Adverse reactions during transfusion of thawed haematopoietic progenitor cells from apheresis are closely related to the number of granulocyte cells in the leukapheresis product

Martín-Henao, G A; Resano, Pilar; Villegas, Janeth; Manero, P. P.; Sánchez, J.; Bosch, María; Codins, A. E.; Bruguera, Miguel; Infante, Lulette; Oyarzábal, Alfonso; Soldevila, R. N.; Caiz, D. C.; Bosch, Lluís; Barbeta, E. Contreras; Ronda, J. R. G.

doi:10.1111/j.1423-0410.2010.01341.x

Cited by 35 publications

(59 citation statements)

References 35 publications

(73 reference statements)

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“…DMSO can be present in patients during therapy with some drugs, or it can be used as anti-inflammatory and anesthetic agent [27]. Also DMSO is used in cell cryopreservation, and, therefore, in stem cell transplantation [28]–[30]. The blood concentration of this agent after intravenous infusion can be estimated by dividing the total volume of DMSO by 4–5 liters of blood.…”

Section: Discussionmentioning

confidence: 99%

“…The blood concentration of this agent after intravenous infusion can be estimated by dividing the total volume of DMSO by 4–5 liters of blood. Thereby, we can calculate that DMSO concentration in the blood of the patient can be equal to 0.2–0.4% [28], [29], but sometimes can reach 0.56% [30] and even 1.2% [29], [31]. The mechanism of DMSO action is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

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Antiplatelet Agents Can Promote Two-Peaked Thrombin Generation in Platelet Rich Plasma: Mechanism and Possible Applications

et al. 2013

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BackgroundThrombin generation assay is a convenient and widely used method for analysis of the blood coagulation system status. Thrombin generation curve (TGC) is usually bell-shaped with a single peak, but there are exceptions. In particular, TGC in platelet-rich plasma (PRP) can sometimes have two peaks.ObjectiveWe sought to understand the mechanism underlying the occurrence of two peaks in the PRP thrombin generation curve.MethodsTissue factor-induced thrombin generation in PRP and platelet-poor plasma (PPP) was monitored using continuous measurement of the hydrolysis rate of the thrombin-specific fluorogenic substrate Z-Gly-Gly-Arg-AMC. Expression of phosphatidylserine (PS) and CD62P on the surface of activated platelets was measured by flow cytometry using corresponding fluorescently labeled markers.ResultsThe addition of the P2Y12 receptor antagonist MeS-AMP (160 µM), 83 nM prostaglandin E1 (PGE1), or 1.6% DMSO to PRP caused the appearance of two peaks in the TGC. The PS exposure after thrombin activation on washed platelets in a suspension supplemented with DMSO, PGE1 or MeS-AMP was delayed, which could indicate mechanism of the second peak formation. Supplementation of PRP with 1.6% DMSO plus 830 nM PGE1 mediated the disappearance of the second peak and decreased the amplitude of the first peak. Increasing the platelet concentration in the PRP promoted the consolidation of the two peaks into one.ConclusionsProcoagulant tenase and prothrombinase complexes in PRP assemble on phospholipid surfaces containing PS of two types - plasma lipoproteins and the surface of activated platelets. Thrombin generation in the PRP can be two-peaked. The second peak appears in the presence of platelet antagonists as a result of delayed PS expression on platelets, which leads to delayed assembly of the membrane-dependent procoagulant complexes and a second wave of thrombin generation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Antiplatelet Agents Can Promote Two-Peaked Thrombin Generation in Platelet Rich Plasma: Mechanism and Possible Applications

et al. 2013

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“…1–3 The presence of DMSO and granulocytes dominate the adverse events (AEs) associated with cryopreserved cellular therapy (CT) infusions. 2,4,5 The DMSO infusion-related AEs are minimalized by limiting receipts to < 1 g/kg of DMSO per day, acetaminophen, histamine blockade and CT infusion via a CVC. 1,2,6 …”

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confidence: 99%

“…In a randomized phase III study of autologous HPC comparing cryopreservation using 10% DMSO versus 5% DMSO/6% HES, similar engraftment kinetics were observed suggesting that lower DMSO concentrations are advantageous since DMSO infusion toxicity is dose related. 4 Recently, Martin-Henao et al . 4 determined that the granulocyte number in cryopreserved HPCs was the most predictive for infusion-related AEs, occurring when the granulocyte content was >5 × 10 8 /kg.…”

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confidence: 99%

“…4 determined that the granulocyte number in cryopreserved HPCs was the most predictive for infusion-related AEs, occurring when the granulocyte content was >5 × 10 8 /kg. 4 They surmised that the increased osmotic fragility of granulocytes as compared with mononuclear cells results in their destruction during the freezing process and hence the infusion-related AEs. In comparison, the autologous lymphocytes infused in this trial contained 2 log fewer granulocyte cells/kg.…”

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confidence: 99%

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Infusion of cryopreserved autologous lymphocytes using a standard peripheral i.v. catheter

Gladstone

Davis-Sproul

Campian

et al. 2014

Bone Marrow Transplant

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Exposure to DMSO during infancy alters neurochemistry, social interactions, and brain morphology in long‐evans rats

et al. 2021

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Introduction Dimethyl sulfoxide (DMSO) is a widely used solvent to dissolve hydrophobic substances for clinical uses and experimental in vivo purposes. While usually regarded safe, our prior studies suggest changes to behavior following DMSO exposure. We therefore evaluated the effects of a five‐day, short‐term exposure to DMSO on postnatal infant rats (P6‐10). Methods DMSO was intraperitoneally injected for five days at 0.2, 2.0, and 4.0 ml/kg body mass. One cohort of animals was sacrificed 24 hr after DMSO exposure to analyze the neurometabolic changes in four brain regions (cortex, hippocampus, basal ganglia, and cerebellum) by hydrophilic interaction liquid chromatography. A second cohort of animals was used to analyze chronic alterations to behavior and pathological changes to glia and neuronal cells later in life (P21‐P40). Results 164 metabolites, including key regulatory molecules (retinoic acid, orotic acid, adrenic acid, and hypotaurine), were found significantly altered by DMSO exposure in at least one of the brain regions at P11 (p < .05). Behavioral tests showed significant hypoactive behavior and decreased social habits to the 2.0 and 4.0 ml DMSO/kg groups (p < .01). Significant increases in number of microglia and astrocytes at P40 were observed in the 4.0 ml DMSO/kg group (at p < .015.) Conclusions Despite short‐term exposure at low, putatively nontoxic concentrations, DMSO led to changes in behavior and social preferences, chronic alterations in glial cells, and changes in essential regulatory brain metabolites. The chronic neurological effects of DMSO exposure reported here raise concerns about its neurotoxicity and consequent safety in human medical applications and clinical trials.

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Adverse reactions during transfusion of thawed haematopoietic progenitor cells from apheresis are closely related to the number of granulocyte cells in the leukapheresis product

Abstract: The incidence and grade of ARs during infusion of cryopreserved HPC-A are related to the amount of granulocytes in the graft.

Cited by 35 publications

References 35 publications

Antiplatelet Agents Can Promote Two-Peaked Thrombin Generation in Platelet Rich Plasma: Mechanism and Possible Applications

Antiplatelet Agents Can Promote Two-Peaked Thrombin Generation in Platelet Rich Plasma: Mechanism and Possible Applications

Infusion of cryopreserved autologous lymphocytes using a standard peripheral i.v. catheter

Exposure to DMSO during infancy alters neurochemistry, social interactions, and brain morphology in long‐evans rats

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