Treatment of Chronic Granulomatous Disease With Allogeneic Stem Cell Transplantation Versus Standard of Care

INCLUSION CRITERIA The following conditions must be met before a patient may be enrolled in the study: Patients ages 2 to 17 years; minimum weight of 12 kg. DHR proven chronic granulomatous disease with gp91 phox or p22 phox deficiency. History of at least one life-threatening infection (defined as any infection requiring treatment with intravenous antibiotic therapy) or a family member with CGD and a history of life-threatening infection. Free of active infection. Patients with consenting HLA-matched related donors that meet donor selection criteria (test patients), or patients without an eligible HLA-matched related donor (control patients). Patients with eligible donors who choose not to undergo stem cell transplantation or patients with eligible but non-consenting donors may be enrolled in the control arm of the study. Patients enrolled in the control arm who complete a 24 month follow-up period may enroll in the transplant arm should an eligible, consenting donor become available. Patients with adequate organ function as measured by: Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction at rest must be greater than 35%. Hepatic: SGOT within 4 times normal range and total bilirubin less than 2mg/dL. Renal: Creatinine clearance greater than or equal to 50 mL/min/ 1.73m(2). A maximum age adjusted serum creatinine will be used for patients who are unable to provide an accurate 24 hour urine collection. For children less than or equal to 5 years of age, the maximum serum creatinine (mg/dl) is 0.8; for children whose age is greater than 5 to less than or equal to 10, the maximum serum creatinine (mg/dl) is 1.0; for children whose age is greater than 10 to less than or equal to age 15, the maximum serum creatinine (mg/dl) is 1.2; and for children whose age is greater than 15, the maximum serum creatinine (mg/dl) is 1.5. Pulmonary: DLCO (diffusion capacity) and FEV1 greater than 45 percent of predicted (corrected for hemoglobin). Minors in whom pulmonary function tests are not possible will be evaluated for significant pulmonary dysfunction by a pulmonary consultant. Written informed consent/assent conforming to institutional guidelines obtained from patient and parent. Absence of co-existing medical problems that would significantly increase the risk of a transplant procedure in the judgment of the principal investigator. EXCLUSION CRITERIA: Any one of the following conditions eliminates a patient from participating in this protocol: Female patients who are pregnant or lactating. ECOG performance status of 2 or more or less than 50 percent on the Lansky scale for ages 0-10. Seropositivity for HIV due to excessive risk of infection and neurotoxicity of antiretroviral medications. Evidence of rapid deterioration due to progressive infection and/or organ damage. Malignant diseases liable to relapse or progress within 5 years. DONOR SELECTION: Donors must be fit to receive G-CSF and give peripheral blood stem cells (normal blood count, normotensive, no history of stroke, no history of severe heart disease, greater than 12kg). Related to the patient and HLA-phenotypically identical with the patient for HLA-A, B and DRB1 alleles. Matching assessed minimally by serology for Class I and DNA typing for Class II antigens. Female x-linked CGD carriers must have greater than 30 percent normal neutrophils. If donor is a sibling who is a minor, he/ she is the oldest eligible sibling and no adult siblings are eligible donors. Written informed consent from donor. Donors who are minors will be evaluated by a social worker, psychologist or psychiatrist prior to the assent process to determine willingness to participate. If willingness to participate has been confirmed, informed consent will be obtained from adult parent or legal guardian. Informed assent will be obtained from minor donor in the presence of a third party who will assess comprehension and voluntary participation.