A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Human erythrocyte antigens, A, B, O
To go or be together with, but not attached. Information that must accompany a cellular therapy product must accompany the product in a sealed package, or alternatively, be attached or affixed.
The measure of exactness of an analytical method, or the closeness of agreement between the value which is accepted either as a conventional, true value or an accepted reference value and the value found.ACD-A
Acid citrate dextrose-formulaAdenovirus
Large group of viruses first isolated from cultures of adenoids. The capsid is an icosahedron of 240 hexons and 12 pentons and is in the form of a base and a fiber with a terminal swelling; the genome consists of a single, linear molecule of double-stranded DNA. They cause various respiratory infections in humans. Some of the avian, bovine, human and simian adenoviruses cause tumors in newborn rodents, generally hamsters. They can be classified into highly; weakly and non- oncogenic viruses from their ability to induce tumors in vivo though all of these groups will transform cultured cells. The viruses are named after their host species and sub-divided into many serological types e.g. Human Adenovirus type 3.
Adverse eventAdverse reaction
Any unintended and unfavorable sign, symptom, abnormality, or condition temporally associated with an intervention that may or may not have a causal relationship with the intervention, medical treatment, or procedure. Adverse reaction is a type of adverse event.
A noxious and unintended response to the collection or infusion of any cellular therapy product for which there is a reasonable possibility that the cellular therapy product caused the response.
Attached in physical contact with the cellular therapy product container.
The clumping together of particles, usually by antibody molecules binding to antigens on the surfaces of adjacent particles. When the particles are red blood cells, the phenomenon is called hemagglutination.Aggregates
Clumps of particles or cells. May be due to the release of DNA from cells with membrane damage.Allogeneic
Cells or tissue derived from a different individual of the same species.
A graft or transplant of tissue from an allogeneic donor. May also be called allotransplant.
To increase the number of copies of a DNA sequence, in vivo by inserting into a cloning vector that replicates within a host cell, or in vitro by polymerase chain reaction (PCR).
AnnealAntibody (or Immunoglobulin)
The pairing of complementary DNA or RNA sequences, via hydrogen bonding, to form a double-stranded polynucleotide. Most often used to describe the binding of a short primer or probe.
Plasma proteins that bind specifically to particular molecules known as antigens. Dependent upon the isotype of antibody, the result of binding can be lysis (mediated by complement), opsonization (enhances phagocytosis), or agglutination (can mask antigen sites which may block the function of the antigen).
Antigen presenting cell (APC)APC
A cell that carries on its surface antigen bound to MHC Class I or Class II molecules, and presents the antigen in this "context" to T-cells. Includes macrophages, endothelium, dendritic cells and Langerhans cells of the skin.
The collection of a blood component, either cellular or non-cellular in composition, from the circulation.
Programmed cell death. An active process requiring metabolic activity by the dying cell; often characterized by cleavage of the DNA into fragments that gives a so-called "laddering pattern" on gels. Cells that die by apoptosis do not usually elicit the inflammatory responses that are associated with necrosis, though the reasons are not clear.
Absence of microorganisms that cause disease.
Practices designed to reduce the risk of contamination with microorganisms.
American Society for Histocompatibility and Immunogenetics
Securely fastened to the cellular therapy product container by means of a tie tag or comparable alternative. Any information required to be attached to a container may alternatively be affixed.
Documented systematic evaluation to determine whether approved policies or procedures have been properly implemented and are being followed.
Cells or tissue derived from a given individual intended for use in that individual.
Available for distribution
The time at which the cellular therapy product has been determined to meet all release criteria and may leave control of the facility.
B cells or B lymphocytes
One of the two major classes of lymphocytes. The B cell antigen receptor is cell-surface immunoglobulin. Upon activation through this receptor, B cells differentiate into plasma cells and produce a soluble form of immunoglobulin (antibody).
Agent that destroys bacteria. Kills gram-negative and gram-positive bacteria unless otherwise specifically stated.Fungicide Kills fungi.Sporicide Kills spores.Virocide Kills viruses.
Balanced salt solution
An isotonic solution of inorganic salts present in correct physiological concentrations. May also contain glucose but usually free of other organic nutrients.
Commercial name for a recombinant form of DNAse, an enzyme that digests released DNA.
Biological product deviation
A deviation from applicable regulations or from applicable standards or established specifications that relate to the prevention of communicable disease transmission or cellular therapy product contamination; or an unexpected or unforeseeable event that may relate to the transmission or potential transmission of a communicable disease or may lead to cellular therapy product contamination.
Biological Safety Cabinet (BSC)
A workstation with filtered air flowing in a laminar, non-turbulent parallel to (horizontal laminar flow) or perpendicular to (vertical laminar flow) the work surface, such as to assist in aseptic handling of products. May also be referred to as a Laminar Hood or simply as a hood. Properly maintained Class I and II BSCs, when used in conjunction with good microbiological techniques, provide an effective containment system for safe manipulation of moderate and high-risk microorganisms (Biosafety Level 2 and 3 agents). Both Class I and II BSCs have inward face velocities (75-100 linear feet per minute) that provide comparable levels of containment to protect laboratory workers and the immediate environment from infectious aerosols generated within the cabinet. Class II BSCs also protect the research material itself through high-efficiency particulate air filtration (HEPA filtration) of the airflow down across the work surface (vertical laminar flow). Class III cabinets offer the maximum protection to laboratory personnel, the community, and the environment because all hazardous materials are contained in a totally enclosed, ventilated cabinet. The BSC in use in the BMT laboratories are of the Class II type.
