DMSO Reduction Strategies Reduce DMSO Induced Post Autologous Transplant Morbidity In Patients with Lymphoma and Myeloma –Results from an EBMT Non Interventional Prospective Study
Authors: Morris Curly TCM , Scholten Marijke , de Wreede Liesbeth , van Biezen Anja , Dickmeiss Ebbe , Trneny Marek , Apperley Jane F. , Chiusolo Patrizia , Van Imhoff Gustaaf , Lenhoff Stig , Uharek Lutz , Martinelli Giovanni , Hentrich Marcus , Sureda Anna , de Witte Theo M , Ruutu Tapani 
Published: October 2019

Abstract
Abstract 2397

Introduction.
DMSO is the universally used cryoprotectant for freezing peripheral blood stem cell for autologous transplantation. DMSO has a significant side effect profile including vasoconstriction, nausea and vomiting and with transplant related mortality now in the region of 1–3% avoiding DMSO toxicity is of increasing importance.

Methods.
The study was questionnaire based looking at centres freezing strategy(s), administration of stem cells to patients and individual forms for each patient transplanted with follow up form for side effect analysis. Side effects were defined using NCI criteria (version 3.0) and assigned to DMSO (or not) by the reporting centres. On account of substantial centre variation noted at initial analysis results were analysed using the Mantel-Haenszel Odds Ratio (OR) averaged over the centres.

Results.
64 centres contributed data for a maximum of 12 months between January 2007 and December 2008. A total of 1651 patients, 1008 male and 637 female, age range 18–76, median 56, with 875 myeloma patients, 540 NHL, 220 Hodgkin‘s Disease and 16 CLL were used for analysis. Almost all myeloma and most of the other patients had melphalan based regimens. From the Centre survey it was noted that 51 centres used 10% DMSO (1273 patients) but on account of multiple centre strategies 15 centres used concentrations down to 5%. Three Centres using 10% DMSO washed cells before infusion while another 9 Centres washed cells occasionally (>10% of transplants). The median amount of DMSO given per patient was 20ml although the upper limit per Centre was often very much higher. 75% of Centres did not use any delay between bags of stem cells and the median duration of infusion was 22 minutes.
440 patients experienced nausea or vomiting related to DMSO, 123 hypo- or hypertension and 84 other side effects. The side effect profile was then amalgamated so that no patient was counted more than once. DMSO was calculated in ml/Kg body weight for each patient then split into quartiles for analysis. The OR for any side effect assigned to DMSO between patients in the highest quartile and patients in the lower three quartiles averaged over age and disease classification was 1.7 (Confidence Interval 1.2 to 2.4, p = 0.003). When split into groups by disease (lymphoma or myeloma) and age (>median and <median) the OR were as follows: young lymphoma 1.6 (0.95 to 2.8) older lymphoma 3.6 (1.5 to 9.1) younger myeloma 0.8 (0.34 to 2.0) older myeloma 1.8 (0.95 to 3.5). The reason for the apparent protective effect in younger myeloma is subject to further analysis but we suggest that in this patient group in particular the effect of the DMSO is obscured by the side effects of the melphalan; this hypothesis is supported by an analysis of all side effects. When results were calculated as DMSO per ml/min it appeared possible that the quicker the DMSO is given the less the adverse effects.

Conclusions.
DMSO contributes to the morbidity of patients undergoing autologous transplantation. Strategies to reduce DMSO exposure can reduce these complications.

Disclosures:
No relevant conflicts of interest to declare.