Xu Jianli, Miao Wenyan, Yuan Hailong, Liu Ying, Chen Gang, Wang Hongbo, Aizezi Gulibadanmu, Qu Jianhua, Duan Xianlin, Yang Ruixue, Muhashi Maliya, Han Chunxia, Ding Linglu, Abulaiti Nadiya, Pang Nannan, Zhang Le, Jiang Ming
Hematologic Disease Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region Research Institute of Hematology, Urumqi 830061, Xinjiang, China.
Hematologic Disease Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region Research Institute of Hematology, Urumqi 830061, Xinjiang, China.
Transplant Cell Ther. 2023 May;29(5):331.e1-331.e8. doi: 10.1016/j.jtct.2023.02.005. Epub 2023 Feb 10.
Reduced-intensity conditioning (RIC) haploidentical (haplo-) hematopoietic stem cell transplantation (HSCT) requires more hematopoietic progenitor and stem cells (HPSCs) to promote engraftment and immune reconstitution and needs a stronger graft-versus-leukemia effect. Peripheral blood stem cells (PBSCs) offer advantages over bone marrow; however, the use of higher-dose non-T cell-depleted (non-TCD) in vitro PBSCs may increase the occurrence of severe graft-versus-host disease (GVHD). This prospective, single-arm clinical study was performed to investigate using high-dose non-TCD in vitro PBSCs as the graft source, using fludarabine/Ara-C/busulfan (FAB) as the conditioning regimen, using rabbit antithymocyte globulin to remove T cells in vivo, and enhancing GVHD prophylaxis with an IL-2 receptor antagonist in RIC-haplo-HSCT in patients with hematologic malignancies age 50 to 70 years or <50 years with comorbidities (Hematopoietic Cell Transplantation Comorbidity Index score ≥2) classified as intermediate to high risk. The primary endpoint was day 100 acute GVHD (aGVHD). A total of 47 patients were enrolled; the median age was 52 years (range, 30 to 68 years), the median duration of follow-up was 34 months (range, 2 to 99 months), and the medium-infused doses of mononuclear cells, CD34 cells, and CD3 cells were 15.93 × 10/kg, 8.68 × 10/kg, and 5.57 × 10/kg, respectively. The cumulative incidence of grade II-IV aGVHD at day 100 was 30.3% (95% confidence interval [CI], 15.9% to 44.8%), and that of grade III-IV aGVHD was 10.2% (95% CI, .6% to 19.8%). The 2-year cumulative incidence of chronic GVHD (cGVHD) was 34.9% (95% CI, 19.0% to 50.8%). The 2-year cumulative incidences of localized and extensive cGVHD were 26.1% (95% CI, 11.80% to 40.40%) and 8.7% (95% CI, 3.26% to 20.65%), respectively. The 2-year cumulative incidence of relapse was 17.3% (95% CI, 5.1% to 29.5%), the 2-year overall survival rate was 71.2% (95% CI, 57.9% to 84.5%), and the 2-year disease-free survival rate was 66.2% (95% CI, 52.1% to 80.3%). The incidence of aGVHD was not high, and the overall efficacy was good. This study demonstrates that this unique RIC-haplo-PBSC transplantation protocol was effective in treating hematologic malignancies. Nonetheless, larger prospective multicenter clinical trials and experimental studies should be performed to further confirm our findings.
减低强度预处理（RIC）单倍体相合造血干细胞移植（HSCT）需要更多的造血祖细胞和干细胞（HPSC）来促进植入和免疫重建，并且需要更强的移植物抗白血病效应。外周血干细胞（PBSC）比骨髓具有优势；然而，使用高剂量非T细胞去除（非TCD）的体外PBSC可能会增加严重移植物抗宿主病（GVHD）的发生率。本前瞻性单臂临床研究旨在探讨使用高剂量非TCD体外PBSC作为移植物来源，使用氟达拉滨/阿糖胞苷/白消安（FAB）作为预处理方案，使用兔抗胸腺细胞球蛋白在体内去除T细胞，并在年龄50至70岁或合并症（造血细胞移植合并症指数评分≥2）分类为中高风险的50岁以下血液系统恶性肿瘤患者的RIC单倍体HSCT中使用IL-2受体拮抗剂加强GVHD预防。主要终点是第100天的急性GVHD（aGVHD）。共纳入47例患者；中位年龄为52岁（范围30至68岁），中位随访时间为34个月（范围2至99个月），单核细胞、CD34细胞和CD3细胞的中位输注剂量分别为15.93×10/kg、8.68×10/kg和5.57×10/kg。第100天II-IV级aGVHD的累积发生率为30.3%（95%置信区间[CI]，15.9%至44.8%），III-IV级aGVHD的累积发生率为10.2%（95%CI，0.6%至19.8%）。慢性GVHD（cGVHD）的2年累积发生率为34.9%（95%CI，19.0%至50.8%）。局限性和广泛性cGVHD的2年累积发生率分别为26.1%（95%CI，11.80%至40.40%）和8.7%（95%CI，3.26%至20.65%）。2年复发累积发生率为17.3%（95%CI，5.1%至29.5%），2年总生存率为71.2%（95%CI，57.9%至84.5%），2年无病生存率为66.2%（95%CI，52.1%至80.3%）。aGVHD的发生率不高，总体疗效良好。本研究表明，这种独特的RIC单倍体PBSC移植方案在治疗血液系统恶性肿瘤方面是有效的。尽管如此，仍应进行更大规模的前瞻性多中心临床试验和实验研究以进一步证实我们的发现。
