Protocol Number: 01-H-0097

Title:

Investigation of G-CSF-Induced Stem Cell Mobilization Potential in Patients with Diamond-Blackfan Anemia

Number:

01-H-0097

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.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Male or female patients greater than or equal to 4 years of age and weighing at least 12 kg (27 lbs) will be included.

Diagnosis of DBA as defined by the onset of anemia before age 2; or, if after age 2, a positive family history of classical DBA or typical physical anomalies; low reticulocyte counts (less than 30,000/ul); absent or blocked maturation of erythroid precursors in the bone marrow.

Red-cell transfusion dependence

Adequate birth control while on protocol

EXCLUSION CRITERIA:

Female patients that are pregnant or lactating

ECOG performance status greater than or equal to 1.

Neutrophil count less than 1000/uL or platelet count less than 100,000/uL

Positive DEB stimulation test

Evidence of transformation to MDS or AML on pre-study marrow aspiration and biopsy, or abnormal marrow cytogenetics.

History or evidence of clinically significant autoimmune inflammatory disease or significant cardiopulmonary disease by history or physical exam

Uncorrected coagulopathy

Renal disease (GFR less than 100mL/min/1/73 M(2)) as estimated for children by Schwartz formula. Adults (age greater than 21) excluded for serum Cr less than 2.5 mg/dL.

Hepatic disease (bilirubin greater than 2 mg/dL or transaminases greater than 7 times the upper limit of normal).

Seropositivity for hepatitis B (HbsAg), hepatitis C, or HIV will be excluded.

Other medical illness or condition which, in the opinion of the Investigators, may contraindicate participation in this study due to risk to patient or comprise of study integrity will be excluded.

Special Instructions: Currently Not Provided

Keywords:

G-CSF

Leukapheresis

Stem Cell Cryopreservation

Central Line Placement

Recruitment Keywords:

Stem Cell Preservation

Diamond Blackfan Anemia

Healthy Volunteer

Conditions:

Diamond Blackfan Anemia

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

A regional experience of red cell aplasia

Diamond-Blackfan anemia in the UK: analysis of 80 cases from a 20-year birth cohort

Diamond-Blackfan anemia

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