24 Clinical Trials for Various Conditions
This is an open-label, single-arm, multicenter Phase 1/2 study evaluating the safety and efficacy of gene therapy by transplantation of Prime Edited autologous CD34+ stem cells modified ex vivo (PM359) in participants with autosomal recessive Chronic Granulomatous Disease (CGD) caused by mutations in the NCF1 (Neutrophil Cytosolic Factor 1) gene.
The primary study objective is to collect biospecimen samples (e.g., blood) from participants diagnosed with Chronic Granulomatous Disease (CGD). The biospecimens will be used to create a biorepository that can be used to identify disease associated biomarkers and potential targets with immune and multi-omics profiling. The disease sample collection and analysis will be the foundation for an extensive network of biospecimen access and linked datasets for future translational research.
Background: Chronic granulomatous disease (CGD) is a rare immune disorder that can cause serious infections throughout the body. The only cure for CGD is a stem cell transplant. Transplants from a sibling are best, but many people must get transplants from unrelated donors. However, these transplants can cause serious complications in people with CGD. Objective: To see if a study drug (JSP191) can help improve the success rates of stem cell transplants for people with CGD from an unrelated donor. Eligibility: People aged 4 to 65 years with CGD who require a transplant. Design: Participants will be screened. Part of the screening will help to identify the best match to a transplant donor. Participants will have a physical exam, including dental and eye exams. They will have blood and urine tests. They will have tests of their breathing and heart function. A bone marrow sample will be taken. They will have their stem cells collected. Participants will have a catheter inserted into a vein in their chest. It will remain in place for the entire period of transplant and recovery. Participants will be in the hospital 40 to 50 days for the transplant. This will include a conditioning phase, to prepare their body for the procedure, as well as the transplant and recovery phases. As part of the conditioning phase, participants will receive JSP191 through a vein for 1 hour. After discharge, participants will have follow-up visits 2 times a week for 100 days. Additional follow-up visits will continue for 5 years....
Background: Chronic granulomatous disease (CGD) affects the immune system. People with CGD are more likely to get infections. Drugs can help control infections, but these treatments can cause side effects including kidney failure and deafness. Stem cell transplants can cure CGD, but these don t always work. Objective: To find out if a different drug treatment can improve the success rates of stem cell transplants in people with CGD. Eligibility: People aged 4-65 years with CGD. Design: Participants will undergo screening. They will have a physical exam. They will have blood and urine tests and tests of their heart function and breathing. They will have imaging scans. They will have a bone marrow biopsy; a needle will be inserted into their hip to draw a sample of tissue from the bone. A tube called a catheter will be placed into a vein in the participant s chest. This catheter will remain in place for the transplant and recovery period. Blood for tests can be drawn from the catheter, and medications and the stem cells can be administered through it. Participants will be in the hospital for either 10 or 21 days to receive 3 or 4 drugs before the transplant. They will get 2 doses of total body radiation on the same day. Participants will receive donor stem cells through the catheter. They will remain in the hospital for 6 weeks afterward. Participants will visit the clinic 2 to 3 times per week for 3 months after discharge. Follow-up visits will continue for 5 years.
Background: CGD is caused by a gene mutation. For people with CGD, their cells cannot kill germs well, so they can get frequent or life-threatening infections. Researchers want to see if a new procedure can help a person s cells kill germs for a short time. It uses messenger RNA (mRNA) to deliver correct instructions for the gene mutation to the cells. Objective: To test a procedure in which mRNA is added to a person s blood cells. Eligibility: Males aged 18-75 with CGD with a mutation in the gene that makes the protein gp91phox. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Swab to test for strep throat Some screening tests will be repeated during the study. Participants will be admitted to the NIH Clinical Center hospital for at least 7 days. They will have apheresis. For this, a medicine is injected under their skin to prepare their white blood cells for collection. An IV line is placed into an arm vein. Blood goes through the IV line into a machine that divides whole blood into red blood cells, plasma, and white blood cells. The white blood cells are removed, and the rest of the blood is returned to the participant through an IV line in their other arm. The next day, they will get their mRNA-corrected cells via IV. They will be monitored for 3 more days. After discharge, participants will keep a symptom diary. They will be contacted weekly for one month, and then once a month. They will have a follow-up visit 3 months after the infusion.
