Retrospective Analysis of Intravenous DMSO Toxicity in Transplant Patients

The cryoprotectant, Dimethyl sulfoxide ( DMSO) is known to have toxic side effects in stem cell transplantation. The overall incidence of DMSO toxicity was approximately one in 70 transplants. The mean incidence of DMSO toxicity per center was 2.1%, when 34,000 transplants had been carried out by 95 centers. DMSO exhibits acute mortality at doses of 30 – 40 mg/kg in animals, and fatal arrhythmias, respiratory arrest with diffuse alveolar hemorrhage, seizures, leukoencephalopathy  and  hemoglobinuria in humans. In light of this, DMSO dose levels per day should be evaluated and certain cutoffs should be mandated for patients' safety.

In order to assess risks of toxicity, our center documented  the retained  plasma levels of DMSO in two patients that were scheduled to receive in excess of 6 bags of autologous units.   Standard practice at our institution is to add 10% DMSO per 100 ml bag for  cryoprotectant. Each 100 ml bag has 50 ml cells plus 50 ml freeze solution (50% freeze solution = 20% DMSO + 2% heprin + 78% plasmalyte A).  Both patients received 6 bags of stem cells on day 1, followed by plasma determination of DMSO.  Repeated levels were obtained prior to and following second day of infusion of autologous units.   Under gas chromatography, plasma DMSO2 concentration increased during first 24 hrs, plateaued at 4.4 +/- 1.2 mmol/L and remained there for 48 hrs. DMSH2 concentrations were at steady state by 5 min and remained between 3 – 5 mmol/L for 48 hrs. Renal clearance of DMSO was 14.1 +/- 3.4 ml/min.

The DMSO dose used and the plasma clearance rates in two different patients are shown in the graphs below.

Based on DMSO clearance rates one would expect clearance of DMSO to be higher than what was clinically found. We believe, this highlights the importance of other factors that can decrease DMSO clearance rates during stem cell transplant. For this reason, limit setting of 100 mg of DMSO per day would be a reasonable to avoid increased levels of toxicity. Based on this algorithm, our center has mandated no more than 6 autologous units be infused per day (SOP 117 OU Medical Center).