Hematopoietic Cell Transplantation for Treatment of Patients With Primary Immunodeficiencies and Other Nonmalignant Inherited Disorders Using Low-dose TBI and Fludarabine With or Without Campath

Inclusion Criteria:

- Primary immunodeficiency disorder or other nonmalignant inherited disease (except
aplastic anemia and Fanconi anemia) treatable by allogeneic HCT

- Patients with pre-existing medical conditions or other factors that renders them at
high risk for regimen related toxicity or ineligible for a conventional myeloablative
HCT

- Donors: Related donor who is human leukocyte antigen (HLA) genotypically identical at
least at one haplotype and may be genotypically or phenotypically identical for
serological typing for HLA-A, B, -C, and at the allele level for -DRB1 and -DQB1;
related donors must be a match or a single allele mismatch at HLA-A, B, and C (at
highest resolution available at the time of donor selection) and matched at DRB1 and
DQB1 by deoxyribonucleic acid (DNA) typing

- Donors: Unrelated donors who are prospectively:

- Matched for HLA-A, B, C, DRB1 and DQB1 by DNA typing at the highest resolution
routinely available at the time of donor selection

- Only a single allele disparity will be allowed for HLA-A, B, or C as defined by
high resolution typing (no mismatching for DRB1 or DQB1 is allowed)

Exclusion Criteria:

- Patients with Aplastic anemia and Fanconi anemia

- Patients with metabolic storage diseases who have severe central nervous system (CNS)
involvement of disease, defined as intelligence quotient (IQ) score < 70

- Cardiac ejection fraction < 30% or, if unable to obtain ejection fraction, shortening
fraction of < 26%) on multi-gated acquisition (MUGA) scan or cardiac echo,
symptomatic coronary artery disease, other cardiac failure requiring therapy;
patients with a history of, or current cardiac disease should be evaluated with
appropriate cardiac studies and/or cardiology consult; patients with a shortening
fraction < 26% may be enrolled if approved by a cardiologist

- Poorly controlled hypertension despite anti-hypertensive medications

- Patients with clinical or laboratory evidence of liver disease will need to be
evaluated for the cause of the liver disease, its clinical severity in terms of liver
function and the degree of portal hypertension; patients will be excluded if they are
found to have: fulminant liver failure, cirrhosis of the liver with evidence of
portal hypertension, bridging fibrosis, alcoholic hepatitis, esophageal varices, a
history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic
synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites
related to portal hypertension, bacterial or fungal liver abscess, biliary
obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dl, or
symptomatic biliary disease (Patients will be allowed on to the protocol with liver
problems if gastroenterology approves the patient for HCT)

- Patients who are seropositive for human immunodeficiency virus (HIV)

- Females who are pregnant or breast-feeding

- Fertile men or women who are unwilling to use contraceptives during HCT and up to 12
months post-treatment

- Patients with fungal pneumonia with radiological progression after receipt of
amphotericin formulation or mold-active azoles for greater than 1 month will not be
eligible for this protocol (either regimen A or B)

- Donors: Identical twin

- Donors: Pregnancy

- Donors: HIV seropositive

- Donors: A positive anti-donor cytotoxic cross match is absolute donor exclusion

- Donors: If a patient is homozygous at a particular loci, mismatching at that loci is
not allowed due to an isolated graft rejection vector, i.e., patient A*0101 and the
donor is A*0101, A*0201; such a mismatch may increase the risk of graft rejection; if
patient and donor pairs are both homozygous at a mismatched loci, they are considered
a two-HLA antigen mismatch, i.e., the patient is A*0101 and the donor is A*0201, and
this type of mismatch is not allowed

- Donor: Donor < 6 months old, > 75 years old