Background: CGD causes infections and inflammation. The only cure currently is a bone marrow transplant. Most often a perfectly matched bone marrow donor is used. Researchers want to see if they can lower the risks of using a mismatched donor. Objectives: To see if it is safe to use a related bone marrow donor who is only a partial match to a person with CGD. To see how well drugs given to a person before and after transplant help the body accept the transplant. Eligibility: People ages 4-65 with CGD for whom stem cell transplant may be a cure and who do not have a perfectly matched donor, related or unrelated. Design: Participants will be screened with: Medical history Physical exam Blood tests Participants will be admitted to the hospital about 2 weeks before the transplant. They will have blood, urine, breathing, and heart tests. They may have CT and/or MRI scans. They will have a needle inserted into their hipbone to remove marrow. They will have dental, neurologic, and psychologic tests. They will have a central catheter placed: A line will be placed into a vein in their upper chest. They will get drugs, chemotherapy, and radiation to prepare for the transplant. Participants will receive the donated cells through their catheter. The cells will be from one of their relatives. Participants will stay in the hospital about 6 weeks after the transplant. After they leave the hospital, participants will have to stay in the area with visits about 2 times a week for approximately 100 days post transplant. Then visits will be every 3 to 6 months for 2 years. Then visits will be once a year.
Chronic granulomatous disease (CGD) is an inherited immune system abnormality in which bone marrow transplantation (BMT) has been shown to be curative. However the risks of transplantation are high and not all patients with CGD may need to undergo this high risk procedure. This study will determine the long term medical condition and daily functioning of participants with CGD after a transplant and if possible, compare these results to participants who do not undergo a transplant.
This research study is designed to assess the prevalence of specific antibodies and inflammatory cytokines in adult and pediatric participants with CGD.
Background: Chronic granulomatous disease (CGD) is a rare immune disorder caused by a mutation in the CYBB gene. People with CGD have white blood cells that do not work properly. This places them at risk of developing infections that may be life-threatening. Stem cell transplant can cure CGD but transplanting stem cells donated by other people can have serious complications. In addition, not everyone has a matched donor. Another approach is a type of gene therapy that involves base-editing to correct the mutation in a person s own stem cells. Researchers want to know if the base-edited stem cells can improve the white cells' functioning and result in fewer CGD-related infections. Objective: To learn if base-edited stem cells will improve white blood cells' ability to fight against infections in people with CGD. Eligibility: Males aged 18 years and older with X-linked CGD. Design: This is a non-randomized study. Participants with the specific mutation under study will be screened during the initial phase. During the development phase, participants will undergo apheresis to collect stem cells for base-editing correction of the mutation. During the treatment phase, participants will receive the base-edited cells after chemotherapy with busulfan. Participants will remain in the hospital until their immunity recovers. Follow-up visits will continue for 15 years.
Background: - Abscesses are a pocket of infection in an organ or tissue. Patients with a disease called chronic granulomatous disease (CGD) often develop these abscesses. CGD is an inherited disorder that affects how white blood cells function. Liver abscesses in people with CGD often require surgery to remove them and treat the infection. However, some people with CGD cannot have full surgery because it would be too risky. Researchers want to try a procedure called radiofrequency ablation (RFA) to treat these liver abscesses. RFA can usually be done without a major operation. This study will see if RFA is a safe and effective treatment for liver abscesses in patients with CGD. Objectives: - To see if RFA is a safe and effective treatment for CGD-related liver abscesses. Eligibility: - Individuals between 18 and 75 years of age with CGD who have liver abscesses that cannot be treated with surgery. Design: * Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies will be performed on the liver. * Participants will have RFA for the abscesses. RFA is an image-guided technique that heats and destroys specific tissue, such as tumor tissue. It will target any abscesses on the liver. * After the procedure, participants will stay in the hospital for monitoring before being released. * Participants will have regular follow-up visits for up to 1 year after treatment. Blood and urine samples will be collected. Additional imaging studies will be performed.