Blast-forming unit, erythroid (BFU-E)
Precursor cell of the red blood cell lineage which in vitro forms colony of cells arranged in burst forming unit.
Blood Group Antigens
Polymorphic surface molecules on red blood cells that are detectable (and identified) with antibodies from other individuals. Major blood group antigens include the ABO and Rh systems.
Bone marrow mononuclear cell
Blood and Marrow Transplantation
The site of hematopoiesis or the generation of the cellular elements of the blood. A source of stem cells used for transplantation of the hematopoietic system. May be referred to as marrow. Proper FACT name is Hematopoietic Progenitor Cells, Marrow or HPC-M. This terminology should be used in all relevant laboratory documents.
The white blood cell layer obtained when centrifuging whole blood or marrow components. Proper FACT name is Buffy Coat Enriched.
To set measurement equipment against a known standard.
Periodic scheduled activity to check and maintain the accuracy of measurements against a known standard.
Cluster of differentiation
A 120 kD glycoprotein antigen expressed on a subset of cells expressing high levels of CD34. Contains a population of repopulating HPC. Defined by the monoclonal antibody AC133. May also be found on neural and endothelial stem cells and other primitive cells such as retina and retinoblastoma and developing epithelium.
A subunit of the T cell receptor complex that includes CD3 gamma, delta and epsilon. CD3 is expressed by thymocytes in a developmentally regulated manner and by all mature T cells. Cross linking of CD3 epsilon with appropriate antibodies can result in T cell activation and proliferation. Binding of antibodies such as OKT3 to the T cell surface can induce such activation whereas CD3 antibodies that do not bind to CD3 epsilon such as T10B9 do not induce T cell activation.
The 115 kD glycoprotein antigen, expressed by 1-2% of normal bone marrow mononuclear cells, that is defined by a specific monoclonal antibody (anti-CD34) using the standardized cluster of differentiation (CD) terminology.
Growth of cells disassociated from the parent tissue by spontaneous migration, migration or enzymatic dispersal.
A propagated culture after the first subculture.
Cell mediated immunity
Immune response that involves effector T-lymphocytes and not the production of humoral antibody. Responsible for allograft rejection, delayed hypersensitivity and in defense against viral infection and intracellular protozoan parasites.
The administration of products with the intent of providing effector cells in the treatment of disease or support of other therapy.
Cellular therapy product
Somatic cell-based product (e.g., mobilized hematopoietic progenitor cells, therapeutic cells, cord blood, pancreatic islets) that is procured from a donor and intended for processing and administration.
Code of Federal Regulations
Colony-forming Unit-Granulocyte, Erythroid, Megakaryocytic, Macrophage
Colony-forming Unit-Granulocyte, Macrophage
Current Good Manufacturing Practices
Current Good Tissue Practices
Clinical Laboratory Improvement Amendments
Clinical Transplantation Program
An integrated medical team housed in geographically contiguous or proximate space with a single Clinical Program Director and common staff training programs, protocols, and quality assessment systems. The Clinical Program shall use hematopoietic cell collection and processing facilities that meet FACT-JACIE Standards with respect to their interactions with the Clinical Program. Clinical programs that include non-contiguous institutions in the same metropolitan area shall demonstrate common protocols, staff training procedures, quality management systems, review of clinical results and evidence of regular interaction. Several clinical sites, particularly with different Directors, or outside a single metropolitan area, joining together for the purpose of meeting criteria to qualify as a Clinical Program do not fulfill the intent of these Standards. In contrast, collection facilities and/or processing facilities serving one or more clinical programs are acceptable.
A strain of genetically identical cells descended in culture or in vivo from a single cell.
Cluster of differentiation (CD)
Clusters of differentiation (CD) are groups of monoclonal antibodies that identify the same cell-surface molecule.
Any procedure for harvesting cellular therapy products, including labeling, regardless of technique or source.
Colony-forming unit, C
Refers to the sum of CFU-E, CFU-GEMM and CFU-GM.
Colony-forming unit, erythroid (CFU-E)
Further differentiated precursor than BFU-E, forming only erythroid elements in culture.
Colony-forming unit, granulocyte macrophage (CFU-GM)
Precursor cell that in vitro forms cells of both granulocytic and macrophage morphology.
Colony-forming unit, granulocyte, erythroid, megakaryocytic, macrophage (CFU-GEMM)
Hematopoietic precursor cells that in vitro form colonies containing cells of the indicated lineages.
Any one of a number of peptides able to stimulate the growth of hematopoietic colonies in vitro. Includes: G-CSF, GM-CSF, SCF, and IL-3.
Ability to adequately perform a specific procedure or task according to direction.
Any written, oral, or electronic communication about a problem associated with a distributed cellular therapy product or with a service related to the collection, processing, storage, distribution, or infusion of a cellular therapy product.
A multi-component enzyme system present in plasma that acts together to induce the lysis of targeted cells. This system may be activated directly by certain pathogens (alternative pathway) or secondary to certain subclasses of antibody binding to a cell surface. Antibodies of the IgG2, IgG3 and IgM subclasses activate complement most readily.
Soiled or infected by microorganism(s).
Continuous temperature monitor
A device that measures the temperature of the environment on a continuous basis over time and captures and stores temperature data at defined intervals.
Freezing of biologic material at a predetermined rate; to decrease in temperature at designated rate per minute.
The whole blood including hematopoietic progenitor cells, collected from placental and umbilical cord blood vessels after the umbilical cord has been clamped.
Cord Blood Bank
Facility in which hematopoietic progenitor cells collected from the placental and umbilical cord blood vessels are processed, cryopreserved and/or stored. For purposes of FACT Standards, a Cord Blood Bank is considered a laboratory facility.
