This study will test whether stem cells collected from the bloodstream (peripheral blood stem cells) can be used instead of cells collected from bone marrow for unrelated donor transplantation. Stem cells are cells produced by the bone marrow that mature into the various blood components-white and red blood cells and platelets.

Unlike bone marrow, the bloodstream contains few stem cells. Therefore, donors are given G-CSF (also called filgrastim)-a growth factor naturally produced by the body-before cell collection. G-CSF boosts bone marrow production of stem cells and mobilizes them to enter the bloodstream, allowing enough cells to be collected for transplantation. G-CSF-mobilized blood stem cells are often used for transplantation in recipients who are related to their donors. This study will evaluate a system for using this same method in unrelated donors and recipients.

The Food and Drug Administration has approved G-CSF for several uses, including collection of blood stem cells from patients who are receiving transplants of their own stem cells; for patients with cancer who are receiving chemotherapy; patients who are getting bone marrow transplants; and patients with diseases that cause very low white blood cells counts.

Individuals matched by the National Marrow Donor Program with a potential recipient for blood stem cell donation are eligible for this study. Participants will receive oral and written information about all the procedures involved in both bone marrow and peripheral blood stem cell collection, from donor evaluation and testing through post-donation followup. They will then have a medical examination, including blood tests and urinalysis, electrocardiogram and chest X-ray, to make sure that neither the donor nor the recipient will incur unexpected risks from the procedure. If the evaluation confirms that the donation can proceed, the donor will receive G-CSF injections under the skin once a day for 4 or 5 days. Blood samples (1/2 to 1 tablespoon each) will be collected on the first and fourth days of G-CSF injections to measure blood cell counts.

Stem cells will then be collected by a procedure called apheresis. The donor lies in a recliner chair, and a needle is placed in a vein in each arm. Blood is collected from one arm and passes through a special machine called a blood cell separator. The machine collects the stem cells in a bag and directs the rest of the blood back through the needle in the other arm. One or two donations will be needed, depending on the size of the recipient and the number of stem cells circulating in the donor's bloodstream. Each donation takes about 4 to 5 hours. One-half tablespoon of blood is drawn before and after each donation to measure blood cell counts.

Two days after donation and again one week after donation, donors will be questioned about any symptoms the may experience. Another blood sample (1/2 tablespoon) will be collected 1 month after cell donation and then yearly for an indefinite number of years to measure cell counts.

Condition	Treatment or Intervention	Phase
Hematopoietic Stem Cell Mobilization	Drug: Filgrastim	Phase III

Further Study Details: 

Expected Total Enrollment:  600

The National Marrow Donor Program (NMDP) was established 15 years ago to provide unrelated bone marrow donors for persons in need of a stem cell transplant, but lacking suitable family donors. As of February 2002, the Program has facilitated nearly 13,800 marrow transplants via its national and international network of Donor Centers, Transplant Centers, and Collection Centers, and is currently operating at about 150 transplants facilitated per month. The program has had phenomenon success in recruiting potential donors, and the Registry size is now 4.6 million. Transplant outcomes have been more problematic, with acute transplant-related mortality and more severe grades of acute and chronic graft-versus-host disease occurring with nearly twice the frequency seen in related, HLA-matched sibling donor transplants.

Peripheral blood stem cell (PBSC) grafts, collected by apheresis of filgrastim-mobilized donors, are being increasingly used in the setting of related-donor, HLA-identical transplants. The advantages of PBSC over marrow in allotransplant settings include more rapid engraftment, decreased acute transplant-related mortality, more rapid immunologic reconstitution, and larger stem cell doses. From the donor's perspective, PBSC harvests do not require anesthesia and pelvic surgery, and may result in less discomfort and long-term sequelae than marrow harvests. These potential advantages to both the donor and the recipient have led to the creation of the current protocol, which describes a system for the collection and evaluation of PBSC as an alternative to marrow in unrelated donor stem cell transplantation. The protocol describes processes for donor evaluation and education, establishes procedures for administration and monitoring of filgrastim and indefinite donor follow-up, and includes policies for the collection of PBSC components by leukapheresis. This protocol will apply to all PBSC collections performed by NMDP Donor and Apheresis Centers and will interface with IRB-approved transplantation protocols maintained separately by NMDP Transplant Centers.

Since filgrastim is not licensed for use in healthy subjects as a mobilizing agent to facilitate collection of PBSC's by apheresis, this protocol is being performed under an FDA IND sponsored by the NMDP. It is intended for use with minimal changes by participating institutions, per IND application.

The NIH Marrow Donor Center, operated by the CC Department of Transfusion Medicine (DTM), currently has a registry size of 60,700 local participants and has provided 270 marrow or blood stem cell donors for NMDP-facilitated transplants to date. DTM staff consider the mission of the NMDP to be of critical national importance and have been prime movers in the creation of this protocol. Drs. Stroncek and Leitman were members of the Writing Group for this study.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
PBSC donors must meet the same criteria as NMDP marrow donors. These criteria are set forth in NMDP Standards and the Donor center manual of Operations.
EXCLUSION CRITERIA:
Failure to qualify as an NMDP marrow donor.
Pregnancy or uninterruptible breast-feeding. Pregnancy is an absolute contraindication under this protocol. Women who are breast-feeding must be willing and able to interrupt breast-feeding during the administration of Filgrastim and for two days following the final dose.
Sensitivity to Filgrastim or to E. coli-derived recombinant protein products.
History of autoimmune disorders, including rheumatic diseases and thyroid disorders. Exception: As with bone marrow donations, donors with a history of autoimmune thyroid disease who have undergone medical or surgical thyroid ablation may be eligible. Approval must be obtained from the NMDP.
History of deep vein thrombosis or pulmonary embolism. History of iritis or episcleritis. Thrombocytopenia less than 150 x 10(9)/L (less than 150,000/microliter) at baseline evaluation.
Current treatment with Lithium. Drug interactions between Filgrastim and Lithium which may potentiate the release of neutrophils, have not been fully evaluated.
History of coronary artery disease. History of chest pain consistent with angina shall be evaluated by cardiology consultation, and subjects with symptomatic coronary heart disease shall be excluded.

Maryland
      Warren G. Magnuson Clinical Center (CC), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  000165; 00-CC-0165
Record last reviewed:  October 7, 2004
Last Updated:  November 23, 2004
Record first received:  July 1, 2000
ClinicalTrials.gov Identifier:  NCT00005930
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08