This study will evaluate patients with abnormal immune function that results in recurrent or unusual infections or chronic inflammation. This may include inherited conditions, such as X-linked severe combined immunodeficiency (XSCID), chronic granulomatous disease (CGD), and leukocyte adhesion deficiency (LAD), or conditions resulting from outside factors, such as graft-versus-host disease (GVHD). The information from this study will be used to establish the pattern and pace of change of the disease and to help develop new treatments. The period of observation and study following enrollment in this study may be for up to one year. In addition these studies may provide the medical information needed to determine eligibility for enrollment in other clinical study protocols and more prolonged follow up. Patients of any age with abnormal immune function who have recurrent or unusual infections, whose blood tests show evidence of immune dysfunction, or who have GVHD, XSCID, CGD or LAD may be eligible for this study. Patients' parents, siblings, grandparents, children, aunts, uncles and first cousins of any age also may be included. Healthy normal volunteers between 18 and 85 years of age are recruited as controls. Normal volunteers undergo a physical examination and provide blood, saliva, and urine samples for immune function studies. Patients' family members provide a medical history, have a physical examination, and give blood and urine samples, and possibly a saliva sample. The samples are used for genetic and routine laboratory studies. Investigators may request tissue samples, such as biopsy specimens, previously removed for medical reasons to be sent to NIH for study. Patients undergo the following tests and procedures: 1. Medical history and physical examination. 2. Blood and urine tests, including analysis for genes involved in immune disorders. 3. Buccal smear (in some patients) for genetic studies. This involves scraping the lining of the mouth near the cheek. 4. Specialized tests to evaluate specific conditions in patients who have an immune disorder that might affect lung function, gum infections or eye problems. These may include chest x-ray, CT scan, breathing function test, dental, eye, and hearing examinations. 5. Follow-up visits of patients with immune problems may occur at 6 months and at one year after the first visit (or more frequently if medically required) to include: * Medical history update * Physical examination * Follow-up on abnormal test results and medical treatments initiated at NIH * Collection of blood, saliva, urine, or wound drainage samples for repeat immune function studies * Tissue study of specimens removed for medical reasons at other institutions besides NIH
Background: The way the body heals and protects itself from getting sick is called the immune response. Some people with weak immune systems get sick often or get rashes and skin infections. Researchers want to find out how the immune system and skin problems are related so they can help these people. Objective: To learn about how immune response and skin healing are related to each other. Eligibility: People ages 18-65 with hyper IgE syndrome or Job syndrome or people ages 7-65 with chronic granulomatous disease. Healthy volunteers ages 18 65 are also needed. Design: Participants will be screened with: Medical history Physical exam Possible urine tests Participants will have 1 to 3 visits within about a week. Visits will include the following: Participants will have a wells device strapped to the inside of the forearm. It will suction the skin and pull the top layer away to form 8 blisters. The skin over the blisters and the liquid inside will be collected. Participants will have up to 4 skin biopsies. A sharp tool will remove a small plug of skin from the forearm. Participants may have blood and urine tests. The skin on participants skin will be rubbed with a cotton swab. Some participants will have an overnight visit. They will have the blister device placed back on the arm. The wells will be lined up over the blister wounds. The wells will be filled with either saline or the participant s blood serum. The device will be covered and left on the arm for up to 24 hours. Doctors will periodically remove some liquid from the wells.
The purpose of this study is to determine whether bilateral orthotopic lung transplantation (BOLT) followed by cadaveric partially-matched hematopoietic stem cell transplantation (HSCT) is safe and effective for patients aged 5-45 years with primary immunodeficiency (PID) and end-stage lung disease.
