Fatal cardiac arrhythmia after infusion of dimethyl sulfoxide-cryopreserved hematopoietic stem cells in a patient with severe primary cardiac amyloidosis and end-stage renal failure

Abstract

Amyloidosis (AL) is a rapidly fatal plasma cell dyscrasia causing progressive multiorgan failure. Recently, substantial improvement of survival was reported following high-dose chemotherapy with peripheral blood stem cell (PBSC) rescue. We describe a patient with AL with severe cardiac and renal involvement who received high-dose melphalan followed by fractioned autologous PBSC transplantation (455 ml on day 1 and 350 ml on day 2). Immediately after the second infusion of the PBSCs, life-threatening cardiac arrhythmias occurred and, despite intensive treatment, the patient died less than 24 h later. The infusion of cryopreserved PBSCs may be associated with complications, including cardiac toxicity. Dimethyl sulfoxide (DMSO) is the most frequently used cryopreservation agent. In the present case, we suggest that DMSO could have played an important role in causing the fatal cardiac arrhythmias. The mechanisms of the cardiovascular effects of DMSO and the possible preventive measures are discussed. Given the poor prognosis of AL and the promising results of dose-intensive chemotherapy with autologous PBSC transplantation, careful patient selection and intensive monitoring are mandatory in order to further pursue this therapeutic approach.

Variation in dimethyl sulfoxide use in stem cell transplantation: a survey of EBMT centres

“…From this brief questionnaire we were unable to extract data regarding the severity or mortality related to DMSO but case reports of fatalities do exist. 5 Although the need to protect the viability of the cryopreserved stem cells is paramount it does seem reasonable that strategies to reduce DMSO should be investigated in a prospective manner. We would suggest that the time is right for a more detailed prospective analysis of DMSO toxicity to be undertaken by transplant centres with a view to production of guidelines, which should lead to a fall in the incidence of morbidity and mortality on DMSO administration.…”

Adverse reactions during stem cell infusion in children treated with autologous and allogeneic stem cell transplantation

“…1,2 Rare but serious side effects of cryopreserved products include severe respiratory depression, 7 neurotoxicity resulting in amnesia, loss of consciousness or seizure 5,6 and fatal cardiac arrhythmia. 4 Efforts aimed at reducing the DMSO content of infused grafts either by washing or other means have resulted in a reduction of ARs among some studies, 8,9 but not others. 10 No relationship between DMSO and ARs in cord blood transplants has been observed.…”

“…These range from common mild reactions including nausea, vomiting, flushing, fever, chills and cough [1][2][3] to rare life-threatening reactions affecting the cardiovascular, respiratory and neurological systems. [4][5][6][7] Infusion-related ARs have been attributed to both cellular and non-cellular elements within the cellular therapy product (CTP). In addition to the desired CD34 + hematopoietic stem cells, CTPs contain a wide variety RBC, cytokines and WBC including mature granulocytes, lymphocytes and monocytes, all of which may contribute to infusion-related reactions.…”

Recovery, viability and clinical toxicity of thawed and washed haematopoietic progenitor cells: analysis of 952 autologous peripheral blood stem cell transplantations

“…Headache, abdominal cramps, diarrhoea, flushing, chills, fever and chest tightness have also been described. [10][11][12] Severe reactions, such as life threatening cardiologic, neurologic, pulmonary, anaphylactic and renal events [13][14][15][16][17][18] are considered to be rare events.…”