Abstract：
Reduced-intensity conditioning (RIC) regimens allogeneic hematopoietic stem cell transplantation (HSCT) was developed for older patients or those with poor functional status. Haploidentical donor was appropriate alternative donor for patients without matched donors or patients with emergency disease state. However, there was few studies report the outcomes of RIC regimen of anti-thymocyte globulin (ATG) based haploidentical HSCT. The selection of the appropriate RIC regimen based on age and comorbidities in ATG-based haploidentical HSCT remains poorly described. To investigate the safety and efficacy of RIC regimen ATG-based haploidentical HSCT in older or unfit patients. Additionally, to explore the potential factors that impact the prognosis of RIC regimen of ATG-based haploidentical HSCT. We included a retrospective cohort of 63 patients with hematologic malignant diseases who underwent their first RIC haploidentical HSCT from November 2016 to June 2022 at our institutions. The conditioning regimen involved fludarabine (Flu) 30 mg/m²/kg 6 days combined with busulfan 3.2 mg/kg 2 days (Bu2) or 3 days (Bu3). ATG-Fresenius (ATG-F) was administered 10 mg/kg in total, ATG-thymoglobulin (ATG-T) was administered 6 mg/kg in total. The median age of patients in the entire cohort was 60 (32-67) years with a median follow-up of 496 (83-2182) days. There were 29 patients with AML, 20 patients with MDS, and 14 patients with ALL. A total of 32 patients underwent Bu2 RIC haplo-HSCT and 31 patients were treated with Bu3 RIC haplo-HSCT. The 2-year overall survival (OS) and 2-year disease-free survival (DFS) in whole cohort were 67.7% (95% confidence interval [CI], 53.8 - 85.1%) and 61.4% (95% CI, 48.8 - 77.3%) respectively. The cumulative incidence rates of grades II to IV and grades III to IV acute graft-versus-host disease (aGVHD) in whole cohort were 15.8% (95% CI, 4.8 - 19.6%) and 9.7% (95% CI, 0.0 - 11.8%) respectively. The 2-year cumulative incidence of chronic GVHD was 34.0% (95% CI, 18.9 - 46.3%). The 2-year cumulative incidence rates of relapse (IR) and non-relapse mortality (NRM) rates in whole cohort were 27.5% (95% CI, 14.5 - 33.7%) and 11.6% (95% CI, 2.2 - 21.9%) respectively. The probability of 2-year OS were 60.2% (95% CI:42.5-85.3%) in Bu2 and 85.5%(95% CI:73.0-100%) in Bu3 group respectively(P = 0.150). The probability of 2-year DFS were 49.7% (95% CI:33.0-74.8%) in Bu2 and 72.6% (95% CI:55.5-95.5%) in Bu3 group respectively (P = 0.045). The 2-year IR of Bu2 group was significantly higher than Bu3 group (P = 0.045). However, the 2-year NRM were not significantly different between Bu2 and Bu3 group(P > 0.05). In multivariable analysis, RIC regimen of Bu3 had superior OS and DFS than Bu2 group respectively [HR 0.42, 95% CI 0.18-0.98; P = 0.044; HR 0.34, 95% CI 0.14-0.86; P = 0.022]. Besides, RIC regimen of Bu3 had lower IR than Bu2 group [HR 0.34, 95% CI 0.13-0.89; P = 0.029]. The RIC regimen of ATG-based haploidentical HSCT is a safe and effective treatment option for patients who are older or have poor functional status. In particular, a relatively high-intensity pre-treatment regimen consisting of Bu achieves significant improvements in OS and DFS, thus providing more favorable post-transplantation clinical outcomes.
摘要：
低强度预处理（RIC）方案针对老年患者或功能状态较差的患者开发了异基因造血干细胞移植（HSCT）。对于没有匹配供体的患者或患有紧急疾病状态的患者，单倍体供体是合适的替代供体。然而,很少有研究报道基于单倍体相合HSCT的抗胸腺细胞球蛋白(ATG)RIC方案的结局.在基于ATG的单倍体相合HSCT中，根据年龄和合并症选择合适的RIC方案的描述仍然很少。探讨RIC方案基于ATG的单倍体相合HSCT在老年或不健康患者中的安全性和有效性。此外,探讨影响ATG单倍体HSCTRIC方案预后的潜在因素。我们纳入了一项回顾性队列，纳入了2016年11月至2022年6月在我们机构接受了首次RIC单倍体HSCT的63例血液恶性疾病患者。预处理方案包括氟达拉滨（Flu）30mg/m²/kg6天，白消安3.2mg/kg2天（Bu2）或3天（Bu3）。ATG-Fresenius（ATG-F）总共给药10mg/kg，ATG-胸腺球蛋白(ATG-T)总共施用6mg/kg。整个队列中患者的中位年龄为60（32-67）岁，中位随访时间为496（83-2182）天。有29例AML患者，20例MDS患者，14名ALL患者。共有32例患者接受了Bu2RIC单张-HSCT，31例患者接受了Bu3RIC单张-HSCT治疗。整个队列的2年总生存率（OS）和2年无病生存率（DFS）为67.7％（95％置信区间[CI]，53.8-85.1%）和61.4%（95%CI，48.8-77.3%）。整个队列中II至IV级和III至IV级急性移植物抗宿主病（aGVHD）的累积发病率分别为15.8％（95％CI，4.8-19.6％）和9.7％（95％CI，0.0-11.8％）。慢性GVHD的2年累积发病率为34.0％（95％CI，18.9-46.3％）。整个队列的2年累积复发率（IR）和非复发死亡率（NRM）分别为27.5％（95％CI，14.5-33.7％）和11.6％（95％CI，2.2-21.9％）。Bu2组2年OS概率为60.2%(95%CI:42.5-85.3%),Bu3组2年OS概率为85.5%(95%CI:73.0-100%)(P=0.150)。Bu2组2年DFS发生率为49.7%(95%CI:33.0~74.8%),Bu3组2年DFS发生率为72.6%(95%CI:55.5~95.5%)(P=0.045)。Bu2组的2年IR显著高于Bu3组(P=0.045)。然而,Bu2和Bu3组的2年NRM差异无统计学意义（P>0.05）。在多变量分析中，Bu3的RIC方案的OS和DFS分别优于Bu2组[HR0.42，95％CI0.18-0.98；P=0.044；HR0.34，95％CI0.14-0.86；P=0.022]。此外,Bu3的RIC方案的IR低于Bu2组[HR0.34，95％CI0.13-0.89；P=0.029]。对于年龄较大或功能状态较差的患者，基于ATG的单倍体HSCT的RIC方案是一种安全有效的治疗选择。特别是,由Bu组成的相对高强度的预处理方案在OS和DFS方面实现了显着改善，从而提供更有利的移植后临床结果。
