Background:Immunotherapies such as adoptive immune cell infusion and immune-modulating agents are widely used for cancer treatment,and the concomitant symptoms,including cytokine release syndrome(CRS)or immune-related...Background:Immunotherapies such as adoptive immune cell infusion and immune-modulating agents are widely used for cancer treatment,and the concomitant symptoms,including cytokine release syndrome(CRS)or immune-related adverse events(irAEs),are frequently reported.However,clinical manifestations induced by mismatched donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell(GPBMC)infusion in patients receiving microtransplant(MST)have not yet been well depicted.Methods:We analyzed 88 cycles of mismatched GPBMC infusion in patients with acute myeloid leukemia receiving MST and 54 cycles of chemotherapy without GPBMC infusion as a comparison.Clinical symptoms and their correlation with clinical features,laboratory findings,and clinical response were explored.Results:Fever(58.0%[51/88])and chills(43.2%[38/88])were the significant early-onset symptoms after GPBMC infusion.Patients possessing less human leukocyte antigen-matching loci with the donor or those with unrelated donors experienced more chills(3[2–5]loci vs.5[3–5]loci,P=0.043 and 66.7%[12/18]vs.37.1%[26/70],P=0.024).On the other hand,those with decreased CD4^(+)/CD8^(+)T-cell ratio developed more fever(0.8[0.7–1.2]vs.1.4[1.1–2.2],P=0.007).Multivariable analysis demonstrated that younger patients experienced more fever(odds ratio[OR]=0.963,95%confidence interval[CI]:0.932–0.995,P=0.022),while patients with younger donors experienced more chills(OR=0.915,95%CI:0.859–0.975,P=0.006).Elevated ultra-sensitive C-reactive protein levels in the absence of cytokine storm were observed following GPBMC infusion,which indicated mild and transient inflammatory response.Although no predictive value of infusion-related syndrome to leukemia burden change was found,the proportion of host pre-treatment activated T cells was positively correlated with leukemia control.Conclusions:Mismatched GPBMC infusion in MST induced unique infusion-related symptoms and laboratory changes,which were associated with donor-or recipient-derived risk factors,with less safety and tolerance concerns than reported CRS or irAEs.展开更多
Microtransplantation of rat brain neurolemma into the plasma membrane of Xenopus laevis oocytes is an ex vivo method used to study channels and receptors in their native state using standard electrophysiological appro...Microtransplantation of rat brain neurolemma into the plasma membrane of Xenopus laevis oocytes is an ex vivo method used to study channels and receptors in their native state using standard electrophysiological approaches.In this review,we show that oocytes injected with adult rat brain neurolemma elicited tetrodotoxin-sensitive inward ion currents upon membrane depolarization,which were increased in a concentration-dependent manner by treatment with the pyrethroid insecticides permethrin and deltamethrin.Under our initial protocols,oocyte health was reduced over time and neurolemma incorporation varied between batches of oocytes from different frogs,limiting the usefulness of the assay for regulatory issues.A collection of changes to the assay procedure,data acceptance criteria,and analysis method yield substantially improved precision and,hence,assay performance.These changes established this ex vivo approach as a toxicologically relevant assay to study the toxicodynamic action of pyrethroids on ion channels in their native state using neurolemma fragments prepared from juvenile and adult rat brains.展开更多
基金National Natural Science Foundation of China(Nos.81800150,81670110,and 31500732)Translational Research Grant of NCRCH(No.2020ZKZB02)+1 种基金Key Discipline Construction Project of Chinese PLA Medical College,the Foundation for Young Scientists of Chinese PLA General Hospital(Nos.QNF19043,QNF19041,and QNC19034)the Innovative Foundation of Chinese PLA General Hospital(No.CX19016)
文摘Background:Immunotherapies such as adoptive immune cell infusion and immune-modulating agents are widely used for cancer treatment,and the concomitant symptoms,including cytokine release syndrome(CRS)or immune-related adverse events(irAEs),are frequently reported.However,clinical manifestations induced by mismatched donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell(GPBMC)infusion in patients receiving microtransplant(MST)have not yet been well depicted.Methods:We analyzed 88 cycles of mismatched GPBMC infusion in patients with acute myeloid leukemia receiving MST and 54 cycles of chemotherapy without GPBMC infusion as a comparison.Clinical symptoms and their correlation with clinical features,laboratory findings,and clinical response were explored.Results:Fever(58.0%[51/88])and chills(43.2%[38/88])were the significant early-onset symptoms after GPBMC infusion.Patients possessing less human leukocyte antigen-matching loci with the donor or those with unrelated donors experienced more chills(3[2–5]loci vs.5[3–5]loci,P=0.043 and 66.7%[12/18]vs.37.1%[26/70],P=0.024).On the other hand,those with decreased CD4^(+)/CD8^(+)T-cell ratio developed more fever(0.8[0.7–1.2]vs.1.4[1.1–2.2],P=0.007).Multivariable analysis demonstrated that younger patients experienced more fever(odds ratio[OR]=0.963,95%confidence interval[CI]:0.932–0.995,P=0.022),while patients with younger donors experienced more chills(OR=0.915,95%CI:0.859–0.975,P=0.006).Elevated ultra-sensitive C-reactive protein levels in the absence of cytokine storm were observed following GPBMC infusion,which indicated mild and transient inflammatory response.Although no predictive value of infusion-related syndrome to leukemia burden change was found,the proportion of host pre-treatment activated T cells was positively correlated with leukemia control.Conclusions:Mismatched GPBMC infusion in MST induced unique infusion-related symptoms and laboratory changes,which were associated with donor-or recipient-derived risk factors,with less safety and tolerance concerns than reported CRS or irAEs.
基金supported by the Council of the Advancement of Pyrethroid Human Risk Assessment(CAPHRA)(#S17110000000004).
文摘Microtransplantation of rat brain neurolemma into the plasma membrane of Xenopus laevis oocytes is an ex vivo method used to study channels and receptors in their native state using standard electrophysiological approaches.In this review,we show that oocytes injected with adult rat brain neurolemma elicited tetrodotoxin-sensitive inward ion currents upon membrane depolarization,which were increased in a concentration-dependent manner by treatment with the pyrethroid insecticides permethrin and deltamethrin.Under our initial protocols,oocyte health was reduced over time and neurolemma incorporation varied between batches of oocytes from different frogs,limiting the usefulness of the assay for regulatory issues.A collection of changes to the assay procedure,data acceptance criteria,and analysis method yield substantially improved precision and,hence,assay performance.These changes established this ex vivo approach as a toxicologically relevant assay to study the toxicodynamic action of pyrethroids on ion channels in their native state using neurolemma fragments prepared from juvenile and adult rat brains.
