During the COVID-19 pandemic, many stem cell transplant centers (including guidance from the National Marrow Donor Program [NMDP]) recommend that stem cell products be frozen for preservation. However, findings from a study by Duncan Purtill, MD, and colleagues in Blood Advances suggest that the freezing process can decrease the quality of stem cells, particularly if they were manipulated before being preserved, if they had high white blood cell content, or if they were stored for a long period of time.
Before the coronavirus outbreak, it was not common to freeze allogeneic donor stem cells prior to infusion. However, due to the pandemic’s effects on donor and hospital availability, as well as new travel and transportation restrictions, more transplant centers, including the NMDP, are recommending cryopreservation.
Duncan Purtill, MD
“Prior to COVID-19, the donor and transplant systems were well coordinated and effective. Now, with irregular flights and closed borders, travel and transportation are not assured,” said lead study author Dr. Purtill, of Fiona Stanley Hospital in Western Australia. “Five to 7 days before stem cell transplant, the recipient usually starts chemotherapy to remove all their bone marrow cells. Without a healthy transplant to replace the cells on the same day, they would be left with no functioning bone marrow, which would of course be very high risk and carry a poor prognosis. Life literally depends on the safe arrival and immediate infusion of stem cells.”
Recovery of Products
Dr. Purtill and his team analyzed 305 samples of allogeneic stem cell products that were cryopreserved at participating Australian cell processing labs between 2015 and 2019. They found that, on average, the recovery of the stem cell products was 74%. This is considered an acceptable, viable recovery, enabling the cells to be used in transplantation. However, some products did not recover to that level: around 15% of the surveyed products had a cell recovery of less than 50%. In fact, the study found that quality recovery could range as low as just 6%. Such a significant cell loss after thawing may mean that the remaining cells may be too few, or too damaged, to achieve timely bone marrow recovery in the patient after infusion.
“It seems that there is variability in recovery and more work needs to be done to determine why,” said Dr. Purtill. “When we freeze stem cells and then thaw them afterwards, we sometimes get unexpected results. In this study, we identified some possible factors influencing that variability.”
The research team pointed to three possible reasons for the loss of quality in some of the stem cells products they analyzed:
- First, they noted that prolonged transportation and storage time prior to cryopreservation was associated with a loss of quality.
- They also found that higher white cell concentration of the product affected its quality. It was thought that the presence of other white cells could adversely affect the stem cells, either by releasing damaging enzymes or chemicals, or else by consuming nutritional elements within the product and resulting in less healthy stem cells.
- Finally, they pointed out that a small proportion of cells which underwent complex manipulation before being frozen also suffered quality loss—for instance, when the cell processing lab removed lymphocytes or washed the product to remove plasma and other noncellular components.
Dr. Purtill and his collaborators expressed hope that their findings could serve to inform and improve stem cell transplantation, collection, and processing procedures.
“Our findings could be a note of caution for transplant centers to not take for granted that the frozen product they have received will show perfect recovery once thawed,” said Dr. Purtill. “I hope centers will insist on receiving a pilot vial which has been frozen and transported in the same way. They can assess the pilot vial to determine its viability before they use the full product and start chemotherapy for the patient.”
Disclosure: For full disclosures of the study authors, visit ashpublications.org.
