Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells

This is an interventional treatment trial for Sickle Cell Disease focused on measuring unrelated, BMT, HSCT, bone marrow transplantation, sickle cell disease, thalassemia, CGD, HLH, Blackfan-Diamond anemia, Hurler, leukodystrophy, LAD I, Genetic diseases, Red blood cell defects, Leukocyte defects and immune deficiencies, Hereditary Lymphohistiocytosis, chronic granulomatous disease, Wiskott-Aldrich syndrome, Chediak Higashi syndrome, CD40 ligand deficiency, Hyper IgM syndrome, leucocytes adhesion defect type 1, Osteopetrosis, congenital neutropenia, X-linked lymphoproliferative disease, Platelets defects, Congenital amegakaryocytic thrombocytopenia, Metabolic and storage disorders, Hurler disease, leukodystrophies, Niemann-Pick disease, Fucosidosis, Stem cell defects, reticular agenesis Read More

Inclusion Criteria:

• Lethal or sublethal genetic disease of blood cells, who lack a fully histocompatible sibling or other family donor
• Genetic diseases that would be candidates for this protocol includes those that have been shown to benefit from allogeneic HSCT: Red blood cell defects, Leukocyte defects/ Primary immune deficiencies, Platelets defects, Metabolic/storage disorders and Stem cell defects.
• Renal: creatinine clearance or glomerular filtration rate (GFR) ≥50 ml/min/1.73m2 and not requiring dialysis.
• Pulmonary: FEV1, FVC and DLCO (corrected for hemoglobin) ≥ 50% predicted. if unable to perform pulmonary function tests, then O2 saturation ≥ 92% in room air.
• Cardiac: Left ventricular ejection fraction at rest must be ≥ 40%, or shortening fraction ≥ 26%
• Hepatic: Bilirubin ≤3x upper limit of normal (ULN) and ALT and AST ≤ 5x for age (with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome).
• Patients will be 0-21 years of age.
• Disease specific inclusion criteria (as applicable per protocol).

Exclusion Criteria:

• Recipients should not have any of the general exclusion criteria, and disease specific exclusion criteria when applicable.
• Patient with histocompatible sibling
• End-organ failure that precludes the ability to tolerate the transplant procedure, including the conditioning regimen.
• Creatinine clearance or GFR < 50 ml/min/1.73m2 or renal failure requiring dialysis.
• Congenital heart disease resulting in congestive heart failure.
• Severe residual CNS disease/impairment [(other than hemiplegia alone) e.g. coma or intractable seizures]
• Ventilatory failure
• Major congenital anomalies that adversely affect survival, e.g. CNS malformations
• Lansky score < 40% or Karnofsky score < 60%
• HIV seropositivity
• Diagnosis of Fanconi's anemia, Severe Combined Immunodeficiency (SCID)
• Positive pregnancy test (For female patients in child bearing period)
• Uncontrolled bacterial, viral, or fungal infections (currently taking medication yet clinical symptoms progress)
• Disease specific exclusion criteria (as applicable per protocol).