Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia.
Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia.
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加强的降低强度方案不能改善急性髓系白血病的同种异体移植后结局
DOI：
10.1200/jco.20.02308
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发表时间：
2021-03-01
期刊：
影响因子：
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通讯作者：
Freeman SD
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文献类型：
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作者：
Craddock C;Jackson A;Loke J;Siddique S;Hodgkinson A;Mason J;Andrew G;Nagra S;Malladi R;Peniket A;Gilleece M;Salim R;Tholouli E;Potter V;Crawley C;Wheatley K;Protheroe R;Vyas P;Hunter A;Parker A;Wilson K;Pavlu J;Byrne J;Dillon R;Khan N;McCarthy N;Freeman SD
降低强度预处理（RIC）方案已将异基因干细胞移植的治疗潜力扩展到患有高危急性髓性白血病（AML）和骨髓增生异常（MDS）的老年人，但与疾病复发的高风险相关。迫切需要减少复发的战略。登记数据表明，使用序贯移植方案氟达拉滨/安吖啶/阿糖胞苷-白消安（FLAMSA-Bu）可改善结局，但尚未在随机试验中研究这种强化预处理方案的影响。244例高危AML（n = 164）或MDS（n = 80）患者（中位年龄59岁）以1：1的比例随机分配至基于氟达拉滨的RIC方案或FLAMSA-Bu方案。通过流式细胞术（MFC-MRD）监测移植前可测量残留病变（MRD），并与预后相关。对照组和FLAMSA-Bu组的2年总生存率（风险比1.05 [85%CI，0.80 - 1.38] P = 0.81）或累积复发率（CIR）（风险比0.94 [95%CI，0.60 - 1.46] P = 0.81）无差异。在整个试验队列中，可检测的移植前MFC-MRD与CIR增加相关（2年CIR 41.0% vs 20.0%，P = 0.01），当通过非监督分析方法测量时，具有相当的预后影响。没有证据表明MRD状态和预处理方案强度对复发或生存率有相互作用。在3个月时获得完全供体T细胞嵌合体消除了移植前MRD对CIR和总生存率的不利影响。无论移植前MRD状态如何，强化RIC预处理方案FLAMSA-Bu均未改善因高危AML或MDS移植的成人患者的结局。相反，我们的数据支持探索能够加速获得完全供体T细胞嵌合体的干预措施，作为改善AML同种异体移植患者结局的易处理策略。
Reduced-intensity conditioning (RIC) regimens have extended the curative potential of allogeneic stem-cell transplantation to older adults with high-risk acute myeloid leukemia (AML) and myelodysplasia (MDS) but are associated with a high risk of disease relapse. Strategies to reduce recurrence are urgently required. Registry data have demonstrated improved outcomes using a sequential transplant regimen, fludarabine/amsacrine/cytarabine-busulphan (FLAMSA-Bu), but the impact of this intensified conditioning regimen has not been studied in randomized trials. Two hundred forty-four patients (median age, 59 years) with high-risk AML (n = 164) or MDS (n = 80) were randomly assigned 1:1 to a fludarabine-based RIC regimen or FLAMSA-Bu. Pretransplant measurable residual disease (MRD) was monitored by flow cytometry (MFC-MRD) and correlated with outcome. There was no difference in 2-year overall survival (hazard ratio 1.05 [85% CI, 0.80 to 1.38] P = .81) or cumulative incidence of relapse (CIR) (hazard ratio 0.94 [95%CI, 0.60 to 1.46] P = .81) between the control and FLAMSA-Bu arms. Detectable pretransplant MFC-MRD was associated with an increased CIR (2-year CIR 41.0% v 20.0%, P = .01) in the overall trial cohort with a comparable prognostic impact when measured by an unsupervised analysis approach. There was no evidence of interaction between MRD status and conditioning regimen intensity for relapse or survival. Acquisition of full donor T-cell chimerism at 3 months abrogated the adverse impact of pretransplant MRD on CIR and overall survival. The intensified RIC conditioning regimen, FLAMSA-Bu, did not improve outcomes in adults transplanted for high-risk AML or MDS regardless of pretransplant MRD status. Our data instead support the exploration of interventions with the ability to accelerate acquisition of full donor T-cell chimerism as a tractable strategy to improve outcomes in patients allografted for AML.