Gao Wen-Hui, Zhu Jia-Yan, Wang Li-Ning, Wan Ming, Wang Ling, Devillier Raynier, Jiang Jie-Ling, Blaise Didier, Hu Jiong
Shanghai Institute of Hematology, Blood and Marrow Transplantation Center, Department of Hematology, Collaborative Innovation Center of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Clinical Research Center (SCRC), Fenglin International Centre, Shanghai, China.
Front Med (Lausanne). 2023 Mar 31;10:1140217. doi: 10.3389/fmed.2023.1140217. eCollection 2023.
Post-transplantation cyclophosphamide (PT-Cy) use is a recent graft-versus-host disease (GVHD) prophylaxis strategy for patients undergoing allogeneic stem cell transplantation (allo-HSCT). PT-Cy combined with two immunosuppressants is now widely used after haplo-identical (haplo) and HLA-matched peripheral blood stem cell (PBSC) transplantations with promising GVHD and relapsefree survival (GRFS) probabilities. Although appealing, these results may benefit from improvement notably outside matched sibling donor transplantation, and should be investigated in various ethnic populations.
Therefore, we report our experience of GVHD prophylaxis regimen combining PT-Cy and tacrolimus with addition of post-engraftment low-dose anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation from haplo-identical donors (Haplo). Sixtyseven patients were included in the analysis. All patients received myeloablative or intensified sequential conditioning regimen.
The median follow-up was 521 (range, 10991) days. The cumulative incidences of 100-day grade II-IV acute GVHD was 14.9±4.4%, and no case of grade III-IV acute GVHD was documented. The cumulative incidences of 2-yearchronic GVHD and moderate-to-severe chronic GVHD were 25.4±5.4% and 11.9±4%, respectively. The non-relapse mortality at day+100 and 2year were 7.5±3.2% and 9.0±3.5%, respectively. The cumulative incidence of relapse at 2year was 16±6.4%. The 2-year probability of DFS and OS were 73.8% (95%CI, 61.588.4%) and 72.5% (95% CI, 57.192.1%), respectively. The 2-year GRFS was estimated as 63.6% (95%CI, 50.680%).
Our results suggested that a combination of PT-Cy, tacrolimus, and low-dose post-engraftment ATG was a promising GVHD prophylaxis with low incidence of acute GVHD in the haplo-transplantation setting.
移植后环磷酰胺（PT-Cy）的应用是一种针对接受异基因干细胞移植（allo-HSCT）患者的新型移植物抗宿主病（GVHD）预防策略。PT-Cy联合两种免疫抑制剂目前已广泛应用于单倍体相合（haplo）和人类白细胞抗原（HLA）匹配的外周血干细胞（PBSC）移植后，GVHD和无复发生存（GRFS）概率令人满意。尽管颇具吸引力，但这些结果可能尤其在匹配同胞供体移植之外的情况下需要改进，并且应在不同种族人群中进行研究。
因此，我们报告了在单倍体相合供体（Haplo）的异基因干细胞移植中，将PT-Cy和他克莫司与植入后低剂量抗胸腺细胞球蛋白（ATG）联合用于GVHD预防方案的经验。67例患者纳入分析。所有患者均接受清髓或强化序贯预处理方案。
中位随访时间为521（范围10991）天。100天II-IV级急性GVHD的累积发生率为14.9±4.4%，未记录到III-IV级急性GVHD病例。2年慢性GVHD和中重度慢性GVHD的累积发生率分别为25.4±5.4%和11.9±4%。+100天和2年时的非复发死亡率分别为7.5±3.2%和9.0±3.5%。2年时的复发累积发生率为16±6.4%。2年无病生存（DFS）和总生存（OS）概率分别为73.8%（95%CI，61.588.4%）和72.5%（95%CI，57.192.1%）。2年GRFS估计为63.6%（95%CI，50.680%）。
我们的结果表明，在单倍体移植环境中，PT-Cy、他克莫司和植入后低剂量ATG联合使用是一种很有前景的GVHD预防方法，急性GVHD发生率低。
