Post-thaw removal of DMSO does not completely abrogate infusional toxicity or the need for pre-infusion histamine blockade

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.