Pilot Study of Reduced-Intensity Hematopoietic Stem Cell Transplant of DOCK8 Deficiency

Background: -DOCK8 deficiency is a genetic disorder that affects the immune system and can lead to severe recurrent infections and possible death from infections or certain types of cancers, including blood cancers. A stem cell transplant is a life-saving treatment for this condition. In this study we are evaluating the efficacy and safety of transplant from different donor sources for DOCK8 deficiency. The donors that we are using are matched siblings, matched unrelated donors, and half-matched donors, so called haploidentical related donors, such as mothers or fathers or half-matched siblings. Objectives: -To determine whether transplant of bone marrow cells from different types of donors corrects DOCK8 deficiency. Eligibility: * Donors: Healthy individuals between 2 and 60 years of age who are matched with a recipient. * Recipient: Individuals between 4 and 35 years of age who have confirmed DOCK8 deficiency, have suffered at least one life-threatening infections, or have had certain viral related cancers of cancer and have a stem cell donor. Design: * All participants will be screened with bloodwork, a physical examination and medical history. * DONORS: --Donors who have donate bone marrow cells or blood stem cells will have a sample of blood/bone marrow stored to be compared with the recipients sample after transplant. * RECIPIENTS: * Recipients receiving 10/10 matched related or unrelated donors will receive 4 days of chemotherapy with busulfan and fludarabine to suppress their immune system and prepare them for the transplant. Donors receiving 9/10 matched related or unrelated donors as well as haploidentical related donors will receive 5 days chemotherapy with cyclophosphamide, fludarabine, and busulfan. They will also receive one dose of radiation to suppress their immune system and prepare them for the transplant. * After the initial chemotherapy and radiation (if indicated), recipients will receive the donated stem cells as a single infusion. * After the stem cell transplant, recipients will receive two days of a chemotherapy called cyclophosphamide on day's + 3 and + 4 followed by two drugs tacrolimus and mycophenolate to prevent graft versus host disease where the donor cells attack the patient's body. All patients will remain in the hospital for at least approximately 1 month, and will be followed with regular visits for up to 3 years with periodic visits thereafter to evaluate the success of the transplant and any side effects.

* INCLUSION CRITERIA - RECIPIENT: * Age of 4-35 years * Weight \>= 12 kilograms * DOCK8 deficiency with the two criteria listed below: * Clinical history of one or more episodes of life-threatening or severely disfiguring infection with opportunistic organisms, including severe recurrent cutaneous and sinopulmonary infections with bacterial or fungal infection, or viral infections with herpes simplex, herpes zoster, Molluscum contagiosum, or human papilloma virus. * Homozygous or compound heterozygous mutations in the DOCK8 gene performed by a CLIA-certified laboratory * Available 10/10 or 9/10 HLA-matched related or unrelated donor or a haploidentical related donor * Left ventricular ejection fraction \> 40%, preferably by 2-D echo. If the subject has radiological evidence of aortic, renal artery, or coronary artery vasculitis, a left ventricular ejection fraction \>30% is acceptable. * Pulmonary Function Tests: FEV1 \> 50% of expected Note: For children who are unable to cooperate for PFTs, the criterion is: No evidence of dyspnea at rest, no exercise intolerance, and no requirement for supplemental oxygen therapy * Creatinine: Subjects: less than or equal to 2.0 mg/dl or creatinine clearance greater than or equal to 30 ml/min/1.73 m\^2. Pediatric subjects (\