Mobilization of Stem Cells With G-CSF for Collection From Patients With Diamond-Blackfan Anemia
Status:
Completed
Trial end date:
2006-04-01
Target enrollment:
Participant gender:
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 leukapheresis evaluation. They
will have a bone marrow aspiration and biopsy to confirm the diagnosis of DBA. For these
tests, the hip area is anesthetized and a needle is used to draw bone marrow from the
hipbone. If needed, the procedure will be done under sedation.
Patients will be given G-CSF by injection under the skin for up to 6 days. Blood and stem
cell counts will be measured from a teaspoon of blood drawn each morning. On the morning of
the fifth dose, the patient will undergo leukapheresis for collection of stem cells. For this
procedure, a large catheter (with a diameter no larger than that of a straw) is placed in an
arm vein to allow blood to flow into a cell separator machine. Most children and some adults
do not have veins large and strong enough for this tubing, so a large intravenous line called
a "central line" is placed into a large vein in the neck or groin. This is done under
sedation and with a local anesthetic. While the patient lies on a bed or recliner, whole
blood is collected through a catheter in one arm or the central line, the stem cells are
separated out by spinning, then the red cells, platelets and plasma are returned through a
second catheter in the other arm or a second opening in the central line. The procedure takes
about 3 to 5 hours, during which the patient can watch television or videos and have family
members at the bedside for company. When the procedure is completed, the patient's
participation in the protocol ends.
Some of the stem cells collected by leukapheresis will be used for research and some will be
frozen and stored for possible future transplantation into the patient, if required.