Canterbury DHB
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The first studies of HSC freezing were by Barnes and Loutit in 1955 (Shu, Heimfeld et al. 2014). The first trial of DMSO was by Lovelock and Bishop in 1959. Cells are washed, resuspended in a basic salt solution supplemented with protein to which is added DMSO at a final concentration of 5-10% v/v. The cell suspension is cooled using controlled rate freezing at a rate of –1 to –2.5°C per minute to minus 80°C and then transferred to liquid nitrogen at less than –150°C. Just before HCT, the cells are quickly thawed in a 37°C water bath and infused immediately.
AR may occur due to lysed red cells, senescent granulocytes or DMSO. AR continue to occur even after removal of DMSO and there is debate about the benefit of this practice. However, it is widely practiced and removal of DMSO may also remove other causes of AR such as granulocytes and RBC.
Patient risk factors include young women, Hodgkin’s lymphoma, prior treatment and infusion protocol (speed, pauses, time delay between thaw and infusion) (Shu, Heimfeld et al. 2014).
The median volume, median DMSO and median TNC content of the product were found to be significantly higher in patients with side effects compared to the group without any side effects (1200 mL vs. 910 mL, P<0.03, 1.5 mL/kg vs. 0.92 mL/kg, P<0.01 and 8.90x108/kg vs. 7.83x108/kg, P<0.004, respectively) (Donmez, Tombuloglu et al. 2007).
DMSO can permeate cell membranes to prevent intracellular ice formation and dehydration damage (as extracellular ice draws water out of the cell). It was licensed by the FDA for interstitial cystitis and has been studied in brain edema, amyloidosis, schizophrenia, urinary, musculoskeletal and gastrointestinal disorders, pulmonary adenocarcinoma, rheumatologic and dermatologic diseases, chronic prostatitis, Alzheimer’s disease and as a topical analgesic (Shu, Heimfeld et al. 2014). Reported effects of DMSO include effects on cell metabolism, differentiation of stem cells and apoptosis. DMSO >2% can cause apoptosis of lymphoma cells. Rapid infusion of cryopreserved cells (with intracellular concentration of 10% DMSO) into normal plasma can result in osmotic injury to cells.
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About 45% of DMSO is excreted unchanged in the urine but a proportion is converted to dimethyl sulfide which is excreted through skin, faeces, urine and breath for up to 2 days causing a noxious garlic odour and taste.
DMSO can induce histamine release and can affect the limbic-hypothalamic pathways causing nausea, vomiting, diarrhoea, headache, flushing, fever, chills, dyspnoea, anaphylaxis, vasodilation and hypotension, pulmonary or abdominal complaints and complex effects on emotion and cognition. As such, anti-histamines are usually prescribed as prophylaxis.
DMSO can produce neurotoxic AR in a dose-dependent manner. DMSO may cause apoptosis in the developing nervous system. A maximum dose of 1 g/kg has been suggested.
From Shu, Z., et al. (2014). "Hematopoietic SCT with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal before infusion." Bone Marrow Transplant 49(4): 469-476.
Shu, Z., et al. (2014). "Hematopoietic SCT with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal before infusion." Bone Marrow Transplant 49(4): 469-476.
Donmez, A., et al. (2007). "Clinical side effects during peripheral blood progenitor cell infusion." Transfus Apher Sci 36(1): 95-101.
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Topic Code: 145475
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