Canterbury DHB

Context

Infusion-related Reactions in HCT

In This Section

Introduction

Adverse Reactions (AR)

References

Introduction

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.

Adverse Reactions (AR)

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.

Factors influencing AR

  1. DMSO itself, by virtue of direct physiological impact.
  2. Post-thaw cell aggregation and dead cell debris.
  3. Lysis of RBCs, with release of Hb, electrolytes and membrane fragments.
  4. Total nucleated cell content and volume of cell suspension.
  5. Low temperature of infused products.
  6. Electrolyte imbalance.
  7. Premedication given before transfusion, for example, antiemetics, corticosteroids, diuretics and antihistamines, which are used to neutralize DMSO-induced histamine release but may cause bradycardia at the same time.8,13

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

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.

  • Solvent for water-insoluble compounds.
  • A hydrogen-bond disrupter.
  • A cell-differentiating agent.
  • A hydroxyl radical scavenger.
  • An intracellular LDL-derived cholesterol.
  • Mobilizing agent.

DMSO toxicity

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.

Preventing AR

AR after cryopreserved HSCT

AR after cryopreserved HSCT.png

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.

References

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.

About this Canterbury DHB document (145475):

Document Owner:

Andrew Butler (see Who's Who)

Issue Date:

December 2016

Next Review:

December 2018

Keywords:

Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document. Disclaimer

Topic Code: 145475