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

• Status: Unknown status
• Trial end date: 2013-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Reduced intensity conditioning followed by allogeneic stem cell transplantation will result in mixed/complete donor chimerism and potentially alter the natural history and outcome of patients with non-malignant diseases.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Columbia University
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Vidarabine

Criteria

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.