Part B- G1X-CGD (Lentiviral Vector Transduced CD34+ Cells) in Patients With X-Linked Chronic Granulomatous Disease

Background: X-Linked Chronic Granulomatous Disease (X-CGD) is caused by a gene mutation that makes the immune system to not work properly. Researchers want to see if a lentiviral gene transfer treatment will have the ability to make the patient s immune system more normal, in particular reduce the risk of CGD related infections. The gene transfer takes a person s own stem cells, cultures them to put the normal gene in, then gives the cells back to the person. Objective: To test a gene transfer treatment for X-CGD. Eligibility: Participants aged 3-60 with X-CGD Design: Participants will be screened under protocol 05-I-0123. They will undergo: Medical history Physical exam Heart tests Imaging tests, as needed Blood tests Lung function tests, as needed Dental and audiology exams, if needed Quality of life questionnaire Bone marrow aspiration. A needle will be inserted into the hip bone or breastbone to collect bone marrow. Some screening tests will be repeated during the study. Participants will have an apheresis procedure under protocol 94-I-0073. Stem cells will be collected. Participants will get a series of drugs to prepare them for the gene transfer. Participants will stay at the NIH Clinical Center for a little over a month. They will get a central line. It is a large intravenous (IV) catheter that is placed into a vein of the neck, chest, or arm. They will get chemotherapy and their corrected stem cells through their IV line. Participants will have 12 follow-up outpatient visits in the 2 years after their gene transfer, as well as visits with their local doctor. Then they will enroll in another study for long-term follow-up visits that will last for 13 years.

-INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: * Must have confirmed molecular diagnosis of X-linked CGD confirmed by deoxyribonucleic acid (DNA) sequencing and supported by laboratory evidence for absent or reduction \>90% of the biochemical activity of the NADPH-oxidase. * At least 1 prior ongoing or refractory severe infection and/or inflammatory complications requiring hospitalization despite conventional therapy. * No 10/10 HLA-matched donor available after initial search of National Marrow Donor Program (NMDP) registries within the last year. * Must weigh at least 15 kg. * Male or female, and must be at least 3 years of age but no older than 60. * Parent/guardian must be willing to sign and date informed consent form for child and where appropriate, child may sign assent. * Stated willingness to comply with all study procedures and availability for the duration of the study. * Ability to take oral medication and be willing to adhere to the prophylactic regimen. * Apheresis of patients for the hematopoietic stem cells collected as a part of this protocol will be performed according to the Standard of Care apheresis practices established in the NIH CC Department of Transfusion Medicine for such procedures. * For apheresis, pediatric patients: --Must weigh at least 15 kg body weight; --Preserved renal function (creatinine \= 5.1 mmol/L or \< 1.9 mmol/L. * Serum transaminases \> 5X the upper limit of normal (ULN). Serum bilirubin \> 2X the upper limit of normal (ULN). Serum glucose \> 1.5X the upper limit of normal (ULN). * General * Expected survival \< 6 months. * Major congenital anomaly. * Known allergic reactions to components of busulfan or dimethyl sulfoxide (DMSO) or contraindication for administration of conditioning medication. * Evidence of active malignant disease. * Treatment with another investigational drug or other intervention within 6 months. * Unable to undergo apheresis as per the NIH CC Department of Transfusion Medicine Standard of Care apheresis procedures. 1. Patients who are hemodynamically unstable (systolic or diastolic blood pressure fall of 20 mm Hg from the stable patient's baseline measurement) or requiring mechanical respiratory assistance are excluded. History of vasculitis. * Administration of gamma-interferon within 30 days before the infusion of transduced, autologous CD34+ cells. * Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful study completion.