Background: * Atherosclerosis, the arterial plaques or blockages that cause heart disease, develops in many people by the time they are in their mid-20s. The rate of atherosclerosis in patients with immune system disorders has not been well studied, but it may be very different from the general population. * Patients with chronic granulomatous disease (CGD) produce less of a group of molecules known as free radicals, which help to fight infection and may play a role in the development of atherosclerosis. Patients with CGD may develop atherosclerosis much more slowly than people without CGD. On the other hand, carrier mothers of children with genetically-linked CGD often have problems with autoimmune problems in addition to a problem with making free radicals. Patients with other immune system disorders also have very different responses to infection, and many of them also have autoimmune-like problems that may change the risk of developing atherosclerosis. Objectives: - To study the prevalence of atherosclerosis in patients with immune system disorders, compared with healthy individuals. Eligibility: - Individuals at least 18 years of age who either have been diagnosed with an immune system disorder or are healthy volunteers. Design: * The active part of the study involves one or two visits to the National Institutes of Health Clinical Center for a series of imaging tests and scans. * Participants will have the following tests during the active part of the study: * (1) CAT scan to obtain images of the chest arteries and measure the amount of calcium in the artery walls. * (2) Magnetic resonance imaging scan to obtain images of the coronary and carotid arteries in the chest and neck. * (3) Electrocardiogram to provide data on current heart function. * (4) Blood samples to provide data on heart, kidney, and immune system function. * Participants will be contacted every 2 years in the future for up to 30 years to determine whether they have developed heart disease. Researchers will ask participants to provide contact information for two other people who may likely know how to get in touch with the participant in the future.
This is a data collection study that will examine the general diagnostic and treatment data associated with the reduced-intensity chemotherapy-based regimen paired with simple alemtuzumab dosing strata designed to prevented graft failure and to aid in immune reconstitution following hematopoietic stem cell transplantation.
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.
X-linked Chronic Granulomatous Disease (CGD) is an inherited disorder caused by an abnormal gene that fails to make the protein known as gp91 phox. This protein is part of a group of proteins that work to create hydrogen peroxide in neutrophils. Neutrophils are a type of white blood cell that helps fight infections. As a result, patients who do not make this gp91 phox frequently develop life-threatening infections. In addition, these neutrophils often act abnormally, resulting in the creation of a granuloma, which is an abnormal collection of cells. These granulomas can then become large enough to block organs, such as the bladder and/or intestines, causing significant problems. Patients are usually treated with antibiotics (often needed for extended periods of time) for the infections caused by CGD, and with corticosteroids for the granulomas. However, these drugs do not cure CGD itself, and can have significant side effects. Thus patients with CGD do not have a normal life expectancy. The only available cure to date for CGD is Bone Marrow Transplantation (BMT), where the blood-making cells from a specially matched brother or sister donor (allogeneic) or a similarly matched unrelated donor are given to the patient after the patient has undergone some kind of chemotherapy or radiation in preparation for receiving the cells. If the cells from the donor engraft (or survive in the marrow), the patient can be cured; however, there is a risk that the cells may not engraft or that they may later get rejected from the body. Also, the cells from the donor can react against the patient, causing a serious disorder called "Graft Versus Host Disease" (GVHD). Although there are a number of methods used to try to reduce and/or prevent graft rejection and/or GVHD, these complications can still occur even with the newer methods now being developed. The risks of such complications are lower when a brother or sister is used as the donor; however, not all patients (even those with siblings) will have an ideally matched donor. Hence, transplantation, especially when using an unrelated donor, is not always a perfect cure. Because the gene responsible for making the gp91 phox is known, it is possible to use gene therapy to try to cure this disease. In gene therapy, some of the blood-making cells are taken from the patient using a technique called apheresis. The normal gene is placed into the cells using special viruses called retroviruses. The cells are then able to produce the normal protein. In this trial, the patient will receive a small dose of chemotherapy called busulfan, lower than what is traditionally used in allogeneic BMT, and the newly corrected cells will then be put back into the patient. Even with the best standard of care, a number of patients with CGD will still die from infection. For those patients who have an unresponsive or progressive infection and do not have a possible sibling donor, their only hope is either a Matched Unrelated Donor (MUD) transplant, which has a high risk of causing death itself, or gene therapy. Hence, we would propose using gene therapy in these patients as this has less risk of causing death, but can still possibly offer a cure. Even if the corrected cells do not remain life long to rid the patients entirely of their disease, as long as they persist for even a few months, they would be able to at least clear the current infection for which the patients are being considered for enrollment in this protocol. Further, they would still be eligible to undergo a matched unrelated donor transplant in the event that gene therapy does not confer any benefit.
