Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease-Based Definition of Complete Remission?
Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease-Based Definition of Complete Remission?
复制标题
DOI：
10.1200/jco.2015.63.3826
复制
发表时间：
2016-02-01
影响因子：
45.3
通讯作者：
Walter, Roland B.
中科院分区：
文献类型：
--
作者：
Araki, Daisuke;Wood, Brent L.;Walter, Roland B.
目的
在异基因造血细胞移植（HCT）的治疗方案中，形态学完全缓解的急性髓系白血病（AML）患者通常与活动性疾病患者（即形态学上骨髓原始细胞≥5%）分开考虑，这意味着这两组患者有不同的预后。众所周知，对于形态学缓解的患者，移植时微小残留病（MRD）的存在与移植后不良预后相关。移植前MRD的这种影响促使我们比较连续的MRD阳性缓解患者与在我们机构接受清髓性异基因HCT的活动性AML患者的预后。
患者与方法
我们回顾性研究了2006年至2014年间359例连续的接受外周血或骨髓供者清髓性异基因HCT的成年AML患者。移植前疾病分期包括对所有患者的骨髓穿刺液进行10色多参数流式细胞术检测。任何水平的残留疾病都被视为MRD阳性。
结果
MRD阳性形态学缓解的76例患者3年复发率估计为67%，活动性AML的48例患者为65%，而MRD阴性缓解的235例患者为22%。这三组患者的3年总生存率估计分别为26%、23%和73%。经过多变量调整后，与MRD阳性形态学缓解状态或患有活动性疾病相比，MRD阴性缓解状态在统计学上仍与更长的总生存期和无进展生存期以及更低的复发风险显著相关，后两组之间预后相似。
结论
HCT时MRD阳性形态学缓解患者与活动性疾病患者预后的相似性支持使用基于MRD而非基于形态学的疾病评估的治疗方案。
PurposePatients with acute myeloid leukemia (AML) who are in morphologic complete remission are typically considered separately from patients with active disease (ie, >= 5% marrow blasts by morphology) in treatment algorithms for allogeneic hematopoietic cell transplantation (HCT), which implies distinct outcomes for these two groups. It is well recognized that the presence of minimal residual disease (MRD) at the time of transplantation is associated with adverse post-HCT outcome for those patients in morphologic remission. This effect of pre-HCT MRD prompted us to compare outcomes in consecutive patients in MRD-positive remission with patients with active AML who underwent myeloablative allogeneic HCT at our institution.Patients and MethodsWe retrospectively studied 359 consecutive adults with AML who underwent myeloablative allogeneic HCT from a peripheral blood or bone marrow donor between 2006 and 2014. Pre-HCT disease staging included 10-color multiparametric flow cytometry on bone marrow aspirates in all patients. Any level of residual disease was considered to be MRD positive.ResultsThree-year relapse estimates were 67% in 76 patients in MRD-positive morphologic remission and 65% in 48 patients with active AML compared with 22% in 235 patients in MRD-negative remission. Three-year overall survival estimates were 26%, 23%, and 73% in these three groups, respectively. After multivariable adjustment, MRD-negative remission status remained statistically significantly associated with longer overall and progression-free survival as well as lower risk of relapse compared with MRD-positive morphologic remission status or having active disease, with similar outcomes between the latter two groups.ConclusionThe similarities in outcomes between patients in MRD-positive morphologic remission and those with active disease at the time of HCT support the use of treatment algorithms that use MRD-rather than morphology-based disease assessments.