Mobilization of Stem Cells With G-CSF for Collection From Patients With Diamond-Blackfan Anemia

Diamond-Blackfan anemia (DBA) is a congenital hypoproliferative anemia that generally presents in infancy. The mainstays of treatment, prednisone and transfusion therapy, have long-term toxicity in many patients, and bone marrow transplantation with an HLA-matched donor is an option for only a minority of patients. Most importantly, patients with DBA have an increased risk of progression of myelodysplastic syndrome, leukemia, and aplastic anemia compared to the general population.

The characterization of potentially mutated genes in DBA is an area of active research, and at least one mutation present in about one-fourth of DBA patients may cause disease due to decreased production of a ribosomal protein. This finding raises the possibility that the disease, at least in some patients, may be correctable by genetic therapy, by which a normal copy of the mutated gene can be introduced into the "stem cells" which give rise to red cells.

It is therefore of interest to identify any particular characteristics of DBA patients which might delay or hinder the application of gene therapy to their disease. This pilot study of 15 patients is designed to evaluate: 1) the CD34+ cell mobilization response to administration of standard doses of granulocyte-colony stimulating factor (G-CSF), 2) the potential for stem cells from DBA patients to be collected by large volume leukapheresis of subjects who have been given G-CSF, and 3) the ability of these G-CSF mobilized cells to be transduced with vectors being developed for gene therapy applications. Outcome parameters to be monitored are the mobilization response to G-CSF, the safety profile and tolerance of G-CSF and leukapheresis, and the efficiency of transduction of DBA stem cells with standard gene therapy vectors. Effectiveness will be gauged by historical comparison of these parameters to normal healthy age-matched volunteer.

It is important to point out that there is no therapeutic intent to the majority of this protocol or direct benefit for enrolled patients. We do plan, however, to cryopreserve the remainder of the mobilized cells collected by apheresis for possible autologous transplantation in the event of the patient's progression to leukemia of bone marrow failure in the future.