Stuut A H G, Nijssen C, van der Wagen L, van Rhenen A, Daenen L G M, Janssen A, Verheij F A, Brinkman I, Verduyn Lunel F M, Koene H, Fijnheer R, Prins H J, Westinga K, Drylewicz J, Kuball J, de Witte M A
Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
Bone Marrow Transplant. 2025 May;60(5):673-681. doi: 10.1038/s41409-025-02538-w. Epub 2025 Mar 15.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) aims to cure patients without inducing severe graft-versus-host disease (GVHD) or relapse. In prospective studies of mostly pediatric patients with haploidentical donors, ex vivo αβTCR/CD19 depletion has shown to have low incidences of GVHD, but data for adults with matched related (MRD) or unrelated donors (MUD) remain limited. We analyzed the outcomes of recipients who received a myeloablative regimen plus ATG, followed by an αβTCR/CD19-depleted allograft (cohort D+ATG (n = 122)), and compared outcomes to T cell-replete cohorts (cohort R (N = 60)); without ATG; R+ATG = with ATG (N = 129) in a single-center retrospective analysis. In D+ATG, the incidence of aGVHD grade III-IV was 7%, compared to 13% in R and 16% in R+ATG (p = 0.09). Extensive cGVHD was reduced from 23% in R and 10% in R+ATG to 2% in D+ATG (p < 0.001). The reduced incidence of cGVHD led to a superior GVHD-relapse-free survival (GRFS) of 56.7% in D+ATG versus 36.7% in R and 42.8% in R+ATG (p = 0.03) at 2 years. In conclusion, the combination of myeloablative conditioning, ATG, and ex vivo αβTCR/CD19 depletion appears to be a promising approach to enhance GRFS in adult patients up to 75 years of age undergoing allo-HSCT.
异基因造血干细胞移植（allo-HSCT）旨在治愈患者，同时不引发严重的移植物抗宿主病（GVHD）或复发。在大多针对单倍体相合供体的儿科患者的前瞻性研究中，体外αβTCR/CD19去除已显示出GVHD发生率较低，但关于匹配的相关供体（MRD）或无关供体（MUD）的成人患者的数据仍然有限。我们分析了接受清髓方案加抗胸腺细胞球蛋白（ATG），随后接受αβTCR/CD19去除的同种异体移植物的受者（队列D+ATG（n = 122））的结局，并在一项单中心回顾性分析中将结局与T细胞充足的队列（队列R（N = 60））；无ATG；R+ATG = 有ATG（N = 129）进行比较。在D+ATG组中，急性GVHD III-IV级的发生率为7%，而在R组中为13%，在R+ATG组中为16%（p = 0.09）。广泛性慢性GVHD从R组的23%和R+ATG组的10%降至D+ATG组的2%（p < 0.001）。慢性GVHD发生率的降低导致D+ATG组在2年时的无GVHD复发生存率（GRFS）更高，为56.7%，而R组为36.7%，R+ATG组为42.8%（p = 0.03）。总之，清髓预处理、ATG和体外αβTCR/CD19去除的联合应用似乎是一种有前景的方法，可提高75岁以下接受allo-HSCT的成年患者的GRFS。
