Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Screening | Blood donor screening | Blood donor testing | Donor deferral | Laboratory | Case reports | Sample assessment & plan | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2 | Board review style question #3 | Board review style answer #3Cite this page: Tanhehco YC. Stem cell collection. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedstemcellcollection.html. Accessed April 1st, 2025.
Definition / general
- Hematopoietic stem cell transplantation, also known as bone marrow transplantation, is a procedure whereby stem cells are infused into a recipient after a conditioning regimen in order to repopulate the bone marrow that is depleted or dysfunctional (Biol Res 2012;45:307)
- Stem cells may be obtained from the bone marrow, peripheral blood or cord blood
- Stem cells may be from the recipient of the transplant (autologous) or from a healthy donor (allogeneic) (Biol Res 2012;45:307)
Essential features
- Minimum of 2 x 106 CD34+ cells/kg recipient weight must be collected for successful neutrophil and platelet engraftment (Pharmacotherapy 2010;30:485)
- Bone marrow, peripheral blood and cord blood are 3 sources of stem cells that each have pros and cons
- Bone marrow derived stem cells are associated with less graft versus host disease but lead to slower engraftment when compared with peripheral blood derived stem cells
- Human leukocyte antigen (HLA) matching for HLA-A, B, Cw, DR, DQ (10/10 match) ideal but transplantation may occur with fewer matches
- Donors are evaluated for suitability and eligibility prior to stem cell collection
Terminology
- Hematopoietic stem cell transplantation
- Stem cell transplantation
- Hematopoietic progenitor cell transplantation
Pathophysiology
- Stem cells are self renewing
- Stem cells differentiate into all blood cell lineages (i.e. white blood cells, red blood cells, platelets)
- Stem cells adhere to niche spaces in the bone marrow via adhesion molecule interactions
- CD34 antigen is a marker of stem cells
- At least 2 x 106 CD34+ cells/kg recipient weight is necessary for engraftment after transplantation
- Reference: Curr Opin Hematol 2019;26:258
Clinical features
- Bone marrow derived stem cells
- Operating room procedure
- Patient placed under anesthesia (i.e. general, epidural, spinal)
- Bone marrow harvested using syringe and needle
- Typical harvest sites are posterior iliac crest and anterior iliac crest
- Typical bone marrow product collected approximately 1 liter
- Collection takes several hours
- Large number of stem cells may be collected with fewer mature T cells
- Lower risk of chronic graft versus host disease compared with peripheral blood derived stem cells
- Slower engraftment compared with peripheral blood derived stem cells
- Peripheral blood derived stem cells
- Apheresis procedure
- Vascular access (e.g. peripheral venous, central venous catheter) required for apheresis collection
- 2 - 5 total blood volumes typically processed
- Collection takes several hours
- Mobilization agent (e.g. granulocyte colony stimulating factor [G-CSF], plerixafor) required to dissociate stem cells from the bone marrow into the peripheral blood (Pharmacotherapy 2010;30:485)
- Multiple days of collection possible to reach target CD34+ cell yield
- Fastest rate of engraftment compared with bone marrow derived stem cells and cord blood derived stem cells
- Highest rate of chronic graft versus host disease compared with bone marrow derived stem cells and umbilical cord blood derived stem cells
- Umbilical cord blood derived stem cells
- Collected from umbilical vein before or after placenta is delivered
- Low CD34+ cell content (approximately 3 - 4 x 106 cells per collection)
- Collection takes several minutes
- Lowest rate of acute and chronic graft versus host disease compared with bone marrow derived stem cells and peripheral blood derived stem cells
- Higher probability of finding a match if recipient has rare human leukocyte antigen type
- Rapidly available for procurement (approximately 2 weeks)
- No donor attrition
- Lower incidence of viral contamination
- Single collection only
- Common clinical indications (Br J Haematol 2016;174:515):
- Stroke or neurological event or deficit
- Recurrent acute chest syndrome
- Recurrent severe pain crises despite supportive care
- Recurrent vaso-occlusive painful episodes or recurrent priapism
- End organ damage (lung, heart, kidneys)
- Multiple red blood cell transfusions per year to prevent vaso-occlusive complications
- Clinical indications for HSCT (Center for International Blood & Marrow Transplant Research: The US Summary Slides - HCT Trends and Survival Data [Accessed 23 August 2021]):
- Autologous transplants:
- Multiple myeloma
- Lymphoma (Non-Hodgkin lymphoma and Hodgkin disease)
- Other malignancy
- Multiple myeloma and Lymphoma (Non-Hodgkin lymphoma and Hodgkin disease) accounted for 37% of all hematopoietic stem cell transplants in the U.S. in 2019
- Allogenenic transplants:
- Acute leukemias (acute myeloid leukemia, acute lymphoblastic leukemia)
- Myelodysplastic syndrome
- Nonmalignant disease
- Aplastic anemia
- Chronic myelogenous leukemia
- Other leukemia
- Acute leukemias (acute myeloid leukemia, acute lymphoblastic leukemia) and myelodysplastic syndrome accounted for 76% of all hematopoietic stem cell transplants in the U.S. in 2019
- Autologous transplants:
Screening
- Optimal adult donor matched at high resolution to HLA class I: A, B, C; HLA class II: DRB1 to prevent graft versus host disease, graft rejection and engraftment failure (N Engl J Med 2014;371:339)
- ABO antigen mismatch between donor and recipient is not a barrier to successful transplantation (Biol Blood Marrow Transplant 2013;19:1152)
Blood donor screening
- Donor suitability:
- Focuses on health of donor (i.e. is the donor healthy enough to donate stem cells?)