Background: Chronic granulomatous disease (CGD) is a genetic disorder. People with CGD are missing a gene that affects their white blood cells. White cells are part of the immune system, and people with GCD are vulnerable to many infections. Researchers want to test a new treatment to replace the missing gene that may be safer than the current treatment for CGD. Objective: To test a new type of gene therapy in people with CGD. Eligibility: People aged 3 years or older with CGD. Design: Participants will undergo apheresis: Blood will be collected through a tube attached to a needle inserted in a vein; the blood will run through a machine that separates certain cells (stem cells); the remaining blood will be returned to the body through a second needle. The participant s stem cells will be modified in a laboratory to add the gene they are missing. Participants will stay in the hospital for about 40 days. For the first 10 days, they will undergo many exams, including imaging scans and tests of their heart and lung function. They will receive drugs to prepare their bodies for the gene therapy. They will receive a "central line": A hollow tube will be inserted into a vein in the chest, with a port opening above the skin. This port will be used to draw blood and administer drugs without the need for new needle sticks. For the gene therapy, each participant s own modified stem cells will be put into their body through the port. Participants will have 8 follow-up visits over 3 years.
Chronic Granulomatous Disease (CGD) is an inherited immunodeficiency disorder which results from defects that prevent white blood cells from effectively killing bacteria, fungi and other microorganisms. Chronic granulomatous inflammation may compromise vital organs and account for additional morbidity. CGD is thought to affect approximately 1 in 200,000 persons, although the real incidence might be higher due to under-diagnosis of milder phenotypes. The first gene therapy approaches in X-CGD have shown that effective gene therapy requires bone-marrow (BM) conditioning with chemotherapy to make space for the gene-modified cells to engraft. These studies demonstrated that transplantation of gene modified stem cells led to production of white blood cells that could clear existing infections. However, some trials using mouse-derived retroviral vectors were complicated by the development of myelodysplasia and leukemia-like growth of blood cells. This trial will evaluate a new lentiviral vector that may be able to correct the defect, but have much lower risk for the complication. This study is a two-part, prospective non-controlled, non-randomized Phase I/II clinical trial to assess the safety, feasibility and efficacy of cellular gene therapy in patients with chronic granulomatous disease using transplantation of autologous bone marrow CD34+ cells transduced ex vivo by the G1XCGD lentiviral vector containing the human CGD gene. Primary objectives include evaluation of safety and evaluation of efficacy by biochemical and functional reconstitution in progeny of engrafted cells and stability at 12 months. Secondary objectives include evaluation of clinical efficacy, longitudinal evaluation of clinical effect in terms of augmented immunity against bacterial and fungal infection, transduction of CD34+ hematopoietic cells from X-CGD patients by ex vivo lentivirus-mediated gene transfer, and evaluation of engraftment kinetics and stability. Approximately 3-6 patients will be treated per site with a goal of 16 total patients to be treated with G1XCGD lentiviral vector.