Cell Processing Laboratory
Critical Control Point
Points or where things can go wrong. These represent major or critical process within the system, the correct performance of which is required to ensure the quality of the finished product or service.
The reciprocal testing of serum and red blood cells from the intended donor and recipient of a blood transfusion to detect the presence of antibody to blood group antigens.
Transfer of element(s) from one product, reagent, document or electronic record to another causing original, pure state to be compromised.
The preservation of material in a frozen state. Human blood or bone marrow cryopreservation requires a cryoprotectant agent, usually dimethyl sulfoxide (DMSO), glycerol or a combination to prevent ice crystal formation and to maintain cell integrity during the freezing process.
Cytotoxic T lymphocyte
Current Good Manufacturing Practice (cGMP)
Regulations as specified by the US FDA or other regulatory body that describes the methods, equipment and control procedures required for food processing, medical device manufacturing and related industries. Such regulations are subject to change, thus the need to monitor such changes so as to be "current”. Products covered under cGTP are considered as 351 products, under PHS 351 regulations. Processing of such products will be under IND or IDE. Covers most of the product processed in the MCW LPL. See required reading folder for cGMP training presentation.
Current Good Tissue Practice (cGTP)
The methods used in, and the facilities and controls used for, the manufacture of HCT/P’s including recordkeeping and the establishment of a quality program as required by the U.S. Food and Drug Administration for HCT/P establishments. Products covered under cGTP are considered as 361 products, under PHS 361 regulations. Such products are not processed under IND or IDE. Covers most of the products processed in the MCW CPL. See required reading folder for cGTP training presentation.
A soluble protein mediating signals between different or the same cell population (e.g., interleukin-1, interleukin-2).
Probably the most widespread of the Herpes virus group. Infected cells enlarge and have a characteristic inclusion body (composed of virus particles) in the nucleus. Causes disease only in utero (leading to abortion or stillbirth or to various congenital defects), although can be opportunistic in the immunocompromised host.
Deficiency in cellular elements of the blood.
Cytotoxic T cells (CTL)
Subset of T lymphocytes (mostly CD8) responsible for lysing target cells and for killing virus-infected cells (in the context of Class I histocompatibility antigens). CD4+ T cells can also exhibit cytotoxic functions and kills in the context of Class II histocompatibility antigens.
A gradient formed by materials of different density either in a discontinuous or in a continuous fashion.
DNAase. An endonuclease with preference for DNA. Pancreatic DNAse I yields di- and oligo-nucleotide 5’ phosphates, pancreatic DNAse II yields 3’ phosphates. In chromatin, the sensitivity of DNA to digestion by DNAse I depends on its state of organization, transcriptionally active genes being much more sensitive than inactive gene.
An individual who is given the authority to assume a specific responsibility based upon his or her experience or expertise to perform the task.
The relative proportion of white blood cell types composing the total white blood cell count. Most often identified based on staining characteristics or cells size and granularity. The major types of mature white blood cells in the circulation are Neutrophil, Eosinophils, Basophils (the first 3 collective called Granulocytes), Lymphocytes, and Monocytes.
The development of cells according to distinct lineages with different morphology and functions.
Dimethyl sulfoxide (DMSO)
A cryoprotectant; chemical used together with electrolyte solutions to suspend cells as means of protection from cell membrane injury during the cryopreservation process.
For the purposes of the FACT Standards, there are five categories of Director:Program Director- Physician responsible for all administrative and clinical operations of the clinical transplantation program, including compliance with FACT standards. The Clinical Program Director shall be appropriately licensed to practice medicine in the jurisdiction in which the program is located and board certified (or non-U.S. equivalent) in one or more of the following specialties: Hematology, Medical Oncology, Adult or Pediatric Immunology, or Pediatric Hematology/Oncology. A non-board certified physician who completed medical training prior to 1985 may serve as Clinical Program Director if she/he has documented experience and published contributions in the field of hematopoietic cell transplantation extending over ten years. The Clinical Program Director shall participate regularly in educational activities related to the field of hematopoietic stem cell transplantation. The Program Director also has oversight of the care provided by the Clinical Program.Collection Facility Director- An individual with a medical degree or doctoral degree in a relevant science, qualified by postgraduate training or experience for the scope of activities carried out in the Collection Facility. The Collection Facility Director is responsible for all technical procedures, performance of the collection procedure, supervision of staff and administrative operations of the Collection Facility. The Collection Facility Director shall participate regularly in educational activities related to the field of cell collection and/or transplantation. The Collection Facility Director may also serve as the Medical Director if appropriately credentialed.Collection Facility Medical Director- A licensed physician with postgraduate training in cell collection and/or transplantation. This individual, or designee, is directly responsible for the medical care of patients undergoing apheresis or marrow harvest, including the pre-collection evaluation of the donor at the time of donation and care of any complications resulting from the collection procedure. The Collection Facility Medical Director shall participate regularly in educational activities related to collection of cellular therapy products. The Collection Facility Medical Director may also serve as the Collection Facility Director if appropriately credentialed.Processing Facility Director- An individual with a medical degree or a doctoral degree in a relevant science, qualified by training or experience for the scope of activities carried out in the Processing Facility. The Processing Facility Director is responsible for all procedures and administrative operations of the Processing Facility, including compliance with these Standards. The Processing Facility Director shall participate regularly in educational activities related to the field of hematopoietic cell processing and/or transplantation. The Processing Facility Director may also serve as the Processing Facility Medical Director if appropriately credentialed.Processing Facility Medical Director- A licensed physician with postgraduate training and/or one year’s experience in the preparation and clinical use of cell therapy products. The Processing Facility Medical Director or designee is directly responsible for all medical aspects related to the Processing Facility. The Processing Facility Medical Director shall participate regularly in educational activities related to the field of cellular processing and/or administration. The Medical Director may also serve as the Processing Facility Laboratory Director if appropriately credentialed.
