Beta Thalassemia, Bone Marrow Failure, Histiocytosis, Immunodeficiencies, Inborn Errors of Metabolism, Leukemia, Lymphoma, Sickle Cell Disease
Conditions
Keywords
unrelated donor transplant, CD34 selection
Brief summary
CD34+ stem cell selection in children, adolescents and young adults receiving partially matched family donor or matched unrelated adult donor allogeneic bone marrow or peripheral blood stem cell transplant will be safe and well tolerated and be associated with a low incidence of serious (Grade III/IV) acute and chronic graft versus host disease (GVHD).
Detailed description
The selection of CD34+ cells is associated with the simultaneous depletion of T cells that are responsible for severe acute and chronic graft versus host disease (GVHD). Successful engraftment is reported in adult patients with malignant and non-malignant disease who received CD34+ selected stem cells from HLA-matched or mismatched mobilized peripheral blood (PBSC) or bone marrow. Study Design: Selected patients defined in the eligibility criteria will enrolled on this study. Patients will receive one of either full intensity or reduced intensity regimen based on the patient's disease status, organ function and performance and determined by the PI and will have peripheral blood undergo CD34 selection.
Interventions
DRUGFull Intensity with TBI
Patients will start their pre-conditioning regimen on Day -8. Fractionated TBI will be administered twice daily for 3 days on Days -8, -7, and -6. Patients will receive Thiotepa on Days -5, -4, Cyclophosphamide on Days -3, -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1. The stem cell infusion will be performed on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus only.
DRUGFull Intensity
Patients will start their pre-conditioning regimen on Day -9. Patients will receive busulfan twice daily on Days - 8, -7, -6, and -5 and Melphalan on Days -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1 with stem cell infusion on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus only.
DRUGReduced Intensity
Patients will start their GVHD prophylaxis with Tacrolimus on Day -9. Patients will receive busulfan twice daily on Days -8, -7, -6, and -5; fludarabine on Days -7, -6, -5, -4, -3 and -2 and alemtuzumab on Days -5, -4, -3, -2, and -1. The stem cell infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus only.
DRUGReduced Intensity (Fanconi)
Patients will start their pre-conditioning regimen on Day -6. Patients will receive TBI as a single fraction on Day -6. Patients will receive fludarabine and cyclophosphamide on Days - 5, -4, -3, and -2 and antithymocyte globulin (horse) on Days -5, -4, -3, -2 and -1. The stem cell infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus only.
Sponsors
New York Medical College
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 70 Years
Healthy volunteers
No
Inclusion criteria
* Adequate renal function defined as:Serum creatinine \<1.5 x normal, or Creatinine clearance or radioisotope GFR \>60 ml/min/m2 or an equivalent GFR as determined by the institutional normal range. * Adequate liver function defined as:Total bilirubin \<1.5 x normal, or SGOT (AST) or SGPT (ALT) \<3.0 x normal * Adequate cardiac function defined as:Shortening fraction \>27% by echocardiogram, or Ejection fraction of \>47% by radionucleotide angiogram or echocardiogram. * Adequate pulmonary function defined as:Uncorrected DLCO \>50% by pulmonary function test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \>94% on room air. Eligibility for Reduced Intensity Regimen: * Adequate renal function defined as:Serum creatinine 2.0 x normal, or creatinine clearance or radioisotope GFR \> 40 ml/min/m2 or an equivalent GFR as determined by the institutional normal range. * Adequate liver function defined as:Total bilirubin \< 2.5 x normal; or SGOT (AST) or SGPT (ALT) \< 5.0 x normal. * Adequate cardiac function defined as:Shortening fraction of \>25% by echocardiogram, or Ejection fraction of \>40% by radionuclide angiogram or echocardiogram. * Adequate pulmonary function defined as:DLCO \>35% by pulmonary function test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \>94% in room air.
Exclusion criteria
* Pregnancy/Breast Feeding: Females who are pregnant or breast-feeding are not eligible. * Infection: Patients with documented uncontrolled infection at the time of study entry are not eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The safety CD34+ stem cell selection | 100 days | serious adverse events will be monitored post transplant to determine if there is an increase vs. historical data related to the CD34+ selection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune reconstitution (T, B, DC) following CD34+ selection | 3 years | immune subsets will be drawn post transplant to determine the rate of reconstitution post CD34+ transplant to determine if this process increases or decreases the reconstitution time. |
Countries
United States
Outcome results
None listed