Mismatched donor cell infusion-related syndrome following microtransplant in patients with acute myeloid leukemia

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.