曲硫丹因其清髓性和低毒性而在异基因造血细胞移植(HCT)中显示出希望。在这项单中心回顾性倾向评分匹配的队列研究中,我们比较了同种异体HCT中基于甲磺胺和白消安的条件对骨髓增生异常综合征(MDS)患者的影响。这项研究包括138名成年人,他们在玛格丽特公主医院接受了因MDS或慢性粒单核细胞白血病(CMML)的同种异体HCT,多伦多2015-2022年。使用倾向得分匹配,我们比较了两个匹配良好的队列的移植结局,这些队列接受了氟达拉滨-曲硫丹(FT)(n=46)或氟达拉滨-白消安-全身照射(FBT200)(n=92)的预处理.基于患者年龄的评分系统,根据Karnofsky表现评分和造血细胞移植合并症指数,根据适合度将患者分为低剂量(30g/m2)或高剂量(42g/m2)曲硫丹:32例(69.6%)接受高剂量曲硫丹。两组的种族组成相似,有27.2%和21.7%的FBT200和FT接受者,分别,非白种人(P=0.61)。在747天的中位随访中分析主要结果。在所有参与者中,116(84.0%)接受了移植后环磷酰胺(PTCY)和抗胸腺细胞球蛋白(ATG)的移植物抗宿主病(GVHD)预防。与接受FBT200的患者相比,接受FT的患者具有优于2-y的总生存率(OS):66.9%(95%置信区间(CI):46.1-81.2)与44.5%(95%CI:34-54.4),危险比(HR):0.43,95%CI:0.22-0.84(P=0.013)。在多变量分析(MVA)中,仅使用新鲜移植物(P=0.02)和FT(P=0.01)与OS改善相关。与FBT200相比,FT与优于2-y无复发生存率(RFS)相关:63.1%(95%CI:42.6-77.9)与39.1%(95%CI:29.1-49.1),HR:0.44(95%CI:0.24-0.81),P=0.008。在MVA中,使用新鲜移植物(P=0.03)和FT(P=0.009)与RFS改善相关.与接受FBT200的患者相比,FT的接受者表现出优异的2-y移植物抗宿主病无复发生存率(GRFS):57.4%(95%CI:37.8-72.8)与35.1%(95%CI:25.5-45)。在MVA中,只有FT与优越的GRFS相关(P=0.02)。在单因素分析中,与FBT200的接受者相比,FT接受者表现出明显优于1-y无事件生存率(EFS)(40.3%(95%CI:25.9-54.2)与9.2%(95%CI:4.4-16.3),HR:0.47(95CI:0.30-0.72),P<0.001)和MVA(P=0.004)。在单因素分析中,与FBT200相比,FT与较低的1-y非复发死亡率(NRM)相关(9.9%(95%CI:3.0-21.8)与29.7%(95%CI:20.6-39.3),HR:0.41(95%CI:0.17-0.96),P=0.04)和MVA(P=0.04)。我们的研究利用倾向评分匹配来证明在MDS患者的干细胞移植中,基于甲硫丹的预处理优于基于白消安的预处理,并且是第一个评估基于甲硫丹的预处理与ATG和PTCY组合的性能的研究。因此,它有助于越来越多的证据支持曲硫丹的安全性,即使在42克/平方米的剂量。
Treosulfan has shown promise in allogeneic hematopoietic cell transplantation (HCT) for its myeloablative properties and low toxicity. In this single-center retrospective propensity score-matched cohort
study we compared treosulfan- and
busulfan-based conditioning in allogeneic HCT for patients with myelodysplastic syndrome (MDS). This
study included 138 adults who underwent allogeneic HCT for MDS or chronic myelomonocytic leukemia at Princess Margaret Hospital, Toronto, from 2015 to 2022. Using propensity score matching, we compared transplant outcomes between 2 well-matched cohorts who received conditioning with either fludarabine-treosulfan (FT) (n = 46) or fludarabine-
busulfan with total body irradiation (FBT200) (n = 92). A scoring system based on patient age, Karnofsky performance score, and hematopoietic cell transplant comorbidity index was used to assign patients based on fitness to low-dose (30 g/m2) or high-dose (42 g/m2) treosulfan: 32 (69.6%) received high-dose treosulfan. The racial composition of the 2 groups was similar, with 27.2% and 21.7% of FBT200 and FT recipients, respectively, identifying as non-Caucasian (P = .61). Primary outcomes were analyzed at a median follow-up of 747 days. Of all participants, 116 (84.0%) received graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCY) and antithymocyte globulin (ATG). Patients who received FT had a superior 2-year overall survival (OS) compared to those who received FBT200: 66.9% (95% confidence interval (CI): 46.1 to 81.2) versus 44.5% (95% CI: 34 to 54.4), hazard ratio (HR): 0.43, 95% CI: 0.22 to 0.84 (P = .013). In multivariate analysis (MVA), only the use of fresh grafts (P = .02) and FT (P = .01) were associated with improved OS. FT was associated with superior 2-year relapse-free survival (RFS) compared to FBT200: 63.1% (95% CI: 42.6 to 77.9) versus 39.1% (95% CI: 29.1 to 49.1), HR: 0.44 (95% CI: 0.24 to 0.81), P = .008. In MVA, the use of fresh grafts (P = .03) and FT (P = .009) were associated with improved RFS. Recipients of FT demonstrated superior 2-year graft-versus-host disease relapse-free survival (GRFS) compared to those who received FBT200: 57.4% (95% CI: 37.8 to 72.8) versus 35.1% (95% CI: 25.5 to 45). In MVA, only FT was associated with superior GRFS (P = .02). FT recipients exhibited markedly superior 1-year event-free survival compared to recipients of FBT200 in univariate analysis (40.3% (95% CI: 25.9 to 54.2) versus 9.2% (95% CI: 4.4 to 16.3), HR: 0.47 (95% CI: 0.30 to 0.72), P < .001) and MVA (P = .004). FT was associated with lower 1-year nonrelapse mortality compared to FBT200 in univariate analysis (9.9% (95% CI: 3.0 to 21.8) versus 29.7% (95% CI: 20.6 to 39.3), HR: 0.41 (95% CI: 0.17 to 0.96), P = .04) and MVA (P = .04). Our
study utilized propensity score matching to demonstrate superiority of treosulfan- over
busulfan-based conditioning in stem cell transplantation of patients with MDS and is the first to evaluate the performance of treosulfan-based conditioning in combination with ATG and PTCY. As such, it contributes to the increasing body of evidence supporting the safety of treosulfan, even at the dose of 42 g/m2.