Today, hematopoietic stem cell transplantation (HSCT) can be performed by using stem cells that have been obtained from three major sources such as bone marrow, peripheral blood and umbilical cord blood from autologous, related allogeneic or unrelated allogeneic donors.
Autologous HSCT is not prescribed for most medical indications and only about a third of the patients requiring HSCT have a suitable matched donor. Although, tens of millions of adult volunteer donors are currently registered worldwide, about 60% of the patients cannot find a suitable unrelated adult donor who matches the human leukocyte antigen (HLA), and therefore will not be able to access HSCT. For minority patients, the likelihood of finding HLA-matched unrelated adult donor is further reduced. Since the process of finding an adult donor often takes several months, a significant proportion of the patients will become more at risk or ineligible for HSCT, or even die awaiting a donor match.
On the contrary, without possibility of last-minute donor failure, umbilical cord blood products are available on demand and can be shipped immediately to any transplant center in the world. It is important to note that cord blood transplantation is associated with a lower incidence and severity of graft-versus-host disease (GvHD), and partial HLA match between the donor and recipient is acceptable, making it an ideal donor source for minority patients without large adult donor registries.
Compared with historical bone marrow or peripheral blood HSCT controls, umbilical cord blood transplantation has shown a favorable clinical outcome despite significantly worse HLA match. In pediatric practice, cord blood transplantation can now be considered as the established practice. For adults, the adoption of cord blood transplantation was slower due to cell dose limitations.
Many strategies are being developed to overcome these limitations, including double umbilical cord blood transplantation, the use of two cord blood transplants, a combination of an unrelated cord blood transplant with haploidentical donor stem cells, and rejection of post umbilical stem cells, and foregoing the post-thaw wash with direct infusion or reconstitution/dilution washing that has shown promising results.
The engraftment and survival are apparently at least equivalent or may even exceed historical data using post-thaw wash for cord blood products versus when umbilical cord blood was not washed. One of the areas that many studies have been focused on was optimization of the entire umbilical cord blood banking process, in particular, umbilical cord blood processing and thaw manipulations.
Almost all available data on umbilical cord blood processing showed significant cell loss with various treatment methods with a decrease in the volume of red cell reduction (RCR). This is one of the areas that umbilical cord blood banks can have an impact. Another area that has a significant impact on cord blood potency and clinical outcomes is thawing and post-thawing manipulations of umbilical cord blood products.
Transplant centers that do not follow the prescribed and approved procedure for thawing risk to reduce viability of umbilical cord blood product for their patients, delay engraftment, transplant failure, transplant mortality, and the potential for severe adverse events in rare cases due to thaw and Dimethyl sulfoxide toxicity mediated release of free hemoglobin, red cells and white cell lysates, chemokines and cytokines that may cause hemodynamic destabilization.
Although every step from collection to infusion of umbilical cord blood affects the engraftment and ultimately patient survival, in the following blog posts we will describe the role of processing and post-thaw manipulations.