Department of Hematology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing 100071, China.
Chin Med J (Engl). 2023 Apr 5;136(7):815-821. doi: 10.1097/CM9.0000000000002611.
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.
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.
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.
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.
免疫疗法，如过继免疫细胞输注和免疫调节药物，被广泛用于癌症治疗，伴随的症状，包括细胞因子释放综合征（CRS）或免疫相关不良事件（irAEs），经常被报道。然而，接受微移植（MST）的患者接受异基因粒细胞集落刺激因子动员外周血单个核细胞（GPBMC）输注引起的临床表现尚未得到很好的描述。
我们分析了 88 例接受 MST 的急性髓系白血病患者接受异基因 GPBMC 输注的周期，以及 54 例接受无 GPBMC 输注化疗的周期作为对照。探讨了临床症状及其与临床特征、实验室检查和临床反应的相关性。
输注 GPBMC 后，发热（58.0%[51/88]）和寒战（43.2%[38/88]）是早期显著的症状。与供体 HLA 匹配较少的患者或无关供体的患者经历更多的寒战（3[2-5]个匹配位点与 5[3-5]个匹配位点，P=0.043；66.7%[12/18]与 37.1%[26/70]，P=0.024）。另一方面，CD4+/CD8+T 细胞比值降低的患者发热更多（0.8[0.7-1.2]与 1.4[1.1-2.2]，P=0.007）。多变量分析表明，年轻患者发热更多（比值比[OR] = 0.963，95%置信区间[CI]：0.932-0.995，P=0.022），而年轻供体的患者寒战更多（OR = 0.915，95%CI：0.859-0.975，P=0.006）。输注 GPBMC 后，超敏 C 反应蛋白水平升高但无细胞因子风暴，提示轻度和短暂的炎症反应。虽然输注相关综合征与白血病负荷变化无预测价值，但宿主预处理激活 T 细胞的比例与白血病控制呈正相关。
MST 中的异基因 GPBMC 输注引起了独特的输注相关症状和实验室变化，这些变化与供体或受体来源的危险因素有关，与报道的 CRS 或 irAEs 相比，安全性和耐受性问题较少。
