Myeloablative Versus Reduced-Intensity Conditioning With Fludarabine/Busulfan for Myelodysplastic Syndrome: A Propensity Score-Matched Analysis
Myeloablative Versus Reduced-Intensity Conditioning With Fludarabine/Busulfan for Myelodysplastic Syndrome: A Propensity Score-Matched Analysis
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DOI：
10.1016/j.jtct.2022.03.011
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发表时间：
2022-06-09
影响因子：
3.2
通讯作者：
Ishiyama, Ken
中科院分区：
文献类型：
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作者：
Kurosawa, Shuhei;Shimomura, Yoshimitsu;Ishiyama, Ken
在接受异基因造血干细胞移植（allo-HSCT）的骨髓增生异常综合征（MDS）患者中，比较氟达拉滨/白消安（Flu/Bu 4）清髓性预处理和氟达拉滨/白消安（Flu/Bu 2）降低强度预处理的数据有限。我们回顾性分析了全国范围内的登记数据，并通过倾向评分（PS）匹配比较了接受Flu/Bu 4和Flu/Bu 2治疗的MDS成人患者的结局。符合以下标准的患者有资格入组：（1）年龄≥ 16岁;（2）诊断为新发MDS;（3）在2006年至2018年期间首次进行allo-HSCT;（4）来自HLA匹配供体的相关骨髓移植（BMT）或外周血干细胞移植，来自HLA匹配或HLA-1等位基因不匹配供体的无关BMT，或无关的脐带血移植;和（5）接受Flu/Bu 4或Flu/Bu 2作为预处理方案。Flu/Bu 4包括静脉注射白消安（总剂量，12.8 mg/kg）和氟达拉滨（总剂量，125-180 mg/m2）。Flu/Bu 2包括静脉注射白消安（总剂量，6.4 mg/kg）和相同剂量的氟达拉滨。为了尽量减少选择偏倚和混杂因素，我们进行了倾向评分（PS）匹配分析。主要终点是allo-HSCT后的总生存期（OS）。在2006年至2018年期间，共有3386例新发MDS患者接受了首次allo-HSCT。其中，202例患者在PS匹配分析后被分配到Flu/Bu 4和Flu/Bu 2组。中位年龄为61岁（四分位数，57-65）。Flu/Bu 4和Flu/Bu 2组的3年OS率分别为44.8%（95%置信区间[CI]，37.1-52.1%）和46.9%（95% CI，39.2-54.2%）（P = 0.67）。3年无移植物抗宿主病（GVHD）生存率和无复发生存率（GRFS）分别为28.8%（95%CI，22.2-35.7%）和33.0%（95%CI，26.2-40.0%）（P = 0.36）。3年累积复发率分别为28.9%（95%CI，22.6-35.6%）和30.0%（95%CI，23.6-36.6%）（P = 0.47）。非复发死亡率（NRM）的3年累积发生率分别为28.2%（95% CI，21.7-35.0%）和27.1%（95% CI，20.6-33.9%）（P = 0.60）。Flu/Bu 4组中II=IV级急性GVHD的100天累积发生率显著高于Flu/Bu 2组（41.7% [95%CI，34.8%-48.4%] vs 29.3% [95%CI，23.2%-35.7%]，P = 0.012）。为了确定使用2种方案中的一种方案的患者具有更有利的结局，我们在按年龄、造血细胞移植-合并症指数、细胞遗传学风险、allo-HSCT时的疾病状态、干细胞来源和供体类型分层后比较了2组之间的结局。在任何亚组分析中，两组之间的OS、GRFS、复发和NRM均无差异。预处理方案的选择与任何其他因素之间没有显著的相互作用。Flu/Bu 4和Flu/Bu 2之间的生存率没有差异，尽管我们的研究人群是通过PS匹配高度选择的。需要更多患者和前瞻性研究的数据来确定MDS患者预处理方案的最佳强度。(c)2022年美国移植和细胞治疗学会。爱思唯尔公司出版All rights reserved.
There are limited data comparing myeloablative conditioning with fludarabine/busulfan (Flu/Bu4) and reduced-intensity conditioning with fludarabine/busulfan (Flu/Bu2) in patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed nationwide registry data and compared the outcomes of adult patients with MDS receiving Flu/Bu4 and Flu/Bu2 by propensity score (PS) matching. Patients who met the following criteria were eligible for enrollment: (1) age >= 16 years; (2) diagnosis of de novo MDS; (3) first allo-HSCT between 2006 and 2018; (4) related bone marrow transplantation (BMT) or peripheral blood stem cell transplantation from an HLA-matched donor, unrelated BMT from an HLA-matched or HLA-1 allele-mismatched donor, or unrelated cord blood transplantation; and (5) receiving Flu/Bu4 or Flu/Bu2 as a conditioning regimen. Flu/Bu4 comprised intravenous busulfan (total dose, 12.8 mg/kg) combined with fludarabine (total dose, 125-180 mg/m(2)). Flu/Bu2 comprised intravenous busulfan (total dose, 6.4 mg/kg) combined with the same dose of fludarabine. To minimize selection bias and confounding factors, we performed a propensity score (PS)-matched analysis. The primary endpoint was overall survival (OS) after allo-HSCT. A total of 3386 patients with de novo MDS underwent their first allo-HSCT between 2006 and 2018. Among them, 202 patients were assigned each to the Flu/Bu4 and Flu/Bu2 groups after PS-matched analysis. The median age was 61 (interquartile, 57-65) years. The 3-year OS rates were 44.8% (95% confidence interval [CI], 37.1-52.1%) and 46.9% (95% CI, 39.2-54.2%) in the Flu/Bu4 and Flu/Bu2 groups, respectively (P = .67). The 3-year rates of graft-versus-host disease (GVHD)-free survival, relapse-free survival (GRFS) were 28.8% (95% CI, 22.2-35.7%) and 33.0% (95% CI, 26.2-40.0%), respectively (P = .36). The 3-year cumulative incidence rates of relapse were 28.9% (95% CI, 22.6-35.6%) and 30.0% (95% CI, 23.6-36.6%), respectively (P = .47). The 3-year cumulative incidence rates of non-relapse mortality (NRM) were 28.2% (95% CI, 21.7-35.0%) and 27.1% (95% CI, 20.6-33.9%), respectively (P = .60). The 100-day cumulative incidence rate of grade II=IV acute GVHD was significantly higher in the Flu/Bu4 group than in the Flu/Bu2 group (41.7% [95% CI, 34.8%-48.4%] versus 29.3% [95% CI, 23.2%-35.7%], P = 0.012). To identify patients who had more favorable outcomes with 1 of the 2 regimens, we compared the outcomes between the 2 groups after stratifying by age, hematopoietic cell transplantation-comorbidity index, cytogenetic risk, disease status at allo-HSCT, stem cell source, and donor type. OS, GRFS, relapse, and NRM did not differ between the 2 groups in any subgroup analyses. There were no significant interactions between the choice of conditioning regimens and any other factors. There are no differences in survival between Flu/Bu4 and Flu/Bu2, although our study population was highly selected by PS matching. Data from more patients and prospective studies are needed to determine the optimal intensity of conditioning regimens in patients with MDS. (c) 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.