Background: - Chronic granulomatous disease (CGD) is an immunodeficiency disease in which white blood cells are unable to kill certain bacteria and fungi. People with CGD are more likely to develop recurrent life-threatening infections. Certain changes or mutations in genes contribute to the severity of CGD, and also appear to affect the success of treatment with interferon-gamma, a substance that is used to improve the immune system s ability to fight infection. Researchers are interested in studying changes in the immune system caused by interferon-gamma treatment of CGD in individuals with different mutations that cause CGD. Objectives: - To compare changes in the immune system caused by interferon-gamma treatment for CGD in individuals with different mutations that cause CGD. Eligibility: - Individuals of any age who have been diagnosed with CGD and have specific types of mutations that cause CGD (to be determined after testing). Design: * Participants will be screened with a medical history, physical examination, and blood and urine tests. Participants must weigh more than 11 kilograms (\~24 pounds) to participate in the study. * Participants will receive injections of interferon-gamma once weekly for 4 weeks, twice weekly for 4 weeks, and then three times weekly for 4 weeks (a total of 24 injections). * Blood will be drawn periodically during treatment and for 8 weeks after the treatment, for a total of 21 weeks on the study. Participants will regularly provide information on their symptoms and responses to treatment to the study researchers.
Background: People who get chronic illnesses as children are living longer. When they turn 18, they switch from pediatric care to adult care. This can be a difficult change. Chronic Granulomatous Disease (CGD) is an inherited disease. It causes long-term, repeated infections. People with CGD are usually diagnosed when they are very young children. Researchers want to find out more about how young people with CGD handle the change to adult care. What they learn may make this easier for people with CGD in the future. Objective: - To identify what helped or hurt young adults with CGD as they went from pediatric to adult care. Eligibility: - Adults with CGD who were 18 24 years old between January 2011 and February 2014. Design: * Participants will already be enrolled in NIH studies. * Eligible people will get materials in the mail. They will get a letter with study information, an interview questionnaire, and an information sheet. * Researchers will call participants 1 week after the packets are sent. They will talk about the study and find out if the person wants to join. * An interview will be completed immediately or scheduled for the future. The interview will take about 45 minutes. The researcher will ask the participant about their disease. They will also ask about travel to NIH, being an outpatient or inpatient there, and legal documents. * Researchers may contact the subjects again by phone if they need more information at any point during the study.
This study will determine if the drug infliximab is safe for treating inflammatory bowel disease (IBD) in patients with chronic granulomatous disease (CGD). IBD is an inflammation or irritation of the gut that leads to symptoms such as diarrhea, bloating and stomach cramps. CGD is an inherited disease affecting white blood cells called neutrophils in which patients are susceptible to repeated bacterial and fungal infections. They also have a higher incidence of some autoimmune diseases, such as IBD. Infliximab is approved to treat Crohn's disease, an IBD similar to that seen in patients with CGD. Patients 10 years of age and older with CGD and IBD may be eligible for this study. Candidates are screened with a medical history, physical examination, blood and urine tests, electrocardiogram (EKG), tuberculosis skin test (PPD skin testing), and stool test for the presence of infections. Additional tests may be done, including colonoscopy (procedure using a flexible tube through the rectum to examine the lining of the gut) and imaging studies such as an x-ray, chest CT scan (test using a special x-ray machine), MRI (test using a magnetic field and radio waves), and barium studies (study using a drinkable solution of barium to help enhance the x-ray pictures of the gut). Participants are divided into patients with IBD symptoms (Group 1) and patients without IBD symptoms (Group 2) for the following procedures: Group 1 Patients are evaluated every 6 months with a medical history and physical examination for signs and symptoms of IBD. Patients who are taking moderate to high doses of steroid medications have their medication slowly lowered (tapered) and are evaluated every 3 months for a total of 2 years. Patients in this group who start to develop IBD symptoms are moved to Group 2 for treatment with infliximab (see below). Group 2 Patients in Group 2 receive infliximab infusions at 2-week intervals for three doses. The drug is given over a 2-hour period through a catheter placed in a vein. Patients are evaluated with a medical history, physical exam, and blood tests the day of each dose. One week after the last dose, they have another evaluation, including a colonoscopy. Patients who respond well to infliximab may continue to receive the drug every 2 months for a total of 1 year, with evaluations at every dosing visit. At the end of the first year of receiving infliximab, all patients have follow-up evaluations every 6 months for a total of 2 years. Group 3 Subjects who volunteer to undergo colonoscopy and research biopsies that serve as controls for evaluation of the patient gut samples.
