National Institute of Allergy and Infectious Diseases (NIAID)
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.
Chronic Granulomatous Disease (CGD) is an inherited disorder resulting from a failure to produce nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, necessary for protection against a number of infectious organisms. Patients are subject to recurrent infections and inflammatory complications. The current management of these patients is limited to close surveillance for infections, administration of prophylactic antimicrobials, and rapid and aggressive treatment of suspected and documented infections with broad-spectrum antibiotics. Although often effective, these treatments can require…
* INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all the following criteria: * Must have the ability to comprehend and a willingness to sign the informed consent. For pediatric patients, must have a parent/guardian who can sign consent if the donor is a minor; assent will be obtained from minors as appropriate. * Must have confirmed diagnosis of CGD. * Must have sufficient complications from underlying disease to warrant undergoing transplantation (either a history of or ongoing inflammation/CGD-related autoimmunity OR a CGD-related infectio…
Post transplant drug - Immunosuppressant to prevent donor peripheral blood stem cell rejection and graft versus host disease. This is a well studied drug, and is not under an IND.
Post transplant drug - cyclophosphamide give to prevent graft versus host disease. This is a well studied drug and s not under an IND.
Transplant Conditioning Drug - Monoclonal antibody that targets recipient and donor T-cells to prevent graft versus host disease. Not an IND. This is a well-studied drug, and is not under an IND.
Transplant Conditioning Drug - Chemotherapy to create space in the patient's bone marrow so that the donor peripheral blood stem cells can repopulate in the patient's bone marrow. This is a well studied drug, and is not under IND.
Donor peripheral blood stem cells either matched unrelated donors or matched related relative to replace the patient's immune cells with functional immune cells. The peripheral blood stem cells are not regulated by the FDA.
Transplant conditioning drug for High Risk Group only - An interferon gamma blocking antibody used to prevent inflammation/engraftment syndrome post HSC transplant.
Transplant Conditioning Drug - An interleukin-6 (IL-6) receptor antagonist used to decrease Chronic Granulomatous Disease (CGD) inflammation during the HSC transplant process.
Transplant Conditioning - Total Body Irradiation (300 cGy in fractionated doses) to create space n the subject's bone marrow so that the donor peripheral blood stem cells can repopulate in the subject's bone marrow.