Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases

This is an interventional treatment trial for Bone Marrow Failure focused on measuring Bone marrow Failure, Fanconi, SCID Read More

Inclusion Criteria

• Patients must meet the eligibility criteria for organ function regardless of diagnosis:

  • Age < 30 or = 30 years of age
  • Adequate renal function defined as serum creatinine < or = 1.5 x normal, or creatinine clearance or radioisotope GFR > or =40 ml/min/m2 or >60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
• Adequate liver function defined as SGOT (AST) or SGPT (ALT) < 5.0 x normal
• Adequate cardiac function defined as shortening fraction of > or = 28% by echocardiogram, or ejection fraction of > or = 48% by radionuclide angiogram or echocardiogram
• Adequate pulmonary function defined as asymptomatic or, if symptomatic, DLCO >45% of predicted (corrected for hemoglobin level). If unable to obtain pulmonary function test, O2 saturation >85% in room air.

Bone Marrow Failure Syndromes

Patients with the following diagnoses are eligible:

Severe Aplastic Anemia:

• Hypocellular bone marrow biopsy (<25% cellularity) and 2/3 of the following (at diagnosis or nadir):
• Absolute Neutrophil Count (ANC) <200/mm3,
• Platelets <20,000/mm3
• Reticulocyte count <60,000/mm3

Fanconi Anemia:

• Abnormal clastogenic studies (all patients)
• Severe Congenital Neutropenia (Kostmann's Syndrome)
• Amegakaryocytic Thrombocytopenia
• Severe thrombocytopenia (< or =20,000/mm3) at diagnosis
• Severe depletion of megakaryocytes on bone marrow aspirate (< or =25% normal)

Diamond-Blackfan Anemia:

• Corticosteroid dependent for > 6 months OR Transfusion dependent OR refractory acquired pure red cell aplasia.
• Infantile Osteopetrosis
• Schwachman-Diamond Syndrome
• Dyskeratosis Congenita

Other bone marrow failure syndromes at discretion of co-principal investigators

• Immunodeficiencies
• SCIDS, all subtypes
• Combined Immunodeficiency Syndrome
• Wiskott-Aldrich Syndrome
• Chronic Granulomatous Disease
• Chediak-Higashi Syndrome
• Leukocyte Adhesion Deficiency
• Other immunodeficiencies at discretion of co-principal investigators
• Inborn Errors of Metabolism (IEOM)

Transplant is recommended for the following disorders:

• Hurler syndrome (alpha-L-iduronidase deficiency, MPS-I), preferably before age 24 months
• Maroteaux-Lamy syndrome (galactosamine-4-sulfatase deficiency,MPSVI)
• Sly syndrome (beta-glucuronidase deficiency, MPS-VII)
• Globoid cell leukodystrophy (galactocerebrosidase deficiency), with careful attention to neurologic status in the infantile form
• Metachromatic leukodystrophy (arylsulfatase A deficiency),juvenile or adult onset form; late infantile MLD only if pre-symptomatic
• Childhood-onset X-linked adrenoleukodystrophy (X-ALD), at initial signs of neuropsychological deterioration, with dietary modification prior to transplant
• Fucosidosis (fucosidase deficiency)
• Mannosidosis
• Aspartylglucosaminuria
• Niemann-Pick Disease Type B (acid sphingomyelinase deficiency) Other diagnoses may be considered at the discretion of the co-principal investigators
• For X-ALD patients greater than 5 years of age, IQ >80 is required. For other patients greater than 5 years of age, IQ > 70 is required.
• For Gaucher disease (glucocerebrosidase deficiency) Type I (non-neuropathic), the primary therapy is enzyme replacement, but allogeneic stem cell transplant has been used effectively.

• Histiocytoses

  • Hemophagocytic Lymphohistiocytosis (HLH)
  • Familial Erythrophagocytic Lymphohistiocytosis
  • Langerhans Cell Histiocytosis Patients with multi-system disease whose initial disease is stable or progressive after minimum 6 weeks of appropriate therapy, OR Patients with recurrent multi-system disease.
  • Malignant Histiocytosis
• Other non-malignant diseases not listed above may be eligible if deemed appropriate by the co-principal investigators.