Stem Cell

Source

Bone Marrow

• Each aspirate is limited to 5 to 10 mL to reduce contamination by peripheral blood. The goal of collection is usually 1 to 1.5 L and is based on recipient weight, with a target of nucleated cell count of at least 2.5 × 10^8/kg recipient weight.
• The marrow product is prepared for infusion by filtering out osseous particles and fat globules. Ideally, marrow is infused in the patient immediately after harvesting.
• Life-threatening complications from marrow harvesting, usually related to anesthesia, have been reported in 0.27% to 0.4% of donors.

Peripheral Blood

• Myeloid growth factors activate neutrophils to release serine proteases, which in turn cleave vascular adhesion molecules releasing stem cells from the marrow niche allowing them to circulate in the peripheral blood.
• The number of colony-forming units in peripheral blood increased markedly during recovery from chemotherapy or following administration of a myeloid growth factor.
• Plerixafor is an antagonist of CXCR4, which blocks its interaction with SCF-1, resulting in mobilization of CD34 cells from the marrow. The addition of plerixafor allows for successful stem cell collections in most patients who fail to mobilize sufficient stem cells using G-CSF alone.
  • Side effects of plerixafor include diarrhea, nausea, fatigue, headaches, and arthralgias.
• When more than 5 x 10^6 CD34+ peripheral blood stem cells are infused, engraftment (absolute neutrophil count [ANC] > 500) is seen at approximately 2 weeks post-HCT.
• Peripheral blood also has a higher proportion of T cells than marrow, the incidence of chronic GVHD may be higher with PBSCT than BMT, but disease recurrence appears to be less and survival equivalent or higher in the HLA-matched sibling setting.

Cord Blood

• CB is rich in CD34+ cells. Compared with a usual peripheral blood collection, one CB unit contains about a log less CD34+ stem cells per kg; however, the stem cells have potential for rapid expansion.
• Decreased number of mature T cells in CB → matching criteria are less stringent, allowing treatment for patients with up to two mismatches (HLA 4 of 6 with antigen matches at A and B and allele match at DR).
  • Recent data from the CIBMTR suggest that allele-level matching at A, B, C, and DR in single CBT leads to better outcomes.
• Advantages: greater HLA disparity, rapid availability, and possibly an increased GVT effect especially when two cords are used.
  • T cells are more naïve and lower in number (approximately 10^4 per kg recipient weight) as compared to adult donor blood (approximately 10^8) or marrow (approximately 10^7)., leading to less severe acute and chronic GVHD.
• Disadvantages: slower engraftment and immune recovery, higher incidence of graft failure, and the inability to go back to the donor in the event of relapse.
• Higher number of cells per kg, younger age, and greater degree of match were associated with improved survival.
• A threshold dose of 5 × 10^7 total nucleated cell and 1.5 × 10^5 CD34+/kg is recommended.
  • Low CB cell dose is associated with increased graft failure, delayed engraftment, and delayed immune recovery.
  • In an effort to use CBT in adult recipients, two CB units are often used to achieve the sufficient cell dose.
  • Even though ultimately only one cord engrafts, use of two cords reduces the risk of graft failure and is associated with an apparent increased GVT effect.

Donor

Autologous