- Evaluated through medical history, physical exam, laboratory studies
- Donor eligibility:
- Focuses on health of recipient (i.e. are the stem cells from the donor safe for the recipient?)
- Evaluation of risk factors for infectious diseases
- Evaluated through donor history questionnaire, medical records review, physical exam, infectious disease marker testing from a blood sample
- References: U.S. Food & Drug Administration: CFR - Code of Federal Regulations Title 21, Subpart C, Sec. 1271 [Accessed 21 June 2021], U.S. Food & Drug Administration: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products [Accessed 21 June 2021], Foundation for the Accreditation of Cellular Therapy: Establishing Global Standards in Cellular Therapies [Accessed 21 June 2021]
Blood donor testing
- Infectious disease marker testing
- Human immunodeficiency virus (HIV), types 1 and 2
- Hepatitis B virus (HBV)
- Hepatitis C virus (HCV)
- Human T lymphotropic virus (HTLV), types 1 and 2
- Treponema pallidum (syphilis)
- Trypanosoma cruzi (Chagas)
- West Nile virus (WNV)
- Zika virus
- References: U.S. Food & Drug Administration: CFR - Code of Federal Regulations Title 21, Subpart C, Sec. 1271 [Accessed 21 June 2021], U.S. Food & Drug Administration: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products [Accessed 21 June 2021], Foundation for the Accreditation of Cellular Therapy: Establishing Global Standards in Cellular Therapies [Accessed 21 June 2021]
Donor deferral
- Donors with medical conditions that make stem cell collection unsafe are deemed unsuitable and are deferred from donation
- Donors with risk factors for infectious diseases or who have positive infectious disease markers are deemed ineligible and are deferred from donation; ineligible donors (i.e. nonconforming donors) may be used if there is documentation of urgent medical need
- Any potential donor who exhibits 1 or more of the following conditions or behaviors is determined to be ineligible (adapted from FDA: Guidance for Industry - Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) [Accessed 11 June 2021], FDA: Tissue Guidances [Accessed 11 June 2021]):
- Men who have had sex with another man in the preceding 5 years
- Persons who have injected drugs for a nonmedical reason in the preceding 5 years
- Persons with hemophilia or other related clotting disorders who have received human derived clotting factor concentrates in the preceding 5 years
- Persons who have engaged in sex in exchange for money or drugs in the preceding 5 years
- Persons who have had sex in the preceding 12 months with any person in the previous 4 bullet points or with any person who has HIV infection, HBV infection or a clinically active HCV infection
- Persons who have been exposed in the preceding 12 months to known or suspected HIV, HBV or HCV infected blood through a needlestick or through contact with an open wound, nonintact skin or mucous membrane
- Children born to mothers with or at risk for HIV infection if 18 months of age or younger or if breastfed within the preceding 12 months
- Persons who have been in juvenile detention, lockup, jail or prison for more than 72 consecutive hours in the preceding 12 months
- Persons who have lived with another person who has HBV or clinically active HCV infection in the preceding 12 months
- Persons who have undergone tattooing, ear piercing or body piercing in the preceding 12 months without using sterile procedures, supplies or equipment
- Persons who have had a past diagnosis of clinical, symptomatic viral hepatitis after their eleventh birthday, unless there is documented evidence that hepatitis A virus, Epstein-Barr virus or cytomegalovirus was the cause
- Persons who are deceased and have a documented medical diagnosis of sepsis or have documented clinical evidence consistent with a diagnosis of sepsis that is not explained by other clinical conditions at the time of death
- Persons who have had a smallpox vaccination in the preceding 8 weeks
- Persons who acquired a clinically recognizable vaccinia virus infection by contact with someone who received the smallpox vaccine
- Persons who have had a medical diagnosis or suspicion of WNV infection should be deferred for 120 days following diagnosis or onset of illness, whichever is later
