Title (Pediatric) 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


CC 11-697

Hospital Main Campus

Stage N/A

Phase N/A

Disease Blood & Marrow Transplant (BMT), Nonmalignant Inherited Disorders, Primary Immunodeficiencies

Drug Alemtuzumab , Fludarabine



  1. Primary
    • Improve donor chimerism levels in patients with inherited nonmalignant disorders undergoing HCT using a reduced intensity conditioning regimen either through the addition of Campath? or a slightly higher dose of TBI.
  2. Secondary
    • Decrease the incidence and severity of acute and chronic GVHD through use of marrow as the stem cell source and Campath
    • Assess disease response following HCT
    • Immune reconstitution following HCT
    • Incidence of infections
    • Overall survival
    • Percent of patients with CD33/CD19 donor chimerism > 50%
Inclusion Criteria

Inclusion Criteria

  1. Age < 55 years with primary immunodeficiency disorder or other nonmalignant inherited disease (except aplastic anemia and fanconi anemia) treatable by allogeneic HCT.
  2. 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.
Exclusion Criteria

Exclusion Criteria

  1. Patients with Aplastic anemia and Fanconi anemia
  2. Patients with metabolic storage diseases who have severe CNS involvement of disease, defined as IQ score < 70.
  3. Patients with the following organ dysfunction:
    • a) Cardiac: cardiac ejection fracture < 30% or, if unable to obtain ejection fraction, shortening fraction of < 26%) or 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 your cardiologist
    • Poorly controlled hypertension despite anti-hypertensive medications.
    • Hepatic: 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 > 3 mg/dl, or symptomatic biliary disease. Note: Patients will be allowed on to the protocol with liver problems if gastroenterology approves the patient for HCT.
  4. Patients who are seropositive for human immunodeficiency virus (HIV).
  5. Females who are pregnant or breast-feeding.
  6. Fertile men or women who are unwilling to use contraceptives during HCT and up to 12 months post-treatment.
  7. 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).