Wang Lining, Dai Bo, Gao Wenhui, Wang Jing, Wan Ming, Wang Runshu, Wang Ling, Jiang Jieling, Blaise Didier, Hu Jiong
Shanghai Institute of Hematology, Blood and Marrow Transplantation Center, Collaborative Innovation Center of Hematology, Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Clinical Research Center, Fenglin International Centre, Shanghai, China.
Front Med (Lausanne). 2022 Apr 7;9:820591. doi: 10.3389/fmed.2022.820591. eCollection 2022.
Allogeneic stem cell transplantation from haplo-identical donors (haplo-HSCT) has become a well-established therapeutic option for hematological malignancies. The fever of unknown origin (haplo-fever) early after the infusion of T cell repleted graft, which returned to normal right after post-transplantation cyclophosphamide (PTCy), is a unique clinical feature in patients undergoing haplo-HSCT. In the current study, the characteristics of haplo-fever and cytokine profiles during haplo-fever were retrospectively analyzed in a cohort of 37 patients undergoing T cell repleted haplo-HSCT with PTCy as graft versus host disease (GvHD) prophylaxis. In total, 33 patients (89.2%) developed haplo-fever from day 0 to day +7. Patients with high peak temperatures tended to have a lower incidence of chronic GvHD (cGvHD) ( = 0.07), moderate to severe cGvHD ( = 0.08), and superior GvHD and relapse-free survival (GRFS, = 0.04). During the haplo-fever, there were significant increases in multiple cytokines, such as interferon gamma, interleukin (IL) 6, IL2, IL2 receptor, IL8, IL10, IL17, and tumor necrosis factor (TNF). The increases in IL2 receptor ( = 0.037) and TNF ( < 0.001) on day +4 were correlated with the lower risk of cGvHD. Increased TNF > 1.8055-fold on day +4 was the best predictive threshold for cGvHD, and was correlated with a lower incidence of cGvHD ( < 0.001), moderate to severe cGvHD ( = 0.003), and superior GRFS ( < 0.001). These observations may reflect the early reactivation of donor T cells after haplo graft infusion, which would potentially be eliminated by PTCy. Further studies with larger independent cohorts of patients are warranted, to clarify the clinical significance of haplo-fever, and day +4 TNF as a potential biomarker to predict GvHD and GRFS.
来自单倍体相合供者的异基因干细胞移植（单倍体造血干细胞移植）已成为血液系统恶性肿瘤一种成熟的治疗选择。输注富含T细胞的移植物后早期出现的不明原因发热（单倍体发热），在移植后环磷酰胺（PTCy）治疗后随即恢复正常，这是接受单倍体造血干细胞移植患者的一个独特临床特征。在本研究中，对37例接受富含T细胞的单倍体造血干细胞移植并使用PTCy预防移植物抗宿主病（GvHD）的患者队列进行回顾性分析，以了解单倍体发热的特征以及发热期间的细胞因子谱。共有33例患者（89.2%）在第0天至第+7天出现单倍体发热。高热峰值的患者慢性移植物抗宿主病（cGvHD）发生率较低（ = 0.07），中重度cGvHD发生率较低（ = 0.08），移植物抗宿主病及无复发生存率（GRFS， = 0.04）较高。在单倍体发热期间，多种细胞因子显著升高，如干扰素γ、白细胞介素（IL）6、IL2、IL2受体、IL8、IL10、IL17和肿瘤坏死因子（TNF）。第+4天时IL2受体升高（ = 0.037）和TNF升高（ < 0.001）与cGvHD风险较低相关。第+4天时TNF升高>1.8055倍是cGvHD的最佳预测阈值，且与cGvHD发生率较低（ < 0.001）、中重度cGvHD发生率较低（ = 0.003）以及较好的GRFS相关（ < 0.001）。这些观察结果可能反映了单倍体移植物输注后供体T细胞的早期重新激活，这可能会被PTCy消除。有必要对更大的独立患者队列进行进一步研究，以阐明单倍体发热的临床意义，以及第+4天的TNF作为预测移植物抗宿主病和GRFS的潜在生物标志物的意义。
