Filgrastim-Mobilized Stem Cells for Transplantation Using Unrelated Donors

For many years, allogeneic bone marrow transplantation has been used to successfully treat
leukemias, other hematologic conditions and congenital disorders. The first unrelated donor
transplants were performed in the late 1970s, but this procedure did not become widely
available until the development of several consolidated unrelated donor registries around
the world. The National Marrow Donor Program, established in 1987, is the world's largest
registry and currently lists more than 7 million donors. Since its beginning, NMDP has
facilitated more than 30,000 unrelated transplants.

Although not a licensed indication, considerable experience has been accumulated concerning
administration of filgrastim to normal adults. Most of these adults were volunteer research
subjects or donors of PBSC for use in related donor transplants. Beginning in February 1997,
filgrastim stimulated PBSC have been collected from NMDP donors under protocol. The protocol
(locally referred to as G2) began under an NMDP-sponsored Investigational New Drug (IND)
application filed with FDA for collecting PBSC for a second donation following an initial
donation of bone marrow. In 1999 a second protocol was opened (locally referred to as G1) as
requests for PBSC as a primary donation source became more common. In 2005 the two protocols
were combined to eliminate redundancy and provide for ease of use.

The protocol establishes and evaluates a system to supply peripheral blood stem cell (PBSC)
products for use in unrelated donor hematopoietic stem cell (HSC) transplantation. The
protocol describes processes for donor identification, education and evaluation. Procedures
for administration and monitoring of the stem cell mobilizing agent filgrastim are included.
The protocol also describes procedures for the collection of PBSC products by leukapheresis
and includes provisions for long term donor follow-up.

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:

- Pregnancy or uninterruptible breastfeeding. Pregnancy is an absolute contraindication
under this protocol. Women who are breastfeeding must be willing and able to
interrupt breastfeeding 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 thyroid disease
who have undergone successful therapy may be suitable.

- History of deep vein thrombosis or pulmonary embolism.

- History of iritis or episcleritis.

- Thrombocytopenia < 150 x 10(9)/L (< 150,000/µL) 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.

- Positive Hemoglobin-Solubility (e.g., SickleDex™ or equivalent) test.

- Donors receiving experimental therapy or investigational agents.