Agent that kills all growing or vegetative forms of microorganisms, eliminating them from inanimate items.
Disseminated Intravascular Coagulation (DIC)
A condition that begins with excessive clotting. The excessive clotting is usually stimulated by a substance that enters the blood as part of a disease (such as an infection or certain cancers) as a complication of childbirth, retention of a dead fetus, surgery or as an adverse reaction to product infusion.
Any conveyance or shipment (including importation and exportation) of a cellular therapy product that has been determined to meet appropriate release criteria, whether or not such conveyance or shipment is entirely intrastate.
The establishment that determines that a product meets all release criteria (or releases a product under exception) and makes a cellular therapy product available for distribution. Includes distribution to another facility and distribution for administration.
DNA - Deoxyribonucleic acid
The genetic material of all cells and many viruses. A polymer of nucleotides. The monomer consists of phosphorylated 2-deoxyribose N-glycosidically linked to one of four bases adenine, cytosine, guanine or thymine. These are linked together by 3', 5'-phosphodiester bridges. In the Watson-Crick double-helix model two complementary strands are wound in a right handed helix and held together by hydrogen bonds between complementary base pairs. The sequence of bases encodes genetic information. Three major conformations exist A-DNA, B-DNA (that corresponds to the original Watson-Crick model) and Z-DNA. Z-DNA may not occur in genomic DNA.
A technique originally developed to allow viral infection of animal cells by uptake of purified viral DNA rather than by intact virus particles. Term is now generally used to describe applications of same methodology to introduction of other kinds of genes or gene fragments into cells as DNA, such as activated oncogenes from tumors into tissue culture cells.
A person who is the source of cells or tissue for a cellular therapy product.
Epstein Barr Virus
Any record or document consisting of any combination of text or graphics or other data that is created, stored, modified, or transmitted in digital form by a computer.
A cellular therapy product donor who meets all donor screening and testing requirements related to transmission of infectious disease as defined by the U.S. Food and Drug Administration or non-U.S. equivalent.
Enzyme-linked immunosorbent assay
Time to achieve a sustained WBC or platelet count > a defined limit for three consecutive days. Hallmarks for granulocytes are 500 and 1000, for platelets they are 20,000, and 50,000 in the absence of platelet transfusion within the preceding week.
Epstein Barr virus (EBV)
Species of Herpes Virus, that binds CR2 and that causes infective mononucleosis and, in the presence of other factors, tumors such as Burkett’s lymphoma and nasopharyngeal carcinoma. Can immortalize B-lymphocytes in vitro and in vivo.
Any unforeseen or unexpected deviations from applicable regulations, standards, or established specifications that may affect the safety, purity, or potency of a cellular therapy product.
Red blood cell (RBC).
Outside the living body.
Growth of one or more cell populations in an in vitro culture system.
A location where activities covered by these procedures and policies are performed. Such activities include determination of donor eligibility or suitability, product collection, processing, storage, distribution, issue, and administration.
Fluorescent Activated Cell Sorter
Foundation for the Accreditation of Cellular Therapies
Fetal Bovine Serum
Food and Drug Administration
Reagent applied for density gradients.
Fluorescence-activated cell sorter (FACS)
A machine that measures cell size, granularity and fluorescence due to bound florescent antibodies as single cells pass in a stream through a laser light and photo detectors. The analysis of single cells in this way is called flow cytometry and the instruments that carry out the measurements are called flow cytometers.
An unexpanded cellular therapy product that has never been cryopreserved. May also refer to products that are ex vivo expanded from previously frozen cells.
Granulocyte colony stimulating factor
The insertion of one or more exogenous genes into hematopoietic cells or other cell types.
Granulocyte-macrophage colony stimulating factor
Graft-versus-host disease (GVHD)
Manifestations of the reaction of engrafted donor cells against host tissue; clinical symptoms involve the skin, liver, and intestinal tract with potential for effect on additional organs. Acute GVHD occurs usually within the first 100 days post transplant and is initiated by T lymphocytes of donor origin. Chronic GVHD is generally seen after the first 100 days and may also be caused by donor T cells, but cytokines (IFN-g, TNF, IL-1) may also play a role in the disease process.
Graft-versus-leukemia (GVL) effect
The immune mediated elimination of residual leukemia by donor-derived cells infused with the stem cell graft. Similar effects in diseases other than leukemia are termedGraft-versus-Tumor reactions.
Any cell containing granules; leukocyte containing neutrophil, basophil or eosinophil granules in its cytoplasm.
Granulocyte colony-stimulating factor (G-CSF)
A hematopoietic growth factor that induces the growth and differentiation of progenitor cells committed to the neutrophil lineages and enhances the functional activities of effector cells of the granulocyte lineage. Used clinically to increase the rate of granulocyte recovery following chemotherapy and transplantation, and to induce CD34+ hematopoietic progenitor cells into the circulation for the collection of peripheral blood stem cells.
Granulocyte macrophage colony-stimulating factor (GM-CSF)
A hematopoietic growth factor that regulates the growth and differentiation of progenitor cells and enhances the functional activities of effector cells of the granulocyte-macrophage lineage. Used clinically to increase the rate of granulocyte recovery following chemotherapy and transplantation, and to induce CD34+hematopoietic progenitor cells into the circulation for the collection of peripheral blood stem cells.
