Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT (HSCT+RIC)

This is an interventional treatment trial for Primary Immunodeficiency (PID) focused on measuring Severe Combined Immune Deficiency (SCID), 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, Dyskeratosis Congenita (DC), Congenital Amegakaryocytic Thrombocytopenia (CAMT), Osteopetrosis, Mucopolysaccharidoses, Hurler syndrome (MPS I), Hunter syndrome (MPS II), Leukodystrophies, Krabbe Disease, Metachromatic leukodystrophy (MLD), X-linked adrenoleukodystrophy (ALD), Alpha mannosidosis, Gaucher Disease, Thalassemia major, Sickle cell disease (SCD), Diamond Blackfan Anemia (DBA), Crohn's Disease, Inflammatory Bowel Disease, Hematopoietic Stem Cell Transplant (HSCT), Congenital transfusion dependent anemias, Globoid cell leukodystrophy, Hereditary diffuse leukoencephalopathy with spheroids (HDLS), Systemic Juvenile Idiopathic Arthritis (sJIA) Read More

Inclusion:

1. 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.

2. Adequate organ function as measured by:

   1. Creatinine ≤ 2.0 mg/dL and creatinine clearance ≥ 50 mL/min/1.73 m2.
   2. Hepatic transaminases (ALT/AST) ≤ 4 x upper limit of normal (ULN).
   3. Adequate cardiac function by echocardiogram or radionuclide scan (shortening fraction > 26% or ejection fraction > 40% or > 80% of normal value for age).
   4. 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.
3. Written informed consent and/or assent according to FDA guidelines.
4. Negative pregnancy test if pubertal and/or menstruating.
5. HIV negative.

6. A non-malignant disorder amenable to treatment by stem cell transplantation, including but not limited to:

   1. 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

   2. Congenital bone marrow failure syndromes including but not limited to:

      • Dyskeratosis Congenita (DC)
      • Congenital Amegakaryocytic Thrombocytopenia (CAMT)
      • Osteopetrosis

   3. 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.

   4. 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

   5. Inflammatory Conditions

      • Crohn's Disease/Inflammatory Bowel Disease

Exclusion:

1. Allogeneic hematopoietic stem cell transplant within the previous 6 months.
2. Any active malignancy or MDS.
3. Severe acquired aplastic anemia.
4. Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression of clinical symptoms).
5. Pregnancy or nursing mother.
6. Poorly controlled pulmonary hypertension.
7. Any condition that precludes serial follow-up.