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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Investigation of G-CSF-Induced Stem Cell Mobilization Potential in Patients With Diamond-Blackfan Anemia

Brief Summary:

This study will provide information needed to develop more effective treatments for patients with Diamond-Blackfan anemia (DBA). Current treatments include steroids, such as prednisone, and blood transfusions. These treatments have potential long-term risk and side effects, including osteoporosis and impaired growth from steroids or iron overload from transfusions. In addition, as patients reach adulthood, they can develop acute leukemia or bone marrow failure. The only cure for DBA is bone marrow transplant, a procedure that itself carries serious risks and is an option for only about 25 percent of patients.

DBA is caused by a mutation (error) in a gene that codes for producing red blood cells from stem cells (blood-forming cells produced by the bone marrow). In 5 to 10 years, gene transfer therapy may prove to be an effective treatment for DBA. Before this treatment can be considered, however, more information is needed about DBA patients and how their stem cells function. This study will examine: 1) whether stem cells of patients with DBA respond to G-CSF the same way those of healthy people do. (G-CSF is a drug that causes stem cells to move from the bone marrow to the blood stream, where they can be collected more easily and in larger numbers by a procedure called leukapheresis, described below. If G-CSF does not work well in DBA patients, other collection strategies will have to be explored); and 2) whether the genetic error in DBA can be corrected by gene transfer into patients' stem cells.

Patients with Diamond-Blackfan anemia 4 years of age and older who weigh at least 27 pounds and who are dependent on red blood cell transfusions may be eligible for this study. Candidates will have a medical history taken and a physical examination and will be seen by the Clinical Center's Department of Medicine Transfusion for l

Detailed Summary:

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
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

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Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: February 22, 2001
Date Started: February 2001
Date Completion: April 2006
Last Updated: March 3, 2008
Last Verified: April 2006