Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT

Inclusion Criteria55

• A 4/6, 5/6 or 6/6 HLA matched related or unrelated UCB unit available that will deliver a pre-cryopreservation total nucleated cell dose of ≥ 3 x 10e7 cells/kg, or double unit grafts, each cord blood unit delivering at least 2 x 10e7 cells/kg OR an 8 of 8 or 7 of 8 HLA allele level matched unrelated donor bone marrow or peripheral blood progenitor graft.
• Adequate organ function as measured by:
• Creatinine ≤ 2.0 mg/dL and creatinine clearance ≥ 50 mL/min/1.73 m2.
• Hepatic transaminases (ALT/AST) ≤ 4 x upper limit of normal (ULN).
• Adequate cardiac function by echocardiogram or radionuclide scan (shortening fraction \> 26% or ejection fraction \> 40% or \> 80% of normal value for age).
• Pulmonary evaluation testing demonstrating CVC or FEV1/FVC of ≥ 50% of predicted for age and/or resting pulse oximeter ≥ 92% on room air or clearance by the pediatric or adult pulmonologist. For adult patients DLCO (corrected for hemoglobin) should be ≥ 50% of predicted if the DLCO can be obtained.
• Written informed consent and/or assent according to FDA guidelines.
• Negative pregnancy test if pubertal and/or menstruating.
• HIV negative.
• A non-malignant disorder amenable to treatment by stem cell transplantation, including but not limited to:
• Primary Immunodeficiency syndromes including but not limited to:
• Severe Combined Immune Deficiency (SCID) with NK cell activity
• Omenn Syndrome
• Bare Lymphocyte Syndrome (BLS)
• Combined Immune Deficiency (CID) syndromes
• Combined Variable Immune Deficiency (CVID) syndrome
• Wiskott-Aldrich Syndrome
• Leukocyte adhesion deficiency
• Chronic granulomatous disease (CGD)
• X-linked Hyper IgM (XHIM) syndrome
• IPEX syndrome
• Chediak - Higashi Syndrome
• Autoimmune Lymphoproliferative Syndrome (ALPS)
• Hemophagocytic Lymphohistiocytosis (HLH) syndromes
• Lymphocyte Signaling defects
• Other primary immune defects where hematopoietic stem cell transplantation may be beneficial
• Congenital bone marrow failure syndromes including but not limited to:
• Dyskeratosis Congenita (DC)
• Congenital Amegakaryocytic Thrombocytopenia (CAMT)
• Osteopetrosis
• Inherited Metabolic Disorders (IMD) including but not limited to:
• Mucopolysaccharidoses
• Hurler syndrome (MPS I)
• Hunter syndrome (MPS II)
• Leukodystrophies
• Krabbe Disease, also known as globoid cell leukodystrophy
• Metachromatic leukodystrophy (MLD)
• X-linked adrenoleukodystrophy (ALD)
• Hereditary diffuse leukoencephalopathy with spheroids (HDLS)
• Other inherited metabolic disorders
• alpha mannosidosis
• Gaucher Disease
• Other inheritable metabolic diseases where hematopoietic stem cell transplantation may be beneficial.
• Hereditary anemias
• Thalassemia major
• Sickle cell disease (SCD) - patients with sickle disease must have one or more of the following:
• Overt or silent stroke
• Pain crises ≥ 2 episodes per year for past year
• One or more episodes of acute chest syndrome
• Osteonecrosis involving ≥ 1 joints
• Priapism
• Diamond Blackfan Anemia (DBA)
• Other congenital transfusion dependent anemias
• Inflammatory Conditions
• Crohn's Disease/Inflammatory Bowel Disease