Good Tissue Practices
Graft versus host disease
Graft versus leukemia
The collection of HPC-M, HPC-A or other products for use in transplantation.
Hepatitis B core antigen
Hepatitis B surface antigen
Hepatitis B virus
Human cells, tissues, or cellular or tissue-based products
Hepatitis C virus
Sets of T-lymphocytes that specifically are involved in the differentiation of B-lymphocytes into antibody-secreting cells. Loss of T-helper cells, as in HIV infection, leads to immunosuppression. There is also T-cell help of T-cell function. TH1 and TH2 are now recognized, TH1 helping with cellular, TH2 with humoral immunity. Most helper T cells bear the CD4 surface antigen.
Referring to the production of blood.
Hematopoietic Progenitor Cell Therapy
The infusion of HPC products with the intent of providing effector cells in support of therapy of disease or other cell therapy.
Hematopoietic Progenitor Cells (HPC)
Self-renewing and multi-potent stem cells capable of maturation into any of the hematopoietic lineages, lineage-restricted pluri-potent progenitor cells, and committed progenitor cells, regardless of tissue source (bone marrow, umbilical cord blood, peripheral blood, and other tissue sources).
A group of large DNA viruses: Herpes simplex causes cold-sores and genital herpes; Varicella-zoster causes chicken-pox and shingles; cytomegalovirus causes congenital abnormalities and is an opportunistic pathogen; Epstein-Barr virus (EBV) causes glandular fever. Herpes simplex type 2 and EBV are associated with human tumors (cervical carcinoma for the former and Burkett’s lymphoma and nasopharyngeal carcinoma in the case of EBV). Herpes simplex establishes a lifelong latent infection of sensory neurons in human dorsal root ganglia and has a tendency to resurgence if the immune system is suppressed (causing shingles).
Pertaining to the similarity of tissues between different individuals. Literally the ability of tissues to get along. The major histocompatibility complex (MHC) in humans is termed Human Leukocyte Antigens (HLA).
Human Immunodeficiency Virus
Human leukocyte antigen
The replacement or supplementation of a recipient’s cells or tissues with an cell therapy product that performs the same basic function or functions in the recipient as in the donor.
Hematopoietic Progenitor Cell, Apheresis
Hematopoietic Progenitor Cell, Cord Blood
Hematopoietic Progenitor Cell, Marrow
Human serum albumin
Human T-cell lymphotropic virus
Human cells, tissues, or cellular or tissue-based products (HCT/Ps)
Articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient. Note this is the term preferred by FDA, FACT and other accreditation organizations prefer the term cellular therapy product.
Human Leukocyte Antigens (HLA)
The HLA system is comprised of a series of genes grossly divided into Class I and Class II HLA. Class I heavy chain genes are coded for at the highly polymorphic HLA-A, HLA-B and HLA-C loci and are found on the surface of nearly all human cells in association with a non-polymorphic light chain called beta-2 microglobulin. Class II heavy and light chains are encoded at the HLA-DR, HLA-DQ, and HLA-DP loci. HLA-DR includes polymorphic genes at DRB1, DRB3, DRB4, and DRB5 loci, while the DR-alpha chain has limited polymorphism. HLA polymorphism may be identified by antibodies (Serologic level), by T cells (Cellular level) or at the level of DNA (Molecularly defined). Molecular definition gives the highest level of resolution while cellular recognition may be more clinically relevant. Antigens of the HLA system may be the target of cells causing GVHD, GVL, or graft rejection.
Any organ, organ sample or specimen obtained from a living or cadaveric human donor.
Hydroxyethyl starch (HES)
Chemical applied for the separation of leukocytes within whole blood components. Reduces the surface tension of red blood cells causing them to stack up (Rouleaux) and sediment at a rapid rate resulting in the enrichment of leukocytes in the liquid layer.
Investigational device exemption
The ability of an individual to mount a normal immune response to foreign antigens.
Tissue culture or testing of cells outside the individual from which they were obtained; within a receptacle, such as a test tube.
Application or testing within the living body.
ABO incompatibility such that the recipient of a graft possesses antibodies reactive to the red blood cells of the donor. Antibodies commonly found in the plasma of individuals of a given blood type are:
Group A Anti-B
Group B Anti-A
Group AB none
Group O Anti-A and Anti-B
ABO incompatibility such that the donor of a graft (transfusion) has antibodies reactive against recipient red blood cells.
Group A Anti-B
Group B Anti-A
Group AB none
Group O Anti-A and Anti-B
Investigational New Drug
A cellular therapy product donor who does not meet all donor screening and testing requirements related to transmission of infectious disease as defined by the U.S. Food and Drug Administration, or non-U.S. equivalent.
Infectious Disease Testing Results
Human Immunodeficiency Virus 1 (HIV 1)
Human Immunodeficiency Virus 2 (HIV 2)
Human T cell Leukemia Virus (HTLV)
Hepatitis C Virus (HCV)
Human Immunodeficiency Virus (HIV Ag)
Hepatitis B Surface Antigen (Hbs Ag)
Hepatitis B Core (Hbc)
Human Immunodeficiency Virus (NAT-HIV)
Hepatitis C Virus (NAT-HCV)
Institutional Review Board (IRB)
A Board or Committee established by an institution in accordance with the regulations of the United States Department of Health and Human Services, or other governmental agency where applicable, to review biomedical and behavioral research involving human subjects conducted at or supported by that institution.
Cytokine released by subpopulation of T-lymphocytes capable of stimulating itself or other T cells or Natural Killer cells to proliferate and increase functional activity.
