Trapianto di cellule staminali emopoietiche impoverite di cellule T alfa/beta da donatori consanguinei o non consanguinei per malattie del sangue in bambini e giovani adulti

Inclusion Criteria:

• No Human leukocyte antigen (HLA) identical sibling available AND

• NO HLA matched unrelated donor available OR urgent need of HSCT precludes time necessary to search for suitable HLA matched unrelated donor AND

• Haploidentical donor OR closely matched unrelated donor available and willing to undergo mobilization and apheresis

• If subject has genetically confirmed inherited bone marrow failure, related donor must be evaluated for this disorder and testing must be negative.

• If subject has sickle cell disease, donor must be unaffected or have only sickle cell trait

• Patient must be diagnosed with one of the following diseases or disorders:

  • Hemoglobinopathies

    • Sickle Cell Disease for patients ≤ 21 years of age for whom hydroxyurea has been trialed for at least six months, and failed
    • Thalassemia Major for patients ≤ 21 years of age

  • Acquired Bone Marrow Failure Syndromes

    • Paroxysmal Nocturnal Hemoglobinuria with bone marrow failure
    • Myelodysplastic Syndromes (lower risk)
    • Severe acquired aplastic anemia

  • Inherited Bone Marrow Failure Syndromes

    • Fanconi Anemia
    • Diamond Blackfan Anemia
    • Dyskeratosis Congenita and related telomere disorders
    • Congenital Thrombocytopenia Syndromes
    • Severe Congenital Neutropenia
    • Shwachman-Diamond Syndrome

  • Inborn Errors of Immunity (IEI) or Primary Immune Regulatory Disorders (PIRD)

    • Wiskott-Aldrich syndrome (WAS)
    • Chronic granulomatous disease (CGD)
    • Severe combined immunodeficiency (SCID)
    • Primary hemophagocytic lymphohistiocytosis (HLH)

• Age ≤ 25 years (except patients with hemoglobinopathies)

• Life Expectancy ≥ 3 months

• Karnofsky (patients > 16 years)/Lansky (patients ≤ 16 years) index ≥ 60

• Organ Function Requirements

  • Renal Function

    • Creatinine clearance or radioisotope Glomerular Filtration Rate (GFR) greater than or equal to 60 ml/min/1.73m^2

  • Liver Function

    • Total bilirubin < 3 mg/dL
    • Alanine aminotransferase (ALT)/ Serum glutamic-pyruvic transaminase; synonymous with ALT (SCPT) ≤ 3 x Upper Limit of Normal (ULN) for age

  • Cardiac Function

    • Ejection fraction of > 40% by Multiple gated acquisition scan (MUGA) or echocardiogram

  • Pulmonary Function

    • No evidence of dyspnea at rest
    • No supplemental oxygen requirement
    • If measured, carbon monoxide diffusion capacity (DLCO) > 50%

• Willing to use effective birth control method if patient is of reproductive potential

• Informed consent obtained (patient or legal representative)

Exclusion Criteria:

• Pregnant
• HIV infection
• Uncontrolled, serious active infection at screening
• Significant serious intercurrent illnesses
• Enrollment in any other treatment study that would interfere with the endpoints of this study according to judgement of Principal Investigator (or PI designee).