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.
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 infection while on prophylaxis) OR have a Quartile 1 or 2 residual oxidase production level.
Ages 4 years-65 years.
Ejection fraction of less than 30% by echocardiography.
Forced expiratory volume (FEV1%) of less than 35% and/or an adjusted diffusing capacity of lung of carbon monoxide (adj DLCO) of less than 30%.
Transaminases >5x upper limit of normal based on the individual s clinical situation and at the discretion of the investigator.
Psychiatric disorder or mental deficiency severe enough as to make compliance with the HSCT treatment unlikely, and/or to make regulatorily and legally effective informed consent impossible.