Transfusion medicine

Stem cell transplant

Stem cell collection


Editorial Board Member: Kyle Annen, D.O.
Deputy Editor-in-Chief: Patricia Tsang, M.D., M.B.A.
Yvette C. Tanhehco, Ph.D., M.D., M.S.

Topic Completed: 23 August 2021

Minor changes: 23 August 2021

Copyright: 2021, PathologyOutlines.com, Inc.

PubMed Search: Stem cell collection[title] "last 5 years"[DP]

Yvette C. Tanhehco, Ph.D., M.D., M.S.
Page views in 2020: 12
Page views in 2021 to date: 173
Cite this page: Tanhehco YC. Stem cell collection. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedstemcellcollection.html. Accessed December 3rd, 2021.
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
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
Blood donor testing
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
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.
Board review style question #1
Which of the following antigens is a marker of stem cells?

  1. CD20
  2. CD34
  3. CD38
  4. CD45
Board review style answer #1
Board review style question #2
Which stem cell source is associated with the fastest engraftment?

  1. Bone marrow
  2. Cord blood
  3. Liver
  4. Peripheral blood
Board review style answer #2
D. Peripheral blood

Comment Here

Reference: Stem cell collection
Board review style question #3
Which blood cell type is responsible for graft versus host disease?

  1. B cells
  2. Neutrophils
  3. Plasma cells
  4. T cells
Board review style answer #3
D. T cells

Comment Here

Reference: Stem cell collection
Back to top
Image 01 Image 02