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.
Diamond Blackfan anemia syndrome as defined by the known criteria with a known gene mutation
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
Enrolled in Diamond Blackfan Anemia Registry of North America (DBAR)
Chronically red blood cell transfusion dependent for at least 6 months
Receiving prednisone therapy for treatment of DBAS (this does not include patients receiving physiologic steroid replacement for adrenal insufficiency)
Known history of myelodysplasia or presence of a hematopoietic clone
Current malignancy or previous treatment for malignancy
Pregnancy or breast-feeding mother
Patients with Diamond Blackfan Anemia Syndrome (DBAS) ages 3-30 with red blood cell transfusion dependence
Case-only
Prospective
Mobilization Regimen
DrugThis 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.
Feasibility of collecting 5-30 CD34+ cells/µL in patients ages 3 to 30 years with Diamond Blackfan anemia syndrome
This study will analyze the number of participants that successfully achieve 5-30 CD34+ cells/µL peripheral blood during the study period.
Time to successful mobilization of CD34+ cells/µL peripheral blood
For participants who achieve a peripheral blood CD34+ count of 5-30/µL, the time (in days) from the start of mobilization regimen to successful mobilization (the day at which peripheral blood CD34+ count = 5-30/µL) will be quantified
Correlation of bone marrow CD34+ count with the ability to mobilize an adequate number of CD34+ cells in the peripheral blood.
Correlation of mobilization of 5-30 CD34+ cells/µL peripheral blood with subject's age
Correlation of mobilization of 5-30 CD34+ cells/µL peripheral blood with bone marrow cellularity.
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