This study will compare the health and well being of children treated with a modified stem cell transplantation procedure for chronic granulomatous disease (CGD) with that of children receiving standard of care treatment. CGD is an inherited disorder of neutrophils-a type of infection-fighting white blood cell-that leaves patients vulnerable to life-threatening infections. Standard treatment with antibiotics, and sometimes surgery, is not always successful, and patients with persisting infections have a poor long-term prognosis. Transplantation of donated stem cells (cells produced by the bone marrow that mature into white and red blood cells and platelets) can improve immune function in patients with CGD and possibly cure the disease. However, this procedure carries a significant risk of death, because it requires complete suppression of the immune system with high-dose chemotherapy. In addition, lymphocytes-another type of infection-fighting white blood cell-from the donor may cause what is called graft versus host disease (GvHD), in which the donor cells 'see' patient's cells as foreign and mount an immune response to reject them. To try to reduce these risks, patients in this study will be given low-dose chemotherapy that is easier for the body to tolerate and involves a shorter period of complete immune suppression. Also, the donor's lymphocytes will be removed from the rest of the stem cells to be transplanted, reducing the risk of GvHD. Patients with CGD between 2 and 17 years of age who 1) are currently free of active infection, and 2) have a history of at least one life-threatening infection or a family member with CGD and a history of at least one life-threatening infection, and 3) a family member that is a suitable donor may be eligible for this study. Candidates will have a medical history, physical examination and blood tests, lung and heart function tests, x-rays or CT scans of the body, and dental and eye examinations. They will fill out questionnaires that measure emotional well being, quality of life, and intelligence (ability to learn and understand). Stem cells will be collected from both the patient and donor. To do this, the hormone G-CSF will be injected under the skin for several days to move stem cells from the bone marrow to the bloodstream. Then, the stem cells will be collected by apheresis. In this procedure the blood is drawn through a needle placed in one arm and pumped into a machine where the required cells are separated out and removed. Then, the rest of the blood is returned through a needle in the other arm. Several days before the transplant procedure, patients will start a 'conditioning regimen' of chemotherapy with cyclophosphamide, fludarabine and Campath 1H. When the conditioning therapy is completed, the donor's stem cells will be infused. To help prevent rejection of donor cells, cyclosporine will be given by mouth or by vein starting 1 month after the transplant procedure. The average hospital stay for stem cell transplantation is 21 days. After discharge, patients will return to the NIH clinic for follow-up clinic visits weekly or twice weekly for 2 to 3 months. These visits will include a symptom check, physical examination and blood tests. Subsequent clinic visits will be scheduled 1 to 3 times a year for at least 5 years.
This is a clinical trial of bone marrow transplantation for patients with the diagnosis of a genetic disease of blood cells that do not have an HLA-matched sibling donor. Genetic diseases of blood cell include: Red blood cell defects e.g. hemoglobinopathies (sickle cell disease and thalassemia), Blackfan-Diamond anemia and congenital or chronic hemolytic anemias; White blood cells defects/immune deficiencies e.g. chronic granulomatous disease, Wiskott-Aldrich syndrome,Osteopetrosis, Kostmann's syndrome (congenital neutropenia), Hereditary Lymphohistiocytosis (HLH); Platelets defects e.g.Congenital amegakaryocytic thrombocytopenia; Metabolic/storage disorders e.g. leukodystrophies,mucopolysaccharidoses as Hurler disease;Stem cell defects e.g.reticular agenesis, among many other rare similar conditions. The study treatment plan uses a new transplant treatment regimen that aims to try to decrease the acute toxicities and complications associated with the standard treatment plans and to improve outcome The blood stem cells will be derived from either unrelated donor or unrelated umbilical cord blood.