- Persons who have tested positive or reactive for WNV infection using an FDA licensed or investigational WNV NAT (nucleic acid test) donor screening test in the preceding 120 days
- Persons who have been treated for or had syphilis within the preceding 12 months
- Persons who have been diagnosed with variant Creutzfeldt-Jakob disease (vCJD) or any other form of Creutzfeldt-Jakob disease (CJD)
- Persons who have been diagnosed with dementia or any degenerative or demyelinating disease of the central nervous system or another neurological disease of unknown etiology
- Persons who are at increased risk for CJD
- Persons who have a history of CJD in a blood relative
- Persons who spent 3 months or more cumulatively in the United Kingdom from 1980 - 1996
- Persons who are current or former U.S. military members, civilian military employees or dependents of a military member civilian employee who resided at U.S. military bases in Northern Europe for 6 months or more cumulatively from 1980 - 1990 or elsewhere in Europe for 6 months or more cumulatively from 1980 - 1996
- Persons who spent 5 years or more cumulatively in Europe from 1980 to the present
- Persons who received any blood or blood component transfusions in the United Kingdom or France between 1980 and the present
- Persons or their sexual partners who were born or lived in certain countries in Africa after 1977
- Persons who have received a blood transfusion or any medical treatment that involved blood in certain countries in Africa after 1977
- Persons who are recipients of xenotransplantation products or intimate contacts of a xenotransplantation product recipient
- Note: if a donor is ineligible due to 1 or more of the above criteria but there are no acceptable alternative matches / potential donors, the donor can still be used via an urgent medical need pathway, which requires additional disclosure to and consent by the recipient
Laboratory
- Complete blood count
- Complete metabolic panel
- Prothrombin time
- Partial thromboplastin time
- Fibrinogen
- Ionized calcium
- CD34+ cell count
- Note: acceptable values for stem cell collection vary by service / institution
- Reference: Foundation for the Accreditation of Cellular Therapy: Establishing Global Standards in Cellular Therapies [Accessed 21 June 2021]
Case reports
- 25 year old healthy man with a low peripheral blood stem cell collection yield after G-CSF administration (J Clin Apher 2009;24:262)
- 38 year old healthy man with severe hypersensitivity anaphylactoid reaction after G-CSF administration (J Oncol Pharm Pract 2019;25:2056)
- 58 year old man with end stage renal disease who donated peripheral blood stem cells by apheresis (Bone Marrow Transplant 2012;47:157)
- Case series of 5 patients with AL amyloidosis mobilized with plerixafor and G-CSF for peripheral blood stem cell collection (Amyloid 2014;21:149)
Sample assessment & plan
- Assessment:
- 40 year old woman with multiple myeloma who presented for peripheral blood stem cell collection. The patient was mobilized with G-CSF and plerixafor prior to the start of collection. The patient was given 2 g intravenous calcium gluconate in 100 mL normal saline piggyback. The patient did not complain of any symptoms. The procedure was completed without any adverse events. The total amount of CD34+ cells collected was 3 x 106 CD34+ cells/kg recipient weight.
- Plan:
- The patient’s collection goal of at least 5 x 106 CD34+ cells/kg has not been met. The patient will return for a second day of collection tomorrow. The patient will receive another dose of G-CSF tonight and tomorrow morning and plerixafor tonight.
Additional references
Board review style question #1
Which of the following antigens is a marker of stem cells?
- CD20
- CD34
- CD38
- CD45
Board review style answer #1
Board review style question #2
Which stem cell source is associated with the fastest engraftment?
- Bone marrow
- Cord blood
- Liver
- Peripheral blood
Board review style answer #2
Board review style question #3
Which blood cell type is responsible for graft versus host disease?
- B cells
- Neutrophils
- Plasma cells
- T cells
Board review style answer #3