Savani Bipin N, Labopin Myriam, Kröger Nicolaus, Finke Jürgen, Ehninger Gerhard, Niederwieser Dietger, Schwerdtfeger Rainer, Bunjes Donald, Glass Bertram, Socié Gerard, Ljungman Per, Craddock Charles, Baron Frédéric, Ciceri Fabio, Gorin Norbert Claude, Esteve Jordi, Schmid Christoph, Giebel Sebastian, Mohty Mohamad, Nagler Arnon
Vanderbilt University Medical Center, Nashville, TN, USA Acute Leukemia Working Party, EBMT Paris study office / CEREST-TC, France
Acute Leukemia Working Party, EBMT Paris study office / CEREST-TC, France Department of Haematology, Saint Antoine Hospital, Paris, France INSERM UMR 938, Paris, France Université Pierre et Marie Curie, Paris, France.
Haematologica. 2016 Jun;101(6):773-80. doi: 10.3324/haematol.2015.138180. Epub 2016 Mar 11.
The outcome of patients undergoing HLA-matched unrelated donor allogeneic hematopoietic cell transplantation following reduced-intensity conditioning or myeloablative regimens is reported to be equivalent; however, it is not known if the intensity of the conditioning impacts outcomes after mismatched unrelated donor transplantation for acute myeloid leukemia. Eight hundred and eighty three patients receiving reduced-intensity conditioning were compared with 1041 myeloablative conditioning regimen recipients in the setting of mismatched unrelated donor transplantation. The donor graft was HLA-matched at 9/10 in 872 (83.8%) and at 8/10 in 169 (16.2%) myeloablative conditioning recipients, while in the reduced-intensity conditioning cohort, 754 (85.4%) and 129 (14.6%) were matched at 9/10 and 8/10 loci, respectively. Myeloablative conditioning regimen recipients were younger, 70% being <50 years of age compared to only 30% in the reduced-intensity conditioning group (P=0.0001). Significantly, more patients had secondary acute myeloid leukemia (P=0.04) and Karnofsky Performance Status score <90% (P=0.02) in the reduced-intensity conditioning group. Patients <50 and ≥50 years were analyzed separately. On multivariate analysis and after adjusting for differences between the two groups, reduced-intensity conditioning in patients age ≥50 years was associated with higher overall survival (HR 0.78; P=0.01), leukemia-free survival (HR 0.82; P=0.05), and decreased non-relapse mortality (HR 0.73; P=0.03). Relapse incidence (HR 0.91; P=0.51) and chronic graft-versus-host disease (HR 1.31; P=0.11) were, however, not significantly different. In patients <50 years old, there were no statistically significant differences in overall survival, leukemia-free survival, relapse incidence, non-relapse mortality, and chronic graft-versus-host-disease between the groups. Our study shows no significant outcome differences in patients younger than 50 years receiving reduced-intensity vs myeloablative conditioning regimens after mismatched unrelated donor transplantation. Furthermore, the data support the superiority of reduced-intensity conditioning regimens in older adults receiving transplants from mismatched unrelated donors.
据报道，接受减低强度预处理或清髓性预处理方案的HLA匹配的无关供者异基因造血细胞移植患者的结局相当；然而，对于急性髓系白血病患者，在接受不匹配无关供者移植后，预处理强度是否会影响结局尚不清楚。在不匹配无关供者移植的情况下，将883例接受减低强度预处理的患者与1041例接受清髓性预处理方案的患者进行了比较。在接受清髓性预处理的患者中，872例（83.8%）供者移植物的HLA在10个位点中有9个匹配，169例（16.2%）在10个位点中有8个匹配；而在减低强度预处理队列中，分别有754例（85.4%）和129例（14.6%）在9/10和8/10位点匹配。接受清髓性预处理方案的患者更年轻，70%的患者年龄<50岁，而减低强度预处理组中这一比例仅为30%（P=0.0001）。值得注意的是，减低强度预处理组中更多患者患有继发性急性髓系白血病（P=0.04）且卡诺夫斯基功能状态评分<90%（P=0.02）。对年龄<50岁和≥50岁的患者分别进行了分析。多因素分析并校正两组之间的差异后，年龄≥50岁患者接受减低强度预处理与更高的总生存率（HR 0.78；P=0.01）、无白血病生存率（HR 0.82；P=0.05）以及降低的非复发死亡率（HR 0.73；P=0.03）相关。然而，复发率（HR 0.91；P=0.51）和慢性移植物抗宿主病（HR 1.31；P=0.11）无显著差异。在年龄<50岁的患者中，两组之间的总生存率、无白血病生存率、复发率、非复发死亡率和慢性移植物抗宿主病均无统计学显著差异。我们的研究表明，在不匹配无关供者移植后，年龄<50岁的患者接受减低强度与清髓性预处理方案的结局无显著差异。此外，数据支持在接受不匹配无关供者移植的老年患者中，减低强度预处理方案具有优势。
