matched unrelated or non-genotype identical related donor transplantation for chronic granulomatous disease

Conditions: Chronic Granulomatous Disease

Summary: this study is for patients with chronic granulomatous disease (cgd), which is a disorder of the immune system that puts them at risk for severe infections. cgd is caused by a genetic defect that stops or prevents the white blood cells from killing certain bacteria and fungi. this condition cannot presently be cured by standard treatment with drugs or surgery. medicine including antibiotics, antifungals, and interferon gamma, may help some patients with cgd; however even with continuous treatment, most patients with cgd will have chronic and recurrent infections. transfusion of white blood cells may help overcome infection, but white cell transfusions lead to allergic reactions and fever and the benefit of transfusion lasts only a matter of hours. ultimately, chronic infections can damage or injure the body organs. injury to the lung or liver can lead to lung or liver failure and death. medicines used to treat infection can damage body organs too. infections may become resistant to antibiotic or antifungal treatment, and infections not responding to treatment can be deadly. it is now known that under specific conditions and with special treatment, blood stem cells (the cells that make blood) can be transplanted from one person to another. stem cell transplantation has been done for patients with cgd who have a healthy sibling and who share the same immune type (hla type) as the patient. stem cell transplantation allows healthy or normal white cells from the stem cell donor to grow or develop in the patient's bone marrow. these healthy white cells can fight infection and prevent future infections for a patient with cgd. patients on this study will receive stem cells from a related or unrelated donor. the donor will be closely matched to the patient's immune type but the donor is not a sibling. the reason this treatment is investigational is that we do not know the likelihood of benefit that the patient will receive. it is possible that they will have great benefit, like some of the patients who have been transplanted from a brother or sister. it is possible that the side-effects of treatment may be too severe so that the transplant won't work. the purpose of this research study is to evaluate whether or not patients with cgd treated with a stem cell transplant from a non-matched and/or non-related donor can have a good outcome from the procedure with an acceptable number of side-effects.

in order to transplant stem cells we will need to give the patient drugs or high-dose chemotherapy to kill or destroy most of the blood forming and immune cells in the bone marrow. this is necessary to allow the donor stem cells to live and grow (engraft) in the bone marrow space. after the drug treatment is completed, the patient will be given the stem cells from the donor. the drug treatment is as follows: day -9 busulfan day -8 busulfan day -7 busulfan day -6 busulfan day -5 alemtuzumab, fludarabine, cyclophosphamide day -4 alemtuzumab, fludarabine, cyclophosphamide day -3 alemtuzumab, fludarabine, cyclophosphamide day -2 alemtuzumab, fludarabine, cyclosporine, cyclophosphamide day -1 rest day 0 stem cell infusion the day after the chemotherapy treatment is completed, the patient will receive the healthy stem cells by vein, like a blood transfusion. once in the bloodstream, the marrow cells will go to the bone marrow and grow. it is also possible that if the marrow takes, it will cause a disease known as graft-versus-host disease (gvhd). to prevent gvhd, we will give the patient cyclosporine and methotrexate. methotrexate will be administered on days 1, 3, 6 and 11 after the transplant. the cyclosporine therapy will continue for a longer period of time, however if the patient does not develop gvhd, it will be discontinued by 6 months after the stem cell transplant.

Eligibility criteria:
inclusion criteria: cgd patients as documented by an abnormal nbt assay in a male patient and/or abnormal nadph enzyme mutation confirmed by genetic analysis with abnormal nbt. patients must not have an hla genotype identical donor. patients must have a 5/6 or 6/6 hla-matched unrelated donor or a 5/6 or 6/6 hla phenotype-matched related donor. patients must have had at least one serious infection characteristic of those manifested in patients with cgd. patients must not have active infection. an active infection may include the following: 1) clinical findings consistent with an infection such as fever, cavitary organ lesions, osteomyelitis; 2) progression of presumed infection based upon findings of diagnostic imaging (two or more studies at least 1 month a part). no cumulative organ dysfunction that, in the estimation of the treating physicians, will diminish the patient's likelihood to survive this procedure. negative pregnancy test for post-pubertal female patients. echocardiogram shortening fraction \>/= 28%. dlco 50% or greater predicted or fev1 \>/= 50% predicted. exclusion criteria: active or uncontrolled infection (e.g. lung infection, cavitary organ lesions, osteomyelitis). markedly elevated c reactive protein or sedimentation rate relative to patient's baseline. invasive bone or bone marrow disease. lack of potential hematologic blood product donors in the past (related to mcleod phenotype).

Keywords: stem cell transplant chronic granulomatous disease fludarabine busulfan cyclophosphamide