Related Experiment Video
Updated: Jun 13, 2026
Preservation of Porcine Donation after Circulatory Death (DCD) Liver by Perfusion and Orthotopic Liver Transplantation
Published on: June 14, 2024
Post-thaw removal of DMSO does not completely abrogate infusional toxicity or the need for pre-infusion histamine
1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Background:
The infusion of PBSC or BM cells cryopreserved with DMSO is associated with frequent, but generally minor, toxicity. The incidence and severity of infusion-related toxicity is proportional to the amount of DMSO infused. In an attempt to reduce the incidence of symptoms reported by patients receiving cryopreserved PBSC and to avoid the necessity of diphenhydramine premedication, we studied the infusion of PBSC components from which the DMSO was depleted after thawing.
Methods:
This was a Phase I/II study of post-thaw removal of DMSO. Patients undergoing autologous PBSC transplantation with components cryopreserved using 10% DMSO were eligible. The PBSC components were thawed, diluted with 10% dextran-40 and 5% HSA, centrifuged to remove the DMSO, resuspended in dextran and HSA, and infused without prior medication of the patient. Visual analog scale questionnaires were used for measurement of infusion-related symptoms.
Results:
Five patients were enrolled on this study and received washed PBSC components. One patient experienced severe infusion-related toxicity and the study was stopped for safety reasons. Events experienced by these patients included flushing (two patients), emesis (three patients), and post-infusion rigors (two patients). Two patients reported an increase in nausea after the infusion. All patients achieved granulocyte engraftment (an ANC > 0.5 x 10(9)/L) at a median of 14 days and platelet engraftment (platelet count without transfusion > 20 x 10(9)/L) at a median of 11 days. No patient required infusion of additional cells because of engraftment failure.
Discussion:
In theory, the post-thaw reduction of DMSO should reduce the risk of infusion-related toxicity that is commonly attributed to DMSO. Although not demonstrated by the data developed from this study, effective reduction in DMSO could also eliminate the need for pre-infusion histamine blockade. However, the technique used in this study was not adequate and a more rigorous depletion technique must be developed to completely abrogate clinical infusion-related toxicity.
Insights
Removing DMSO from thawed PBSC components reduced infusion toxicity, but the method was insufficient. Further research is needed for effective DMSO depletion to prevent side effects during stem cell transplantation.
Area of Science:
- Hematology
- Transplantation Medicine
- Cellular Therapy
Background:
- Cryopreservation of peripheral blood stem cells (PBSC) or bone marrow (BM) cells with dimethyl sulfoxide (DMSO) is linked to infusion-related toxicity.
- Toxicity incidence and severity correlate with the infused DMSO volume.
- This study aimed to reduce infusion toxicity and avoid diphenhydramine premedication by depleting DMSO post-thaw.
Purpose of the Study:
- To evaluate the safety and efficacy of post-thaw DMSO removal from cryopreserved PBSC components.
- To assess the impact of DMSO depletion on infusion-related toxicity in autologous PBSC transplantation.
- To determine if DMSO reduction can eliminate the need for pre-infusion medication.
Main Methods:
- A Phase I/II study involving autologous PBSC transplantation.
- PBSC components cryopreserved with 10% DMSO were thawed, diluted, centrifuged to remove DMSO, and resuspended.
- Infusion was performed without prior patient medication; visual analog scales measured symptoms.
Main Results:
- One of five patients experienced severe infusion-related toxicity, leading to study termination.
- Commonly reported symptoms included flushing, emesis, and post-infusion rigors.
- All patients achieved successful granulocyte and platelet engraftment without additional cell infusions.
Conclusions:
- Post-thaw DMSO reduction theoretically minimizes infusion-related toxicity.
- The depletion technique used was inadequate for complete abrogation of clinical toxicity.
- More effective DMSO depletion methods are required to eliminate infusion-related toxicity and pre-infusion medication needs.
