Mobilization of CD34+ Peripheral Blood Stem Cells With Filgrastim (Granulocyte-colony Stimulating Factor) and Plerixafor From Patients With Diamond Blackfan Anemia Syndrome
Northwell Health
Summary
Gene therapy is a new possible treatment for the anemia of DBAS. Gene therapy will soon be available for patients with RPS19-mutated DBAS. This involves inserting the corrected RPS19 gene into the cells, leading to correction of the anemia. The application of gene therapy requires sufficient numbers of stem cells on which the correction can be performed. Stem cells must be mobilized (stimulated to move) from the bone marrow to the peripheral blood and then collected (also called 'harvested'). It is not known if patients with DBAS can mobilize enough stem cells into the peripheral blood to allow for the harvesting of sufficient numbers to permit genetic manipulation. It is important to demonstrate the ability to harvest an adequate number of stem cells before gene therapy can be tried in patients with DBAS. The purpose of this study is to determine if mobilization of stem cells from the bone marrow in patients with DBAS is enough to obtain the numbers of peripheral blood stem cells necessary for effective gene therapy. An actual harvest will not be done.
Description
Diamond Blackfan anemia syndrome (DBAS) is a rare, inherited bone marrow failure syndrome, characterized by severe anemia, birth defects and a predisposition to cancer. The majority of patients with DBAS have a mutation in a gene encoding either a small (S) or large (L) subunit-associated ribosomal protein (RP). DBAS typically presents with severe anemia within the first two months of life. Approximately 80% of patients are initially responsive to corticosteroids with an improvement of their anemia, whereas 20% will not respond and will require red blood cell transfusions. Of the 80% of patien…
Eligibility
- Age range
- 3–30 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Diamond Blackfan anemia syndrome as defined by the known criteria with a known gene mutation 2. Male or female patients of all ethnic background, greater than or equal to 3 years of age and weighing at least 10 kg, and less than or equal to 30 years of age 3. Enrolled in Diamond Blackfan Anemia Registry of North America (DBAR) 4. Chronically red blood cell transfusion dependent for at least 6 months 5. Performance scale (Lansky Play-performance Scale for Pediatric Functional Status for age \<16 years; Karnofsky Performance Scale for age ≥16 years) ≥ 70 6. Must sign info…
Interventions
- DrugMobilization Regimen
This study will utilize a standard mobilization regimen that is used for peripheral blood stem cell mobilization in patients with a variety of underlying conditions. Upon study initiation, participants will undergo a peripheral blood draw and bone marrow aspiration and biopsy. They will then begin the following mobilization regimen: 1. Granulocyte-colony stimulating factor (G-CSF; filgrastim) dosed at 10mcg/kg/day administered subcutaneously in the morning for 5-7 days 2. Plerixafor dosed at 0.24mg/kg/day administered subcutaneously in the evening for 1-4 days Participants will undergo daily blood draws until criteria for study completion is achieved.
Location
- Cohen Children's Medical CenterNew Hyde Park, New York