Page 1733 - Hematology_ Basic Principles and Practice ( PDFDrive )

1538 Part IX Cell-Based Therapies

Holders of INDs must provide the agency with an annual report Processing Performed to Address ABO
on the protocol and include a listing of the products administered TABLE Incompatibilities Between Hematopoietic Stem Cell
and those that have been prepared but not used. In addition, cell- 97.1 Donors and Recipients
processing facilities should be prepared to assist the IND sponsor by
providing information on products that have been associated with Recipient ABO Type Donor ABO Type Type of Processing
severe adverse reactions in the recipients, and whether these were ABO identical ABO identical No special processing required
attributable to product quality. For Type 361 products, the facility
must report, as Biological Product Deviations, any contaminated A or B AB RBC depletion
products that have been administered to a patient. O A/B/AB RBC depletion
A B RBC + plasma depletion
PROFESSIONAL STANDARDS B A RBC + plasma depletion
Antibody to RBCs N/A RBC depletion
The two major accrediting organizations in the United States for A/B/AB O Plasma depletion
cellular therapies are FACT and AABB. Whereas FACT offers
accreditation of collection, processing, and clinical use of cellular AB A or B Plasma depletion
therapy products, the AABB focuses on collection and laboratory N/A, Not applicable; RBC, red blood cell.
processing. Both organizations inspect based on standards that are
published every 18 months to 3 years. In the case of FACT, the
standards are published in collaboration with the Joint Committee
on Accreditation in Europe. FACT also publishes separate standards RBC depletion removes incompatible donor erythrocytes that
in collaboration with NetCord that cover cord blood banking. Both would stimulate a reaction by the donor upon administration. Most
organizations have worked to harmonize their standards with Ameri- facilities establish a maximum volume of incompatible RBCs that can
can, Canadian, Australasian, and European regulatory agencies; be infused with HPCs; exceeding this limit can result in hemolysis
therefore, accreditation by either organization is of great assistance and a transfusion reaction. Depletion of erythrocytes can be achieved
on the pathway to regulatory compliance. A number of other profes- most simply by centrifugation. The product is centrifuged at approxi-
sional organizations accredit particular aspects of operations within mately 3000 g for approximately 10 minutes at ambient temperature,
the cell-processing facility. These include the College of American and the leukocyte-rich buffy coat is collected at the interface between
Pathologists, which accredits general laboratories, and hematology the plasma layer and the RBCs.
and flow cytometry facilities; the American Society for Histocompat- RBC depletion can also be achieved by sedimenting erythrocytes
ibility and Immunogenetics; and the European Federation for using hydroxyethyl starch (hetastarch). This promotes RBC sedimen-
Immunogenetics, which accredits histocompatibility-testing labora- tation by formation of erythrocyte rouleaux. The hematocrit of the
tories. Some organizations, such as the College of American Patholo- product is first adjusted to approximately 25% by addition of normal
gists and StemCell Technologies, also provide proficiency testing saline, and 6% hetastarch (Hespan) is added at a volume:volume ratio
services for laboratory staff. of 1 : 6 to 1 : 7. Sedimentation can be performed under gravity or may
be accelerated by centrifugation.
The most rigorous erythrocyte depletion is achieved by centrifuga-
MANIPULATION OF HEMATOPOIETIC STEM CELL tion of the collection on a Ficoll-Hypaque density gradient. This
TRANSPLANTATION PRODUCTS process enriches mononuclear cells at the interface between the gradi-
ent and the layered cells after centrifugation and depletes erythrocytes,
Manipulation of a product for hematopoietic rescue is intended to platelets, and granulocytes. As a result of enrichment for mononuclear
remove a component that is unwanted or may cause adverse effects cells, the overall nucleated cell recovery is lower than with other
+
or to enrich a desired population, such as CD34 cells. As discussed techniques in which granulocytes are retained.
previously, the degree of manipulation may determine the regulations Automated devices are available for preparing buffy coats and
under which the product is manufactured and handled. The FDA density gradient-enriched cells. For larger volumes, the COBE 2991
defines minimal manipulation as processing that does not alter the Cell Processor from Terumo can be used. This requires a minimum
relevant biologic characteristics of the cells or tissues. This includes volume of 150 mL RBCs for operation and may therefore not be
procedures such as RBC and plasma depletion, and cell selection suitable for pediatric processing. It is capable of preparing buffy coats
using an approved device. By contrast, more than minimal manipula- and density-separated cell preparations using a functionally closed
tion would include activities such as culture ex vivo, genetic modifica- disposable set.
tion, and ex vivo activation. The COBE Spectra from Terumo is in common use to collect
peripheral blood progenitor cells by apheresis. The device is also less
Routine Minimal Manipulation for Volume widely used in the processing facility to enrich mononuclear cells
from BM.
Reduction or ABO Incompatibility For smaller starting volumes, the Sepax device from Biosafe can
be used (Fig. 97.1). It has found widespread application in cord blood
The most widely used form of manipulation in the hematopoietic banks for buffy coat preparation (with or without addition of
progenitor cell (HPC)-processing facility is probably removal of hydroxyethyl starch) and has also been used for volume reduction of
erythrocytes and/or plasma to overcome incompatibility between peripheral blood progenitor cell collections, density gradient separa-
donor and recipient (Table 97.1). This process is performed largely tion of BM, and for cell washing. The device has a small footprint,
using techniques that were developed by the blood banking uses functionally closed disposables, and provides a print-out of
industry. operations.
Plasma depletion to remove donor antibodies that may react with Xpress devices for cord blood and marrow processing are available
recipient cells is achieved by centrifugation of the graft, usually in a from Thermogenesis. The AXP AutoXpress is designed for enriching
transfer pack, at approximately 2000 g for 10 minutes at ambient mononuclear cells from cord blood that is transferred to the process-
temperature. The pack then is placed in a plasma expresser, which ing set, which is then placed into the AXP device. This fits into a
compresses the product bag so that plasma can be forced out and into centrifuge bucket, and during spinning the red and mononuclear cells
a separate collection bag. Plasma depletion can also be used to reduce are collected into separate bags and the plasma is retained in the
the volume of ABO-compatible grafts when the donor is large and processing set. The MarrowXpress performs a similar procedure on
the recipient small. marrow harvests. Both devices provide closed sterile systems, and the