Gene Therapy for X-CGD

• Verified diagnosis of the X-linked form of chronic granulomatous disease, with loss of gp91phox expression (Western Blot). Evidence of less than 5% of normal oxidase production in circulating neutrophil granulocytes as measured by dihydrorhodamine- (DHR-) and nitro blue tetrazolium- (NBT-) assay
• History of severe chronic infections with life-threatening course or severe steroid- sensitive or steroid insensitive granulomatous disease, with necessity of inpatient treatment, without sustained improvement even under maximum conservative treatment measures
• No Human Leukocyte Antigen (HLA) identical (10/10 match) sibling- or unrelated donor, or contraindications for allogenic stem cell transplantation in presence of a suitable donor. The lack of an HLA-identical (10/10 match) sibling- or unrelated donor has to be confirmed by an unsuccessful search in national and international donor registers for at leat 3 months
• Normal organ-function: glomerular filtration rate (GFR) ≥ 60ml/min., Bilirubin ≤ 1.5-fold upper reference-level, normal parameters for liver enzymes and clotting (TPZ 75-100%, partial thromboplastin time (PTT) 30-38sec, Fibrinogen 200-400mg/dl), Leukocytes > 3 x 10\^9/l, Granulocytes > 1.5 x 10\^9/l, Thrombocytes >100 x 10\^9/l
• Contraception from start of G-CSF application until 1 year after retransfusion of the gene-corrected cells
• No interferon-gamma injection within two weeks prior to hematopoietic stem cell mobilization
• Karnofsky-Index > 70%
• Signed informed consent

Exclusion Criteria:

• Patients with non-controlled acute infections
• Severe cardiac or pulmonary malfunctions: ejection fraction \< 60%, valvular heart disease > II°, arrhythmia requiring therapy, forced expiratory volume at one second/vital capacity (FEV1/VC) \< 75% , diffusion capacity of lung for carbon monoxide (DLCO) \<60%
• Bilirubin > 1.5-fold upper reference-level
• HIV-, Hepatitis B- or C - infection
• Contraindications for G-CSF administration, as autoimmune vasculitis.
• Contraindications for stem cell apheresis, as low hemoglobin \< 8g/dl, cardiovascular instability or severe coagulopathy
• Pregnancy or breast-feeding
• Drug- or alcohol-abuse
• Lack of search for an unrelated donor
• Patients with a HLA 9/10 mismatched unrelated donor (MMUD) will be excluded, if a thorough risk-benefit analysis favors allogenic hematopoietic stem cell transplantation (HSCT)