that will reduce the likelihood of these complications. - By reducing the number of white blood cells included in the blood taken during the stem cell collection process, and replacing them with a smaller amount of white blood cells collected prior to stem cell donation, the stem cell transplant may be less likely to cause severe complications for the recipient. Researchers are investigating whether altering the stem cell transplant donation procedure in this manner will improve the likelihood of a successful stem cell transplant with fewer complications. Objectives: - To evaluate a new method of stem cell transplantation that may reduce the possibly of severe side effects or transplant rejection in the recipient. Eligibility: - Recipient: Individuals between 4 and 80 years of age who have been diagnosed with a blood disease that can be treated with allogenic stem cell transplants. - Donor: Individuals between 4 and 80 years of age who are related to the recipient and are eligible to donate blood. OR unrelated donors found through the National Marrow Donor Program. Design: - All participants will be screened with a physical examination and medical history. - DONORS: - Donors will undergo an initial apheresis procedure to donate white blood cells. - After the initial donation, donors will receive injections of filgrastim to release bone marrow cells into the blood. - After 5 days of filgrastim injections, donors will have apheresis again to donate stem cells that are present in the blood. - RECIPIENTS: - Recipients will provide an initial donation of white blood cells to be used for research purposes only. - From 7 days before the stem cell transplant, participants will be admitted to the inpatient unit of the National Institutes of Health Clinical Center and will receive regular doses of cyclophosphamide, fludarabine, and anti-thymocyte globulin to suppress their immune system and prepare for the transplant. - After the initial chemotherapy, participants will receive the donated white blood cells and stem cells as a single infusion. - After the stem cell and white blood cell transplant, participants will have regular doses of cyclosporine and methotrexate to prevent rejection of the donor cells. Participants will have three doses of methotrexate within the week after the transplant, but will continue to take cyclosporine for up to 4 months after the transplant. - Participants will remain in inpatient care for up to 1 month after the transplant, and will be followed with regular visits for up to 3 years with periodic visits thereafter to evaluate the success of the transplant and any side effects.
Background: A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders. Pathogenic variant(s) in IBMFS genes are relevant to carcinogenesis in sporadic cancers. Patients with IBMFS who develop cancer differ in their genetic and/or environmental features from patients with IBMFS who do not develop cancer. These cancer-prone families are well suited for cancer screening and prevention trials targeting those at increased genetic risk of cancer. Carriers of IBMFS pathogenic variant(s) are at increased risk of cancer. The prototype disorder is Fanconi's Anemia (FA); other IBMFS will also be studied. Objectives: To determine the types and incidence of specific cancers in patients with an IBMFS. To investigate the relevance of IBMFS pathogenic variant(s) in the carcinogenesis pathway of the sporadic counterparts of IBMFS-associated cancers. To identify risk factors for IBMFS-related cancers in addition to the primary germline pathogenic variant(s). To determine the risk of cancer in IBMFS carriers. Eligibility: North American families with a proband with an IBMFS. IBMFS suspected by phenotype, confirmed by pathogenic variant(s) in an IBMFS gene, or by clinical diagnostic test. Fanconi's anemia: birth defects, marrow failure, early onset malignancy; positive chromosome breakage result. Diamond-Blackfan anemia: pure red cell aplasia; elevated red cell adenosine deaminase. Dyskeratosis congenita: dysplastic nails, lacey pigmentation, leukoplakia; marrow failure. Shwachman-Diamond Syndrome: malabsorption; neutropenia. Amegakaryocytic thrombocytopenia: early onset thrombocytopenia. Thrombocytopenia absent radii: absent radii; early onset thrombocytopenia. Severe Congenital Neutropenia: neutropenia, pyogenic infections, bone marrow maturation arrest. Pearson's Syndrome: malabsorption, neutropenia, marrow failure, metabolic acidosis; ringed sideroblasts. Other bone marrow failure syndromes: e.g. Revesz Syndrome, WT, IVIC, radio-ulnar synostosis, ataxia-pancytopenia. First degree relatives of IBMFS-affected subjects as defined here, i.e. siblings (half or full), biologic parents, and children. Grandparents of IBMFS-affected subjects. Patients in the general population with sporadic tumors of the types seen in the IBMFS (head and neck, gastrointestinal, and anogenital cancer), with none of the usual risk factors (e.g. smoking, drinking, HPV). Design: Natural history study, with questionnaires, clinical evaluations, clinical and research laboratory test, review of medical records, cancer surveillance. Primary endpoints are all cancers, solid tumors, and cancers specific to each type of IBMFS. Secondary endpoints are markers of pre-malignant conditions, such as leukoplakia, serum or tissue evidence of carcinogenic viruses, and bone marrow morphologic myelodyplastic syndrome or cytogenetic clones....