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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6707402","sourcedb":"PMC","sourceid":"6707402","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6707402","text":"Discussion\nGastrointestinal and dermatological adverse reactions were the most commonly reported in the included studies. Cardiac adverse reactions only occurred when DMSO was administered intravenously, whereas dermatological reactions mostly occurred when DMSO was administered on the skin. Serious neurological and cardiac reactions were rare and only described in few studies. There seems to be a dose-response relationship between DMSO and adverse reactions with no or mild reactions in low doses.\nMany studies on the use of DMSO have been performed in Russia. These studies have not been readily accessible to the global community due to the language barrier. In this review, we have included not only studies dating back almost 50 years, but also articles written in Russian, which is an important strength of the review. This study has several limitations: 1) Some studies used the NCI-CTC (National Cancer Institute’s Common Terminology Criteria for adverse events), but often no scale was used, and the occurrence of adverse reactions were poorly reported. 2) It was difficult to make conclusions on the frequency of a specific adverse reaction, because the exact number of patients experiencing a reaction was often not stated. 3) Several studies using DMSO as a cryoprotectant concluded that other factors affected the occurrence of adverse reactions 7, 85, 86. One study prospectively looked at the adverse reactions observed in relation to autologous transplantation in 64 European Blood and Marrow Transplant Group centers 7. They had difficulties isolating the effects of DMSO from confounding factors such as cell breakdown products and conditioning chemotherapy. Factors such as age, gender, volume transfused, granulocyte concentration, clumping of transplant material, and amount of red blood cells played a role in the occurrence of adverse reactions 61, 86, 120– 122. Another study believed that acute volume expansion, electrolyte imbalance and vagal responses to the coldness of the freshly thawed infusate were more likely reasons for cardiac arrhythmias during stem cell transfusions than the DMSO infused 123. This differs from other studies, which found a clear connection between dose of DMSO and occurrence of cardiac adverse reactions 41, 67, 71, 75, 78, 85, 86, 93, 101, 115. Therefore, it is possible that some adverse reactions are more or less common than found in this review. The rarer side effects are often reported in case reports, which often did not meet the eligibility criteria in this review. However, we have included several larger studies in this review, and they found a very small occurrence of serious adverse events 7, 55, 66, 74.\nIn conclusion, adverse reactions due to DMSO are often mild and transient and do not qualify as serious adverse events. Cardiovascular and respiratory adverse reactions occur mostly when DMSO is administered intravenously, whereas dermatological reactions have a higher incidence when DMSO is administered transdermally. An important finding is that the occurrence of adverse reactions seems to be related to the dose of DMSO, and it therefore seems safe to continue the use of DMSO in small 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