Microscope with inverted lens mounted such that objects are viewed from the bottom of the vessel up. In the laboratory used to score hematopoietic colony assays and T cell limiting dilution cultures.
Institutional review board
Critical for the correct performance of the procedure or processing. Used in reference to elements of a procedure, equipment used for the procedure, and supplies and reagents used in the procedure.Labeling
The process of proper physical identification of a hematopoietic stem cell product including: Assignment of a product alphanumeric identifier, cross reference of the identifier with laboratory records such that the donor and all processing steps are identifiable, the proper name of the product, the composition of the product and any product modifications, identity of the intended recipient, review and verification of the labeling accuracy and fixation of the label to the product in a secure fashion. The precise information required on a product label differs based on the processing step. Refer to the FACT standards, and to the CPL labeling procedure for exact specifications and examples.Leukapheresis
The collection of leukocytes by apheresis.Leukemia
Cancer of leukocytes. Most common types are:
Acute Lymphoblastic (Not abbreviated)
Acute Lymphocytic (ALL)
Acute Myelo/Monocytic (AMML)
Acute Non Lymphocytic (ANLL) or Acute Myelogenous (AML)
Chronic Lymphocytic (CLL)
Chronic Monocytic (Not abbreviated)
Chronic Myelogenous (CML)
Hairy Cell (HCL)
Juvenile Chronic Myelogenous (JCML)Leukocyte
White blood cell.Linearity
The ability of the method to elicit test results that are directly proportional to analyte concentration within a given range. Linearity is generally reported as the variance of the slope of the regression line.Liquid nitrogen (LN2)
The liquid form of Nitrogen. Used in the laboratory to maintain hematopoietic cells in the frozen state. The temperature in the liquid phase is -196oC, in the vapor phase temperature can be maintained at -130oC. Nitrogen levels must be controlled so as to maintain the correct temperature.LPL
Lymphocyte Propagation LaboratoryLymphocyte
A mononuclear leukocyte with deeply staining nucleus containing dense chromatin and a pale blue staining cytoplasm. Chiefly a product of lymphoid tissue that participates in humoral and cell-mediated immunity. Includes T cells, B cells, and NK cells.
An ex vivo procedure(s) that selectively removes, enriches, expands, or functionally alters hematopoietic progenitor cells.Minimally Manipulated- Processing that does not alter the relevant biological characteristics of cells or tissues.More than minimally manipulated- Processing that does alter the relevant biological characteristics of cells or tissues.Unmanipulated hematopoietic progenitor cells- Hematopoietic progenitor cells as obtained at the time of collection and not subjected to any form of manipulation.
Includes, but is not limited to, any or all steps in the recovery, processing, storage, labeling, packaging, or distribution of any human cellular or tissue-based product, and the screening and testing of a cell or tissue donor.
A mixture of inorganic salts and other nutrients capable of sustaining cell survival in vitro.
Semisolid, organic chemical used to grow hematopoietic cell colonies in vitro.
Infectious agents including bacterial and fungal organisms.
Minor Histocompatibility Antigens (mHA)
A series of polymorphic self-antigens that are presented to the immune system in the context of MHC antigens. In cases of HLA identity, multiple mHA differences may result in clinical outcomes, GVHD or graft rejection, similar to that seen in transplants differing for MHC.
Monoclonal antibody (Mab)
Antibody generated by a hybridoma obtained by fusion of mouse, rat or human myeloma cell line and specifically sensitized B-lymphocytes usually from the same species. The antibody obtained is of a single specificity that of the B cell fusion partner.
Blood and marrow cells excluding multi-nucleated granulocytes and erythrocytes. Within the peripheral blood this includes lymphocytes and monocytes and hematopoietic stem cells, within marrow those cell types as well as immature myeloid elements form a portion of the mononuclear cells.
Medical Record Number
The manipulation of a cellular therapy product such that a specific cell population(s) is depleted.
Nucleic Acid Testing
That which is not free of pathogenic and/or nonpathogenic microorganisms, including spores.
Any cellular therapy product that does not completely meet the requirements specified by these policies or procedures.
All cells other than red blood cells and platelets.
A nurse with a graduate degree in advanced practice nursing providing patient services in defined areas of practice. These services are provided in collaboration with other health professionals. A type of Mid-Level Practitioner.
The process by which the results of a therapeutic procedure are formally assessed.
Abnormally low counts in all cell lineages.Partial Label
The minimal essential elements that must be affixed to all cellular therapy product containers.Pathogenic
Producing or capable of producing disease.PBMC
Peripheral blood mononuclear cellsPBS
Phosphate Buffered SalinePE
PhycoerythrinPeripheral Blood - Mononuclear Cell Enriched
Blood that has been enriched for mononuclear white blood cells (Lymphocytes and Monocytes). This may be accomplished with the use of density gradient separation medium or with a cell processor. May be referred to as PBMC.Peripheral Blood Progenitor Cells
Hematopoietic cell with multilineage potential obtained from peripheral blood rather than the bone marrow. Hematopoietic progenitor cells are induced to circulate following administration of hematopoietic growth factors (e.g. G-CSF, GM-CSF, SCF, IL-3) or following recovery from myeloablation or a combination. These are normally collected by the process of apheresis and are admixed with other peripheral mononuclear cells. May also be referred to as peripheral blood stem cells (PBSC). Proper name is Hematopoietic Progenitor Cells, Apheresis (HPC-A). This terminology should be used in all relevant laboratory documents.
The entire physical, biochemical and physiological makeup of an individual as determined both genetically and environmentally.
