Use of G-CSF to Obtain Blood Cell Precursors
This protocol is designed to study the techniques needed to develop gene therapy or other treatments for certain inherited immune system diseases.
Healthy normal volunteers between 18 and 65 years of age and patients with chronic granulomatous disease (CGD), X-linked severe combined immune deficiency (X-SCID), leukocyte adhesion deficiency (LAD), interferon gamma receptor deficiency (IGR-deficiency) or other inherited diseases affecting precursor blood cells-bone marrow cells that generate blood cells-may be eligible for this study. Patients who have had repeated severe infections possibly due to an inherited blood cell abnormality may also participate. Candidates will be screened with a medical history, physical examination and blood tests.
Patients with an active infection will be hospitalized during this study. Uninfected participants will be seen as outpatients at the NIH Clinical Center. Participants will have the following procedures:
- G-CSF administration - All participants will have daily injections of granulocyte-colony stimulating factor (G-CSF). This drug is a genetically engineered hormone that stimulates the bone marrow to release white blood cells and white cell precursors into the bloodstream. The injections are given under the skin in the arm or leg, using a very small needle. Patients will have injections for 6 or 7 days, normal volunteers for 5. A small blood sample will be drawn each day of the injections to monitor white cell counts and changes in the number of blood cell precursors. (Smaller children and all children under 10 years of age may have blood drawn on alternate days or less to reduce the number of needle sticks and the amount of blood taken.). Larger blood draws will be taken on days 6 and/or 7 for patients and on days 5 and/or 6 for normal volunteers.
- Leukapheresis - This procedure for collecting larger numbers of circulating blood precursor cells is optional and may take the place of the larger blood draw described above. Patients 5 years old or older may have leukapheresis. Whole blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components. The desired cells are then removed and the rest of the blood is returned to the body, either through the same needle or through a second one placed in the other arm. The cells obtained will be used to purify blood precursors for growing in culture and to examine the ability to transfer new genes into these precursor cells. For patients whose arm veins are too scarred to for needle placement, a vein in the groin area (femoral vein) may be used instead.
- Bone marrow aspiration - This procedure for obtaining a bone marrow sample is optional. Normal volunteers who agree to the procedure may undergo aspiration up to three times. The hip area is anesthetized and a small sample of bone marrow is drawn through a special needle inserted in the hipbone. The first aspiration is done on a day before the G-CSF injections are started; the second is done soon after the last injection (day 6 or 7), and the third is done from 7 to 10 days after the last injection.
- Repeat blood tests - At day 6 or 7 some of the blood tests done at the beginning of the study will be repeated to check blood counts and liver and kidney function.
Four months or more after the end of the study, participants will be asked to repeat the entire procedure to examine the effects of two cycles of G-CSF mobilization in the same individual. This second cycle is optional.
Chronic Granulomatous Disease
Leukocyte Adhesion Deficiency Syndrome
Severe Combined Immunodeficiency
|Official Title:||Recruitment and Apheresis Collection of Peripheral Blood Hematopoietic Stem Cells|
|Study Start Date:||February 1994|
The goal of this study is to obtain CD34+ hematopoietic stem cells (HSC) for clinical and research purposes. We will collect HSC from peripheral blood and/or bone marrow.
Participants include: 1. Patients with any primary immune deficiency (PID); 2. Healthy sibling or other related donor of those patients with PID in need of an allogeneic stem cell transplant; 3. Healthy adult volunteers.
The majority of subjects will have HSC collected from peripheral blood by apheresis. Daily subcutaneous injections of G-CSF (granulocyte colony stimulating factor/filgrastim) for 5 to 6 days is a standard method used to mobilize HSC to the peripheral blood prior to apheresis, and will be used for most subjects. Plerixafor (AMD 3100/Mozobil) has recently been approved for use in combination with G-CSF to mobilize HSC and will be used in those patients or sibling/related donors undergoing clinical collection of HSC by apheresis who do not, or are predicted not to respond adequately to G-CSF.
Some patients and healthy sibling/related donors will have a clinical scale aspiration collection of bone marrow to obtain HSC for clinical use. Some patients and healthy volunteers will have a small sample needle aspiration collection of bone marrow obtained for research purposes.
HSC collection from patients with PID may be used for laboratory research or may be designated for future clinical treatment of the patient. HSC collections from healthy sibling/related donor of those patients with PID in need of an allogeneic stem cell transplant will be designated for clinical treatment of the related patient. HSC collection from healthy volunteers will be designated entirely for laboratory research.
HSC will be used for the following three clinical purposes, where clinical treatments would occur under separate IRB approved protocols: 1. Autologous HSC from patients may be genetically modified and infused into the patient for treatment of an infection or the underlying disease (Gene therapy); 2. Autologous HSC from patients may serve as back up (rescue product) for patients undergoing matched unrelated donor transplantation; 3. HSC from a sibling/related donor may be used as a directed donation for allogeneic transplant of the related patient.
HSC will be used for laboratory research studies that include: Delineating the pathophysiology of inherited immune deficiencies; Delineating the physiology of and improving engraftment of hematopoietic stem cells; Determining how hematopoietic stem cells may be maintained in ex vivo culture without losing pluripotent potential; Delineating the molecular mechanisms responsible for lineage specific differentiation; Developing efficient methods for gene transfer into hematopoietic stem cells for corrective gene therapy.
|Contact: Patricia L Littel, R.N.||(301) firstname.lastname@example.org|
|Contact: Harry L Malech, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Harry L Malech, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|