A person formally trained to provide diagnostic, therapeutic, and preventive health care services with physician supervision. A type of Mid-Level Practitioner.
A plant lectin used to polyclonally stimulate T lymphocytes.
Capable of producing cells of different lineages.
Polymerase chain reaction (PCR)
The first practical system for in vitro amplification of DNA, and as such one of the most important recent developments in molecular biology. Two synthetic oligonucleotide primers, which are complementary to two regions of the target DNA (one for each strand) to be amplified, are added to the target DNA (that need not be pure), in the presence of excess deoxynucleotides and Taq polymerase, a heat-stable DNA polymerase. In a series (typically 30) of temperature cycles, the target DNA is repeatedly denatured (around 90°C), annealed to the primers (typically at 50-60°C) and a daughter strand extended from the primers (72°C). As the daughter strands themselves act as templates for subsequent cycles, DNA fragments matching both primers are amplified exponentially, rather than linearly. The original DNA need thus be neither pure nor abundant, and the PCR reaction has accordingly become widely used not only in research, but also in clinical diagnostics and forensic science.
Enzymes involved in template-directed synthesis of DNA from deoxyribonucleotide triphosphates. I, II and III are known in E. coli ; III appears to be most important in genome replication and I is important for its ability to edit out unpaired bases at the end of growing strands. Animal cells have alpha, beta or gamma polymerases, with alpha apparently responsible for replication of nuclear DNA, and gamma for replication of mitochondrial DNA. All these function with a DNA strand as template. Retroviruses possess a unique DNA polymerase (reverse transcriptase) that uses an RNA template.
Variant forms of a particular gene that occurs simultaneously in a population.
The manipulation of a cellular therapy product such that a specific cell population(s) is enriched.
The measure of the degree of repeatability of a method under normal operation. Normally expressed as the percent relative standard deviation for a statistically significant number of samples.
Early ancestor of a given cell.
A sequence of DNA or RNA, labeled or marked with a radioactive isotope, used to detect the presence of complementary nucleotide sequences.
Documents that explain how the goals of the laboratory will be achieved and serve as guidelines that define the general course and scope of activities permissible for goal accomplishment. Describes the goal-directed interrelated series of actions, events, or steps that are required.
Includes all aspects of manipulation, labeling, and infusion of products, regardless of source.
The harvested material that is being processed at any stage of the processing. Formally referred to as component.
An evaluation of the ability to perform laboratory procedures within acceptable limits of accuracy, through and analysis of unknown specimens distributed at periodic intervals by a source outside the facility performing the proficiency test.
The production of new cells from a given precursor.
Describing the removal of one or more cell populations from a cell suspension.
Relative freedom from extraneous matter in the finished product, whether or not harmful to the recipient or deleterious to the product, including but not limited to relative freedom from residual moisture or other volatile substances and pyogenic substances.
The conformance of a product or process within pre-established specifications or standards.
Describes the actions, planned and performed, to evaluate all systems and elements that influence the quality of the product or service.
Quality Assurance (QA)
Describes the actions, planned and performed, to provide confidence that all systems and elements that influence the quality of the product or service.
Quality Control (QC)
Refers to a component of a quality program that includes the activities and controls used to determine the accuracy and reliability of the establishment’s personnel, equipment, reagents, and operations in the manufacturing of hematopoietic progenitor cell products, including testing and product release.
Quality Improvement (QI)
Describes the actions planned and performed to develop a system to review and improve the quality of a product or process.
Quality Management (QM)
Refers to an integrated program of quality assessment, assurance, control and improvement.
Range is the interval between the upper and lower levels of analyte (inclusive) that have been demonstrated to be determined with precision, accuracy and linearity using the method as written.
Red blood cells
Specific molecule on the surface or within the cell cytoplasm that recognizes and binds with other specific molecules.
Spliced DNA formed from two or more different sources that have been cleaved by restriction enzymes and joined by ligases.
In the context of bone marrow transplant, often referring to the gradual increase of lymphohematopoietic cells after transplantation.
A member of a class of RNA viruses that utilizes the enzyme reverse transcriptase to reverse copy its genome into a DNA intermediate, which integrates into the host cell chromosome.
Reverse transcriptase (RNA-dependent DNA polymerase)
An enzyme isolated from retrovirus-infected cells that synthesizes a complementary (c)DNA strand from an RNA template.
Rhesus blood type
The capacity of a method to remain unaffected by small deliberate variations in method parameters.
Revolutions per minute
Refers to relative freedom from harmful effects to persons affected, directly or indirectly, by a product when prudently administered, taking into consideration the character of the product in relation to the condition of the recipient at the time.
The gradual settling down of cells by gravity.
Standard error of the mean
Severe toxic febrile state resulting from infection with pyogenic microorganisms with or without associated septicemia.
Clinical syndrome characterized by significant invasion of microorganisms from a focus of infection in tissues of the bloodstream. Microorganisms may multiply in the blood. Infection of bacterial origin carried through the bloodstream is sometimes referred to as bacteremia.
The physical act of transferring a cellular therapy product within or between facilities. During shipping the product leaves the control of trained personnel at the transporting or receiving facility.
Standard Operating Procedure
The ability to measure (or remove) accurately and specifically the analyte of interest in the presence of other products that may be expected to be present in the sample or product.
Inactive but viable state of microorganisms in the environment. Certain bacteria and fungi sustain themselves in this form until the environment is favorable for vegetative growth. The spore stage is highly resistant to heat, toxic chemicals and other methods of destruction.
Standard Operating Procedures (SOP) Manual
The compilation of written detailed instructions required to perform procedures.
The current North American edition of Standards for Hematopoietic Progenitor Cell Collection, Processing & Transplantation published by FACT.
The cell attributed to producing all necessary components in a given tissue.
Free of microorganisms, including all spores.
Area that has been prepared and maintained for sterile application with introduction of only other sterile equipment, supplies or reagents.
Methods by which contamination with microorganisms is prevented to maintain sterility throughout laboratory procedures.
Process by which all pathogenic and/or nonpathogenic microorganisms, including spores are killed. This term refers only to a process capable of destroying all forms of microbial life including spores.
Serologic Test for Syphilis
Fluid component in culture system; liquid portion of cells in suspension.
Mechanically cleansed but not sterile. Items are rendered surgically clean by the use of chemical, physical or mechanical means that markedly reduce the number of microorganisms on them.
Hematopoietic progenitor cells obtained from a genetically identical donor (e.g. identical twin).
T cells or T lymphocytes
One of the two major classes of lymphocytes. The T cell antigen receptor is present on the cell-surface and is composed of two chains. A given T cell may possess an alpha and a beta chain or a delta and a gamma chain. T cells are of two major subtypes, CD4+ with helper activity and CD8+ with cytotoxic effector activity. T lymphocytes are thought to be the prime mediators of GVHD when contained in the donor inoculum and residual host derived T cells can mediate graft rejection. The most common form of cell purging performed in the CPL lab is the removal of T lymphocytes from the donor graft prior to transplantation.
Therapeutic Cells, Cytotoxic T Lymphocyte
Therapeutic Cells, Dendritic Cells
Therapeutic Cells, T-cells
Thymidine kinase (TK) (EC 126.96.36.199) is an ubiquitous enzyme that catalyzes the ATP-dependent phosphorylation of thymidine. A comparison of TK sequences has shown [1,2,3] that there are two different families of TK. One family groups together TK from herpes viruses as well as cellular thymidine kinases, while the second family currently consists of TK from the following sources:
- Bacteriophage T4
- African swine fever virus (ASF)
- Fish lymphocystis disease virus (FLDV)
Time of Collection
The time of day at the end of the cellular therapy product collection procedure.
Originally the maintenance and growth of pieces of explanted tissue (plant or animal) in culture away from the source organism. Now usually refers to the (much more frequently used) technique of cell culture, using cells dispersed from tissues, or distant descendants of such cells.
The transfer of a gene from one bacterium to another by a bacteriophage. In generalized transduction any gene may be transferred as a result of accidental incorporation during phage packaging. In specialized transduction only specific genes can be transferred, as a result of improper recombination out of the host chromosome of the prophage of a lysogenic phage. Transduction is an infrequent event but transducing phages have proved useful in the genetic analysis of bacteria.
The introduction of DNA into a recipient eukaryote cell and its subsequent integration into the recipient cell's chromosomal DNA. Usually accomplished using DNA precipitated with calcium ions though a variety of other methods can be used (e.g. electroporation). Only about 1% of cultured cells are normally transfected. Transfection is analogous to bacterial transformation but in eukaryotes transformation is used to describe the changes in cultured cells caused by tumor viruses. Though originally used to describe the situation in which the transfected DNA is integrated, it is now frequently used just to mean introduction of DNA into a target cell, hence the necessity to specify stable transfection.
Transplantation, Hematopoietic Progenitor Cell
The infusion of autologous, syngeneic or allogeneic hematopoietic progenitor cells with the intent of providing transient or permanent engraftment in support of therapy of disease. Transplant are most commonly performed for the treatment of leukemia (see above) but may also be commonly used for the following diagnoses under protocols at MCW:
- Germ Cell Tumors
- Hodgkin’s Disease (HD)
- Myelodysplastic Syndrome (MDS)
- Multiple Myeloma (MM)
- Multiple Sclerosis (MS)
- Non-Hodgkin’s Lymphoma (NHL)
- Severe Aplastic Anemia (SAA)
- Systemic Sclerosis (also called Sclerodema)
- Sickle Cell Anemia (SCA)
- Severe Combined Immune Deficiency (SCID)
Transport Trypan blue
The physical act of transferring a cellular therapy product within or between facilities. During transportation the product does not leave the control of trained personnel at the transporting or receiving facility.
Biological stain used to determine cell viability. Trypan blue is unable to penetrate intact plasma membranes, and so only labels dead cells.
Umbilical Cord Blood
Hematopoietic cells collected from the placental and umbilical cord blood vessels after the umbilical cord is clamped and/or sectioned. These cells are of fetal origin and are enriched for hematopoietic progenitor cells to levels equal to or greater than bone marrow. Proper FACT name is Hematopoietic Progenitor Cells, Cord Blood (HPC-C). This terminology should be used in all relevant laboratory documents.
Unmanipulated Hematopoietic Progenitor Cells
Hematopoietic progenitor cells as obtained at the time of collection and not subjected to any form of manipulation.
The cowpox virus used to vaccinate against smallpox and, experimentally, as a carrier of genes for antigenic determinants cloned from other disease organisms.
Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes. A process is validated to evaluate the performance of a system with regard to its effectiveness based on intended use.
An autonomously replicating DNA molecule into which foreign DNA fragments are inserted and then propagated in a host cell. Also living carriers of genetic material (such as pollen) from plant to plant, such as insects.
Gathering information by investigation that a process is true or correct.
An infectious particle composed of a protein capsule and a nucleic acid core, which is dependent on a host organism for replication. A double-stranded DNA copy of an RNA virus genome that is integrated into the host chromosome during lysogenic infection.
White blood cells
West Nile Virus